Conditions: Lymphoma, Non-Hodgkin; Leukemia, Chronic Lymphocytic
Keywords: Phase 1 Safety Apilimod dimesylate Pharmacokinetics Non-Hodgkin Lymphoma Chronic lymphocytic leukemia
Allocation: NON_RANDOMIZED | Intervention model: SINGLE_GROUP
Enrollment: 62
Healthy volunteers: no

Brief summary:
This is a Phase 1 dose-exploration study of LAM-002A administered by mouth in patients with relapsed or refractory B-cell NHL. Safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD),and preliminary anti-tumor activity will be evaluated.

Detailed description:
LAM-002A is supplied as 25-mg or 50-mg capsules and will be administered two times daily or three times daily by mouth in repeated 28-day cycles. Patients will be advised to take the doses at the same time each day.

A 3 + 3 design will be utilized to define a maximum tolerated dose (MTD). The MTD is defined as the highest dose at which no more than 1 of 6 patients (i.e., \< 33%) experiences a dose-limiting toxicity (DLT) in the dose cohort.

Once the dose and schedule are established, additional patients will be treated to better characterize the safety, tolerability,PK, PD, and anti-tumor activity of LAM-002A when administered alone or in combination with rituximab or atezolizumab.

Arms:
arm 1: All patients will take LAM-002A two times daily by mouth every day until cancer progression or intolerability. arm 2: All patients will receive LAM-002A at escalating dose levels two times daily by mouth for 3 days on therapy followed by 4 days off therapy every week until cancer progression or intolerability. arm 3: All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and rituximab 375 mg/m2 by vein every week for 4 weeks and then every 8 weeks for 4 times (total of 8 infusions) arm 4: All patients will receive LAM-002A 125mg two times daily by mouth every day until cancer progression or intolerability and atezolizumab 1200 mg by vein every 3 weeks until cancer progression or intolerability

Interventions: intervention 1: LAM-002A intervention 2: Rituximab intervention 3: Atezolizumab
Intervention descriptions: intervention 1: 25 mg capsules or 50 mg capsules intervention 2: 375 mg/m2 by vein intervention 3: 1200 mg by vein

Protocol document:
Prot_SAP_000.pdf: 
1.
CLINICAL STUDY PROTOCOL 
•
Protocol Title:  
A PHASE 1 DOSE ESCALATION STUDY OF THE SAFETY  
 
AND PHARMACOKINETICS OF LAM-002A (APILIMOD DIMESYLATE 
CAPSULES) ADMINISTERED ORALLY IN SUBJECTS WITH RELAPSED OR 
REFRACTORY B-CELL NON-HODGKIN'S LYMPHOMA 
•
Protocol Number: LAM-002A-NHL-CLN01 v9 Amend 8 
•
Protocol Date: 
18 FEB 2020
•
NCT: 
 
NCT02594384
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Protocol: LAM-002A-NHL-CLN01 
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INVESTIGATOR’S AGREEMENT 
 
I have read the attached Protocol entitled “A Phase 1 Dose Escalation Study of the Safety and 
Pharmacokinetics of LAM-002A (apilimod dimesylate capsules) Administered Orally in 
Subjects with Relapsed or Refractory B-cell Non-Hodgkin's Lymphoma” dated 18 Feb 2020. I 
agree to abide by all provisions set forth herein. I agree to comply with the International 
Conference on Harmonisation Guidelines on Good Clinical Practice, effective in the United 
States from 09 May 1997, and applicable United States Food and Drug Administration 
regulations set forth in 21 Code of Federal Regulations (CFR) §50, 54, 56, and 312 and any 
applicable local regulatory requirements. I agree to ensure that the confidential information 
contained in this document will not be used for any purpose other than the evaluation and 
conduct of the clinical investigation without the prior written consent of AI Therapeutics, Inc. 
530 Old Whitfield Street, Guilford CT 06437, United States. 
 
 
Printed Name of Investigator 
 
Signature of Investigator 
 
Date 
 
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Protocol: LAM-002A-NHL-CLN01 
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1. 
SYNOPSIS 
Name of Sponsor/Company: 
AI Therapeutics, Inc. (AI Therapeutics) 
530 Old Whitfield Street 
Guilford, CT 06437 
Name of Investigational Product: 
LAM-002A (apilimod dimesylate capsules) 
Name of Active Ingredient: 
(E)-4-(6-(2-(3-methylbenzylidene)hydrazinyl)-2-(2-(pyridin-2-yl)ethoxy)pyrimidin-4-
yl)morpholine dimesylate  
Title of Study:  
A Phase 1 Dose-Escalation Study of the Safety and Pharmacokinetics of LAM-002A 
(apilimod dimesylate capsules) Administered Orally in Subjects with Relapsed or Refractory 
B-cell Non-Hodgkin's Lymphoma 
Study Center(s):  
Dose Escalation Stage: Up to ~10 US sites are planned 
Expansion Stage: ~15 US sites are planned 
Extension Stage: Up to 2 US sites are planned 
Objectives:  
The overall purpose of this Phase 1 study is to explore the safety and tolerability of 
LAM-002A when given alone and in combination for the treatment of subjects with relapsed 
or refractory B-cell non-Hodgkin lymphoma (NHL).  
Primary: 
• To determine the maximum tolerated dose (MTD) of daily oral administration of LAM-
002A in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). 
Secondary: 
• To evaluate the plasma pharmacokinetics (PK) of apilimod, and its active metabolites, 
administered orally in subjects with relapsed or refractory NHL. 
• To evaluate the safety and tolerability of daily oral administration of LAM-002A in 
subjects with relapsed or refractory B-cell NHL. 
• To evaluate the preliminary anti-tumor activity of LAM-002A. 
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Exploratory: 
• To evaluate the pharmacodynamic effects of LAM-002A, administered orally, in plasma 
assays and surrogate tissue (gene expression in peripheral blood mononuclear cells 
[PBMCs]/B cells and plasma cytokines [including (IL)-12 and IL-23]).  
• To evaluate tumor and/or plasma for gene expression and genetic alterations (with saliva 
or B-cell-depleted PBMC collection for germ-line control) and surrogate tissue 
(PBMC/B cells) for gene expression that may predict anti-lymphoma activity. 
• To evaluate plasma for changes in analytes or tumor for protein expression that may 
predict anti-lymphoma activity. 
Methodology:  
This is a Phase 1, single–arm, open-label, dose-escalation and cohort-expansion study 
evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of 
LAM-002A administered orally in subjects with relapsed or refractory B-cell NHL. The 
study consists of 3 stages, a dose-escalation stage, an expansion stage, and an extension 
stage.  
In the dose-escalation stage (Stage 1), a 3 + 3 design will be utilized to define an MTD of 
LAM-002A, first when administered continuously and then when administered 
intermittently. Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher 
starting dose levels of LAM-002A, as indicated in Table S-1. The initial cohort of subjects 
will be prescribed LAM-002A at Dose Level 0 (50 mg twice per day [BID]). Dose level -1 
(25 mg BID) is provided to permit a dose decrement in subjects experiencing DLT at 
Dose Level 0. 
Table S-1. LAM-002A Provisional Starting Dose Levels 
Continuous Administration 
Dose Level 
LAM-002A Dose and Schedule 
LAM-002A Total Daily Dose 
-1  
  25 mg BID 
50 mg 
0 (Initial Dose Level) 
  50 mg BID 
100 mg 
1 
100 mg BID 
200 mg 
1a 
125 mg BID 
250 mg 
1b 
  75 mg TID 
225 mg 
1c 
100 mg TID 
300 mg 
1d 
125 mg TID 
375 mg 
2 
150 mg BID 
300 mg 
3 
200 mg BID 
400 mg 
4 
275 mg BID 
550 mg 
Intermittent Administration 
Dose Level 
LAM-002A Dose and Schedule 
LAM-002A Total Daily Dose 
5 
150 mg BID 
300 mg 
6 
200 mg BID 
400 mg 
7 
250 mg BID 
500 mg 
8 
 300 mg BID 
600 mg 
Abbreviations: BID: Twice daily (or 2 times per day); TID: Thrice daily (or 3 times per day) 
 
 
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For each cohort of 3 subjects in the continuous and intermittent administration approaches, 
dose escalation to the next higher dose may proceed if no dose-limiting toxicity (DLT) is 
observed within the first cycle of the 3 subjects accrued to a cohort. If 1 of 3 subjects in the 
cohort experiences a DLT, up to a total of 6 subjects will be enrolled. If 2 or more of the 3-6 
subjects in a cohort experience a DLT, dose escalation will cease, and additional subjects 
will be treated at a lower dose level or with another schedule. If de-escalation to the previous 
dose cohort is undertaken, this cohort will be expanded to ≥6 subjects. Additional subjects 
(up to 12 total per cohort) may be evaluated to refine the estimation of the MTD and RP2D at 
the planned dose levels or at an intermediate dose level between the highest previously 
tolerated total dose and the next planned total daily dose. The MTD is defined as the highest 
dose at which < 33% of subjects experiences a DLT in the total dose and schedule cohort. 
The investigators and sponsor will review available data including toxicity, PK and anti-
tumor activity data to reach consensus on dose levels and determination of the MTDs with 
continuous and intermittent dosing. 
Once the MTD and/or recommended phase 2 dose (RP2D and schedule is determined, the 
study will enter the expansion stage (Stage 2), in which cohorts of subjects will be accrued in 
order to obtain additional information on safety, tolerability, preliminary anti-tumor activity, 
PK, and pharmacodynamic data at the RP2D and schedule when LAM-002A is administered 
alone or in combination with rituximab/rituximab hyaluronidase human or atezolizumab. 
Expansion-stage cohorts will comprise groups of subjects with specific types of previously 
treated, relapsed, progressive, and measurable NHL who will receive LAM-002A 
monotherapy or LAM-002A-containing combination therapy as shown in Table S-2. For 
both monotherapy and combination cohorts, the starting dose of LAM-002A will be 125 mg 
BID administered continuously. 
Table S-2. Expansion Stage Disease Types and Therapies 
Cohort 
Number 
NHL Type 
Investigational  
Regimen 
Combination  
Drug 
Evaluable  
Subjects, n 
1 
FL 
LAM-002A 
-- 
Up to ~20 
2 
MZL 
LAM-002A 
-- 
6 
3 
DLBCL-GCB 
LAM-002A 
-- 
6 
4 
DLBCL-ABC 
LAM-002A 
-- 
6 
5 
FL or MZL 
LAM-002A 
Rituximab or rituximab 
hyaluronidase human 
Up to ~20 
with FL 
6 
DLBCL-GCB or DLBCL-ABC 
LAM-002A 
Rituximab or rituximab 
hyaluronidase human 
6 
7 
FL or MZL 
LAM-002A 
Atezolizumab 
6 
8 
DLBCL-GCB or DLBCL-ABC 
LAM-002A 
Atezolizumab 
6 
Abbreviations: ABC: activated B-cell (subtype); DLBCL: diffuse large B-cell lymphoma; FL: follicular 
lymphoma; GCB: germinal center B-cell (subtype); MZL: marginal zone lymphoma; NHL: non-Hodgkin 
lymphoma 
The extension stage (Stage 3) can begin once the last study subject has completed at least 
8 cycles of study treatment. At this time, the study sponsor will conclude the dose-escalation 
and expansion stages of the study, will collate and verify all study data through an 
appropriate data cutoff date, and will lock the study database for preparation of a study 
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report. Subjects who are still safely benefiting from Stage 1 or Stage 2 study therapy as of the 
data cutoff date may electively continue their current regimen of study therapy in Stage 3, 
receiving clinical care and diagnostic testing consistent with conventional practice standards 
as deemed appropriate by the treating investigator. Therapy in Stage 3 may continue in the 
absence of protocol-defined reasons to discontinue therapy. During Stage 3, collection of 
clinical data by the sponsor will be limited to serious adverse event (SAE) reports. Study 
drug accountability will be managed per site procedures; relevant pharmacy records may be 
collected by the sponsor to document study drug disposition.  
Each subject’s course on study will consist of the following periods: 
• Pre-Treatment Period: The subject is consented and undergoes screening assessments to 
be qualified for the study. 
• Treatment Period: The subject is treated, monitored for safety (including assessments of 
adverse events [AEs], vital signs, electrocardiograms [ECGs], laboratory tests and 
concomitant medications), and PK and biomarker samples are collected.  
• Post-Treatment Period: Subjects should be followed until the later of either 30 days after 
the last dose of study treatment or until resolution/stabilization of any ongoing drug-
related AEs and/or SAEs. For subjects with events that require follow-up, information 
regarding concomitant medications should be collected. Any necessary follow-up may be 
obtained in person or by telephone contact.  
Subjects who have discontinued study treatment for reasons other than progressive disease 
(PD) will be assessed per standard response criteria for NHL or chronic lymphocytic 
leukemia/small lymphocytic lymphoma (CLL/SLL) at a minimum of every 12 weeks until 
documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (Cycle 1 Day 1), whichever comes first.  
Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month 
intervals at the sponsor’s discretion through 3 years. This long-term follow-up information 
will be gathered during routine clinic visits, other study site contact with the subjects, or via 
telephone or e-mail with the subjects/caregivers or referring physician offices. 
Number of Subjects (planned): 
As many as 145 future subjects may be enrolled, assuming that: 
• In the dose-escalation stage of the study, the total number of subjects will depend upon 
the numbers of subjects accrued to each dose level and the number of dose levels 
evaluated. If 6 subjects are enrolled at all open starting dose levels (Dose Levels 5, 6, 7, 
and 8) and 6 additional subjects are enrolled at the MTD or RP2D, as many as 30 
subjects could be enrolled. To allow for the possibility that some subjects may not be 
fully evaluable for DLT or that an intermediate dose level might be evaluated, up to 
~45 subjects may be enrolled.  
• In the expansion stage of the study, if all 8 potential expansion cohorts are accrued, as 
many as ~76 subjects could be enrolled. To allow for the possibility that some subjects 
may not be fully evaluable for efficacy or to establish bounds on efficacy estimates with 
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greater confidence, up to ~100 subjects may be enrolled. 
• In the extension stage of the study, the total number of subjects will include ≤4 subjects 
who have participated in the expansion stage of the study and are still receiving  study 
therapy on the data cutoff date that concludes the dose-escalation and expansion stages of 
the clinical trial. 
Diagnosis and Main Criteria for Inclusion and Exclusion: 
Inclusion Criteria: 
1. The subject is capable of understanding and complying with the protocol 
requirements and has signed the informed consent document. The subject is able to 
provide signed and dated informed consent prior to initiation of any study-specific 
procedures. 
2. Subjects must have a histologically confirmed diagnosis of B-cell NHL limited to FL, 
DLBCL, mantle cell lymphoma (MCL), MZL, primary mediastinal B-cell lymphoma 
(PMBL), or CLL/SLL according to the World Health Organization (WHO) 
classification, that has progressed and for which standard curative measures do not 
exist or are no longer effective.  
3. Subjects with DLBCL must have progressed after transplant, or be unwilling, unable 
or not an appropriate candidate for an autologous stem cell or bone marrow 
transplant. 
4. Subjects must have radiographically measurable lymphadenopathy or extranodal 
lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures ≥ 2.0 cm in 
the longest dimension [LD] and ≥ 1.0 cm in the longest perpendicular dimension 
[LPD] as assessed radiographically). 
5. The subject is ≥ 18 years old. 
6. The subject has an Eastern Cooperative Oncology Group (ECOG) Performance 
Status of ≤ 2. 
7. The subject has organ and marrow function as follows: 
a. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1,000/mm3) without 
hematopoietic-stimulating factor support 
b. Platelets ≥ 50 × 109/L (50,000/mm3) 
c. Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) except for subjects with 
known Gilbert disease (total bilirubin ≤ 3 x ULN permitted) 
d. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min 
(based on the Cockcroft-Gault formula) 
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) 
≤ 2.5 x ULN if no liver involvement, or ≤ 5 x ULN with liver involvement 
f. Albumin ≥ 2 g/dL 
g. Note: Grade ≥ 3 neutropenia or thrombocytopenia is permitted if the 
abnormality is related to bone marrow involvement with hematological malignancy 
(as documented by bone marrow biopsy/aspirate obtained since the last prior 
therapy). 
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8. The subject has the ability to swallow oral capsules without difficulty. 
9. Sexually active subjects (men and women), even if on oral contraceptives, must agree 
to remain abstinent (refrain from heterosexual intercourse) or use appropriate 
contraceptive methods (see Section 6.10.2) during the treatment period and for 
5 months after the last dose of study therapy.  
10. Women of childbearing potential (WCBP) must have a negative serum or urine 
pregnancy test at screening. WCBP include any woman who has experienced 
menarche and who has not undergone successful surgical sterilization (hysterectomy, 
bilateral tubal ligation, or bilateral oophorectomy) or is not postmenopausal. 
Postmenopausal is defined as: 
a. Amenorrhea ≥ 12 consecutive months without another cause or 
b. For women with irregular menstrual periods and on hormone replacement 
therapy, a documented serum follicle stimulating hormone (FSH) level > 
35 mIU/mL 
11. For subjects with lymphoma: The subject is willing to undergo a pretreatment core 
needle, excisional, or incisional biopsy of a lymphoma nodal lesion (preferred); or is 
willing to undergo a pretreatment bone marrow aspirate if there is known bone 
marrow involvement (≥ 50% NHL cells).  If a biopsy or bone marrow aspirate is not 
possible, archived tumor tissue that was obtained within 4 months prior to the start of 
screening can be used, provided adequate quantities are available.  
12. For subjects with CLL/SLL: The subject has sufficient circulating cells in the 
peripheral blood (e.g., ALC ≥ 10 x 109/L) or is willing to undergo a pretreatment 
bone marrow aspirate to obtain CLL cells. 
Exclusion Criteria: 
1. Subjects with central nervous system (CNS) lymphoma are not eligible for the trial 
unless the disease had been treated and the subject remained asymptomatic (for at 
least 6 months) with no active CNS lymphoma, as determined by lumbar puncture, 
computed tomography scan (CT), or magnetic resonance imaging (MRI). 
2. The subject has received cytotoxic chemotherapy (including investigational cytotoxic 
chemotherapy) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before 
the first dose of study treatment. 
3. The subject has received treatment with a therapeutic antibody less than 4 weeks 
before the first dose of study treatment. For subjects with rapidly progressive or 
aggressive subtypes of lymphoma, a minimum period of 2 weeks between the last 
treatment with a therapeutic antibody and the first dose of study treatment may be 
permitted following discussion with the medical monitor. 
4. The subject has received radioimmunotherapy within 6 weeks of the first dose of 
study treatment. 
5. The subject has received radiation therapy within 14 days of the first dose of study 
treatment. 
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6. The subject has received prior treatment with a small-molecule kinase inhibitor or 
other small-molecule investigational agent within 14 days or 5 half-lives of the 
compound or active metabolites, whichever is greater, before the first dose of study 
treatment. 
7. Stage 2 (study candidates being considered for LAM-002A/rituximab combination 
therapy): Best overall response with the last regimen containing an anti-CD20 
antibody (eg, rituximab, ofatumumab, obinutuzumab) was disease progression. 
8. Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy): Prior exposure to a CD137 agonist or an immune checkpoint 
inhibitor, including an anti-PD1, anti-PDL1, or anti-CTLA4 therapeutic antibody. 
9. Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy):  treatment with a live, attenuated vaccine within 4 weeks prior 
to initiation of study treatment, or anticipation of need for such a vaccine during 
atezolizumab treatment or within 5 months after the last dose of atezolizumab. 
10. Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy):  Current treatment with anti-viral therapy for hepatitis B virus 
(HBV). 
11. Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy):  Treatment with systemic immunostimulatory agents 
(including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 
5 half-lives of the drug (whichever is longer) prior to initiation of study treatment. 
12. The subject is currently receiving treatment with strong inhibitors or inducers of 
CYP450 2C9 or 3A4 enzymes. 
13. The subject is chronically receiving immunosuppressive therapy (eg, with 
cyclophosphamide, azathioprine, thalidomide, lenalidomide, methotrexate, or 
anti-TNF-α agents) within 2 weeks prior to initiation of study treatment or requires 
systemic or enteric corticosteroids at the time of starting study therapy. Study 
candidates using systemic low-dose corticosteroids for orthostatic hypotension or 
adrenal insufficiency or topical, intra-articular, nasal, or inhaled corticosteroids are 
not excluded from study participation. Note: During study therapy, subjects may use 
systemic, enteric, topical, intraarticular, nasal, or inhaled corticosteroids as 
required by protocol or for treatment-emergent conditions. 
14. The subject has not recovered from toxicity due to all prior therapies (i.e., return to 
pre-therapy baseline or to Grade 0 or 1). Persistent > Grade 1 toxicity from prior 
therapy will be considered by the sponsor for inclusion if there is no evidence of an 
overlapping LAM-002A toxicity.  
15. The subject has uncontrolled significant intercurrent illness including, but not limited 
to, ongoing or active infection, history of congestive heart failure within 6 months, 
Grade ≥3 hypertension, unstable angina pectoris within 6 months, stroke within 
6 months, myocardial infarction within 6 months, or cardiac arrhythmias. (Controlled 
chronic atrial fibrillation will not be excluded). 
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16. Severe uncontrolled infection within 2 weeks prior to initiation of study treatment, 
including hospitalization for complications of infection, bacteremia, or severe 
pneumonia or treatment with therapeutic oral or IV antibiotics. Note: subjects 
receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or 
chronic obstructive pulmonary disease exacerbation) are not excluded.  
17. Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy): Active or history of autoimmune disease or immune 
deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune 
hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel 
disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren 
syndrome, Guillain-Barré syndrome, or multiple sclerosis (with the following 
exceptions: history of autoimmune-related hypothyroidism and receiving 
thyroid-replacement hormone; controlled Type 1 diabetes mellitus on an insulin 
regimen; eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic 
manifestations if rash covers < 10% of body surface area, disease is well controlled at 
baseline and requires only low-potency topical corticosteroids, there is no occurrence 
of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet 
A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or 
high-potency or oral corticosteroids within the previous 12 months, and the subject 
does not have extra-cutaneous disease [e.g., psoriatic arthritis]).  
18. The subject has a history of malabsorption or other GI disease that may significantly 
alter the absorption of apilimod (e.g., ≥ Grade 2 nausea, vomiting or diarrhea). 
19. The subject has undergone major surgery within 28 days prior to first dose of study 
drug. 
20. The subject has a QTcF > 470 msec on screening ECG or has a history or risk factors 
for, or use of medications known to prolong QTc interval or that may be associated 
with Torsades de Pointes within 7 days of treatment start. 
21. The subject has past history of tuberculosis (TB) or active infection with TB, human 
immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). 
Note: Subjects must have negative human immunodeficiency virus (HIV) antibody, 
negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) 
antibody or undetectable HBV deoxyribonucleic acid (DNA) by quantitative 
polymerase chain reaction (PCR) testing, and negative HCV antibody or negative 
HCV ribonucleic acid (RNA) by quantitative PCR. 
22. The subject is lactating and breast feeding. 
23. The subject has a previously identified allergy or hypersensitivity to components of 
the study treatment formulation. 
24. Stage 1 (study candidates being considered for LAM-002A intermittent 
administration): Known inability to tolerate the protocol-specified antiemetic and 
antidiarrheal supportive care regimen. 
25. The subject is unable or unwilling to abide by the study protocol or cooperate fully 
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with the investigator or designee. 
26. The subject has a history of other medical or psychiatric illness or organ dysfunction 
which, in the opinion of the investigator, would either compromise the subject’s 
safety or interfere with the evaluation of the safety of the study agent. 
27. The subject has a history of prior cancer (not under study) that has not been in 
remission for at least 3 years. The following are exempt from the 3-year limit: basal 
cell or squamous cell carcinoma of the skin, localized prostate cancer with normal 
prostate-specific antigen (PSA), cervical cancer in situ, or other in situ carcinomas. 
Investigational Product, Dosage and Mode of Administration:  
LAM-002A is supplied as 25 mg or 50 capsules and will be administered with a BID or TID 
oral dosing regimen. Subjects on a BID schedule will be advised to take the doses at the 
same time each day, ~12 hours apart. Subjects on a TID schedule will be advised to take the 
doses at the same time each day at intervals of ~6 to 8 hours. On PK days, subjects on a TID 
schedule should receive the morning dose and complete the blood collections through 
8 hours thereafter before taking the second dose on that day. For the dose-escalation stage of 
the study, the dosing regimens described in Table S-1 above will be evaluated.  For the 
cohort-expansion stage of the study, a LAM-002A starting dosing regimen of 125 mg BID 
will be evaluated when given as monotherapy or in combination.  
Combination Therapy, Dosage and Mode of Administration:  
In the expansion and extension stages (Stages 2 and 3), LAM-002A will be combined with 
either rituximab/rituximab hyaluronidase human or atezolizumab in cohorts of subjects as 
described in Table S-2 above. 
For subjects allocated to LAM-002A/rituximab, the rituximab will be administered 
intravenously or rituximab/hyaluronidase human will be administered subcutaneously in the 
clinic for a total of 8 treatments: 
Intravenous rituximab (Rituxan®) 
• Four induction infusions of 375 mg/mg2 will be administered weekly on 
Cycle 1 Day 1, Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 22.  
• Four subsequent maintenance infusions of 375 mg/mg2 will be administered every 
8 weeks on Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.  
Subcutaneous rituximab (rituximab/hyaluronidase human; Rituxan Hycela®) 
• An initial dose of 375 mg/mg2 will be administered intravenously on Cycle 1 Day1.  
• Three subcutaneous injections of 1,400 mg/23,400 Units (1,400 mg rituximab and 
23,400 Units hyaluronidase human) will be administered weekly on Cycle 1 Day 8, 
Cycle 1 Day 15, and Cycle 1 Day 22.  
• Four subsequent maintenance subcutaneous injections of 1,400 mg/23,400 Units 
(1,400 mg rituximab and 23,400 Units hyaluronidase human) will be administered 
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every 8 weeks on Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.  
For subjects allocated to LAM-002A/atezolizumab, the atezolizumab will be administered 
intravenously in the clinic at a dose of 1200 mg every 3 weeks. 
Duration of Treatment:  
Subjects may continue to receive study therapy until the earliest of subject withdrawal of 
informed consent, documented progression of cancer while on therapy, unacceptable study-
drug-related toxicity despite appropriate dose modification, development of intercurrent 
illness that precludes continued study therapy, physician decision that continuation is not in 
the subject’s best interest, treatment of the cancer with another therapeutic regimen, 
pregnancy or breastfeeding, substantial noncompliance with study procedures, or study 
discontinuation. If medically appropriate, subjects allocated to combination therapy may 
continue with protocol-specified therapy for the therapeutic agent (LAM-002A, rituximab, or 
atezolizumab) that continues to be tolerated, even if the other agent need to be discontinued 
due to drug-specific toxicity. 
Criteria for Evaluation: 
Safety: 
Safety evaluations will include assessments of AEs, vital signs, ECGs, laboratory tests, and 
concomitant medications. Adverse event seriousness, severity grade, and relationship to 
study treatment will be assessed by the investigator. Severity grade will be defined using the 
National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events 
(CTCAE) Version 4.0. 
Pharmacokinetics: 
PK assessments (for apilimod and circulating active metabolites) on Cycle Day 1, Cycle 
1 Day 8, and Cycle 1 Day 15 will determine PK parameters that will be estimated using 
standard non-compartmental methods. Dose proportionality and drug accumulation will be 
assessed. 
Pharmacodynamics: 
Pharmacodynamic evaluations will explore the extent of PIKfyve inhibition as determined by 
plasma assays, changes in gene expression in PBMCs/B cells, changes in plasma cytokines 
(including IL-12 and IL-23), correlations between genetic alterations as determined by next 
generation sequencing and/or gene expression in tumor tissue, plasma or PBMCs/B-cells and 
anti-lymphoma activity following treatment with LAM-002A, and correlations between 
changes in plasma bioanalytes and anticancer activity following treatment with LAM-002A 
as determined by proteomic tools. 
Efficacy:  
Efficacy will be determined based on standard definitions of response and progression for 
NHL and CLL/SLL. Rates of response and time-to-event parameters will be calculated.  
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Statistical Methods: 
Analysis Sets: 
Appropriate data analysis sets will be defined. The full-analysis set will include data from all 
patients who receive ≥1 dose of study therapy. Other analysis sets (responder and evaluable 
analysis sets) will be defined, as appropriate, and will include data from patients who have 
the necessary baseline and on study measurements to provide interpretable results for specific 
parameters of interest.  
Patient Disposition and Baseline Characteristics: 
Based on the full-analysis set, information regarding patient disposition, demographics, 
disease history, tumor characteristics, and other baseline characteristics will be described. 
Study Drug Exposure, Concomitant Medications, and Safety: 
Study drug administration and compliance, concomitant medication use, AEs, laboratory 
abnormalities, vital signs, performance status, body weight, and ECOG performance status 
will be described and summarized. For safety analyses, AEs will be classified using the 
Medical Dictionary for Regulatory Activities (MedDRA). The severity of AEs will be graded 
by the investigator according to the CTCAE, Version 4.03. Standard regulatory definitions of 
seriousness will be applied to AEs. Laboratory abnormalities will be graded according to 
CTCAE severity grade. Concomitant medication use will be coded using the World Health 
Organization Drug Dictionary into Anatomical Therapeutic-Chemical classification (ATC) 
codes. Quantitative and qualitative ECG assessments of rhythm abnormalities, cardiac 
intervals, wave form abnormalities, and ectopy will be reported. 
Pharmacokinetics: 
Noncompartmental methods will be used to derive pharmacokinetic parameters. Drug and 
metabolite concentrations and derived pharmacokinetic parameters will be described and will 
be summarized using appropriate graphical and tabular methods. The relationship between 
the parameters of drug exposure and dose may be examined using the power model or similar 
regression techniques. Drug accumulation over time will be described. 
Pharmacodynamics: 
Pharmacodynamic measures will be listed and will be summarized using appropriate 
graphical and tabular methods. As appropriate, statistical analysis of changes from baseline 
in pharmacodynamic parameters will be performed using appropriate parametric or 
nonparametric methods.  
Efficacy: 
For endpoints relating to tumor control, analyses will be based on the full-analysis and 
responder data sets. Tumor response and progression will be assessed using standard 
response and progression criteria appropriate for the patient’s disease type (NHL or 
CLL/SLL). Response rates will be presented with corresponding 95% CIs. Time-to-event 
endpoints will be summarized using Kaplan-Meier methods. 
Other Analyses: 
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Using appropriate regression or stratification techniques, associations between patient 
characteristics (eg, sex, race, age, weight, tumor characteristics, dose) and outcome measures 
(eg, pharmacodynamic and pharmacokinetic parameters) may be assessed. Similarly, 
associations between outcome measures (eg, relationships between pharmacokinetic and 
pharmacodynamic parameters) may be evaluated. 
Basis for the Planned Sample Size (Dose-Escalation Stage): 
In the dose escalation, the cohort size allows evaluation of regimen safety using a standard 
definition of MTD (i.e., a dose associated with DLT in < 33% of patients during Cycle 1 of 
therapy). With the 3+3 dose-escalation paradigm, there is high probability of dose escalation 
if the true underlying proportion of DLT is low. Conversely, there is a low probability of 
dose escalation if the true underlying proportion of DLT is high. 
Basis for the Planned Sample Sizes (Expansion Stage): 
As indicated in Table S-2 above, expansion cohorts of ≥ 6 subjects will be accrued. 
Enrollment of 6 subjects per cohort offers the opportunity to determine if there is any 
antitumor activity sufficient to warrant further development in the selected tumor types. An 
overall response rate (ORR) of ≥ 35% is considered of potential interest in each of the 
selected indications. If 0/6 subjects in a cohort experience an objective response, then a 
population ORR of ≥ 35% for that cancer can be excluded with > 90% certainty (1-sided 
exact binomial 90% CI upper bound = 32%).   
Based on the observation of objective responses among study subjects with FL receiving 
either LAM-002A monotherapy or LAM-002A/rituximab, expanded accrual of subjects with 
relapsed FL is planned to evaluate the level of activity with these 2 regimens. Preference will 
be given to enrolling subjects to receive LAM-002A monotherapy before enrolling subjects 
to receive LAM-002A/rituximab.  
Based on historical data with other treatments, it is known that an ORR of < 20% in subjects 
with relapsed FL receiving LAM-002A monotherapy would be uninteresting while achieving 
a target ORR of ≥ 40% would suggest that further development is warranted. Sequential 
boundaries will be used to continuously monitor that the ORR is ≥ 40% while excluding an 
ORR of < 20% using a 1-sided test with a significance level of 0.05. A significant result with 
this testing would conclude with 95% confidence that the actual ORR is ≥ 20%. Accrual of 
up to ~20 evaluable subjects will be considered with the potential to stop accrual early if the 
boundary is crossed. Thus, accrual can be considered sufficient if the following n/N values 
are observed: 4/5, 4/6, 4/7, 5/8, 5/9, 5/10, 5/11, 6/11, 6/12, 6/13, 6/14, 7/15, 7/16, 7/17, 8/18, 
8/19, 8/20. For all these values, the ORR is ≥ 40% with a lower 1-sided binomial confidence 
bound of ≥ 20%. 
As noted above, the target ORR with LAM-002A alone is ~40%. Adding rituximab or 
rituximab hyaluronidase human to LAM-002A would be expected to enhance the ORR over 
that associated with single-agent LAM-002A. Thus, the combination of 
LAM-002A/rituximab could warrant further development if an ORR of ≥ 60% could be 
targeted in preference to an ORR of < 40%.  Accordingly, for combination therapy, 
sequential boundaries will be used to continuously monitor that the ORR is ≥ 60% while 
excluding an ORR of 39% using a 1-sided test with a significance level of 0.05. A significant 
result with this testing would conclude with 95% confidence that the actual ORR is > 39%. 
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Accrual of up to ~20 evaluable subjects will be considered with the potential to stop accrual 
early if the boundary is crossed. Thus, accrual can be considered sufficient if the following 
n/N values are observed: 7/10, 8/11, 8/12, 9/13, 9/14, 10/15, 10/16, 11/17, 11/18, 12/19, 
12/20. For all these values, the ORR is ≥ 60% with a lower 1-sided binomial confidence 
bound of ≥ 39%.  
Experience indicates the rates of discontinuations from rituximab or atezolizumab therapy are 
< 5%. A rate of AE discontinuations of therapy due to adverse events of ≥ 25% in the 
2 combination therapy groups of LAM-002A/rituximab (N = 12) or 
LAM-002A/atezolizumab (N = 12) would suggest a potential adverse interaction among the 
components of the combination therapy. Sequential Pocock-type boundaries will be used to 
continuously monitor the rate of AE discontinuations and to test the null hypothesis, after 
each subject, that the event rate is ≥ 0.25 using a 1-sided significance test of ~ 0.05. AE 
discontinuation rates will be considered excessive if the following n/N values are 
observed: -/1, -/2, 3/3, 3/4, 4/5, 4/6, 5/7, 5/8, 5/9, 6/10, 6/11, 7/12. With this method, the 
probability of detecting an AE discontinuation safety signal ranges from 0.091 to >0.820 for 
true discontinuation rates of 25% to ≥ 60%. If excessive levels of AE discontinuation are 
observed, the sponsor, working in collaboration with the investigators, will take appropriate 
actions (eg, continuation of the cohort with modifications in design or monitoring plan, 
interruption of cohort accrual, cohort therapy discontinuation). 
Basis for the Planned Sample Sizes (Extension Stage): The sample size in the extension 
stage of the study will be no higher than the total number of subjects on study therapy on the 
data cutoff date that concludes the dose-escalation and expansion stages of the clinical trial. 
 
 
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2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF 
FIGURES  
TABLE OF CONTENTS 
AI THERAPEUTICS SIGNATURE PAGE ....................................................................................2 
INVESTIGATOR’S AGREEMENT ...............................................................................................3 
PROCEDURES IN CASE OF EMERGENCY ...............................................................................4 
1. 
SYNOPSIS ...................................................................................................................5 
2. 
TABLE OF CONTENTS, LIST OF TABLES, AND LIST OF FIGURES ...............18 
3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS.............................27 
4. 
INTRODUCTION ......................................................................................................31 
4.1. 
Product Summary .......................................................................................................31 
4.1.1. 
Pharmacology .............................................................................................................31 
4.1.2. 
Absorption, Distribution, Metabolism, and Excretion ................................................32 
4.1.3. 
Toxicology ..................................................................................................................33 
4.1.4. 
Pharmacokinetics, Clinical Efficacy and Safety .........................................................34 
4.1.5. 
Overview of Indication ...............................................................................................35 
4.1.6. 
Previous Clinical Experience with Apilimod and Apilimod Dimesylate in 
Nonmalignant Conditions ...........................................................................................36 
4.1.7. 
Starting Dose ..............................................................................................................37 
5. 
TRIAL OBJECTIVES AND PURPOSE ....................................................................38 
5.1. 
Primary Objectives .....................................................................................................38 
5.2. 
Secondary Objectives .................................................................................................38 
5.3. 
Exploratory Objectives ...............................................................................................38 
5.4. 
Primary Endpoints ......................................................................................................38 
5.5. 
Secondary Endpoints ..................................................................................................38 
5.6. 
Exploratory Endpoints ................................................................................................39 
6. 
INVESTIGATIONAL PLAN .....................................................................................40 
6.1. 
Overall Study Design ..................................................................................................40 
6.1.1. 
LAM-002A Dose Escalation Stage (Stage 1) .............................................................40 
6.1.2. 
Expansion Stage (Stage 2) ..........................................................................................40 
6.1.3. 
Extension Stage (Stage 3) ...........................................................................................41 
6.1.4. 
Subject Allocation (Stage 1 and Stage 2) ...................................................................41 
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6.1.5. 
Subject Evaluability ....................................................................................................42 
6.2. 
Number of Subjects ....................................................................................................42 
6.3. 
Randomization and Blinding ......................................................................................42 
6.4. 
Treatment Assignment ................................................................................................42 
6.5. 
Overall Treatment Periods ..........................................................................................43 
6.5.1. 
Pre-Treatment Period ..................................................................................................43 
6.5.2. 
Treatment Period ........................................................................................................43 
6.5.3. 
Post-Treatment Period ................................................................................................43 
6.6. 
LAM-002A Dose-Escalation Procedures ...................................................................43 
6.7. 
Definition of LAM-002A Dose-Limiting Toxicity (DLT) .........................................45 
6.8. 
Treatment Guidelines ..................................................................................................46 
6.8.1. 
Tumor Lysis Syndrome Prophylaxis and Therapy .....................................................46 
6.8.2. 
LAM-002A .................................................................................................................47 
6.8.3. 
Rituximab or Rituximab/Hyaluronidase Human ........................................................51 
6.8.4. 
Atezolizumab ..............................................................................................................55 
6.9. 
Other Supportive Care Recommendations .................................................................58 
6.9.1. 
Antibiotics, Antifungals, and Antivirals .....................................................................58 
6.9.2. 
Anticancer Therapies Other than the Study Drugs .....................................................59 
6.9.3. 
Anticoagulants ............................................................................................................59 
6.9.4. 
Antihistamine, Antiinflammatory, or Antipyretic, Drugs ..........................................59 
6.9.5. 
Corticosteroids ............................................................................................................59 
6.9.6. 
Drugs with Potential for Drug-Drug Interactions with LAM-002A ...........................59 
6.9.7. 
Drugs Known to Prolong the QT Interval ..................................................................60 
6.9.8. 
Hematopoietic Support ...............................................................................................60 
6.9.9. 
Immunization ..............................................................................................................61 
6.9.10. 
Procedures/Surgery .....................................................................................................61 
6.9.11. 
Skeletal Event Prophylaxis .........................................................................................61 
6.10. 
Study Restrictions .......................................................................................................61 
6.10.1. 
Breast Feeding ............................................................................................................61 
6.10.2. 
Contraception ..............................................................................................................62 
6.10.3. 
Diet .............................................................................................................................63 
6.11. 
Duration of Subject Participation ...............................................................................63 
6.12. 
Criteria for Subject Withdrawal from Study Treatment or Study Participation .........64 
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6.13. 
Replacement of Subjects .............................................................................................64 
7. 
SELECTION OF SUBJECTS ....................................................................................65 
7.1. 
Subject Inclusion Criteria ...........................................................................................65 
7.2. 
Subject Exclusion Criteria ..........................................................................................66 
8. 
METHODS OF ASSESSMENT AND ENDPOINTS ...............................................69 
8.1. 
Screening/Baseline Evaluations Only .........................................................................69 
8.1.1. 
Informed Consent .......................................................................................................69 
8.1.2. 
Inclusion and Exclusion Criteria ................................................................................69 
8.1.3. 
Medical History ..........................................................................................................69 
8.1.4. 
Demography ...............................................................................................................69 
8.1.5. 
Disease Status Assessment for Subjects with NHL ....................................................69 
8.1.6. 
Disease Status Assessments for Subjects with CLL/SLL...........................................70 
8.2. 
Baseline Assessment for All Subjects ........................................................................71 
8.2.1. 
Physical Examination and ECOG Performance Status ..............................................71 
8.2.2. 
Pregnancy Test ............................................................................................................71 
8.2.3. 
Urinalysis ....................................................................................................................71 
8.2.4. 
Electrocardiogram .......................................................................................................71 
8.2.5. 
Vital Signs ..................................................................................................................71 
8.3. 
Screening/Baseline, Day 1, 8, 10, 15 (Cycles 1 and 2 Only) and Prior to 
Each Subsequent Cycle and End of Treatment ...........................................................72 
8.3.1. 
Clinical Laboratory Tests ...........................................................................................72 
8.4. 
Disease Assessment ....................................................................................................73 
8.5. 
Adverse Events ...........................................................................................................73 
8.6. 
Treatment Compliance ................................................................................................73 
8.7. 
Schedules of Assessments ..........................................................................................74 
9. 
STUDY DRUG MATERIALS AND MANAGEMENT ...........................................86 
9.1. 
LAM-002A .................................................................................................................86 
9.1.1. 
Description ..................................................................................................................86 
9.1.2. 
LAM-002A  Packaging and Labeling .........................................................................86 
9.1.3. 
Source .........................................................................................................................86 
9.1.4. 
Storage ........................................................................................................................86 
9.1.5. 
Accountability .............................................................................................................86 
9.1.6. 
Handling and Disposal ................................................................................................87 
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9.2. 
Rituximab (for Intravenous Administration) ..............................................................87 
9.2.1. 
Description ..................................................................................................................87 
9.2.2. 
Packaging ....................................................................................................................87 
9.2.3. 
Source .........................................................................................................................87 
9.2.4. 
Storage and Stability ...................................................................................................87 
9.2.5. 
Solution Preparation ...................................................................................................88 
9.2.6. 
Accountability .............................................................................................................88 
9.3. 
Rituximab/Hyaluronidase Human (For Subcutaneous Administration).....................88 
9.3.1. 
Description ..................................................................................................................88 
9.3.2. 
Packaging ....................................................................................................................88 
9.3.3. 
Source .........................................................................................................................88 
9.3.4. 
Storage and Stability ...................................................................................................88 
9.3.5. 
Preparation ..................................................................................................................89 
9.3.6. 
Accountability .............................................................................................................89 
9.4. 
Atezolizumab ..............................................................................................................89 
9.4.1. 
Description ..................................................................................................................89 
9.4.2. 
Packaging ....................................................................................................................89 
9.4.3. 
Source .........................................................................................................................89 
9.4.4. 
Storage and Stability ...................................................................................................90 
9.4.5. 
Solution Preparation ...................................................................................................90 
9.4.6. 
Accountability .............................................................................................................90 
10. 
ASSESSMENT OF SAFETY .....................................................................................91 
10.1. 
Adverse Events ...........................................................................................................91 
10.1.1. 
Definitions ..................................................................................................................91 
10.2. 
Study Drug Related AE or SAE .................................................................................93 
10.3. 
Further AE and SAE Definitions ................................................................................93 
10.4. 
AE and SAE Assessment Criteria ...............................................................................94 
10.4.1. 
Assessment of Causality .............................................................................................94 
10.4.2. 
Grading of Severity .....................................................................................................94 
10.5. 
Responsibilities and Procedures .................................................................................95 
10.6. 
SAE and AESI Reporting ...........................................................................................95 
10.6.1. 
Post-treatment Safety Follow-up ................................................................................96 
10.7. 
Pregnancy Reporting ..................................................................................................96 
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11. 
ASSESSMENT OF EFFICACY ................................................................................97 
12. 
PHARMOCOKINETIC ASSESSMENTS .................................................................98 
13. 
BIOMARKER ASSESSMENTS..............................................................................100 
14. 
STATISTICS ............................................................................................................102 
14.1. 
Determination of Sample Size ..................................................................................102 
14.1.1. 
Dose Escalation Stage (Stage 1) ...............................................................................102 
14.1.2. 
Cohort Expansion Stage (Stage 2) ............................................................................102 
14.1.3. 
Extension Stage (Stage 3) .........................................................................................103 
14.2. 
Statistical and Analytical Plans ................................................................................103 
14.3. 
Analysis Sets .............................................................................................................104 
14.3.1. 
Full Analysis Set .......................................................................................................104 
14.3.2. 
Responding Analysis Set ..........................................................................................104 
14.3.3. 
Evaluable Analysis Sets ............................................................................................104 
14.4. 
Demographics and Baseline Disease Characteristics ...............................................104 
14.5. 
Study Drug Exposure ................................................................................................104 
14.6. 
Concomitant Medications .........................................................................................104 
14.7. 
Safety and Tolerability .............................................................................................104 
14.8. 
Biomarkers ................................................................................................................105 
14.9. 
Efficacy Analysis ......................................................................................................106 
14.10. 
Interim Analysis ........................................................................................................106 
14.11. 
Missing Data and Imputation....................................................................................106 
14.12. 
Protocol Deviations ..................................................................................................107 
15. 
DIRECT ACESS TO SOURCE DATA/DOCUMENTS .........................................108 
16. 
STUDY MONITORING ..........................................................................................109 
16.1. 
Audits and Inspections ..............................................................................................109 
16.2. 
Institutional Review Board .......................................................................................110 
17. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................111 
18. 
ETHICS ....................................................................................................................112 
18.1. 
Ethics Review ...........................................................................................................112 
18.2. 
Ethical Conduct of the Study ....................................................................................112 
18.3. 
Written Informed Consent ........................................................................................112 
19. 
DATA COLLECTION, REPORTING AND PROCESSING ..................................114 
19.1. 
Inspection of Records ...............................................................................................115 
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19.2. 
Retention of Records ................................................................................................115 
19.3. 
Data Recording/Case Report Forms .........................................................................116 
20. 
PUBLICATION POLICY ........................................................................................117 
21. 
STUDY DISCONTINUATION ...............................................................................118 
22. 
LIST OF REFERENCES ..........................................................................................119 
APPENDIX 1. EASTERN COOPERATIVE ONCOLOGY GROUP (ECOG) 
PERFORMANCE STATUS SCALE .......................................................................123 
APPENDIX 2. CRITERIA FOR RESPONSE ASSESSMENT ...............................................124 
1. 
LYMPHOMA ...........................................................................................................124 
1.1. 
Tumor Assessment Criteria ......................................................................................124 
1.2. 
Method of Assessment ..............................................................................................124 
1.3. 
Timing of Assessments .............................................................................................124 
1.4. 
Identification and Follow-up of Tumor Lesions and Organomegaly .......................125 
1.4.1. 
Index Lesions ............................................................................................................125 
1.4.2. 
Nodal Index Lesions .................................................................................................125 
1.4.3. 
Extranodal Index Lesions .........................................................................................126 
1.4.4. 
Non-Index Lesions ....................................................................................................126 
1.4.5. 
Spleen and Liver .......................................................................................................127 
1.4.6. 
Bone Marrow ............................................................................................................127 
1.4.7. 
Lymph Node Biopsy .................................................................................................127 
1.5. 
Definitions of Tumor Response and Progression .....................................................128 
1.5.1. 
Complete Response ..................................................................................................128 
1.5.2. 
Partial Response ........................................................................................................129 
1.5.3. 
Stable Disease ...........................................................................................................129 
1.5.4. 
Progressive Disease ..................................................................................................129 
1.5.5. 
Nonevaluable ............................................................................................................131 
2. 
CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL LYMPHOCYTIC 
LYMPHOMA ...........................................................................................................131 
2.1. 
Tumor Assessment Criteria ......................................................................................131 
2.2. 
Method of Assessment ..............................................................................................131 
2.3. 
Timing of Assessments .............................................................................................132 
2.4. 
Identification and Measurement of Tumor Lesions and Organomegaly ..................132 
2.4.1. 
Index Lesions ............................................................................................................132 
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2.4.2. 
Spleen and Liver .......................................................................................................133 
2.4.3. 
Non-Index Lesions ....................................................................................................134 
2.5. 
Definitions of Tumor Response and Progression .....................................................134 
2.5.1. 
Complete Response and Complete Response with Incomplete Blood Count 
Recovery ...................................................................................................................135 
2.5.2. 
Partial Response ........................................................................................................135 
2.5.3. 
Stable Disease ...........................................................................................................136 
2.5.4. 
Progressive Disease ..................................................................................................136 
2.5.5. 
Nonevaluable ............................................................................................................137 
2.5.6. 
Lymphocytosis during Therapy ................................................................................137 
APPENDIX 3. POTENTIAL DRUG INTERACTIONS WITH LAM-002A ..........................139 
APPENDIX 4. SUMMARY OF PROTOCOL CHANGES .....................................................145 
APPENDIX 5. DETAILED PROTOCOL CHANGES ............................................................150 
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LIST OF TABLES 
Table 1: 
Abbreviations and Specialist Terms ...........................................................................27 
Table 2: 
Expansion Stage Disease Types and Therapies ..........................................................41 
Table 3: 
LAM-002A Provisional Starting Dose Levels ...........................................................44 
Table 4: 
Criteria for Defining Dose-Limiting Toxicities (DLTs) .............................................45 
Table 5: 
Recommended Rituximab or Rituximab/Hyaluronidase Modifications and 
Supportive Care ..........................................................................................................54 
Table 6: 
Recommended Atezolizumab Modifications and Supportive Care ............................56 
Table 7: 
Protocol-Recommended Contraceptive Methods .......................................................63 
Table 8: 
Schedule of Assessments (LAM-002A Continuous Monotherapy 
Administration) ...........................................................................................................74 
Table 9: 
Schedule of Assessments (LAM-002A Intermittent Monotherapy 
Administration) ...........................................................................................................77 
Table 10: Schedule of Assessments (LAM-002A/Rituximab Combination Therapy) ...............80 
Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination Therapy) .........83 
Table 12: LAM-002A Drug Description ....................................................................................86 
Table 13: Pharmacokinetic Sampling Time Points .....................................................................99 
Table 14: Statistical Basis for 3+3 Dose-Escalation Paradigm ................................................102 
Table 15: CYP2C9 and CYP3A Inhibitors and Inducers .........................................................139 
Table 16: Drugs Known to Prolong the QT Interval and/or Cause Torsades De Pointes 
(TDP) ........................................................................................................................141 
 
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LIST OF FIGURES 
Figure 1: 
PIKfyve Kinase ...........................................................................................................32 
Figure 2: 
Transmission of Electronic Data ..............................................................................114 
 
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3. 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviations and specialist terms used in this study protocol are provided in Table 1. 
Table 1: 
Abbreviations and Specialist Terms 
Abbreviation or Specialist Term 
Explanation 
%CV 
percent coefficient of variation 
5PS 
5-point scale 
ABC 
activated B-cell lymphoma 
AE 
adverse event 
ALC 
absolute lymphocyte count 
ALP 
alkaline phosphatase  
ALT 
alanine aminotransferase  
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time  
ASCO  
American Society of Clinical Oncology 
ASCT 
autologous stem-cell transplantation 
AST 
aspartate aminotransferase  
AUC 
area under the concentration curve  
AUC0-t 
area under the plasma concentration versus time curve, as determined 
by a trapezoidal method, from time zero to t hours post-dose 
AUCt 
area under the concentration-time curve calculated to the last 
observable concentration at time t 
BID 
twice daily (or 2 times a day) (“bis in die”) 
BL 
Burkitt lymphoma 
BUN 
blood urea nitrogen 
CAP 
College of American Pathologists 
CFR 
Code of Federal Regulations 
CLL 
chronic lymphocytic leukemia 
CLL/SLL 
chronic lymphocytic leukemia/small lymphocytic lymphoma 
Cmax 
peak (maximum) plasma concentration 
CNS 
central nervous system 
CR 
complete response or complete remission 
CRO 
contract research organization 
CT scan 
computerized tomography scan 
DAT 
direct antiglobulin test 
DLBCL 
diffuse large B-cell lymphoma 
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Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
DLT 
dose-limiting toxicity 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EC 
ethics committee 
EC50 
half maximal effective concentration 
ECOG 
Eastern cooperative oncology group 
EDC 
electronic data capture  
EOT 
end of treatment 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
FISH 
fluorescence in Situ hybridization 
FL 
follicular lymphoma 
FSH 
follicle stimulating hormone 
GCB 
germinal center B-cell lymphoma 
GCP 
good clinical practice 
GI 
gastrointestinal 
HIV 
human immunodeficiency virus 
IB 
investigator brochure 
ICH 
International Conference on Harmonisation 
ID 
identification 
IHC 
immunohistochemistry 
IL-12 
interleukin-12 
IL-23 
interleukin-23 
IND 
investigational new drug 
IRB 
institutional review board 
LAM-002A 
apilimod dimesylate, (E)-4-(6-(2-(3-methylbenzylidene)hydrazinyl)-
2-(2-(pyridin-2-yl)ethoxy)pyrimidin-4-yl)morpholine dimesylate 
capsules 
LDH 
lactate dehydrogenase 
LD 
longest dimension 
LDi 
longest transverse diameter of a lesion 
LPD 
longest perpendicular dimension 
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Table 1: 
Abbreviations and Specialist Terms (Continued) 
Abbreviation or Specialist Term 
Explanation 
MCL 
mantle cell lymphoma 
MedDRA 
medical dictionary for regulatory activities 
mg/kg/day 
milligram/kilogram/day 
mL 
milliliter 
MRD 
minimal residual disease 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MZL 
marginal zone lymphoma 
NCI CTCAE 
National Cancer Institute common terminology criteria for adverse 
events 
NHL 
Non-Hodgkin’s lymphoma 
nM 
nanomolar 
NOEL 
no observed effect level 
PBMC 
peripheral blood mononuclear cells 
PD 
progressive disease 
PDs 
pharmacodynamics 
PE 
physical examination 
PET 
positron emission tomography 
PFS 
progression-free survival 
PI 
phosphatidyl inositol 
PIKfyve 
phosphatidylinositol-3-phosphate- 5 kinase 
PK  
pharmacokinetics 
PPD 
cross product of the longest transverse diameter of a lesion and 
perpendicular diameter 
PR 
partial remission  
PSA 
prostate specific antigen 
QD 
once daily (“quaque die”)  
QRS 
combination of 3 of the graphical deflections seen on a typical 
electrocardiogram (ECG) 
QT 
time of start of Q wave until end of T wave in the heart’s electrical 
cycle 
QTc 
corrected QT interval 
QTcF 
Fridericia correction formula 
R 
accumulation ratio 
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Table 1: 
Abbreviations and Specialist Terms (Continued) 
R-CHOP 
rituximab, cyclophosphamide, doxorubicin, vincristine, and 
prednisone 
RBC 
red blood cell  
RNA 
ribonucleic acid 
RNAi 
RNA interference 
RP2D 
recommended Phase 2 dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAS 
statistical analysis system 
SD 
stable disease 
SDi 
shortest axis perpendicular to the LDi 
SLL 
small lymphocytic lymphoma  
SOP 
standard operating procedure 
SPD 
sum of the product of the perpendicular diameters for multiple lesions  
t½ 
terminal elimination half-life 
TB 
tuberculosis  
T-CLL 
T-cell chronic lymphocytic leukemia 
Th1 
T-helper cell phenotype  
TID 
thrice per day 
TLS 
tumor lysis syndrome 
tmax  
time to maximum concentration 
ULN 
upper limit of normal 
WBC 
white blood cell 
WCBP 
women of child bearing potential 
WHO 
World Health Organization 
WHODD 
World Health Organization drug dictionary 
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4.
INTRODUCTION
AI Therapeutics is developing LAM-002A (apilimod dimesylate capsules) for the treatment of 
patients with malignancies including recurrent B-cell non-Hodgkin lymphoma (NHL). Initially, 
apilimod dimesylate, and apilimod, the free base (LAM-002), were under development by Synta 
Pharmaceuticals, Inc (Synta) for the treatment of psoriasis (IND # 62,112) and Crohn’s Disease 
(IND # 70,204). Under these INDs, over 700 subjects were exposed to total daily doses up to 
200 mg dimesylate and 210 mg free base (the equivalent of 294 mg apilimod dimesylate) for 
time periods ranging from a single day to 12 weeks.  
4.1. 
Product Summary 
LAM-002A is intended for oral administration. Each capsule will contain 25 mg or 50 of 
apilimod dimesylate (equivalent to 17.1 mg or 34.3 mg of apilimod free base, respectively). The 
25-mg capsule is Swedish orange and the 50-mg capsule is white. Both the 25- and 50-mg
capsules are Size 0 and both have a total fill weight of 175 mg.
Inactive components in active capsules are microcrystalline cellulose, silicified microcrystalline 
cellulose, anhydrous lactose, croscarmellose sodium, colloidal silicon dioxide, and magnesium 
stearate.  
4.1.1. 
Pharmacology 
Apilimod and apilimod dimesylate were originally introduced into clinical trials based on 
apilimod’s immunomodulatory properties (Wada 2007; Wada 2012). Apilimod inhibits the 
production of interleukin-12 (IL-12) and interleukin-23 (IL-23), and was effective in preclinical 
animal models of various autoimmune diseases that are mediated by the inappropriate expression 
of T-helper cell phenotype (Th1) cytokines (Wada 2007).  
Recently published data have shown that apilimod is a potent and highly selective first-in-class 
phosphatidylinositol-3-phosphate- 5 kinase (PIKfyve) inhibitor (Cai 2013, Gayle 2017). In total, 
AI Therapeutics has tested 456 kinases, including disease-relevant kinases, for their ability to 
bind to apilimod. The screening concentration of apilimod was 1 µM, a concentration that is > 
12,000 times greater than the Kd (81 picomolar) for apilimod against PIKfyve. The results 
showed that apilimod did not bind to any of the 456 kinases tested. 
Inhibition of PIKfyve by pharmacological methods as well as RNA interference (RNAi) 
produces swollen vacuoles and disruption of endomembrane dynamics. In cell culture, the 
pharmacological disruption of PIKfyve with apilimod induces selective lethality of specific 
cancer cell lines, presumably through disruption of intracellular trafficking that leads to 
noncanonical cell death (Gayle 2017). 
PIKfyve kinase is a 240-kDa endosomal phosphatidyl inositol (PI) 5 lipid kinase that catalyzes 
the phosphorylation of PI3 phosphate to PI (3, 5) P2 as shown in Figure 1.  
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under the curve (AUC) were, in general, less than proportional to the increase in the dose. After 
oral administration, apilimod was rapidly absorbed. The time to maximum concentration (tmax) 
generally occurred within 1 to 2 hours after oral dosing and the terminal elimination half-life (t½) 
ranged from 1 to 4 hours. Apilimod is highly protein bound (≥ 99%) to rat, dog, and human 
plasma proteins. 
Six primary metabolites were identified in vitro (rat and human) and in vivo (rat and dog). 
Human, rat, rabbit and dog studies showed a qualitatively similar metabolic profile. Reaction 
phenotyping studies indicated that CYP3A4, and to a lesser extent CYP1A2 and/or CYP2D6, 
contribute to the metabolism of apilimod. The primary metabolites were STA-5864 
(CYP1A2/2D6), STA-5908 (CYP3A4) and STA-5944 (CYP3A4). STA-5864 is further 
metabolized via CYP3A4 to STA-5919. STA-5908 undergoes CYP3A4-mediated metabolism to 
STA-5919 and STA-6048. Further CYP3A4 mediated metabolism of STA-5944 results in 
STA-6035 and STA-6048. As with the parent compound, the primary metabolites of apilimod 
are similarly short-lived in circulation. Generally, tmax occurred within 1 or 2 hours after the oral 
dose of apilimod, consistent with the rapid elimination of this compound from the circulation. 
The distribution of [14C]-apilimod derived radioactivity was widespread after a single oral 
administration to rats. The tissues with the highest activity were liver, kidney, stomach, adrenal 
gland, Harderian gland, brown fat, preputial gland, spleen, and esophagus. Most tissues reached 
Cmax 1 hour after dosing. Approximately 60% of the total dosed radioactivity was recovered in 
bile from bile duct cannulated rats. Concentrations were generally high in the gastrointestinal 
(GI) tract, consistent with biliary excretion. Renal clearance was a minor route of elimination 
accounting for approximately 20% of the total dosed radioactivity. 
The tissue distribution of apilimod and its metabolites was further evaluated in a study in rats 
using material that was not radiolabeled. In this study it was determined that the rank order for 
plasma AUC and Cmax was STA-5944 > STA-5908 > STA-5326 (apilimod). Brain to plasma 
AUC ratios were highest for STA-5326 (apilimod) > STA-5908 >STA-5944, ranging from 3.1 
for STA-5326 (apilimod) to 0.19 for STA-5944. Tissue to plasma AUC ratios of each analyte 
were greater than 4.6 for intestine, kidneys, and liver. The exception was STA-5944 which 
generally had low liver concentrations. 
4.1.3. 
Toxicology 
A series of nonclinical safety assessment studies was conducted using apilimod and apilimod 
dimesylate in the CD-1 mouse, Sprague-Dawley rat, the beagle dog, and Cynomolgus monkey. 
Studies included safety pharmacology, general toxicology up to 6 to 9 months in duration, and 
fertility and developmental toxicology studies. Assessments of genotoxicity and carcinogenicity 
were also performed. 
Single- and repeat-dose toxicology studies were conducted in the mouse (up to 90 days), rat (up 
to 6 months), dog (up to 9 months) and monkey (up to 9 months). In the mouse, rat and dog, 
clinical signs at toxic doses included GI findings (emesis and soft stools in rats and dogs; 
diarrhea in the dog only), central nervous system (convulsions, tremors, ataxia), hypoactivity, 
ptosis, and hunched posture, decreased weight gain, and reduced food consumption. 
Relevant clinical pathology findings at toxic doses included increases in blood urea nitrogen 
(BUN), creatinine, potassium, inorganic phosphorous, and decreases in total protein and 
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albumin. These increases were attributed to dehydration (pre-renal) as well as decreased 
glomerular filtration (renal).  
Histopathology findings attributed to the investigational drug were intracellular vacuolation in 
the cervix, uterus, liver, spleen, thymus, bone marrow, intestinal tract, adrenal cortex, urinary 
bladder, chief cells in the parathyroid gland, renal tubular epithelium and tubule 
regeneration/degeneration with excess tubular cell mitotic cell figures and the vacuolation of 
epidermal cells in the distal caput and corpus region of the epididymis. Upon cessation of drug 
administration, all histology findings, with the exception of the epididymis, had returned to 
normal. These data strongly suggest the kidney is the target organ of toxicity.  
In an immunotoxicology study in the rat, there were no biologically significant changes in spleen 
or thymus weights or adverse anatomic pathology findings. Additionally, there were no 
significant changes in peripheral blood lymphocyte subsets or immunologically adverse findings 
in splenic antibody-forming cells. In a chronic monkey study in virally infected monkeys, 
apilimod dimesylate did not elicit lymphomas, or compromise T-cell mediated antibody 
responses. 
In a combined male and female fertility and general reproduction toxicity study, oral 
administration of apilimod dimesylate had no effects on libido, mating, fertility and estrus. The 
reproductive no-observed-effect level (NOEL) for male and female rats is 38.38 mg/kg/day. 
Administration of apilimod dimesylate to gravid rats and rabbits during the period of 
organogenesis (implantation to closure of the hard palate) demonstrated that it is a non-selective 
developmental toxicant in the rat. There were no fetal effects in the rabbit.  
Apilimod and apilimod dimesylate were not demonstrated to be mutagenic, clastogenic, or 
aneugenic. In 2-year carcinogenicity studies in rodents, apilimod dimesylate was not 
carcinogenic. 
4.1.4. 
Pharmacokinetics, Clinical Efficacy and Safety 
4.1.4.1. 
Pharmacokinetics 
In humans, apilimod is orally bioavailable, rapidly absorbed, and extensively metabolized. 
Pharmacokinetic studies revealed generally dose-dependent increases in both Cmax and AUC. tmax 
following oral administration was 1 hour in the absence of food and 2 to 3 hours when taken with 
food; in normal healthy volunteers and subjects with psoriasis, tmax ranged from 2 to 4 hours. 
Approximately 90% or more of the absorbed drug was cleared from circulation within 8 to 10 
hours following administration, after which any remaining drug was eliminated with a terminal 
half-life of 5 to 10 hours following administration on the first day, increasing to 12 to 21 hours 
on Day 14. These findings suggest that either daily (QD) or BID dosing regimens may be 
appropriate. A small food effect was observed but is not deemed to be clinically significant. 
The 2 dosage forms (apilimod dimesylate and apilimod formulations) used to date in clinical 
trials are bioequivalent. The 50-mg dose of apilimod dimesylate provides the same amount of 
active ingredient as the previously used 35-mg capsule of apilimod. Similarly, a 100-mg dose of 
apilimod dimesylate is equivalent to 70 mg apilimod. Future studies will utilize apilimod 
dimesylate capsules (LAM-002A). 
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4.1.4.2. 
Efficacy 
In Study LAM-002A-NHL-CLN01, efficacy has been assessed in subjects with NHL. Decreases 
in tumor metabolic activity were noted in 3 subjects with relapsed DLBCL receiving LAM-002A 
monotherapy but these changes did not meet formal criteria for objective response. Nine subjects 
with FL treated with LAM-002A monotherapy, LAM-002A in combination with rituximab, or 
LAM-002A in combination with atezolizumab have had substantial tumor regressions 
compromising 2 complete responses (CRs) and 7 partial responses (PRs). The responses have 
been long-lasting, with durations exceeding 12 months among several subjects with mature data. 
One subject with MZL receiving LAM-002A/rituximab also experienced a durable PR. 
4.1.4.3. 
Safety 
Apilimod dimesylate has been generally well tolerated in humans. In patient populations with 
Crohn’s disease or psoriasis, more frequent (> 10%) AEs experienced to date included headache, 
upper respiratory tract infection, and nausea; less frequent (> 5% to 10%) AEs included 
dizziness, fatigue, and nasopharyngitis; and rare (2% to 5%) AEs included diarrhea, arthralgia, 
fever, abdominal pain, peripheral edema, and vomiting. In general, most AEs were assessed as 
mild in severity.  
In the ongoing trial of LAM-002A in patients with hematological cancers, dose-dependent 
gastrointestinal events of nausea, vomiting, and diarrhea have been observed. One patient with 
DLBCL developed acute transient elevations in serum creatinine and blood-urea nitrogen (BUN) 
due to tumor lysis syndrome (TLS) shortly after starting LAM-002A at a dose of 125 mg BID. 
One patient with a hematological malignancy receiving the drug at 150 mg BID developed 
asymptomatic Grade 3 hyponatremia that was attributed to the combined effects of LAM-002A-
induced diarrhea and hydrochlorothiazide administration. No other clinically significant safety 
signals in laboratory, physical examination, or vital sign findings have been noted. 
Cardiac monitoring in clinical studies to date has not revealed any major issues. However, in a 
thorough QT/QTc study, apilimod dimesylate at doses of 50 mg and 150 mg was associated with 
repolarization findings in excess of those deemed negative by International Conference on 
Harmonisation (ICH) E14 guidance. The magnitude of the change was modest (~8.5 msec) and 
the root-mean-square based analyses did not demonstrate as large an increase in cardiac 
repolarization time (≤ 1.22 msec) as that identified using the Fridericia method. Therefore, the 
significance of this finding is unclear. Preliminary QTc observations in the ongoing study in 
patients with hematological malignancies suggest the potential for dose- and exposure-dependent 
Grade 1 or 2 QT prolongation. 
4.1.5. 
Overview of Indication 
Non-Hodgkin’s lymphoma (NHL) is a collective term for a heterogeneous group of 
lymphoproliferative malignancies with differing severities, ranging from slow growing to 
aggressive subtypes, and varying responses to treatment. In 2015, it is estimated that there will 
be 71,850 new cases of NHL and an estimated 19,790 people will die of this disease 
(National Cancer Institute SEER webpage). The two most common types, diffuse large B-cell 
lymphoma (DLBCL) and follicular lymphoma (FL), will account for about half of these 
(Martelli 2013). Other relatively common lymphomas include chronic lymphocytic leukemia/
small lymphocytic lymphoma (CLL/SLL) (6%), mantle cell lymphoma (MCL, 6%), 
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and marginal zone lymphoma (MZL, 6%). DLBCL is further divided into two subtypes, “GCB” 
and “ABC” (also called “non-GCB”), based on resemblance to normal stages of B-cell 
development by gene expression profiling (Alizadeh 2000, Rosenwald 2002). The GCB 
(germinal center B-cell) type arises from malignant transformation of normal germinal center B-
cells, and the ABC (activated B-cell) type arises from post-germinal center B-cells in the process 
of differentiating into plasma cells. ABC DLBCLs have an inferior prognosis compared to GCB 
DLBCLs, but several novel agents are in development with unique activity in ABC disease 
(Hans 2004, Cultrera 2012).  
The median age at diagnosis of NHL is the seventh decade of life, though they can occur at any 
age. The prognosis of NHL depends on the histologic type, stage, and treatment.  
Management of NHL varies widely depending upon histology. NHL patients are usually treated 
with chemotherapy, with or without radiation. Virtually all B-cell lymphomas are treated with 
chemotherapy in combination with the anti-CD20 monoclonal antibody rituximab 
(Zelenetz 2014). If NHL persists or recurs after standard treatment, autologous stem-cell 
transplantation (ASCT) may be a potentially curative option for patients with DLBCL 
(Raut 2014), though the cure rate for ASCT is low for patients relapsing after standard R-CHOP 
(rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone).  
Patients with DLBCL who relapse after, or who are not candidates for ASCT, as well as patients 
with relapsed MCL, MZL, FL, and CLL/SLL are not considered curable with conventional 
therapies. Patients with recurrent disease are commonly given sequential regimens of 
chemotherapeutic, immunotherapeutic, or investigational agents in an attempt to control disease 
manifestations. Rituximab is commonly employed in combination with other agents 
(Zelenetz 2014). Newer immunopotentiating approaches using anti-PD1/PDL1 inhibitors 
(including atezolizumab [https://clinicaltrials.gov/ct2/show/NCT031206761]) are being explored 
and have shown evidence of activity in patients with recurrent NHL (Ilcus 2017). However, 
despite use of agents with differing mechanisms of action, progressive resistance to treatment 
typically develops. Patients with refractory or multiply relapsed progressive disease have poor 
prognoses and are ultimately likely to die of their cancers. Novel mechanisms of action are 
needed that can be administered alone or in combination with existing chemoimmunotherapeutic 
approaches to offer additional treatment options for patients with hematological cancers who 
have experienced disease progression. 
4.1.6. 
Previous Clinical Experience with Apilimod and Apilimod Dimesylate in 
Nonmalignant Conditions 
There is substantial experience administering apilimod or apilimod dimesylate to human 
subjects. Clinical trials in normal healthy volunteers were initiated in May 2003 by a previous 
pharmaceutical sponsor. These were followed by studies in patients with Crohn’s disease, 
psoriasis and rheumatoid arthritis. To date, more than 700 individuals have participated in 
clinical studies that evaluated apilimod/apilimod dimesylate. Clinical experience has been 
generated in 255 subjects dosed with total daily doses of apilimod dimesylate 100 mg or the 
equivalent apilimod dose of 70 mg free base.  
The starting dose for this Phase 1 clinical study in B-cell NHL is based on 2 Phase 2, 
randomized, double-blind placebo-controlled trials conducted in subjects with Crohn’s disease or 
plaque psoriasis. Study 5326-07 enrolled 220 subjects with Crohn’s disease. Subjects were 
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randomized to once daily placebo or apilimod dimesylate at doses of 50 or 100 mg. Of the 
147 subjects who received any dose of apilimod dimesylate, 46% were dosed for durations 
between 4 and 6 weeks (53% at 50 mg; 38% at 100 mg) while 12% were dosed for more than 
20 weeks. No deaths occurred on study. The most common treatment-emergent AEs reported as 
related to study drug during the blinded portion of the study were nausea (14%), headache (7%), 
and dizziness (5%). The incidence of related nausea was more than double in the 100-mg group 
(20%) compared with the 50-mg group (8%) while the incidence of headache and dizziness was 
identical in the 2 groups. Adverse events of Grade 3 or higher severity were reported for 15% of 
subjects during the blinded portion of the study. A total of 7 subjects discontinued due to an AE.  
Study 5326-04 was a randomized, placebo-controlled, double-blind, study. A total of 
212 subjects with chronic moderate to severe plaque psoriasis were randomized to placebo or to 
apilimod at 7, 21 or 35 mg (equivalent to apilimod dimesylate at 10, 30, 50 mg, respectively) 
twice daily (BID) for 12 weeks. Treatment groups were balanced: 60% of subjects completed the 
study with roughly 30 completers in each treatment group. There were no deaths. Slight trends 
toward increased frequency of AEs (i.e., dizziness, upper respiratory infections) were observed 
in the highest dose group (35 mg BID) though no trends were observed in the most common 
treatment-related AEs (headache and fatigue). A total of 16 (8%) patients discontinued from the 
study due to an AE: 8% in the placebo group, 4% in the 7 mg BID group, 6% in the 21 mg BID 
group, and 12% in the 35 mg BID group.  
4.1.7. 
Starting Dose 
As noted in Studies 5326-04 and 5326-07, apilimod was found to be safe and well-tolerated at 
daily doses up to 100 mg/day as a single daily dose of apilimod dimesylate or BID at a total dose 
of 70 mg of apilimod (equivalent to apilimod dimesylate 100 mg). The starting dose selected for 
this Phase 1 dose escalation trial is LAM-002A 50 mg BID. This dose is expected to achieve a 
Cmax of ~ 70-80 ng/mL, or 180 nM, with predicted plasma half-life of 5 - 10 hours. 
Concentrations required for 90% inhibition of highly sensitive NHL subtypes in in vitro assays is 
~50 nM. It is acknowledged that this starting dose level will likely result in plasma levels over a 
24-hour period that are lower than the in vitro concentrations cited; however, the LAM-002A 
50-mg-BID dose for the first cohort is chosen to minimize the risk of potential toxicities in this 
highly pre-treated NHL population.  
Dose escalation will proceed by a modified Fibonacci schema as outlined in Table 3. If 
additional dose exploration beyond the highest dose shown in Table 3 is required to define the 
maximum tolerated dose (MTD), then dose escalation may proceed at increments ≤ 33%.  
The subject population in this study will be comprised of subjects with B-cell NHL who have 
relapsed or were refractory to previous therapy (including at least one prior 
chemoimmunotherapy regimen), and failed or were ineligible or unwilling to undergo ASCT in 
the setting of DLBCL. 
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5. 
TRIAL OBJECTIVES AND PURPOSE 
The overall purpose of this Phase 1 study is to explore the safety and tolerability of LAM-002A 
when given alone and in combination for the treatment of subjects with relapsed or refractory B-
cell NHL.  
5.1. 
Primary Objectives 
• To determine the maximum tolerated dose (MTD) of daily oral administration of 
LAM-002A in subjects with relapsed or refractory B-cell NHL 
5.2. 
Secondary Objectives 
• To evaluate the plasma pharmacokinetics (PK) of apilimod, and its active 
metabolites, administered orally in subjects with relapsed or refractory B-cell NHL 
• To evaluate the safety and tolerability of daily oral administration of LAM-002A in 
subjects with relapsed or refractory B-cell NHL 
• To evaluate the preliminary anti-tumor activity of LAM-002A  
5.3. 
Exploratory Objectives 
• To evaluate the pharmacodynamic effects of LAM-002A, administered orally, in 
plasma assays and surrogate tissue (gene expression in peripheral blood mononuclear 
cells [PBMCs]/B cells, and plasma cytokines [including (IL)-12 and IL-23]).  
• To evaluate tumor and/or plasma for gene expression and genetic alterations (with 
saliva and/or B-cell-depleted PBMC collection for germ-line control) and surrogate 
tissue (PBMC/B cells) for gene expression that may predict anti-lymphoma activity. 
• To evaluate plasma for changes in analytes or tumor for protein expression that may 
predict anti-lymphoma activity 
5.4. 
Primary Endpoints 
• Frequency of dose-limiting toxicities (DLTs) as a function of the dose of LAM-002A 
during the first cycle of treatment 
5.5. 
Secondary Endpoints 
• Standard PK parameters including but not limited to AUC, t½ and Cmax 
• The type and frequency of AEs, serious adverse events (SAEs) using National Cancer 
Institute (NCI) CTCAE v4.0 (Common Toxicity Criteria for Adverse Events, version 
4.0) as well as changes in clinical laboratory values, electrocardiogram (ECG) 
parameters and vital sign measurements 
• Response as assessed by the investigator according to modified Lugano Response 
Criteria for NHL (Cheson 2014) and revised guidelines for the diagnosis and 
treatment of CLL (Hallek 2008, Cheson 2012) 
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5.6. 
Exploratory Endpoints 
• Extent of PIKfyve inhibition as determined by plasma inhibitory assays 
• Changes in gene expression in PBMCs 
• Changes in plasma cytokines (including IL-12 and IL-23) 
• Correlation between genetic alterations as determined by next generation sequencing 
and/or gene expression in tumor tissue, plasma (circulating tumor DNA), or 
PBMCs/B cells and anti-lymphoma activity following treatment with LAM-002A  
• Correlation between changes in plasma bioanalytes or tumor protein expression and 
anti-lymphoma activity following treatment with LAM-002A as determined by 
proteomic tools 
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6. 
INVESTIGATIONAL PLAN 
6.1. 
Overall Study Design 
This is a Phase 1, single-arm, open-label, dose-escalation study of safety and PK of apilimod 
administered to subjects with refractory or relapsed B-cell NHL. This study will be conducted in 
3 stages. 
6.1.1. 
LAM-002A Dose Escalation Stage (Stage 1) 
The maximum tolerated dose (MTD) will be determined during the dose-escalation stage, 
evaluating both continuous and intermittent dosing regimens. Subjects will accrue using a 3 + 3 
design. During this stage, the decision to open a new cohort at a higher or lower dose level will 
be made by the participating clinical investigators and sponsor when all subjects in the current 
cohort have been treated through at least Week 4 or once 2 DLTs have occurred in that dose 
cohort. All available safety and PK data will be considered in a decision by the medical monitor 
in collaboration with the investigators to dose escalate, de-escalate, expand the current cohort or 
explore alternate regimens of drug administration. The MTD will be determined based primarily 
on DLTs observed through Week 4 in ≥ 6 subjects.  
6.1.2. 
Expansion Stage (Stage 2) 
Once the MTD and/or recommended phase 2 dose (RP2D) and schedule is determined, the study 
will enter the expansion stage, in which cohorts of subjects will be accrued in order to obtain 
additional information on safety, tolerability, preliminary anti-tumor activity, PK, and 
pharmacodynamic data at the RP2D and schedule when LAM-002A is administered alone or in 
combination with rituximab/rituximab hyaluronidase or atezolizumab. Expansion-stage cohorts 
will comprise groups of subjects with specific types of previously treated, relapsed, progressive, 
and measurable NHL who will receive LAM-002A monotherapy or LAM-002A-containing 
combination therapy as shown in Table 2. For both monotherapy and combination cohorts, the 
starting dose of LAM-002A will be 125 mg BID administered continuously.  
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Table 2: 
Expansion Stage Disease Types and Therapies 
Cohort 
Number 
NHL Type 
Investigational  
Drug 
Combination  
Drug 
Evaluable  
Subjects, n 
1 
FL 
LAM-002A 
-- 
Up to ~20  
2 
MZL 
LAM-002A 
-- 
6 
3 
DLBCL-GCB 
LAM-002A 
-- 
6 
4 
DLBCL-ABC 
LAM-002A 
-- 
6 
5 
FL or MZL 
LAM-002A 
Rituximab or rituximab 
hyaluronidase human 
Up to ~20 
with FL 
6 
DLBCL-GCB or DLBCL-ABC 
LAM-002A 
Rituximab or rituximab 
hyaluronidase human 
6 
7 
FL or MZL 
LAM-002A 
Atezolizumab 
6 
8 
DLBCL-GCB or DLBCL-ABC 
LAM-002A 
Atezolizumab 
6 
Abbreviations: ABC: activated B-cell (subtype); DLBCL: diffuse large B-cell lymphoma; FL: follicular 
lymphoma; GCB: germinal center B-cell (subtype); MZL: marginal zone lymphoma; NHL: non-Hodgkin 
lymphoma 
6.1.3. 
Extension Stage (Stage 3) 
The extension stage (Stage 3) can begin once the last study subject has completed at least 
8 cycles of study treatment. At this time, the study sponsor will conclude the dose-escalation and 
expansion stages of the study, will collate and verify all study data through an appropriate data 
cutoff date, and will lock the study database for preparation of a study report. Subjects who are 
still safely benefiting from Stage 1 or Stage 2 study therapy as of the data cutoff date may 
electively continue their current regimen of study therapy in Stage 3, receiving clinical care and 
diagnostic testing consistent with conventional practice standards as deemed appropriate by the 
treating investigator. Therapy in Stage 3 may continue in the absence of protocol-defined reasons 
to discontinue therapy. During Stage 3, collection of clinical data by the sponsor will be limited 
to serious adverse event (SAE) reports. Study drug accountability will be managed per site 
procedures; relevant pharmacy records may be collected by the sponsor to document study drug 
disposition.  
6.1.4. 
Subject Allocation (Stage 1 and Stage 2) 
Subjects will be allocated to the cohorts by the study sponsor working in collaboration with each 
investigator considering the availability of openings for enrollment in Stage 1 or 2, disease type 
(i.e., FL, MZL, DLBCL-GCB, DLBCL-ABC, or other indications), therapy history (e.g., prior 
use of anti-CD20 or anti-PD1/PDL1 antibodies), and current disease status (e.g., potential to 
benefit from rituximab treatment based on past responses to anti-CD20 antibody therapy).  
During Stage 1 dose ranging with LAM-002A monotherapy, allocation will be performed 
according to a 3+3 dose-escalation procedure with the requirement that each cohort of 3 subjects 
be observed for ≥4 weeks before another cohort is enrolled (as detailed in Section 6.6). During 
Stage 2 cohort expansion evaluating LAM-002A monotherapy, allocation will be performed as 
subjects present to the accruing clinics and there will be no specific restrictions on the cadence of 
enrollment.  During Stage 2 cohort-expansion of LAM-002A combinations with rituximab and 
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atezolizumab, enrollment of the first 3 subjects in each combination cohort will be restricted 
such that each subject must be enrolled sequentially and observed for ≥3 weeks before the next 
subject is enrolled. Beginning with the 4th patient in each combination group, further enrollment 
may proceed without restriction as long as the continuous reassessment boundaries for toxic drug 
discontinuations are not met (as detailed in Section 6.8.4.4 and Section 14.1.2). 
6.1.5. 
Subject Evaluability  
A Stage 1 subject will be considered evaluable if the subject meets the definition for evaluability 
of Cycle 1 DLT as described in Section 6.6. A Stage 2 subject will be considered evaluable if the 
subject has both baseline and ≥1 on-study tumor assessments sufficient to allow a determination 
of response to study therapy. 
6.2. 
Number of Subjects 
As many as 145 subjects will be enrolled, assuming that: 
• In the dose-escalation stage of the study, the total number of subjects will depend upon the 
numbers of subjects accrued to each dose level and the number of dose levels evaluated. If 6 
subjects are enrolled at all open starting dose levels (Dose Levels 5, 6, 7, and 8) and 
6 additional subjects are enrolled at the MTD or RD, as many as 30 subjects could be 
enrolled. To allow for the possibility that some subjects may not be fully evaluable for DLT 
or that an intermediate dose level might be evaluated, up to ~45 subjects may be enrolled.  
• In the expansion stage of the study, if all 8 potential expansion cohorts are accrued, as many 
as ~76 subjects could be enrolled. To allow for the possibility that some subjects may not be 
fully evaluable for efficacy or to establish bounds on efficacy estimates with greater 
confidence, up to ~100 subjects may be enrolled.  
• In the extension stage of the study, the total number of subjects will include ≤4 subjects who 
have participated in the expansion stage of the study and are still receiving  study therapy on 
the data cutoff date that concludes the dose-escalation and expansion stages of the clinical 
trial. 
6.3. 
Randomization and Blinding 
This is an open-label study and there is no randomization of subjects. 
6.4. 
Treatment Assignment 
Inclusion and exclusion criteria will be reviewed for each potential subject by the investigator. If 
the consented subject is eligible for study participation, the site will send the eligibility form to 
Ce3 (see Study Manual).  
Ce3 will review the subject’s eligibility form to confirm each subject’s eligibility and will 
complete the enrollment form with treatment cohort, treatment dose and frequency. The 
enrollment form will be signed and a copy sent to the study site. Once the site receives the 
completed enrollment form, the subject will begin treatment accordingly. The treatment will be 
conducted in an open-label manner. Study sites cannot start dosing the subject without receiving 
the assigned dose on the returned Subject Enrollment and Eligibility Form.  
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Subject identification (ID) will be in the format of Site XXX-Subject XXX, for example, 
001-001 is for Site 001 first subject. Site ID will be assigned consecutively and subject ID will 
be sequential per site.  
Subject replacement is described in Section 6.13  
6.5. 
Overall Treatment Periods 
6.5.1. 
Pre-Treatment Period 
The subject is consented and undergoes screening assessments to be qualified for the study. The 
Schedule of Assessments can be found in Section 8.7. 
6.5.2. 
Treatment Period 
The subject is treated and monitored for safety (including assessments of AEs, vital signs, ECGs, 
laboratory tests and concomitant medications). Additionally, preliminary anti-tumor activity will 
be assessed and PK and biomarker samples will be collected.   
6.5.3. 
Post-Treatment Period  
Subjects should be followed until the later of either 30 days after the last dose of study treatment 
or until resolution/stabilization of any ongoing drug-related AEs and/or SAEs. For subjects with 
events that require follow-up, information regarding concomitant medications should be 
collected. Any necessary follow-up may be obtained in person or by telephone contact. 
Subjects who have discontinued study treatment for reasons other than PD will be assessed per 
Revised Response Criteria for NHL or Guidelines for the diagnosis and treatment of CLL at a 
minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for 
up to 1 year from the last enrolled subject’s first treatment (Cycle 1 Day 1) whichever comes 
first.  
Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month 
intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will 
be gathered during routine clinic visits, other study site contact with the subjects, or via 
telephone or e-mail with the subjects/caregivers or referring physician offices. 
6.6. 
LAM-002A Dose-Escalation Procedures 
LAM-002A will be administered on a twice daily (BID), or thrice daily (TID) oral dosing 
regimen with a cycle length of 28 days. Subjects on a BID schedule will be advised to take the 
doses at the same time each day, ~12 hours apart. Subjects on a TID schedule will be advised to 
take the doses at the same time each day at intervals of ~6 to 8 hours. On PK days, subjects on a 
TID schedule should receive the morning dose and complete the blood collections through 
8 hours thereafter before taking the second dose on that day.  
Other drug administration schedules may be considered if the initial BID or TID regimen’s 
safety, PK and/or pharmacodynamics suggest that a different schedule would be better tolerated 
and might allow for serum exposures required for anti-lymphoma activity. This might include a 
treatment break such as 3 weeks on/1 week off treatment or 5 days on/2 days off over a 4-week 
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cycle or an asymmetric (AM dosing > PM dosing) or once-daily dosing schedule. If another 
treatment regimen is evaluated, then the initial dose tested on this schedule will be no higher than 
the total daily dose that has been previously evaluated and tolerated.  
Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher starting dose 
levels of LAM-002A, as indicated in Table 3. The initial cohort of subjects will be prescribed 
LAM-002A at Dose Level 0 (50 mg BID). Dose level -1 (25 mg BID) is provided to permit a 
dose decrement in subjects experiencing DLT at Dose Level 0. 
Table 3: 
LAM-002A Provisional Starting Dose Levels 
Continuous Administration 
Dose Level 
LAM-002A Dose and Schedule 
LAM-002A Total Daily Dose 
-1 
  25 mg BID 
50 mg 
0 (Initial Dose Level) 
  50 mg BID 
100 mg 
1 
100 mg BID 
200 mg 
1a 
125 mg BID 
250 mg 
1b 
  75 mg TID 
225 mg 
1c 
100 mg TID 
300 mg 
1d 
125 mg TID 
375 mg 
2 
150 mg BID 
300 mg 
3 
200 mg BID 
400 mg 
4 
275 mg BID 
550 mg 
Intermittent Administration 
Dose Level 
LAM-002A Dose and Schedule 
LAM-002A Total Daily Dose 
5 
150 mg BID 
300 mg 
6 
200 mg BID 
400 mg 
7 
250 mg BID 
500 mg 
8 
 300 mg BID 
600 mg 
Abbreviations: BID: Twice daily (or 2 times per day); TID: Thrice daily (or 3 times per day) 
A 3 + 3 design will be utilized to define an MTD. For cohorts consisting of 3 subjects, dose 
escalation to the next higher dose may proceed if no DLT is observed within the first cycle of the 
3 evaluable subjects accrued to a cohort (See Section 6.1.1). If 1 of 3 subjects in the cohort 
experiences a DLT, up to a total of 6 evaluable subjects will be enrolled. If 2 or more of the 3-
6 evaluable subjects in a cohort experience a DLT, dose escalation will cease, and additional 
subjects will be treated at a lower dose level or with another schedule. If de-escalation to the 
previous dose cohort is undertaken, this cohort may be expanded to ≥6 subjects. Additional 
subjects (up to 12 total per cohort) may be evaluated to refine the estimation of the MTD and 
RP2D at the planned dose levels or at an intermediate dose level between the highest previously 
tolerated total dose and the next planned total daily dose. The MTD is defined as the highest dose 
at which < 33% of subjects experience a DLT in the total dose cohort. 
Dose escalation decisions will be evaluated in a DLT-evaluable population. The DLT-evaluable 
population will include subjects who complete Cycle 1 dosing or who are withdrawn from study 
due to a DLT in Cycle 1. A subject will be deemed non-evaluable for determining DLTs and will 
not be counted toward the total cohort size if the subject did not experience a DLT, did not 
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receive at least 75% (42/56 BID schedule; 63/84 TID schedule, 18/24 intermittent schedule) of 
the planned first-cycle doses or discontinued from the study prior to completing necessary safety 
evaluations through the first 28 days of study treatment. These subjects may be replaced unless 
accrual to the cohort has stopped due to DLT. 
Following the above guidelines, the participating investigators and sponsor will review available 
data including toxicity, PK and anti-tumor activity data to reach consensus on dose levels and 
determination of the MTD. This group will review available safety data for each cohort and will 
determine whether the MTD has been reached and decide upon further subject enrollment. Any 
detected cumulative toxicity may require later dose reductions or other action as appropriate, and 
may be evaluated in determining the RP2D and schedule.  
The RP2D and schedule will be determined in discussion between the sponsor and participating 
investigators. Observations related to PK, pharmacodynamics and any drug-related toxicities 
may be included in the rationale supporting the RP2D and schedule. 
6.7. 
Definition of LAM-002A Dose-Limiting Toxicity (DLT) 
A DLT will be defined as an AE or abnormal laboratory value meeting the criteria in Table 4 and 
that is assessed as unrelated to disease, a comorbid condition, intercurrent illness, or concomitant 
medications). For the purposes of dose escalation and determination of the LAM-002A MTDs, 
DLTs that occur within the first cycle of treatment must be included in decisions regarding dose 
escalation. DLTs or other clinically significant toxicities that occur after Cycle 1 may also be 
considered when determining the RP2D. 
Table 4: 
Criteria for Defining Dose-Limiting Toxicities (DLTs) 
Toxicity 
Criteria 
Hematology 
CTCAE Grade 4 neutropenia lasting ≥ 7 days 
CTCAE Grade 4 febrile neutropenia  
CTCAE Grade 3 thrombocytopenia with bleeding that requires transfusion 
therapy 
CTCAE Grade 4 thrombocytopenia  
Toxicity 
Criteria 
Gastrointestinal 
≥ CTCAE Grade 3 vomiting or nausea despite the use of optimal anti-emetic 
treatments 
≥ CTCAE Grade 3 diarrhea despite the use of optimal anti-diarrheal treatments 
Renal 
Serum creatinine > 3.0 x ULN 
Hepatic 
Total bilirubin ≥ CTCAE Grade 3 
Total bilirubin ≥ CTCAE Grade 2 and ALT or AST ≥ CTCAE Grade 2 
or,  
for subjects with liver metastases at baseline, total bilirubin ≥ 2.0 x ULN and 
ALT or AST ≥ CTCAE Grade 3  
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Toxicity 
Criteria 
Treatment 
interruption/delays 
Inability to administer ≥28/56 (BID schedule) or ≥42/84 (TID schedule) or 
≥12/24 (intermittent schedule) planned LAM-002A doses in a treatment cycle 
due to drug-related AEs 
or 
Failure to recover from LAM-002A-related toxicities to baseline within 14 days 
from the last dose of LAM-002A in a cycle 
Other adverse events 
not listed above 
Non-hematologic toxicities of CTCAE ≥ Grade 3 except for the following. 
•
Alopecia
•
CTCAE Grade 3 fatigue for < 72 hours
•
Asymptomatic Grade 3 elevations in biochemistry laboratory values that
last for ≤ 7 days that are not deemed to be clinically relevant. This
includes electrolyte abnormalities that respond to medical intervention.
Any LAM-002A-related adverse event that, in the opinion of the investigator, 
requires a dose reduction or discontinuation of treatment. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CTCAE: Common terminology 
criteria for adverse events; DLT: Dose-limiting toxicity; ECG: Electrocardiogram; NHL: Non-Hodgkin 
lymphoma; ULN: Upper limit of normal 
6.8. 
Treatment Guidelines 
6.8.1. 
Tumor Lysis Syndrome Prophylaxis and Therapy 
The risk for TLS must be considered based on established algorithms (Cairo 2010, 
MDACC 2013, Roberts 2016): 
•
Low-risk: Serum LDH ≤ ULN, all measurable lymph nodes < 5 cm, and absolute lymphocyte
count (ALC) < 25 × 109/L
•
Intermediate risk: Serum LDH > 1 to ≤ 2 × ULN, ≥ 1 measurable lymph node with an LD of
≥ 5 but < 10 cm, or ALC ≥ 25 × 109/L
•
High risk: Serum LDH > 2 × ULN, ≥ 1 measurable lymph node with a LD of ≥ 10 cm, or
both ≥ 1 measurable lymph node with an LD of ≥ 5 but < 10 cm and ALC ≥ 25 × 109/L
Subjects who are at intermediate or high risk of TLS must receive medical prophylaxis according 
to the following prophylaxis regimens or similar institutional regimens: 
•
Intermediate Risk of TLS: These subjects should receive allopurinol, 100 to 300 mg orally
every 8 hours starting ≥ 24 to 48 hours before the initial administration of LAM-002A on
Cycle 1-Day 1 of therapy; of note, the maximum daily allopurinol dose is 800 mg, doses ≤
300 mg need not be divided (but may be insufficient for high-risk subjects), and doses should
be reduced by ≥ 50% in subjects with renal insufficiency. In addition, subjects who develop
hyperuricemia should receive rasburicase, 0.2 mg/kg.
•
High Risk of TLS: These subjects should receive allopurinol, 100 to 300 mg orally every
8 hours starting ≥ 24 to 48 hours before the initial administration of LAM-002A on
Cycle 1-Day 1 of therapy; of note, the maximum daily allopurinol dose is 800 mg, doses ≤
300 mg need not be divided (but may be insufficient for high-risk subjects), and doses should
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be reduced by ≥ 50% in subjects with renal insufficiency. In addition, high-risk subjects 
should receive rasburicase, 0.2 mg/kg, administered 3 to 4 hours prior to the first dose of 
LAM-002A. 
In addition, subjects who are at high risk of TLS should be considered for in-hospital monitoring 
during the first 24 to 48 hours of LAM-002A administration. 
Subjects who develop TLS may experience hyperkalemia, hypocalcemia, hyperuricemia, 
hyperphosphatemia, cardiac dysrhythmias, and acute renal failure; thus, close monitoring of 
electrolytes is important after initial therapy.  
Subjects with TLS should receive intravenous hydration, rapid reversal of hyperkalemia, 
antihyperuricemic agents, and appropriate cardiac and renal support, including dialysis as 
indicated. Upon recovery to baseline functioning and as medically appropriate, such subjects 
should continue with protocol therapy to maintain tumor control. 
6.8.2. 
LAM-002A 
6.8.2.1. 
Premedications 
Subjects taking LAM-002A by continuous administration may be offered antiemetics and 
antidiarrheals as necessary to control gastrointestinal symptoms as described in Section 6.8.2.6.1. 
For subject who do develop such adverse effects, sites should consider providing study 
participants with antiemetics and antidiarrheals so that these supportive care medications are 
readily available in case gastrointestinal symptoms related to LAM-002A recur or persist.  
Subjects taking LAM-002A by intermittent administration are required to receive prophylactic 
antiemetic supportive care as described in Section 6.8.2.6.2.   
6.8.2.2. 
In-Clinic LAM-002A Administration  
For subjects receiving the continuous LAM-002A regimen, the morning dose of LAM-002A 
should be orally administered on Cycle 1 Day 1 and Cycle 1 Day 8 (after a minimum fast of 
6 hours) by site staff after the collection of the biomarker samples and pre-dose PK sample. 
Subjects are allowed to eat after PK Sample #4 (Hour 2) has been collected. On Cycle 1 Day 15, 
the morning dose of LAM-002A should be orally administered (after a minimum fast of 6 hours) 
by site staff immediately after collection of the pre-dose PK and biomarker samples.  
For subjects receiving the intermittent LAM-002A regimen, prophylactic antiemetics are a 
required component of the regimen as described in Section 6.8.2.6.2. After initiation of the 
antiemetic regimen, the morning dose of LAM-002A should be orally administered on Cycle 1 
Day 1 and Cycle 1 Day 10 (after a minimum fast of 6 hours) by site staff after the collection of 
the biomarker samples and pre-dose PK sample. Subjects are allowed to eat after PK Sample #4 
(Hour 2) has been collected. Similarly, on Cycle 1 Day 8 and Cycle 1 Day 15, the antiemetic 
regimen should be initiated and the morning dose of LAM-002A should be orally administered 
(after a minimum fast of 6 hours) by site staff immediately after collection of the pre-dose 
samples.  
When given as a component of combination therapy with rituximab, LAM-002A will be started 
on Cycle 1 Day 1 with a BID schedule. LAM-002A will be administered after administration of 
premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of the initial 
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rituximab infusion.  On Cycle 1 Day 8, the morning dose of LAM-002A will be administered 
after premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the rituximab 
infusion/injection. 
When given as a component of combination therapy with atezolizumab, LAM-002A will be 
started on Cycle 1 Day 1 with a BID schedule. LAM-002A will be administered ~15 to 
30 minutes prior to the start of the initial atezolizumab infusion.  On Cycle 1 Day 8, the morning 
dose of LAM-002A will be administered in the clinic. 
6.8.2.3. 
LAM-002A Self-Administration  
Except for the days where treatment is administered in the clinic, LAM-002A will be self-
administered orally, BID or TID of each 28-day cycle until disease progression or other 
discontinuation criteria are met. When taking the drug at home, subjects should be advised to 
take LAM-002A with ≥ 4 oz. (~160 mL) of water at the same times each day. Subjects on a BID 
schedule will be advised to take the doses at ~12 hours apart (e.g., 8:00 AM and 8:00 PM) (+/-
 1-hour window). Subjects on a TID schedule will be advised to take the doses at intervals of ~6 
to 8 hours. When self-administering LAM-002A at home, subjects may take the drug in the fed 
or fasted state. On PK days, subjects should come to clinic fasted (a minimum fasting state of 6 
to 8 hours) and take the dose at the site under supervision. All subjects will be required to 
complete a dosing diary, which must be returned to the site for review at each site visit.   
For those subjects taking LAM-002A with continuous administration, the drug should be taken 
according the prescribed BID or TID schedule without interruption unless toxicity or intercurrent 
illness requires a modification to the dosing regimen (see Section 6.8.2.5).  
For those subjects taking LAM-002A with intermittent administration, the drug should be taken 
in repeated 7-day sequences comprising BID self-administration for 3 days (6 doses) followed by 
4 days without dosing. If the cadence of the on-off periods is interrupted due to toxicity, 
intercurrent illness, or other reasons, the medical monitor should be consulted regarding the 
timing of therapy resumption and dose modification (see Section 6.8.2.5).  
6.8.2.4. 
LAM-002A Dose Schedule Interruptions and Vomited Doses 
Subjects on a BID schedule who have a delay in administration of a dose of LAM-002A of 
< 6 hours should take the planned dose as soon as possible after the intended time of 
administration. For subjects who have a delay in administration of LAM-002A of ≥ 6 hours, the 
dose should not be taken. The planned timing of subsequent LAM-002A dosing should not be 
altered.  
Subjects on a TID schedule who inadvertently have a delay in administration of a dose 
LAM-002A of ≤ 1 hour, the planned dose should be taken with no changes to the subsequent 
dose schedule. For subjects who have a delay of > 1 hour but ≤ 4 hours, the planned dose should 
be taken; however, all future doses for that day should be shifted later by a corresponding 
amount. It is recommended that subjects take the last dose of study medication no later than 
12:00 midnight on any study treatment day. For example, if the 7:00 AM dose is taken at 
10:00 AM, the next dose should be taken ≥ 6 hours later (after 5:00 PM), and the last dose 
should be taken ≥ 6 hours thereafter (between 11:00 PM and 12:00 midnight). For subjects on a 
TID schedule who have a delay in administration of LAM-002A of > 4 hours, the dose should 
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not be taken. LAM-002A administration may continue but the missed dose should not be made 
up and the planned timing of subsequent LAM-002A dosing should not be altered. 
For subjects who vomit shortly after taking LAM-002A, the vomited dose should not be 
replaced. The planned timing of subsequent LAM-002A dosing should not be altered. 
6.8.2.5. 
LAM-002A Dose Modifications 
The AEs associated with LAM-002A administration have included gastrointestinal toxicities of 
nausea, vomiting, and diarrhea, typically beginning shortly after initiation of drug administration.  
If a subject experiences an AE that is suspected to be related to LAM-002A, appropriate 
supportive care (e.g., antiemetics, antidiarrheals, therapy for tumor lysis syndrome [TLS]) should 
be instituted consistent with the nature of the event.  
If a subject experiences an LAM-002A-related DLT (reference Table 4) or other AE requiring a 
dose modification, then the LAM-002A administration should be interrupted until the toxicity 
recovers to Grade ≤ 1 or baseline. Upon resumption of LAM-002A, the total daily dose of 
LAM-002A should be reduced using an appropriate dose level or schedule (reference Table 3) as 
agreed between the investigator and medical monitor. Successive adjustments to progressively 
lower total daily dose levels can be made. If the subject cannot tolerate LAM-002A after a 
decrease to Dose Level -1 (25 mg BID), then the subject should be discontinued from 
LAM-002A therapy unless continued treatment is permitted by the medical monitor.  
After the LAM-002A dose is reduced, the dose can be maintained at that dose level or schedule, 
even if there is minimal or no toxicity with the reduced dosing regimen. However, if the subject 
tolerates a reduced total daily dose of LAM-002A for ≥ 4 weeks then the LAM-002A dosing 
regimen may be reescalated to a higher total daily dose level at the discretion of the investigator 
and with the concurrence of the medical monitor. Such reescalation may be particularly 
warranted if the AE comprised TLS or if further evaluation reveals that the AE that led to the 
dose reduction was not related to LAM-002A. Successive adjustments to progressively higher 
total daily dose levels can be made. However, the escalated dose cannot exceed the total daily 
starting dose level for that subject during the first 2 cycles of therapy.  
Individual subjects who initiated treatment at a total daily dose level at or below the lower of the 
currently established MTD or the RP2D and who have not experienced a DLT after ≥ 2 cycles of 
treatment may have the LAM-002A total daily dose escalated to the next higher dose level if 
both the principal investigator and the medical monitor agree that a dose escalation is medically 
warranted (e.g., for a subject with stable disease who is tolerating the current dose level of 
LAM-002A therapy). In such subjects, successive adjustments to progressively higher total daily 
dose levels can be made at intervals of ≥ 4 weeks with the condition that the escalated total daily 
dose level cannot exceed a LAM-002A dose of 150 mg BID when administered continuously or 
the lower of the currently established MTD or RP2D of LAM-002A when given intermittently.  
In a subject who experiences a DLT precluding resumption of LAM-002A therapy during a 
cycle, a new cycle of treatment may begin at the later of Day 29 or when AEs or laboratory 
abnormalities related to LAM-002A have returned to baseline levels. If drug-related AEs or 
laboratory abnormalities precluding further administration of study drug are not resolved to 
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baseline by Day 29, week-by-week delays in initiating the new cycle of treatment should be 
instituted. When all drug-related AEs and laboratory abnormalities have returned to baseline, the 
next cycle of therapy can be initiated. Upon initiation of a new cycle of therapy, the prior cycle 
of therapy will be considered completed. 
Investigators are to discuss modifications in the dosing regimen with the medical monitor. The 
appropriate clinic staff should dispense the LAM-002A for the new dose level or schedule and 
instruct the subject/caregiver about the change in the dosing regimen. 
6.8.2.6. 
LAM-002A Supportive Care 
6.8.2.6.1. Antiemetics for Subjects Taking LAM-002A by Continuous Administration 
For subjects taking LAM-002A via continuous administration, sites should consider providing 
study participants with antiemetics and antidiarrheals so that these supportive care medications 
are readily available in case gastrointestinal symptoms related to LAM-002A develop.  
For subjects taking LAM-002A via continuous administration, it is recommended that, if 
prophylactic or therapeutic antiemetics are required, subjects be offered 2 mg of the serotonin 
antagonist, granisetron (Kytril®, Granisol®), as an oral tablet or solution every 6 hours as 
needed. If subjects have persistent nausea or vomiting, consideration can be given to a 10-mg 
subcutaneous injection of the extended release form of granisetron (Sustol®). Alternatively, 
application of a 31.3 mg granisetron transdermal patch (Sancuso®) every 3 to 7 days can be 
offered. For transdermal prophylaxis, 24 to 48 hours may be necessary to allow a sufficient 
period to achieve effective granisetron systemic concentrations. Use of the serotonin antagonists, 
ondansetron (Zofran®, Zuplenz®) or dolasetron (Anzemet®), is discouraged due to the 
possibility that such agents could prolong the cardiac QT interval.  
The dopamine antagonist, olanzapine (Zyprexa®), at doses of 2.5 to 10 mg, may be considered 
alone or in conjunction with serotonin antagonists or other types of antiemetic agents. 
Olanzapine doses of 10 mg may be sedating, which could be helpful for certain subjects, but may 
represent a concern for others, particularly for those who are elderly.  
Based on currently available information regarding LAM-002A metabolism, the neurokinin 1 
receptor antagonist, rolapitant (Varubi®), can be considered, but aprepitant (Emend®) or 
netupitant+palonosetron (Akynzeo®) should be avoided because these drugs may inhibit 
CYP3A4 and/or CYP2C9 activity.   
Other classes of antiemetic medications that may be employed include dopamine antagonists or 
benzodiazepines if such drugs do not pose risks of QT prolongation or drug-drug interactions. 
Given the possibility that LAM-002A may alter immunological mechanisms, use of systemic 
corticosteroids (e.g., dexamethasone) should be minimized (particularly when coadministered 
with atezolizumab) to avoid immunocompromise; however, corticosteroids can be introduced if 
other types of antiemetic agents are not sufficiently effective.  
6.8.2.6.2. Antiemetics for Subjects Taking LAM-002A by Intermittent Administration 
Because LAM-002A induces dose-dependent nausea and vomiting, subjects who are taking 
LAM-002A by intermittent administration are required to receive antiemetic supportive care.  
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The following prophylaxis regimen should be started ≥30 minutes before initiation of each 
LAM-002A 3-day treatment sequence: 
•
Dexamethasone 12 mg PO on Day 1 and then 8 mg PO on Day 2 and Day 3
•
Granisetron 2 mg PO on Day 1 and then 1 mg PO BID on Days 2 and 3
•
Olanzapine, 10 mg PO on Day 1 and then 10 mg PO on Days 2 and 3
The study subject must be sent home from the clinic with sufficient dexamethasone, granisetron, 
and olanzapine to ensure that the supportive care medications are readily available to the subject 
for each of the four 3-day courses of LAM-002A therapy during each 28-day cycle.   
Doses of dexamethasone and olanzapine may be adjusted to tolerance.  Other antiemetic drugs 
(eg, neurokinin 1 receptor antagonists, dopamine antagonists, or benzodiazepines) may be 
considered in consultation with the medical monitor. 
6.8.2.6.3. Antidiarrheals 
For management of diarrhea related to LAM-002A, it is recommended that subjects take 
loperamide, 4 mg, at the occurrence of the first loose stool and then 2 mg every 2 hours until 
they are diarrhea-free for at least 12 hours. More aggressive loperamide prophylactic or 
therapeutic administration and titration of loperamide dosing for each loose bowel movement 
may be considered. During the night, subjects may take 4 mg of loperamide every 4 hours. 
Subjects should be advised to avoid dehydration through adequate fluid intake. Drugs such as 
5HT3 antagonists or octreotide may be considered for their anti-secretory effects.  For subjects 
who develop diarrhea while also receiving atezolizumab, the possibility of atezolizumab-induced 
colitis should be considered (see Section 6.8.4.4). 
6.8.3. 
Rituximab or Rituximab/Hyaluronidase Human 
6.8.3.1. 
Premedications 
In accordance with rituximab/rituximab hyaluronidase human prescribing information 
(Genentech 2016, Genentech 2018), subjects should be premedicated with an antipyretic and an 
antihistamine to reduce the incidence and severity of infusion/injection reactions. A 
recommended regimen is diphenhydramine, 25 mg orally, and acetaminophen (paracetamol), 
650 mg orally, both given ~30 minutes prior to each rituximab administration. Intravenous 
corticosteroids may also be administered as a premedication. Local practices and guidelines may 
be followed. 
6.8.3.2. 
Rituximab Administration 
Based on past experience with this regimen (Ghielmini 2004, Martinelli 2010), rituximab will 
be administered intravenously or rituximab/hyaluronidase human will be administered 
subcutaneously in the clinic for a total of 8 treatments: 
Intravenous rituximab (Rituxan®) 
•
Four induction infusions of 375 mg/m2 will be administered weekly on Cycle 1 Day 1,
Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 22.
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•
Four subsequent maintenance infusions of 375 mg/m2 will be administered every 8 weeks
on Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.
Subcutaneous rituximab (rituximab/hyaluronidase human; Rituxan Hycela®) 
•
An initial dose of 375 mg/mg2 will be administered intravenously on Cycle 1 Day1.
•
Three subcutaneous injections of 1,400 mg/23,400 Units (1,400 mg rituximab and
23,400 Units hyaluronidase human) will be administered weekly on Cycle 1 Day 8,
Cycle 1 Day 15, and Cycle 1 Day 22.
•
Four subsequent maintenance subcutaneous injections of 1,400 mg/23,400 Units
(1,400 mg rituximab and 23,400 Units hyaluronidase human) will be administered every
8 weeks on Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.
The dose calculation of body surface area for infused rituximab will be based on the subject’s 
height and actual body weight prior to therapy. Once established based on the pretreatment body 
weight, the total dose of rituximab for the subject should not be altered during therapy based on 
fluctuations in body weight unless required by institutional policy. 
At Cycle 1 Day 1, ~30 minutes after administration of the required antipyretic and antihistamine 
premedications and ~15 to 30 minutes after administration of the first dose of LAM-002A, the 
first infusion of rituximab will be administered via an infusion pump. For the initial infusion, the 
recommended infusion rate is 50 mg/hour. In the absence of infusion toxicity, the infusion rate 
can be increased in 50-mg/hour increments every 30 minutes, to a maximum of 400 mg/hour. 
For subsequent rituximab infusions, the required antipyretic and antihistamine premedications 
will be given and the rituximab will be infused via an infusion pump. For these infusions, the 
infusion can be initiated at 100 mg/hour. In the absence of infusion toxicity, the infusion rate can 
be increased in 100-mg/hour increments every 30 minutes, to a maximum of 400 mg/hour. 
Alternatively, for subjects who tolerate the first infusion with Grade ≤3 infusion toxicity, 
subsequent infusions can be administered over a planned infusion time of 90 minutes, with ~20% 
of the total dose administered in the first 30 minutes and the remaining 80% of the total protein 
dose administered in the subsequent 60 minutes (Dakhil 2014, Genentech 2016).  
For subsequent rituximab/hyaluronidase human injections, the required antipyretic and 
antihistamine premedications will be given and the rituximab/hyaluronidase human will be 
injected into the subcutaneous tissue of the abdomen over ~5 minutes. Areas where the skin is 
red, bruised, tender or hard, or areas where there are moles or scars should be avoided. No data 
are available on performing the injection at other sites of the body. If administration of 
rituximab/hyaluronidase human is interrupted, drug administration can continue at the same site 
or at a different site but restricted to the abdomen. Patients should be observed for ≥15 minutes 
following the completion of injection. During treatment with rituximab/hyaluronidase human, do 
not administer other medications for subcutaneous use at the same sites. 
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6.8.3.3. 
Management of Rituximab Infusion/Injection Toxicity 
Rituximab can cause severe, including fatal, infusion reactions (Genentech 2016). Patients with 
pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary 
adverse reactions to rituximab, and those with high numbers of circulating malignant cells 
(≥25 x 109/L) may be at particular risk. Severe reactions typically occur during the first infusion 
and are generally less frequent and less severe with subsequent infusions. The time to onset of 
infusion toxicity ranges from 30 to 120 minutes. Rituximab-induced infusion reactions and 
sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary 
infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, 
cardiogenic shock, and/or anaphylactoid events. 
Rituximab infusions/injections should be interrupted or slowed in subjects experiencing Grade 
≥3 rituximab-related infusion reactions. Medical management (eg, oxygen, epinephrine, 
bronchodilators, and/or glucocorticoids) should be instituted, as needed. Upon improvement of 
symptoms, the infusion may be continued at 50% of the previous rate. At the discretion of the 
investigator, rituximab therapy may be permanently discontinued in subjects with Grade 4 
infusion/injection reactions or with reactions requiring substantial intervention. 
6.8.3.4. 
Rituximab/Rituximab Hyaluronidase Human Dose Modifications and 
Supportive Care 
Rituximab-related noninfectious pneumonitis has been described (Subramanian 2010) with an 
incidence of ~4.3% (Salmasi 2010). In patients developing rituximab-associated pneumonitis, 
the mean time from the first rituximab infusion to the onset of respiratory symptoms was 
3 months, with a peak incidence after administration of a mean cumulative dosage of 
1600 mg/m2 (Lioté 2010). 
Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab 
during infusion or at later timepoints. Non-infusion related events have included paraneoplastic 
pemphigus, Stevens Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and 
toxic epidermal necrolysis (Genentech 2016). The onset of these reactions has varied from 1 to 
13 weeks following initiation of rituximab exposure. 
Among patients receiving rituximab in combination with chemotherapy, rare instances of life-
threatening bowel obstruction or perforation has been observed (Ram 2009), primarily in 
patients with NHL. In post-marketing reports, the mean time to documented gastrointestinal 
perforation was 6 (range 1–77) days from start of chemoimmunotherapy.  
Fulminate and fatal HBV infection and reactivation can occur during or after treatment with 
rituximab (Genentech 2016). The risk is very low among patients with negative anti-HBc 
serology (Matsue 2010) and/or undetectable HBV DNA as assessed by quantitative PCR. 
Because subjects with such evidence of persistent HBV infection are excluded from this study, 
reactivation is not anticipated. Other serious bacterial, fungal, and new or reactivated viral 
infections have also occurred during and for ~1 year following rituximab-based therapy 
(Gea-Banacloche 2010). Other new or reactivated viral infections in patients receiving rituximab 
have included CMV, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile 
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virus, and HCV. Progressive multifocal leukoencephalopathy (PML) due to polyomavirus JC has 
been observed in patients who have received rituximab therapy for hematologic malignancies 
(Carson 2009).  
No dose reductions of rituximab/rituximab hyaluronidase human are recommended. If a subject 
experiences an AE that is suspected to be related to rituximab/rituximab hyaluronidase human 
and is of sufficient severity to warrant modification of therapy, administration of the drug should 
be interrupted or discontinued. Protocol-recommended management of selected adverse events 
and appropriate supportive care is described in Table 5. 
Table 5: 
Recommended Rituximab or Rituximab/Hyaluronidase Modifications and 
Supportive Care 
Adverse 
Event 
Rituximab Interruption 
and Resumption 
Rituximab 
Permanent 
Discontinuation 
Supportive Care 
Pneumonitis 
Interrupt for Grade 2; 
resume when Grade ≤ 1 
Grade ≥3 
For Grade ≥2, 
corticosteroids, 1-2 mg/kg 
of prednisone equivalents  
Rash 
Interrupt for Grade 3; 
resume when Grade ≤ 1 
Grade 4 
For Grade 2, topical 
corticosteroids. For 
Grade ≥ 3, corticosteroids, 
1-2 mg/kg of prednisone
equivalents
Hepatitis 
Grade ≥3 elevations of 
serum AST or ALT (> 5 x 
ULN); resume when 
Grade ≤ 1 
-- 
Evaluate for HBV 
positivity; if HBV 
reactivation, treat with 
appropriate antiviral 
considering any potential 
for drug-drug interaction 
with LAM-002A. 
Bowel 
obstruction 
or 
perforation 
-- 
Any grade 
Provide appropriate 
antibiotic therapy and 
surgical supportive care. 
Infection 
Grade ≥3; resume when 
control of infection 
achieved 
-- 
Treat with appropriate 
systemic antibiotics for 
suspected or confirmed 
infections 
Abbreviations: ALT=alanine aminotransferase, AST=aspirate aminotransferase, ULN=upper limits of 
normal 
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6.8.4. 
Atezolizumab 
6.8.4.1. 
Premedications 
No specific premedications are recommended for administration prior to atezolizumab 
administration. Given the potential for interference with desired atezolizumab 
immunopotentiation, systemic corticosteroid administration should be avoided. 
6.8.4.2. 
Atezolizumab Administration 
Atezolizumab will be administered intravenously in the clinic every 3 weeks.  The dose for each 
infusion will be 1200 mg. 
Using an infusion pump, atezolizumab should be administered through an intravenous line with 
or without a sterile, non-pyrogenic, low-protein binding in-line filter (pore size of 0.2 to 
0.22 μm). Other drugs should not be coadministered with atezolizumab through the same 
intravenous line. 
At Cycle 1 Day 1, ~15 to 30 minutes after administration of the first dose of LAM-002A, the 
first infusion of atezolizumab will be administered over 60 minutes. If the first infusion is 
tolerated, all subsequent infusions may be delivered over 30 minutes. Atezolizumab should not 
be administered as an intravenous push or bolus.  
6.8.4.3. 
Management of Atezolizumab Infusion Toxicity 
While infrequent (incident <2%), severe infusion reactions have occurred in clinical trial subjects 
receiving atezolizumab. For subjects with Grade 1 or 2 infusion reactions, the atezolizumab 
infusion should be interrupted or slowed. For subjects with Grade ≥3 infusion reactions, 
atezolizumab therapy should be permanently discontinued. 
6.8.4.4. 
Atezolizumab Dose Modifications and Supportive Care 
In clinical trials supporting its approval as therapy for patients with previously treated advanced 
non-small cell lung cancer and metastatic bladder cancer (Weinstock 2017, Ning 2017), 
atezolizumab administration has been associated with immune-related AEs of pneumonitis, 
hepatitis, pancreatitis, colitis, endocrinopathies (hypophysitis, thyroiditis, adrenal insufficiency, 
diabetes mellitus), and neurological toxicity (meningitis/encephalitis, motor/sensory 
neuropathies, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome). Immune-
related AEs can be observed within days to months after starting atezolizumab therapy 
(Genentech 2017). 
Severe infections, including pneumonias, urinary tract infections, sepsis, herpes encephalitis, and 
mycobacterial infection have occurred.  
Systemic immune activation is a rare condition characterized by an excessive immune response.  
Given the mechanism of action of atezolizumab, systemic immune activation is considered a 
potential risk when atezolizumab is given in combination with other immunomodulating agents.  
Systemic immune activation should be included in the differential diagnosis for study subjects 
who, in the absence of an alternative etiology, develop a sepsis-like syndrome after 
administration of atezolizumab.  The initial evaluation should include: 
•
CBC with peripheral smear
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• PT, PTT, fibrinogen, and D-dimer 
• Ferritin 
• Triglycerides 
• AST, ALT, and total bilirubin 
• LDH 
• Complete neurologic and abdominal examination (assessing for hepatosplenomegaly) 
If systemic immune activation is suspected after the initial evaluation, the medical monitor 
should be contacted in consultation.  
Reference should be made to Section 6 of the atezolizumab investigator brochure for a detailed 
description of anticipated safety risks for atezolizumab. 
No dose reductions of atezolizumab are recommended. If a subject experiences an AE that is 
suspected to be related to atezolizumab and is of sufficient severity to warrant modification of 
therapy, administration of the drug should be interrupted or discontinued. Protocol-recommended 
management of selected adverse events is described in Table 6. 
Table 6: 
Recommended Atezolizumab Modifications and Supportive Care 
Adverse 
Event 
Atezolizumab  
Interruption and 
Resumption 
Atezolizumab  
Permanent 
Discontinuation 
Supportive Care 
Pneumonitis 
Interrupt for Grade 2; 
resume when Grade ≤ 1 
Grade ≥3 
For Grade ≥2, 
corticosteroids, 1-2 mg/kg 
of prednisone equivalents  
Hepatitis 
Interrupt for Grade 2 
elevations of serum AST 
or ALT (> 3-5 x ULN) or 
total bilirubin (> 1.5-3 x 
ULN); resume when 
Grade ≤ 1 
Grade ≥3 elevations of 
serum AST or ALT (> 5 x 
ULN) or total bilirubin 
(> 3 x ULN) 
For Grade ≥2, 
corticosteroids, 1-2 mg/kg 
of prednisone equivalents  
Colitis 
Interrupt for Grade 2 or 3; 
resume if Grade ≤ 1 within 
12 weeks on ≤ 10 mg oral 
prednisone equivalents 
Grade 4 
For Grade 2 recurrent or 
persistent (> 5 days), 
corticosteroids, 1-2 mg/kg 
of prednisone equivalents; 
For Grade ≥3, 
methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
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Adverse 
Event 
Atezolizumab  
Interruption and 
Resumption 
Atezolizumab  
Permanent 
Discontinuation 
Supportive Care 
Pancreatitis 
Interrupt for Grade 2 or 3 
pancreatitis or Grade ≥3 
increases in serum amylase 
or lipase levels (>2 x 
ULN); resume if Grade ≤ 1 
within 12 weeks on 
≤ 10 mg oral prednisone 
equivalents 
Grade 4 pancreatitis or any 
grade of recurrent 
pancreatitis 
For Grade ≥2, 
methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
Hypophysitis 
Interrupt for symptoms; 
resume when Grade ≤ 1 
-- 
Administer corticosteroids 
and hormone replacement 
as clinically indicated 
Thyroid 
disorders 
Interrupt for symptoms; 
resume when Grade ≤ 1 
-- 
For symptomatic hypo- or 
hyperthyroidism, initiate 
hormone replacement or 
anti-thyroid drug, as 
needed 
Adrenal 
insufficiency 
Interrupt for symptoms; 
resume if Grade ≤ 1 within 
12 weeks on ≤ 10 mg oral 
prednisone equivalents 
-- 
For symptoms, 
methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
Diabetes 
mellitus 
Interrupt for Grade ≥3 
hyperglycemia (serum 
glucose ≥ 250 mg/dL; 
resume when blood sugar 
control achieved 
-- 
Insulin for Type 1 
diabetes mellitus 
Meningitis, 
encephalitis, 
myasthenic 
syndrome, 
myasthenia 
gravis, or 
Guillain-
Barré 
syndrome 
-- 
Any grade 
Methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
Rash 
Interrupt for Grade 3; 
resume when Grade ≤ 1 
Grade 4 
For Grade 2, topical 
corticosteroids. For 
Grade ≥ 3, corticosteroids, 
1-2 mg/kg of prednisone 
equivalents 
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Adverse 
Event 
Atezolizumab  
Interruption and 
Resumption 
Atezolizumab  
Permanent 
Discontinuation 
Supportive Care 
Infection 
Grade 3 or 4; resume when 
control of infection 
achieved 
-- 
Treat with appropriate 
systemic antibiotics for 
suspected or confirmed 
infections 
Abbreviations: ALT=alanine aminotransferase, AST=aspirate aminotransferase, ULN=upper limits of 
normal 
6.9. 
Other Supportive Care Recommendations 
Consistent with subject safety and comfort, administration of any prescription or over-the-
counter drug products other than study medication will be minimized during the study period. 
Subjects should be discouraged from use of herbal remedies, self-prescribed drugs, tobacco 
products, or street drugs during their participation in the clinical study and should be counseled 
to minimize use of alcohol or nonmedical marijuana. 
If considered necessary for the subject’s well-being, drugs for concomitant medical conditions or 
for symptom management may be given at the discretion of the investigator. The investigator’s 
decision to authorize the use of any drug other than study drug will take into account subject 
safety, the medical need, the potential for drug interactions, the possibility for masking 
symptoms of a more significant underlying event, and whether use of the drug will compromise 
the outcome or integrity of the study. 
Subjects will be instructed about the importance of the need to inform the clinic staff of the use 
of any drugs or remedies (whether prescribed, over-the-counter, or illicit) before and during the 
study.  
Recommendations regarding specific types of concomitant therapies, supportive care, diet, and 
other interventions are provided below. To minimize variations in supportive care, the 
recommended supportive care agents (eg, loperamide, granisetron) should be used unless there is 
a medical rationale in a specific subject for use of an alternative product. 
6.9.1. 
Antibiotics, Antifungals, and Antivirals 
Care should be taken to avoid or minimize concomitant administration of prophylactic or 
therapeutic antibacterial, antifungal, or antiviral, agents that are moderate or strong CYP3A4 or 
CY2C9 inhibitors or inducers (see Section 6.9.6 and Appendix 3).  
For subjects with a history of recurrent infections, prophylaxis with intravenous gamma-globulin 
may be offered and consideration may be given to initiation of antibiotic prophylaxis against 
pneumocystis infection (eg, with trimethoprim-sulfamethoxazole, dapsone, aerosolized 
pentamidine, or atovaquone) beginning prior to study drug administration. Such support also 
offers the benefit of reducing the risk for other bacterial infections (Stern 2014). Local practices 
or guidelines regarding infection prophylaxis may be followed.  
Subjects developing an intercurrent infection during study drug treatment may receive 
therapeutic antibacterial, antiviral, or antifungal drugs for intercurrent infections as needed. 
Continuation of study therapy during treatment for an intercurrent infection is at the discretion of 
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the investigator but guidance in Section 6.8.3.4 and Section 6.8.4.4 should be considered in 
subjects receiving combination therapy. 
6.9.2. 
Anticancer Therapies Other than the Study Drugs 
No systemic anticancer therapies (including chemotherapy, antibody therapy, hormonal therapy, 
immunotherapy, or other experimental therapies) for the subject’s cancer are permitted while the 
subject is receiving study treatment. Subjects are not allowed to participate concurrently in any 
other therapeutic clinical or imaging study. 
The use of palliative radiotherapy should be minimized given the potential of such treatment to 
confuse assessments of study drug safety or therapeutic effect. However, administration of 
limited-fraction radiotherapy is permitted to control local tumor-related symptoms if irradiation 
is unlikely to induce major organ toxicity or affect target lesions being followed for tumor 
response and progression. 
If required to maintain disease control, study drugs may be continued with caution during 
radiotherapy administration. 
6.9.3. 
Anticoagulants 
Use of local anticoagulation or antithrombotic agents to maintain a venous access catheter is 
permitted. While not prohibited, use of systemic anticoagulants (eg, unfractionated heparin, low-
molecular-weight heparin, fractionated heparin, warfarin or other oral anticoagulants, aspirin) 
after a subject is on study should be avoided unless necessary for development of a serious 
intercurrent thrombotic or embolic condition. Subjects who develop conditions that require 
anticoagulant therapy are permitted to receive such drugs and are not required to discontinue 
study participation if they appear to be safely benefiting from study therapy. Subjects should be 
closely monitored for bleeding events when on systemic anticoagulant therapy. 
6.9.4. 
Antihistamine, Antiinflammatory, or Antipyretic, Drugs 
Antihistamines (eg, cetirizine, diphenhydramine), and antiinflammatory/antipyretic drugs (eg, 
acetaminophen [paracetamol], nonsteroidal anti-inflammatory drugs [NSAIDs]), may be used 
during the study, as medically warranted. The potential for adverse hepatic effects with 
acetaminophen and platelet inhibitory effects with NSAIDs should be considered in the selection 
of the appropriate drug for the clinical situation. 
6.9.5. 
Corticosteroids 
At study entry, subjects may not be using systemic or enteric corticosteroids but may be 
receiving inhaled or topical corticosteroids. During study therapy, subjects may use systemic, 
enteric, topical or enteric corticosteroids as required by protocol or for treatment-emergent 
conditions. Use of systemic or enteric corticosteroids as premedications or for other reasons 
should be minimized but can be considered after consultation with the medical monitor.  
6.9.6. 
Drugs with Potential for Drug-Drug Interactions with LAM-002A 
No information is available regarding interactions of LAM-002A with therapeutic agents or other 
substances in humans. In vitro data suggest that concomitant administration of potent inhibitors 
or inducers of CYP3A4 or CYP2C9 might alter LAM-002A clearance and lead to clinically 
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significant increases or decreases in LAM-002A exposure. Consequently, the concomitant use of 
strong inhibitors or inducers of CYP3A4 or CYP2C9 (see Table 15) should be avoided when 
possible.  
Based on these considerations, protocol candidates who require therapy with strong CYP3A4 or 
CYP2C9 inhibitors or inducers listed in Table 15 should not be enrolled into the study.  
During study participation, coadministration of LAM-002A with CYP3A4 or CYP2C9 inhibitors 
or inducers (see Table 15) should be avoided, if possible. However, a subject who develops a 
condition that may require use of such drugs is not required to permanently discontinue 
LAM-002A if the subject is experiencing clinical benefit and other options for treating the 
subject’s cancer are limited. If medically appropriate, investigators may wish to use a therapeutic 
alternative that would not be expected to affect these enzymes. For subjects who require 
temporary use of a drug that does affect these enzymes (e.g., treatment with a systemic 
antifungal agent), LAM-002A can be interrupted (or the doses reduced) during use of the other 
medication and then resumed after completion of the other drug. For subjects who require 
initiation of chronic therapy with a drug that potently affects these enzymes, investigators must 
consult with the medical monitor to consider the best course of action.  
6.9.7. 
Drugs Known to Prolong the QT Interval 
In a thorough QTc study, apilimod dimesylate at doses of 50 mg and 150 mg was associated with 
repolarization findings in excess of those deemed negative by regulatory guidance. The 
magnitude of the change was modest (~8.5 msec), peaked at 4 hours and did not demonstrate a 
dose trend. Preliminary QTc observations in the ongoing study in patients with hematological 
malignancies suggest the potential for dose- and exposure dependent Grade 1 or 2 QT 
prolongation. 
As a precaution, the clinical potential of LAM-002A to prolong the QT interval will be assessed 
in this study. Accordingly, co-administration of LAM-002A and known QT-prolonging drugs is 
to be minimized because use of such drugs might confound interpretation of QT data from the 
trial.  
Based on these considerations, protocol candidates who require therapy with drugs known to 
prolong the QT interval (as listed in Table 16) should not be enrolled into the study. If medically 
justified, protocol candidates may be enrolled if such drugs can be discontinued or alternative 
drugs that do not affect QT can be substituted >7 days before the first dose of study drug.  
After the subject is enrolled to the protocol, use of drugs known to prolong the QT interval 
should be minimized but is not prohibited if administration of such drug is necessary and the 
subject appears to be benefiting from protocol therapy. 
6.9.8. 
Hematopoietic Support 
Granulocyte colony-stimulating factor (G-CSF) (eg, filgrastim, filgrastim snd, pegfilgrastim, 
lenograstim) may be administered in response to Grade ≥3 neutropenia or neutropenic 
complications. 
Granulocyte-macrophage colony-stimulating factor (GM-CSF) should not be administered given 
the potential for GM-CSF-related inflammatory symptoms.  
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Use of erythropoietic agents (eg, erythropoietin or darbepoetin) is not recommended. 
Red blood cell or platelet transfusions may be administered as medically indicated. 
6.9.9. 
Immunization 
There is no information regarding the effects of LAM-002A or atezolizumab on the safety or 
response to immunization against infectious pathogens.  
In randomized clinical trials, rituximab has been shown to reduce the antibody response to 
pneumococcal vaccination (a T-cell-independent antigen) or to anti-keyhole limpet hemocyanin 
antibodies (a novel protein antigen) (Genentech 2016). Response to tetanus toxoid vaccine (a 
T‑cell-dependent antigen with existing immunity) or maintenance of a positive Candida skin test 
(as a measure of T-cell-mediated delayed-type hypersensitivity) was not altered. The specific 
clinical relevance of these findings is unknown.  
For subjects who are at substantial risk of an infection (eg, influenza) that might be prevented by 
immunization, consideration should be given to providing the vaccine prior to initiation of study 
therapy. Vaccination with live virus vaccines during study treatment is not recommended. 
6.9.10. 
Procedures/Surgery 
The extent to which LAM-002A or other study drugs may affect wound healing or the risk of 
would infection is unknown. Investigators may use clinical discretion in deciding whether to 
interrupt protocol therapy before and after surgery or other invasive procedures.  
6.9.11. 
Skeletal Event Prophylaxis 
Bisphosphonates or denosumab are permitted if a subject was receiving such therapy at the time 
of screening and will continue on a stable regimen throughout protocol therapy. The need to start 
such drugs while on therapy may be an indication of disease progression and should be discussed 
with the sponsor prior to implementation. 
6.10. 
Study Restrictions 
6.10.1. 
Breast Feeding 
There is no information regarding the presence of LAM-002A or its metabolites in animal or 
human breast milk and the effects of the drug on the breastfed infant or on milk production are 
unknown. 
Rituximab is secreted in the milk of lactating cynomolgus monkeys, but it is not specifically 
known whether rituximab is secreted into human milk (Genentech 2016). There is similarly no 
information regarding the presence of atezolizumab in human milk (Genentech 2017). However, 
because human IgG is excreted in human milk, there is a hypothetical potential for absorption 
and harm to an infant from administration of these types of therapeutic antibodies.  
For these reasons, women who are nursing are not eligible to participate in this study. Lactating 
women who do participate in this clinical trial must discontinue nursing during protocol therapy 
and should avoid nursing for ≥2 months after LAM-002A and for ≥5 months after the last dose 
of rituximab or atezolizumab.  
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6.10.2. 
Contraception 
Animal studies have been conducted to assess the effects of apilimod on fertility and 
organogenesis. In studies conducted to date, apilimod or apilimod dimesylate did not affect 
fertility or cause reproductive harm. One patient receiving the drug for Crohn disease conceived 
during therapy; a normal pregnancy was carried to term and a healthy infant was born. However, 
no other experience is available with the drug in pregnant patients.  
Reproduction studies of rituximab in cynomolgus monkeys at maternal exposures similar to 
human therapeutic exposures have shown no teratogenic effects (Genentech 2016). However, B-
cell lymphoid tissue was reduced in the offspring of these animals; B-cell counts returned to 
normal levels and immunologic function was restored within 6 months of birth. In humans,
B-cell lymphocytopenia generally lasting <6 months can occur postnatally in infants exposed to 
rituximab in utero.
Animal reproduction studies have not been conducted with atezolizumab to evaluate its effect on 
reproduction and fetal development. A literature-based assessment of the effects on reproduction 
demonstrated that a central function of the PD-L1/PD-1 pathway is to preserve pregnancy by 
maintaining maternal immune tolerance to a fetus (Genentech 2017). Blockage of PD-L1 
signaling has been shown in murine models of pregnancy to disrupt tolerance to a fetus and to 
result in an increase in fetal loss; therefore, potential risks of administering atezolizumab during 
pregnancy include increased rates of abortion or stillbirth. As reported in the literature, there 
were no malformations related to the blockade of PD-L1/PD-1 signaling in the offspring of these 
animals; however, immune-mediated disorders occurred in PD-L1 and PD-1 knockout mice. 
Based on its mechanism of action, fetal exposure to atezolizumab may increase the risk of 
developing immune-mediated disorders or altering the normal immune response. 
Accordingly, sexually active females of childbearing potential must agree to use a protocol-
recommended method of contraception during heterosexual intercourse from the start of the 
screening period until ≥5 months days after the final dose of study therapy.  
In the context of this protocol, a female subject is considered to be of childbearing potential 
unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has 
medically documented ovarian failure (with serum follicle stimulating hormone (FSH) level 
> 35 mIU/mL and a negative serum or urine beta βHCG); or is menopausal (amenorrhea for
≥12 months).
Sexually active male subjects who can father a child and are having intercourse with females of 
childbearing potential who are not using adequate contraception must agree to use a protocol-
recommended method of contraception from the start of study therapy until ≥5 months days after 
the final dose of the study therapy and to refrain from sperm donation from the start of study 
therapy until ≥5 months after administration of the final dose of study therapy. 
In the context of this protocol, a male subject is considered able to father a child unless he has 
had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. 
Protocol-recommended contraceptive methods are described in Table 7. 
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Table 7: 
Protocol-Recommended Contraceptive Methods 
Individual Methods 
Combination Methods 
Hormonal Methods 
(One method to be used  
with a barrier method) 
Barrier Methods 
(Both methods to be used OR one 
method to be used with one 
hormonal method) 
IUD (eg, Copper T380A, LNg20) 
Estrogen and progesterone 
Diaphragm with spermicide 
Tubal sterilization 
Oral contraceptives 
Male condom (with spermicide) 
Hysterectomy 
Transdermal patch 
 
Vasectomy 
Vaginal ring 
 
 
Progesterone injection or implant 
 
Abbreviation: IUD=intrauterine device 
6.10.3. 
Diet 
Because LAM-002A is a substrate of CYP3A4, subjects should be advised to avoid ingestion of 
grapefruit, grapefruit juice, or Seville oranges (which contains a potent CYP3A4 inhibitor) and 
should not use St. John’s wort, which is a potent CYP3A4 inducer. No other specific dietary 
restrictions are required. 
6.11. 
Duration of Subject Participation 
Subjects may continue receiving LAM-0002A until the occurrence of any events requiring 
treatment discontinuation as defined in Section 6.8.2.5 and Section 6.12. 
Subjects allocated to LAM-0002A/rituximab may continue to receive rituximab or rituximab 
hyaluronidase human until the earliest of a maximum of 8 infusions or the occurrence of any 
events requiring treatment discontinuation as defined in Section 6.8.3.4 and Section 6.12. 
Subjects allocated to LAM-0002A/atezolizumab may continue to receive atezolizumab until the 
earliest of any events requiring treatment discontinuation as defined in Section 6.8.4.4 or 
Section 6.12. 
Note: If medically appropriate, subjects allocated to combination doublet therapy may 
continue with protocol-specified therapy for the therapeutic agent (LAM-002A, rituximab, 
rituximab hyaluronidase human, or atezolizumab) that continues to be tolerated, even if the 
other agent need to be discontinued due to drug-specific toxicity. 
Subjects who have discontinued study treatment for reasons other than PD will be assessed per 
Revised Response Criteria for NHL or Guidelines for the diagnosis and treatment of CLL at a 
minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for 
up to 1 year from the last enrolled subject’s first treatment (Cycle 1 Day 1), whichever comes 
first. Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month 
intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will 
be gathered during routine clinic visits, other study site contact with the subjects, or via 
telephone or e-mail with the subjects/caregivers or referring physician offices. 
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6.12. 
Criteria for Subject Withdrawal from Study Treatment or Study 
Participation 
Subjects may be withdrawn from further study treatment for any of the following reasons: 
• Subject withdrawal of informed consent 
• Disease progression of cancer while receiving study therapy Note: Apparent worsening of 
disease during temporary interruption of study therapy (e.g., for drug-related toxicity or 
intercurrent illness) may not indicate true cancer progression. Study subjects undergoing 
PET for lymphoma assessment can experience transient disease flare on imaging before 
having subsequent therapy-induced tumor regression. Worsening of constitutional 
symptoms or performance status in the absence of objective evidence of worsening 
lymphoma (e.g., due to infection) may not represent definitive disease progression. For 
these reasons, if there is uncertainty regarding whether there is true disease progression 
and if medically appropriate, the subject may continue or resume study treatment and 
remain under close observation (e.g., evaluated at 4- to 8-week intervals) while relevant 
radiographic, clinical, and/or laboratory assessments are performed to document whether 
tumor control can be maintained or whether disease progression has truly occurred. If 
subsequent evaluations suggest that the subject has experienced persistent definitive 
disease progression, then the date of progression will be the timepoint at which 
progression was first objectively documented.  
• Unacceptable study-drug-related toxicity despite appropriate dose modification 
• Development of intercurrent illness that precludes continued study therapy 
• Physician decision that continuation is not in the subject’s best interest 
• Treatment of the cancer with another therapeutic regimen 
• Subject becomes pregnant or begins breastfeeding 
• Substantial noncompliance with study drug administration, study procedures, or study 
requirements in circumstances that increase risk or substantially compromise the 
interpretation of study results 
• Termination of the study by the sponsor, relevant regulatory agencies, or the IRB/IEC 
The investigator must determine the primary reason for a subject’s withdrawal from the study 
and record this information on the electronic case report form (eCRF). 
Unless they withdraw consent for further follow-up, subjects who discontinue study therapy will 
continue on study for acquisition of safety information through ≥30 days after the last dose of 
study treatment, and for further collection of long-term information regarding survival. 
6.13. 
Replacement of Subjects 
Subjects not meeting the criteria for evaluability defined in Section 6.1.5  may be replaced at the 
discretion of the sponsor. If a subject needs to be replaced, the associated subject ID will not be 
used again. 
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7. 
SELECTION OF SUBJECTS 
7.1. 
Subject Inclusion Criteria 
1. The subject is capable of understanding and complying with the protocol requirements 
and has signed the informed consent document. The subject is able to provide signed and 
dated informed consent prior to initiation of any study-specific procedures. 
2. Subjects must have a histologically confirmed diagnosis of B-cell NHL limited to FL, 
DLBCL, MCL, MZL, primary mediastinal B-cell lymphoma (PMBL), or CLL/SLL 
according to the World Health Organization (WHO) classification, that has progressed 
and for which standard curative measures do not exist or are no longer effective.  
3. Subjects with DLBCL must have progressed after transplant, or be unwilling, unable or 
not an appropriate candidate for an autologous stem cell or bone marrow transplant. 
4. Subjects must have radiographically measurable lymphadenopathy or extranodal 
lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures ≥ 2.0 cm in the 
longest dimension [LD] and ≥ 1.0 cm in the longest perpendicular dimension [LPD] as 
assessed radiographically). 
5. The subject is ≥ 18 years old. 
6. The subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 
≤ 2. 
7. The subject has organ and marrow function as follows: 
a. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1,000/mm3) without hematopoietic-
stimulating factor support 
b. Platelets ≥ 50 × 109/L (50,000/mm3) 
c. Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) except for subjects with 
known Gilbert disease (total bilirubin ≤ 3 x ULN permitted) 
d. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min (based 
on the Cockcroft-Gault formula) 
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN 
if no liver involvement, or ≤ 5 x ULN with liver involvement 
f. Albumin ≥ 2 g/dL 
g. Note: Grade ≥ 3 neutropenia or thrombocytopenia is permitted if the abnormality is 
related to bone marrow involvement with hematological malignancy (as documented by 
bone marrow biopsy/aspirate obtained since the last prior therapy). 
8. The subject has the ability to swallow oral capsules without difficulty. 
9. Sexually active subjects (men and women), even if on oral contraceptives, must agree to 
remain abstinent (refrain from heterosexual intercourse) or use appropriate contraceptive 
methods (see Section 6.10.2) during the treatment period and for 5 months after the last 
dose of study therapy.  
10. Women of childbearing potential (WCBP) must have a negative serum or urine 
pregnancy test at screening. WCBP include any woman who has experienced menarche 
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and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation, or bilateral oophorectomy) or is not postmenopausal. Postmenopausal is defined 
as: 
a. Amenorrhea ≥ 12 consecutive months without another cause or 
b. For women with irregular menstrual periods and on hormone replacement therapy, a 
documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL 
11. For subjects with lymphoma: The subject is willing to undergo a pretreatment core 
needle, excisional, or incisional biopsy of a lymphoma nodal lesion (preferred); or is 
willing to undergo a pretreatment bone marrow aspirate if there is known bone marrow 
involvement (≥ 50% NHL cells).  If a biopsy or bone marrow aspirate is not possible, 
archived tumor tissue that was obtained within 4 months prior to the start of screening 
can be used, provided adequate quantities are available.   
12. For subjects with CLL/SLL: The subject has sufficient circulating cells in the peripheral 
blood (e.g., ALC ≥ 10 x 109/L) or is willing to undergo a pretreatment bone marrow 
aspirate to obtain CLL cells.  
7.2. 
Subject Exclusion Criteria 
1. Subjects with central nervous system (CNS) lymphoma are not eligible for the trial unless 
the disease had been treated and the subject remained asymptomatic (for at least 6 
months) with no active CNS lymphoma, as determined by lumbar puncture, computed 
tomography scan (CT), or magnetic resonance imaging (MRI). 
2. The subject has received cytotoxic chemotherapy (including investigational cytotoxic 
chemotherapy) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before the 
first dose of study treatment. 
3. The subject has received treatment with a therapeutic antibody less than 4 weeks before 
the first dose of study treatment. For subjects with rapidly progressive or aggressive 
subtypes of lymphoma, a minimum period of 2 weeks between the last treatment with a 
therapeutic antibody and the first dose of study treatment may be permitted following 
discussion with the medical monitor. 
4. The subject has received radioimmunotherapy within 6 weeks of the first dose of study 
treatment. 
5. The subject has received radiation therapy within 14 days of the first dose of study 
treatment. 
6. The subject has received prior treatment with a small-molecule kinase inhibitor or other 
small-molecule investigational agent within 14 days or 5 half-lives of the compound or 
active metabolites, whichever is greater, before the first dose of study treatment. 
7. Stage 2 (study candidates being considered for LAM-002A/rituximab combination 
therapy): Best overall response with the last regimen containing an anti-CD20 antibody 
(eg, rituximab, ofatumumab, obinutuzumab) was disease progression. 
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8. Stage 2 (study candidates being considered for LAM-002A/atezolizumab combination 
therapy): Prior exposure to a CD137 agonist or an immune checkpoint inhibitor, 
including an anti-PD1, anti-PDL1, or anti-CTLA4 therapeutic antibody. 
9. Stage 2 (study candidates being considered for LAM-002A/atezolizumab combination 
therapy):  treatment with a live, attenuated vaccine within 4 weeks prior to initiation of 
study treatment, or anticipation of need for such a vaccine during atezolizumab treatment 
or within 5 months after the last dose of atezolizumab. 
10. Stage 2 (study candidates being considered for LAM-002A/atezolizumab combination 
therapy):  Current treatment with anti-viral therapy for hepatitis B virus (HBV). 
11. Stage 2 (study candidates being considered for LAM-002A/atezolizumab combination 
therapy):  Treatment with systemic immunostimulatory agents (including, but not limited 
to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 half-lives of the drug 
(whichever is longer) prior to initiation of study treatment. 
12. The subject is currently receiving treatment with strong inhibitors or inducers of 
CYP450 2C9 or 3A4 enzymes. 
13. The subject is chronically receiving immunosuppressive therapy (eg, with 
cyclophosphamide, azathioprine, thalidomide, lenalidomide, methotrexate, or anti-TNF-α 
agents) within 2 weeks prior to initiation of study treatment or requires systemic or 
enteric corticosteroids at the time of starting study therapy. Study candidates using 
systemic low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency or 
topical, intra-articular, nasal, or inhaled corticosteroids are not excluded from study 
participation. Note: During study therapy, subjects may use systemic, enteric, topical, 
intraarticular, nasal, or inhaled corticosteroids as required by protocol or for treatment-
emergent conditions. 
14. The subject has not recovered from toxicity due to all prior therapies (i.e., return to 
pre-therapy baseline or to Grade 0 or 1). Persistent > Grade 1 toxicity from prior therapy 
will be considered by the sponsor for inclusion if there is no evidence of an overlapping 
apilimod toxicity.  
15. The subject has uncontrolled significant intercurrent illness including, but not limited to, 
ongoing or active infection, history of congestive heart failure within 6 months, Grade ≥3 
hypertension, unstable angina pectoris within 6 months, stroke within 6 months, 
myocardial infarction within 6 months, or cardiac arrhythmias. (Controlled chronic atrial 
fibrillation will not be excluded). 
16. Severe uncontrolled infection within 2 weeks prior to initiation of study treatment, 
including hospitalization for complications of infection, bacteremia, or severe pneumonia 
or treatment with therapeutic oral or IV antibiotics. Note: subjects receiving prophylactic 
antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary 
disease exacerbation) are not excluded.   
17. Stage 2 (study candidates being considered for LAM-002A/atezolizumab combination 
therapy): Active or history of autoimmune disease or immune deficiency, including, but 
not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus 
erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid 
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antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré 
syndrome, or multiple sclerosis (with the following exceptions: history of autoimmune-
related hypothyroidism and receiving thyroid-replacement hormone; controlled Type 1 
diabetes mellitus on an insulin regimen; eczema, psoriasis, lichen simplex chronicus, or 
vitiligo with dermatologic manifestations if rash covers < 10% of body surface area, 
disease is well controlled at baseline and requires only low-potency topical 
corticosteroids, there is no occurrence of acute exacerbations of the underlying condition 
requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, 
oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 
12 months, and the subject does not have extra-cutaneous disease [e.g., psoriatic 
arthritis]).  
18. The subject has a history of malabsorption or other GI disease that may significantly alter 
the absorption of apilimod (e.g., ≥ Grade 2 nausea, vomiting or diarrhea). 
19. The subject has undergone major surgery within 28 days prior to first dose of study drug. 
20. The subject has a QTcF > 470 msec on screening ECG or has a history or risk factors for, 
or use of medications known to prolong QTc interval or that may be associated with 
Torsades de Pointes within 7 days of treatment start. 
21. The subject has past history of tuberculosis (TB) or active infection with TB, human 
immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). 
Note: Subjects must have negative human immunodeficiency virus (HIV) antibody, 
negative hepatitis B surface antigen (HBsAg) and negative hepatitis B core (HBc) 
antibody or undetectable HBV deoxyribonucleic acid (DNA) by quantitative 
polymerase chain reaction (PCR) testing, and negative HCV antibody or negative HCV 
ribonucleic acid (RNA) by quantitative PCR. 
22. The subject is lactating and breast feeding. 
23. The subject has a previously identified allergy or hypersensitivity to components of the 
study treatment formulation. 
24. Stage 1 (study candidates being considered for LAM-002A intermittent administration): 
Known inability to tolerate the protocol-specified antiemetic and antidiarrheal supportive 
care regimen. 
25. The subject is unable or unwilling to abide by the study protocol or cooperate fully with 
the investigator or designee. 
26. The subject has a history of other medical or psychiatric illness or organ dysfunction 
which, in the opinion of the investigator, would either compromise the subject’s safety or 
interfere with the evaluation of the safety of the study agent. 
27. The subject has a history of prior cancer (not under study) that has not been in remission 
for at least 3 years. The following are exempt from the 3-year limit: basal cell or 
squamous cell carcinoma of the skin, localized prostate cancer with normal Prostate 
Specific Antigen (PSA), cervical cancer in situ or other in situ carcinomas. 
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8. 
METHODS OF ASSESSMENT AND ENDPOINTS 
All trial data during the dose-escalation stage (Stage 1) and expansion stage (Stage 2) will be 
recorded on the eCRFs. Timing of study procedures for the dose-escalation stage (Stage 1) and 
expansion stage (Stage 2) are listed in schedules of assessments tables – Table 8: Schedule of 
Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: Schedule of 
Assessments (LAM-002A Intermittent Monotherapy Administration), Table 10: 
Schedule of 
Assessments (LAM-002A/Rituximab Combination Therapy), and Table 11: 
Schedule of 
Assessments (LAM-002A/Atezolizumab Combination Therapy) – in Section 8.7.  During the 
extension stage (Stage 3), collection of clinical data by the sponsor will be limited to serious 
adverse event (SAE) reports. Study drug accountability will be managed per site procedures; 
relevant pharmacy records may be collected by the sponsor to document study drug disposition. 
8.1. 
Screening/Baseline Evaluations Only 
8.1.1. 
Informed Consent 
Each potential subject must sign a written informed consent form (ICF) prior to performing any 
study-specific procedure. Principal investigators (PIs) at each site are responsible for maintaining 
a record of all subjects screened, including both those who enter the study and those who are 
excluded. 
8.1.2. 
Inclusion and Exclusion Criteria 
During Screening, inclusion and exclusion criteria will be reviewed for each potential subject 
and confirmed by Day 1 of Cycle 1.  
8.1.3. 
Medical History 
At Screening, a complete medical history will be obtained from each subject, including relevant 
medical history, current primary cancer diagnosis, pathology reports (including corresponding 
flow cytometry and cytogenetic reports), prior cancer treatments (chemo- and immunotherapies, 
radiation therapy, surgeries), and disease-specific characteristics, such as tumor stage and 
histology.  
8.1.4. 
Demography 
At Screening, subject demographic data will be collected, including date of birth, gender, race, 
and ethnicity. 
8.1.5. 
Disease Status Assessment for Subjects with NHL 
Pretreatment tumor assessments will be performed within 30 days of the first dose of study 
treatment and will include diagnostic CT scans (with intravenous contrast) or Positron Emission 
Tomography (PET)/Computerized Tomography Scans (CT scan) for patients with lymphoma, 
bone marrow aspirate/biopsy, complete blood counts and physical examination. It is anticipated 
that in most cases the PET/CT scans will be conducted using a single instrument, i.e., as a 
PET/CT scan (CT scans should be performed using a contiguous reconstruction algorithm of 
≤ 5 mm). However, MRI is an acceptable alternative method for assessing disease in subjects 
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who cannot receive intravenous contrast with CT scans. In such subjects MRI and PET scans 
will have to be obtained separately. 
Suitable scans performed prior to screening and within 30 days before first dose may be used for 
baseline tumor assessments. Similarly bone marrow biopsies/aspirates performed within 
2 months prior to first dose may be used for baseline assessments. For subjects with NHL, 
baseline bone marrow biopsies/aspirates may be omitted if not deemed essential for response 
assessment or patient management and there is another source of tumor tissue for pretreatment 
evaluation of gene expression and prognosis. For subjects with CLL/SLL, a baseline bone 
marrow aspirate is required unless the presence of sufficient circulating cells in the peripheral 
blood (e.g., ALC ≥ 10 x 109/L) permits assessment of baseline parameters for gene expression 
and prognosis. Details of assessments will be collected on the eCRF and must be filed in the 
subject’s medical record. 
Fresh tumor tissue (preferred) or archival tumor tissue that was obtained within 4 months prior to 
the start of screening (provided adequate quantities are available)  must be obtained pretreatment 
for nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be 
acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 
16-gauge core needle).  Confirmation of tumor in biopsy with fine needle aspirate, touch prep, or 
FFPE processing is requested when possible.  The tumor lesion selected should not have been 
previously irradiated and should not be an index lesion that is followed for response assessment. 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow 
involvement due to NHL (≥50% of cells). Tissue will be submitted for evaluation of the 
percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anti-lymphoma activity and/or pharmacodynamics activity.  
In addition, tumor tissue from the fresh biopsy or most recently availably biopsy or surgery will 
be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; 
expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, 
and for immune infiltration. The baseline biopsy procedure (if required) should ideally be 
performed after the study candidate has undergone the baseline radiology examination and is 
otherwise considered eligible for study participation. 
8.1.6. 
Disease Status Assessments for Subjects with CLL/SLL  
All subjects with CLL must have baseline imaging (with CT scans [preferred] or MRI scans).  
Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor 
cells or a bone marrow aspirate sample pretreatment. Tissue will be submitted for evaluation of 
the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anticancer activity and/or pharmacodynamic activity. In addition, for subjects with 
CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a sponsor-
specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH 
panel [chromosome 11q deletion, 13q deletion, 17p deletion and 12 trisomy], DNA mutational 
analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL [e.g., Notch]; 
flow cytometry [for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda 
light chains and ZAP-70], and/or β2-microglobulin). The baseline bone marrow aspiration 
procedure (if required) should ideally be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participation.  
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8.2. 
Baseline Assessment for All Subjects  
8.2.1. 
Physical Examination and ECOG Performance Status 
Complete physical examination (PE) will be performed at Screening and may include evaluation 
of head, ears, eyes, nose, and throat, dermatological, respiratory, cardiovascular, gastrointestinal, 
endocrine/metabolic, neurological, lymphatic, and musculoskeletal systems. A directed PE, 
including weight, will be performed within 72 hours prior to the start of each cycle and at End of 
Treatment.  
ECOG Performance Status will be assessed at the same time points as PEs (See Appendix 1). 
8.2.2. 
Pregnancy Test  
Serum or urine pregnancy test will be performed for WCBP at Screening, within 72 hours of 
Day 1 of each treatment cycle, and at the EOT visits. The test does not need to be repeated at 
Cycle 1 Day 1 if baseline testing was performed within 72 hours of first dose. However, the 
result must be negative for the subject to be enrolled in the study and to continue participation.  
8.2.3. 
Urinalysis  
A urine sample will be obtained at Screening, within 72 hours of Day 1 of each treatment cycle, 
and at the EOT visit. Analysis will include assessment of appearance, specific gravity and pH as 
well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes and blood. Microscopic examination of sediment will be performed if urinalysis is 
positive for white blood cells (WBCs), proteins, or blood. 
8.2.4. 
Electrocardiogram  
A 12-lead ECG with subject resting for 5 minutes will be done at Screening. Additional ECGs 
will be conducted according to Table 8: Schedule of Assessments (LAM-002A Continuous 
Monotherapy Administration), Table 9: Schedule of Assessments (LAM-002A Intermittent 
Monotherapy Administration), Table 10: Schedule of Assessments (LAM-002A/Rituximab 
Combination Therapy), and Table 11: 
Schedule of Assessments (LAM-002A/Atezolizumab 
Combination Therapy) – in Section 8.7 and more often if clinically indicated. Parameters 
measured will include heart rate, PR, QRS, QT, and QTc intervals (calculated by the Fridericia 
correction formula. Bazett’s correction is acceptable if institutional policy). See Section 12 for 
PK time points. The ECGs will be reviewed and signed by the investigator. 
8.2.5. 
Vital Signs 
Vital signs including temperature (°C), blood pressure, pulse, and respiration rate will be 
measured at each indicated visit including screening, prior to the start of each cycle, prior to each 
PK time point, at the End of Treatment, and more often if clinically indicated. 
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8.3. 
Screening/Baseline, Day 1, 8, 10, 15 (Cycles 1 and 2 Only) and Prior 
to Each Subsequent Cycle and End of Treatment 
8.3.1. 
Clinical Laboratory Tests 
Clinical laboratory tests during the first 2 cycles will be performed by the investigative site’s 
local laboratory. Samples will be collected from subjects at scheduled study visits before the 
administration of study drug unless otherwise noted, and more frequently if clinically indicated. 
Clinical laboratory tests may be performed up to 72 hours prior to the scheduled visits (see 
Section 8.7 for Schedules of Assessments). Upon completion of Cycle 2, subjects may use the 
investigative site’s laboratory or their local laboratory for clinical laboratory assessments. 
Accredited certification, such as College of American Pathologists (CAP) and Clinical 
Laboratory Improvement Amendments (CLIA), and valid reference ranges must be collected for 
all clinical laboratories used by subjects. 
The following clinical laboratory tests will be collected: Hematology, Coagulation, Blood 
Chemistry and PK Assessments. 
8.3.1.1. 
Hematology 
Hemoglobin, hematocrit, WBC count with differential, red blood cell (RBC) count, and platelet 
count will be collected according to the relevant schedule of events; see Table 8: Schedule of 
Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: Schedule of 
Assessments (LAM-002A Intermittent Monotherapy Administration), Table 10: 
Schedule of 
Assessments (LAM-002A/Rituximab Combination Therapy), and Table 11: 
Schedule of 
Assessments (LAM-002A/Atezolizumab Combination Therapy) in Section 8.7. 
Coagulation parameters (aPTT [or PTT] and INR) should be performed at Screening.  
8.3.1.2. 
Blood Chemistry 
Albumin, alkaline phosphatase (ALP), total bilirubin, calcium, carbon dioxide, chloride, 
creatinine, glucose, inorganic phosphorus, potassium, total protein, ALT, AST, lactate 
dehydrogenase (LDH), sodium, BUN, and uric acid will be collected according to the relevant 
schedule of events; see Table 8: Schedule of Assessments (LAM-002A Continuous 
Monotherapy Administration), Table 9: Schedule of Assessments (LAM-002A Intermittent 
Monotherapy Administration), Table 10: Schedule of Assessments (LAM-002A/Rituximab 
Combination Therapy), and Table 11: 
Schedule of Assessments (LAM-002A/Atezolizumab 
Combination Therapy) in Section 8.7. If the total bilirubin concentration is > 1.5 times the upper 
normal limit, total bilirubin should be differentiated and the total and direct bilirubin should be 
reported. 
8.3.1.3. 
PK and Biomarker Assessments  
Pharmacokinetic samples will be collected for determination of apilimod and metabolite 
concentrations in plasma at the time points indicated in Section 12. All subjects must participate 
in PK assessments. Fasting status must be recorded at the time of each PK blood draw. 
Comprehensive information on blood sample acquisition, handling, storage and sample 
shipments can be found in the laboratory manual “Procedures for Processing and Shipping PK 
and Biomarker Samples.”  
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Biomarker samples will be obtained at time points indicated in Section 13. Comprehensive 
information on tissue acquisition, handling, storage, and sample shipments can be found in the 
laboratory manual “Procedures for Processing and Shipping PK and Biomarker Samples.” 
8.4. 
Disease Assessment 
The type of assessment and schedule is defined by the subject’s disease. Therefore, the type and 
schedule of assessments is presented in Appendix 2 for subjects with relapsed or refractory 
B-cell NHL and CLL/SLL.
8.5. 
Adverse Events 
Adverse Events will be assessed using the National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 4.0 (NCI 2010). AEs, including SAEs, will be captured on 
the eCRFs from Cycle 1 Day 1 through 30 days after the last dose of study treatment. Study 
treatment related AEs/SAEs that are ongoing 30 days after the last dose of study treatment 
should continue to be followed until resolution or stabilization. AE assessment will be done at a 
minimum at each scheduled visit. For the weeks that the subject is not required to come to the 
study site, the investigator will monitor each subject for possible AEs via telephone contact as 
needed. 
8.6. 
Treatment Compliance 
The investigator will dispense the study medication only for use by subjects enrolled in the study 
as described in this protocol. The study medication is not to be used for reasons other than those 
described in this protocol. 
The investigator or other study staff will supervise LAM-002A treatment given at the site and 
instruct the subject on study medication self-administration. Subjects will be asked to bring their 
dosing diary with them at each visit. Compliance with protocol-defined LAM-002A intake will 
be checked by pill count at the end of each cycle and compliance decisions will be made by the 
investigator. 
A subject is considered to be DLT-evaluable if he/she has taken at least 75% (42/56 BID 
schedule; 63/84 TID schedule, 18/24 intermittent schedule) of the planned first-cycle doses and 
has sufficient safety data, or has experienced a DLT in the first cycle.  
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8.7. 
Schedules of Assessments 
Table 8: 
Schedule of Assessments (LAM-002A Continuous Monotherapy Administration) 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
-28 to -1 
1 
2 
3 
8 
15 
1 
15-28 
1 
15-28 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
Xc 
 
 
 
 
X 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
X 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
X 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xj 
 
 
 
 
 
 
Xk 
 
Xk 
Xl 
 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
 
 
PK/PD plasma samplingn  
 
X 
 
 
X 
X 
 
 
 
 
 
 
Bone marrow aspirate/biopsy 
 Xo 
 
 
 
 
 
 
Xp 
 
Xp 
 
 
Biomarker – tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAr 
 
X 
 
 
 
X 
 
 
 
 
X 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
 
 
 
 
X 
 
Biomarker – PBMC/B cellt 
X 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – salivau 
X 
 
 
 
 
 
 
 
 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
 
 
 
 
 
 
Adverse events 
 
Throughout Study 
 
Concomitant medicationsw 
 
Throughout Study 
 
Long-term follow-up (F/U)x 
 
 
 
 
 
 
 
 
 
 
 
X 
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A Eligibility will be confirmed by C1D1. 
B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the start of 
each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 for all cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F 
All hematology and chemistry laboratory parameters should be assessed at Screening and at C1D1, C1D8, C1D15, C≥2D1 (all subsequent cycles), and then at 
least once prior to the start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of Cycle 1 is only required 
in subjects with intermediate or high risk of TLS (per the risk definition in Section 6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters may be 
obtained within 72 hours prior to the planned day of collection. Abnormal test values should be monitored per protocol guidance. 
G Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, leukocytes, 
and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained within 
72 hours prior to the planned day of collection. 
I 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J 
Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to 
screening and within 30 days before first dose may be used for baseline tumor assessments. 
K Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as appropriate 
for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 months until PD or use 
of alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may be every 6 months. Subjects with 
CLL who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M  Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. Tissue 
will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anticancer activity 
and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a 
sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q deletion, 13q deletion, 
17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL [e.g., Notch]; flow cytometry 
[for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], and/or β2-microglobulin). The baseline bone 
marrow aspiration procedure (if required) should be performed after the study candidate has undergone the baseline radiology examination and is otherwise 
considered eligible for study participation. All subjects with CLL/SLL must have baseline imaging (with CT scans [preferred] or MRI scans).  
N Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D8 as follows: 
pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D15 will be pre-dose only. Subjects are required to come to the study site in 
a fasting state prior to the collection of certain PK samples.  
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O Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, baseline 
bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of tumor 
tissue for pretreatment evaluation of gene expression and prognosis. For subjects with CLL/SLL, a baseline bone marrow aspirate is required unless the 
presence of sufficient circulating cells in the peripheral blood (e.g., absolute lymphocyte count [ALC] ≥ 10 x 109/L) permits assessment of baseline 
parameters as described in Footnote m, above. 
P 
If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and physical 
examination. 
Q Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 months prior to the start of screening) must be 
obtained pretreatment for nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional 
biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle aspirate, touch prep, or FFPE 
processing is requested when possible.  The tumor lesion selected should not have been previously irradiated and should not be an index lesion that is 
followed for response assessment. Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL 
(≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or 
surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and 
MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if required) should ideally be performed after the 
study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation. 
R Plasma will be collected on C1D1 pretreatment, on C1D15 pretreatment, and at EOT visit for evaluation of circulating tumor DNA to measure tumor burden 
and mutational changes. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) predose on each of C1D1, C1D8, and C1D15 and at EOT. 
T  PBMCs/B-cells will be collected during Screening for determination of changes in gene expression that may predict or correlate with anti-lymphoma activity 
and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors. 
U  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors.  
V LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). 
W  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
X Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised Response Criteria for NHL or Guidelines for the 
diagnosis and treatment of CLL at a minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (C1D1) whichever comes first. Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This long-
term follow-up information will be gathered during routine clinic visits, other study site contact with the subjects, or via telephone or e-mail with the 
subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID, twice per day; BUN: Blood urea nitrogen; CBCs: Complete blood 
counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; hrs: Hours; 
LDH: Lactate dehydrogenase; min: Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; 
PD: Progressive disease; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; 
SAE: Serious adverse event; TLS: tumor lysis syndrome; WBC: White blood cell; WCBP: Women of child bearing potential 
 
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Table 9: 
Schedule of Assessments (LAM-002A Intermittent Monotherapy Administration) 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
-28 to -1 
1 
2 
3 
8 
10 
15 
1 
15-28 
1 
15-28 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
X 
Xd 
Xd 
X 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
X 
Xd 
 
X 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
 
X 
X 
 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
 
X 
X 
 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
 
X 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xj 
 
 
 
 
 
 
 
Xk 
 
Xk 
Xl 
 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK/PD plasma samplingn  
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
Bone marrow aspirate/biopsy 
 Xo 
 
 
 
 
 
 
 
Xp 
 
Xp 
 
 
Biomarker – tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAr 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
X 
 
 
 
 
X 
 
Biomarker – PBMC/B cellt 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – salivau 
X 
 
 
 
 
 
 
 
 
 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
Adverse events 
 
Throughout Study 
 
Concomitant medicationsw 
 
Throughout Study 
 
Long-term follow-up (F/U)x 
 
 
 
 
 
 
 
 
 
 
 
 
X 
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A Eligibility will be confirmed by C1D1. 
B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the start of 
each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 for all cycles. For C1D1 and C1D10 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D8 and C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F 
All hematology and chemistry laboratory parameters should be assessed at Screening and C1D1, C1D8, C1D15, C≥2D1 (all subsequent cycles), and then at 
least once prior to the start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of Cycle 1 is only required 
in subjects with intermediate or high risk of TLS (per the risk definition in Section 6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters may be 
obtained within 72 hours prior to the planned day of collection. Abnormal test values should be monitored per protocol guidance. 
G Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, leukocytes, 
and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained within 
72 hours prior to the planned day of collection. 
I 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J 
Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to 
screening and within 30 days before first dose may be used for baseline tumor assessments. 
K Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as appropriate 
for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 months until PD or use 
of alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may be every 6 months. Subjects with 
CLL who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M  Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. Tissue 
will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anticancer activity 
and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a 
sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q deletion, 13q deletion, 
17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL [e.g., Notch]; flow cytometry 
[for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], and/or β2-microglobulin). The baseline bone 
marrow aspiration procedure (if required) should be performed after the study candidate has undergone the baseline radiology examination and is otherwise 
considered eligible for study participation. All subjects with CLL/SLL must have baseline imaging (with CT scans [preferred] or MRI scans).  
N Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D10 as 
follows: pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D8 and C1D15 will be pre-dose only. Subjects are required to 
come to the study site in a fasting state prior to the collection of certain PK samples.  
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O Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, baseline 
bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of tumor 
tissue for pretreatment evaluation of gene expression and prognosis. For subjects with CLL/SLL, a baseline bone marrow aspirate is required unless the 
presence of sufficient circulating cells in the peripheral blood (e.g., absolute lymphocyte count [ALC] ≥ 10 x 109/L) permits assessment of baseline 
parameters as described in Footnote m, above. 
P 
If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and physical 
examination. 
Q Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 months prior to the start of screening) must be 
obtained pretreatment for nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional 
biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle aspirate, touch prep, or FFPE 
processing is requested when possible.  The tumor lesion selected should not have been previously irradiated and should not be an index lesion that is 
followed for response assessment. Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL 
(≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or 
surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and 
MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if required) should ideally be performed after the 
study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation. 
R Plasma will be collected on C1D1 (predose), on C1D15 (predose), and at EOT visit for evaluation of circulating tumor DNA to measure tumor burden and 
mutational changes. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) on C1D1 (predose), C1D8 (predose), C1D10 (predose), and 
C1D15 (predose) and at EOT. 
T  PBMCs/B-cells will be collected during Screening for determination of changes in gene expression that may predict or correlate with anti-lymphoma activity 
and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors.  
U  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors. 
V LAM-002A to be administered with antiemetic prophylaxis according to intermittent schedule (see Section 6.8.2.1, Section 6.8.2.2, and Section 6.8.2.3). On 
the designated days the subject will take LAM-002A in the clinic (with recording of the date and actual clock time of the LAM-002A administration). 
W  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
X Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised Response Criteria for NHL or Guidelines for the 
diagnosis and treatment of CLL at a minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (C1D1) whichever comes first. Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This long-
term follow-up information will be gathered during routine clinic visits, other study site contact with the subjects, or via telephone or e-mail with the 
subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID, twice per day; BUN: Blood urea nitrogen; CBCs: Complete blood 
counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; hrs: Hours; 
LDH: Lactate dehydrogenase; min: Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; 
PD: Progressive disease; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; 
SAE: Serious adverse event; TLS: tumor lysis syndrome; WBC: White blood cell; WCBP: Women of child bearing potential 
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Table 10: 
Schedule of Assessments (LAM-002A/Rituximab Combination Therapy) 
Assessment 
Screening 
Cycle 1 
Cycles ≥2 
End of 
Treatment 
(EOT) 
Long-Term 
F/U 
Day 
Day 
 
-28 to -1 
1 
2 
3 
8 
15 
22 
1 
22-28 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
ECOG performance Status 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xj 
 
 
 
 
 
 
 
Xk 
Xl 
 
PK/PD samplingm 
 
X 
 
 
X 
X 
 
 
 
 
 
Bone marrow aspirate/biopsy 
 Xn 
 
 
 
 
 
 
 
Xo 
 
 
Biomarker – tumor tissuep 
X 
 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAq 
 
X 
 
 
 
X 
 
 
 
X 
 
Biomarker – plasma cytokinesr 
 
X 
 
 
X 
X 
 
 
 
X 
 
Biomarker – PBMC/B cells 
X 
 
 
 
 
 
 
 
 
 
 
Biomarker – salivat 
X 
 
 
 
 
 
 
 
 
 
 
Premedicationu 
 
X 
 
 
X 
X 
X 
 Xu 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
 
 
 
 
 
Rituximab infusion/injectionw 
 
X 
 
 
X 
X 
X 
 Xw 
 
 
 
Adverse events 
 
Throughout study 
 
Concomitant medicationsx 
 
Throughout study 
 
Long-term F/Uy 
 
 
 
 
 
 
 
 
 
 
X 
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A Eligibility will be confirmed by C1D1. 
B Complete PE will be performed at Screening. A directed PE, including weight, will be performed within 72 hours prior to the start of each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 for all cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F 
All hematology and chemistry laboratory parameters should be assessed at Screening, on C1D1, C1D8, C1D15, C≥2D1 (all subsequent cycles), and at EOT. 
Obtaining a chemistry laboratory parameter on C1D2 and C1D3 is only required in subjects with intermediate or high risk of TLS (per the risk definition in 
Section 6.8.1).  Except for C1D1, C1D2, and C1D3, these parameters may be obtained within 72 hours prior to the planned day of collection.  
G Serum chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, leukocytes, 
and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained within 
72 hours prior to the planned day of collection. 
I 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J 
Imaging as appropriate for disease indication will be conducted within 30 days before C1D1. Suitable scans performed prior to Screening and within 30 days 
before first dose may be used for baseline tumor assessments. 
K Assessment of disease status will be conducted with standard imaging as appropriate for indication. During treatment, scans will be repeated for tumor 
assessment within 7 days before C3D1, C5D1, C7D1, and then every 3 cycles (12 weeks) until PD or use of alternative antineoplastic therapy.  
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 4 weeks of EOT visit. 
M Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D8 as follows: 
pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D15 will be pre-dose only. Subjects are required to come to the study site in 
a fasting state prior to the collection of certain PK samples.  
N Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of tumor tissue for 
pretreatment evaluation of gene expression and prognosis.  
O If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and PE 
p 
Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 months prior to the start of screening) must be 
obtained pretreatment for nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional 
biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle aspirate, touch prep, or FFPE 
processing is requested when possible.  The tumor lesion selected should not have been previously irradiated and should not be an index lesion that is 
followed for response assessment. Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL 
(≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or 
surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and 
MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if required) should ideally be performed after the 
study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation. 
Q Plasma will be collected on C1D1 (predose), on C1D15 (predose), and at EOT visit for evaluation of circulating tumor DNA to measure tumor burden and 
mutational changes. 
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R  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) on C1D1 (predose), C1D8 (predose), and C1D15 (predose) and at 
EOT. 
S  PBMCs/B-cells will be collected during Screening for determination of changes in gene expression that may predict or correlate with anti-lymphoma activity 
and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors. 
T  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors. 
U Oral antipyretic, oral or intravenous antihistamine, and intravenous corticosteroid (at investigator discretion) (see Section 6.8.3.1) to be administered to the 
subject ~30 minutes prior to each rituximab infusion/injection (see Footnote w). 
v 
LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). On C1D1, 
LAM-002A will be started on a BID schedule after administration of premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of the initial 
rituximab infusion. On C1D8, the morning dose of LAM-002A will be administered after premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to 
the rituximab infusion/injection. 
W Rituximab, 375 mg/m2, will be administered by intravenous infusion ~30 minutes after premedication weekly on C1D1, C1D8, C1D15, and C1D22 and then 
every 8 weeks on C4D1, C6D1, C8D1, and C10D1 for a total of 8 infusions. Alternatively, rituximab, 375 mg/m2, will be administered by intravenous 
infusion ~30 minutes after premedication weekly on C1D1 and then rituximab hyaluronidase human, 1,400 mg rituximab and 23,400 Units hyaluronidase 
human per 11.7 mL, will be administered by subcutaneous injection on C1D8, C1D15, and C1D22 and then every 8 weeks on C4D1, C6D1, C8D1, and 
C10D1 for a total of 8 treatments. 
X  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
Y Subjects who have discontinued study treatment for reasons other than PD will be assessed at a minimum of every 12 weeks until documentation of PD, start 
of new anti-cancer therapy or for up to 1 year from the last enrolled subject’s first treatment (C1D1) whichever comes first. Long-term follow-up survival 
information will be obtained in all surviving subjects who permanently discontinue study therapy. Such information may be collected at ~3- to 6-month 
intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will be gathered during routine clinic visits, other study site 
contact with the subjects, or via telephone or e-mail with the subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID: twice per day; BUN: Blood urea nitrogen; CBCs: Complete blood 
counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; F/U: Follow-up; 
LDH: Lactate dehydrogenase; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: Progressive disease; PDL1: programmed 
death ligand-1; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; SAE: 
Serious adverse event; TLS: tumor lysis syndrome; WBC: White blood cell; WCBP: Women of child-bearing potential
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Confidential and Proprietary
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Table 11: 
Schedule of Assessments (LAM-002A/Atezolizumab Combination Therapy) 
Assessment 
Screening 
Cycle 1 
Cycles ≥2 
End of 
Treatment 
(EOT) 
Long-Term 
F/U 
Day 
Day 
 
-28 to -1 
1 
2 
3 
8 
15 
1 
15-22 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
X 
 
X 
 
ECOG performance Status 
X 
Xc 
 
 
 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
 
X 
 
Serum thyroid functionh 
X 
 
 
 
 
 
X 
 
 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
Urinalysisi 
X 
Xc 
 
 
 
 
X 
 
X 
 
Pregnancy testing 
X 
Xj 
 
 
 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xk 
 
 
 
 
 
 
Xl 
Xm 
 
PK/PD samplingn 
 
X 
 
 
X 
X 
 
 
 
 
Bone marrow aspirate/biopsy 
 Xo 
 
 
 
 
 
 
Xp 
 
 
Biomarker – tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAr 
 
X 
 
 
 
X 
 
 
X 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
X 
 
X 
 
Biomarker – PBMC/B cellst 
X 
 
 
 
 
 
 
 
 
 
Biomarker – salivau 
X 
 
 
 
 
 
 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
 
 
 
 
Atezolizumab infusionw 
 
X 
 
 
 
 
 Xw 
 
 
 
Adverse events 
 
Throughout study 
 
Concomitant medicationsx 
 
Throughout study 
 
Long-term F/Uy 
 
 
 
 
 
 
 
 
 
X 
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A Eligibility will be confirmed by C1D1. 
B Complete PE will be performed at Screening. A directed PE, including weight, will be performed within 72 hours prior to the start of each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 for all cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F 
All hematology and chemistry laboratory parameters should be assessed at Screening, on C1D1, C1D8, C1D15, C≥2D1 (all subsequent cycles), and at EOT. 
Obtaining a chemistry laboratory parameter on C1D2 and C1D3 is only required in subjects with intermediate or high risk of TLS (per the risk definition in 
Section 6.8.1).  Except for C1D1, C1D2, and C1D3, these parameters may be obtained within 72 hours prior to the planned day of collection.  
G Serum chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Serum thyroid function tests include TSH, free T3, and free T4 at C3D1, C5D1, C7D1, C9D1, and then every 4 cycles (12 weeks).. 
i 
Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, leukocytes, 
and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained within 
72 hours prior to the planned day of collection. 
J 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
K Imaging as appropriate for disease indication will be conducted within 30 days before C1D1. Suitable scans performed prior to Screening and within 30 days 
before first dose may be used for baseline tumor assessments. 
L Assessment of disease status will be conducted with standard imaging as appropriate for indication. During treatment, scans will be repeated for tumor 
assessment within 7 days before C3D1, C5D1, C7D1, C9D1, and then every 4 cycles (12 weeks) until PD or use of alternative antineoplastic therapy.  
M Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 4 weeks of EOT visit. 
N Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D8 as follows: 
pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D15 will be pre-dose only. Subjects are required to come to the study site in 
a fasting state prior to the collection of certain PK samples.  
O Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of tumor tissue for 
pretreatment evaluation of gene expression and prognosis.  
P 
If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and PE. 
Q Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 months prior to the start of screening) must be 
obtained pretreatment for nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional 
biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle aspirate, touch prep, or FFPE 
processing is requested when possible.  The tumor lesion selected should not have been previously irradiated and should not be an index lesion that is 
followed for response assessment. Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL 
(≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or 
surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and 
MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if required) should ideally be performed after the 
study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation. 
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R Plasma will be collected on C1D1 (predose), on C1D15 (predose), and at EOT visit for evaluation of circulating tumor DNA to measure tumor burden and 
mutational changes. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) on C1D1 (predose), C1D8 (predose), C1D15 (predose), C2D1, 
and at EOT. 
T PBMCs/B-cells will be collected during Screening for determination of changes in gene expression that may predict or correlate with anti-lymphoma activity 
and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors. 
U  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors. 
V LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). On C1D1, 
LAM-002A will be started on a BID schedule after administration of premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of the initial 
atezolizumab infusion. On C1D8, the morning dose of LAM-002A will be administered after premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior 
to the atezolizumab infusion 
w Atezolizumab, 1200 mg, will be administered by intravenous infusion over ~30 minutes every 3 weeks. 
X  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
Y Subjects who have discontinued study treatment for reasons other than PD will be assessed at a minimum of every 12 weeks until documentation of PD, start 
of new anti-cancer therapy or for up to 1 year from the last enrolled subject’s first treatment (C1D1) whichever comes first. Long-term follow-up survival 
information will be obtained in all surviving subjects who permanently discontinue study therapy. Such information may be collected at ~3- to 6-month 
intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will be gathered during routine clinic visits, other study site 
contact with the subjects, or via telephone or e-mail with the subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID: twice per day; BUN: Blood urea nitrogen; CBCs: Complete blood 
counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; F/U: Follow-up; 
LDH: Lactate dehydrogenase; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: Progressive disease; PE: Physical exam; 
PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; SAE: Serious adverse event; 
T3: triiodothyronine; T4: thyroxine; TLS: tumor lysis syndrome; TSH: thyroid-stimulating hormone; WBC: White blood cell; WCBP: Women of child-bearing 
potential 
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9. 
STUDY DRUG MATERIALS AND MANAGEMENT  
9.1. 
LAM-002A 
9.1.1. 
Description 
LAM-002A drug description is provided in Table 12. 
Table 12: 
LAM-002A Drug Description 
Product Name: 
LAM-002A 
Dosage Form: 
Capsule 
Unit Dose 
25 mg or 50 mg 
Route of Administration 
Oral 
Physical Description 
Each capsule will contain 25 mg or 50 of apilimod dimesylate (equivalent 
to 17.1 mg or 34.3 mg of apilimod free base, respectively). The 25-mg 
capsule is Swedish orange and the 50-mg capsule is white. Both the 25- and 
50-mg capsules are Size 0 and both have a total fill weight of 175 mg. 
Inactive components in active capsules are microcrystalline cellulose, 
silicified microcrystalline cellulose, anhydrous lactose, croscarmellose 
sodium, colloidal silicon dioxide, and magnesium stearate.   
Manufacturer 
Patheon 
9.1.2. 
LAM-002A  Packaging and Labeling 
LAM-002A  will be provided in bulk bottles to each investigational pharmacy for dispensing. 
The pharmacist will dispense capsules into bottles for each subject (based on Cohort assignment) 
following applicable state and federal laws and site policies. Details on the labeling, dispensing, 
and administration of LAM-002A  are provided in the Pharmacy Manual. 
9.1.3. 
Source 
LAM-002A will be provided by the sponsor. 
9.1.4. 
Storage 
The LAM-002A  must be stored in a secure storage area, with limited access, under 
environmental conditions appropriate for the product. LAM-002A capsules should be stored at 2 
to 8°C. 
9.1.5. 
Accountability 
LAM-002A  will be dispensed to subjects in labeled bottles at the beginning of each cycle. 
Subjects should be instructed to bring all bottles, including empty bottles, to each Day 1 or End 
of Treatment study visit for a compliance and product accountability check. Returned 
LAM-002A should be retained for monitor review prior to destruction at the site, unless 
contraindicated by site standard operating procedures (SOPs). If contraindicated by the site SOP, 
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approval of site process by the sponsor must be obtained and filed in the pharmacy file and/or 
regulatory binder. The investigational pharmacy must maintain contemporary and accurate 
records on product receipt, storage temperature, stock, dispensation, return and disposal. These 
records should be available for review during monitoring visits and copies available for retrieval 
for the Trial Master File.  
9.1.6. 
Handling and Disposal 
LAM-002A  accountability and inventory records will be inspected by the sponsor prior to final 
disposition. Instructions will be provided by the sponsor for shipment to and destruction of 
unused LAM-002A product by the designated packaging depot, to include unopened bulk bottles 
at the end of the study and expired product. Unused product returned by study subjects or opened 
bulk bottles will be destroyed by each site per site SOPs. LAM-002A  should only be shipped or 
destroyed upon written authorization from the sponsor. Documentation of return of shipment, 
including a packing list and copy of the tracking label, should be retained in the Pharmacy and/or 
regulatory files.  
9.2. 
Rituximab (for Intravenous Administration) 
9.2.1. 
Description 
Rituximab (Rituxan, MabThera) is a genetically engineered chimeric murine/human 
monoclonal IgG1 kappa antibody directed against the CD20 antigen found on pre-B and mature 
B cells (Genentech 2016). Rituximab is produced by mammalian Chinese hamster ovary cells. 
The protein has an approximate molecular weight of 145 kD. 
The drug is provided as a clear, colorless, preservative-free liquid concentrate containing 
10 mg/mL of rituximab. The product is formulated in 9 mg/mL sodium chloride, 7.35 mg/mL 
sodium citrate dihydrate, 0.7 mg/mL polysorbate 80, and water for injection with a pH of 6.5. 
9.2.2. 
Packaging 
Rituximab is supplied in 100-mg (10-mL) or 500-mg (50-mL) single-use vials. 
9.2.3. 
Source 
Unless otherwise instructed by the sponsor, the rituximab to be used in this study may be 
obtained from available commercial supplies.  
9.2.4. 
Storage and Stability 
Rituximab vials are stable at 2°C–8°C (36°F–46°F). Vials should be protected from direct 
sunlight and should not be frozen or shaken. 
Diluted rituximab solutions for infusion may be stored at 2°C–8°C (36°F–46°F) for 24 hours and 
are known to be stable for an additional 24 hours at room temperature. However, since rituximab 
solutions do not contain a preservative, diluted solutions should be stored refrigerated (2°C–
8°C). 
No incompatibilities between rituximab and polyvinylchloride or polyethylene bags have been 
observed. 
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9.2.5. 
Solution Preparation 
Before use, the rituximab vials should be inspected for particulate matter or discoloration. Any 
vial with evidence of particulates or discoloration should not be used. 
Using aseptic technique, the necessary amount of rituximab should be withdrawn from the vial 
and diluted to a final concentration of 1 to 4 mg/mL in an infusion bag containing either 0.9% 
Sodium Chloride, USP or 5% Dextrose in Water, USP. The bag should be gently inverted to mix 
the solution. The infusion solution should not be mixed or diluted with other drugs. Any unused 
portion of rituximab remaining in the vial should be discarded. 
9.2.6. 
Accountability 
Acquisition, storage, control, and disposal of rituximab used in the study should be performed 
according to institutional procedures and policies. 
The investigator and/or the responsible site personnel must maintain accurate records of the 
source, dates of administration, quantities of administration, and lot numbers of the rituximab 
dispensed for this study. 
9.3. 
Rituximab/Hyaluronidase Human (For Subcutaneous 
Administration) 
9.3.1. 
Description 
Rituximab/hyaluronidase human (Rituxan Hycela®) is a genetically engineered chimeric 
murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen found on 
pre-B and mature B cells. In this formulation, it is combined with hyaluronidase human, an 
endoglycosidase (Genentech 2018). Rituximab is produced by mammalian Chinese hamster 
ovary cells. The protein has an approximate molecular weight of 145 kD. Hyaluronidase human 
increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan.  
The drug is provided as a colorless to yellowish, clear to opalescent, preservative-free liquid 
solution. Each mL of solution contains rituximab (120 mg), hyaluronidase human (2,000 Units), 
L-histidine (0.53 mg), L-histidine hydrochloride monohydrate (3.47 mg), L-methionine
(1.49 mg), polysorbate 80 (0.6 mg), α,α-trehalose dihydrate (79.45 mg), and Water for Injection.
9.3.2. 
Packaging 
For use in patients with FL/DLBCL, rituximab/hyaluronidase human is supplied in single-dose 
vials containing 1,400 mg rituximab and 23,400 Units hyaluronidase human per 11.7 mL of 
solution.  
9.3.3. 
Source 
Unless otherwise instructed by the sponsor, the rituximab/hyaluronidase human to be used in this 
study may be obtained from available commercial supplies.  
9.3.4. 
Storage and Stability 
Rituximab/hyaluronidase human vials are stable at 2°C-8°C (36°F-46°F). Vials should be 
protected from direct sunlight and should not be frozen or shaken. 
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Diluted rituximab/hyaluronidase human solutions for injection may be stored at 2°C-8°C 
(36°F-46°F) for 48 hours and are known to be stable for an additional 8 hours at room 
temperatures up to 30°C (86°F) in diffuse light. However, since rituximab solutions do not 
contain a preservative, solutions should be used as soon as possible after withdrawal from the 
vial. 
Rituximab/hyaluronidase is compatible with polypropylene and polycarbonate syringe material 
and stainless-steel transfer and injection needles.  
9.3.5. 
Preparation 
Before use, the rituximab/hyaluronidase human vials should be inspected for particulate matter 
or discoloration. Any vial with evidence of particulates or discoloration should not be used. 
Using aseptic technique, the entire 11.7 mL of rituximab/hyaluronidase human should be 
withdrawn from the vial via a hypodermic needle into a syringe and the vial should be discarded. 
9.3.6. 
Accountability 
Acquisition, storage, control, and disposal of rituximab/hyaluronidase used in the study should 
be performed according to institutional procedures and policies. 
The investigator and/or the responsible site personnel must maintain accurate records of the 
source, dates of administration, quantities of administration, and lot numbers of the 
rituximab/hyaluronidase dispensed for this study. 
9.4. 
Atezolizumab 
9.4.1. 
Description 
Atezolizumab (TECENTRIQ) is an Fc-engineered, humanized, monoclonal antibody that binds 
to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors (Genentech 2017). 
Atezolizumab is a non-glycosylated IgG1 kappa immunoglobulin that has a calculated molecular 
mass of 145 kDa. 
The drug is provided as a sterile, preservative-free, colorless to slightly yellow solution in single-
dose vials. Each mL of TECENTRIQ contains 60 mg of atezolizumab and is formulated in 
glacial acetic acid (16.5 mg), L-histidine (62 mg), sucrose (821.6 mg), polysorbate 20 (8 mg). 
The solution has a pH of 5.8. 
9.4.2. 
Packaging 
Atezolizumab is supplied in a carton containing one 1200-mg/20-mL single-dose vial. 
9.4.3. 
Source 
The atezolizumab to be used in this study will be supplied by Genentech, Inc. via the study 
sponsor (AI Therapeutics, Inc.).  
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9.4.4. 
Storage and Stability 
Atezolizumab vials are stable at 2°C–8°C (36°F–46°F). Vials should be stored in the original 
cartons protected from light and should not be frozen or shaken. 
Atezolizumab does not contain a preservative; thus, diluted solutions should be administered as 
soon as possible after preparation.  If the diluted atezolizumab solution is not used immediately, 
it may be stored or maintained at room temperature (e.g., 20°C–25°C; 68°F–77°F). for ≤6 hours 
from the time of preparation, including time for administration of the infusion. Alternatively, it 
may be stored under refrigeration at 2°C–8°C (36°F–46°F) for ≤24 hours. 
9.4.5. 
Solution Preparation 
Before use, the atezolizumab vials should be inspected for particulate matter or discoloration. 
Any vial with evidence of particulates or discoloration should not be used.  The vial should not 
be shaken. 
Using aseptic technique, 20 mL of atezolizumab should be withdrawn from the vial and diluted 
into a 250-mL polyvinyl chloride, polyethylene, or polyolefin infusion bag containing 0.9% 
Sodium Chloride Injection, USP. The bag should be gently inverted to mix the solution. Shaking 
of the bag must be avoided. The infusion solution should not be mixed or diluted with other 
drugs. Used or empty vials of atezolizumab should be discarded. 
The intravenous solution should be prepared and dispensed by the study center pharmacist and 
should be infused by a qualified nurse with experience in monitoring the administration of 
chemotherapeutic agents. 
9.4.6. 
Accountability 
Acquisition, storage, control, and disposal of atezolizumab used in the study should be 
performed according to institutional procedures and policies. 
The investigator and/or the responsible site personnel must maintain accurate records of the 
source, dates of administration, quantities of administration, and lot numbers of the atezolizumab 
dispensed for this study. 
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10. 
ASSESSMENT OF SAFETY 
10.1. 
Adverse Events 
The investigator is responsible for the detection and documentation of events meeting the 
definition of an AE or SAE as provided in this protocol. Monitoring of AEs will be initiated 
upon treatment with LAM-002A . 
10.1.1. 
Definitions 
10.1.1.1. Adverse Events 
An AE is defined as any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. An AE (also referred to as an adverse 
experience) can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with the use of a 
drug, and does not imply any judgment about causality (i.e., whether or not considered related to 
the drug). An AE can arise with any use of the drug (e.g., use in combination with another drug) 
and with any route of administration, formulation, or dose, including an overdose.  
Note that progressive disease should not be reported as an AE. In cases of SAEs, sites can use 
progressive disease if there are no alternative terms that can be satisfactorily substituted. In those 
cases, the AE can match the SAE. 
10.1.1.2. Suspected Adverse Reaction 
Suspected adverse reactions are a subset of all AEs for which there is a reasonable possibility 
that the drug caused the AE. Reasonable possibility means that there is evidence to suggest a 
causal relationship between the drug and the AE. A suspected adverse reaction implies a lesser 
degree of certainty about causality than adverse reaction, which means any AE caused by a drug. 
The investigator is responsible for determining whether there is a reasonable possibility that the 
drug caused the AE, and will capture the causality assessment in the eCRF. 
10.1.1.3. Adverse Reaction 
An adverse reaction means any AE caused by a drug. Adverse reactions are a subset of all 
suspected adverse reactions where there is reason to conclude the drug caused the event. 
10.1.1.3.1. Unexpected 
An AE or suspected adverse reaction is considered “unexpected” if it is not listed in the 
investigator brochure (IB) or is not listed at the specificity or severity that has been observed. 
The sponsor is responsible for determining whether an event meets the definition of 
“unexpected,” based on adverse reactions listed in the Apilimod IB. 
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10.1.1.3.2. Serious 
An AE or suspected adverse reaction is considered “serious” if, in the view of either the 
investigator or sponsor, it results in any of the following outcomes: 
• Death  
• Life-threatening AE 
− Note: An AE or suspected adverse reaction is considered “life-threatening” if, in the 
view of either the investigator or sponsor, its occurrence places the subject at 
immediate risk of death. It does not include an AE or suspected adverse reaction that, 
had it occurred in a more severe form, might have caused death. 
• Inpatient hospitalization is a hospital admission that lasts more than 24 hours or 
prolongation of existing hospitalization 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions  
• Leads to congenital anomaly/birth defect 
• Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the subject and/or may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. Examples of such 
medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse.  
10.1.1.4. Adverse Events of Special Interest 
Adverse events of special interest (AESIs) comprise TLS occurring in any study subject. Among 
study subjects receiving atezolizumab the following treatment-emergent AEs will be considered 
AESIs: 
• AE suggestive of hypersensitivity, infusion-related reactions, cytokine-release syndrome, 
influenza-like illness, systemic inflammatory response syndrome, or systemic immune 
activation 
• Autoimmune hemolytic anemia 
• Cardiac disorders Grade ≥ 2: atrial fibrillation, myocarditis, pericarditis 
• Colitis 
• Cutaneous reactions: Stevens-Johnson syndrome, bullous dermatitis, toxic epidermal 
necrolysis 
• Drug-induced liver injury (Grade ≥ 3 serum ALT or AST increase in combination with a 
Grade ≥ 2 serum total bilirubin) 
• Endocrinopathy: diabetes mellitus, pancreatitis, adrenal insufficiency, hyperthyroidism, 
or hypophysitis 
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• Hepatitis (Grade ≥3 serum ALT or AST increase) 
• Muscular disorders: myositis, myopathy, rhabdomyolysis 
• Nephritis 
• Neurological disorders: Guillain-Barre syndrome, myasthenic syndrome or myasthenia 
gravis, or meningoencephalitis 
• Ocular toxicities: uveitis, retinitis, optic neuritis 
• Pneumonitis 
• Systemic lupus erythematosus 
• Transmission of an infectious agent due to contamination of atezolizumab 
• Vasculitis 
AESIs will be described in narratives as indicated in Section 10.6. 
10.2. 
Study Drug Related AE or SAE 
A study drug-related AE or SAE is defined as an AE or SAE that is related to the treatment with 
study drug. 
10.3. 
Further AE and SAE Definitions 
Wherever possible, a specific disease or syndrome rather than individual associated signs and 
symptoms should be identified. However, if an observed or reported sign or symptom is not 
considered a component of a specific disease or syndrome by the investigator, it should be 
recorded as a separate AE. Laboratory data are to be collected as stipulated in this protocol. 
Clinical syndromes associated with laboratory abnormalities are to be recorded as appropriate 
(e.g., diabetes mellitus rather than hyperglycemia). 
Scheduled hospitalizations or elective surgical procedures will not be considered as AEs or 
SAEs. Prolongation of a scheduled hospitalization can be considered an SAE as discussed in 
Section 10.1.1.3.2. Complications associated with scheduled procedures are considered AEs or 
SAEs. 
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An abnormal test finding will be classified as an AE if one or more of the following criteria are 
met: 
•
The test finding is accompanied by clinical symptoms
•
The test finding necessitates additional diagnostic evaluation(s) or medical/surgical
intervention; including significant additional concomitant drug treatment or other
therapy. Note: simply repeating a test finding, in the absence of any of the other listed
criteria, does not constitute an AE
•
The test finding leads to a change in study drug dosing or discontinuation of subject
participation in the clinical research study
•
The test finding is considered an AE by the investigator
10.4. 
AE and SAE Assessment Criteria 
AEs and SAEs are evaluated and severity determined by the investigator. 
10.4.1. 
Assessment of Causality 
The relationship between an AE and the study product will be determined by the investigator on 
the basis or his/her clinical judgment and the following definitions: 
10.4.1.1. Related 
The AE follows a reasonable temporal sequence from study drug administration, and cannot be 
reasonably explained by the subject’s clinical state or other factors (e.g., disease under study, 
comorbid diseases, concomitant medications) or is a known reaction to the drug under study or 
its chemical group, or is predicted by known pharmacology, or a known reaction to agent or 
chemical group. 
10.4.1.2. Not Related 
The AE does not follow a reasonable sequence from study drug administration, or can be 
reasonably explained by the subject’s clinical state or other factors (e.g., disease under study, 
comorbid diseases, and concomitant medications). 
10.4.2. 
Grading of Severity 
Each AE or SAE will be graded for severity using the National Cancer Institute Common 
Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0. (NCI 2010) However for 
those events not listed in the NCI CTCAE, the following scale should be used: 
•
Mild: Minor awareness of signs and symptoms that are easily tolerated without specific
medical intervention
•
Moderate: Discomfort that interferes with usual activities and may require minimal
intervention
•
Severe: Significant signs or symptoms that are incapacitating with an inability to work or
perform routine activities and/or that require medical intervention
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• Life threatening: immediate risk of death from the reaction 
10.5. 
Responsibilities and Procedures 
The responsibility for the safety of an individual subject lies in all cases with the investigator. 
This includes the timely review of all safety data obtained during the course of the study. An 
investigator must instruct his/her subjects to report any AE and SAEs they experience. 
Investigators capture, evaluate, and document all AEs and SAEs occurring during a subject’s 
enrollment in the study, commencing with first treatment up to 30 days after the last dose of 
study drug on source documents and on designated eCRF pages. 
Investigators should assess AEs at each scheduled and non-scheduled visit, by the use of 
open-ended questioning, physical examination, and review of laboratory results. 
Note: It is important to record all AEs and SAEs that result in temporary and permanent 
discontinuation of study drug, regardless of severity. 
Investigators are required to promptly report all events to the Institutional Review Board (IRB) 
according to the IRB’s reporting requirements. 
10.6. 
SAE and AESI Reporting 
• The investigator is obligated to immediately report to AI Therapeutics each SAE and each 
AESI that occurs during this investigation, within 24 hours from knowledge of the event, 
whether or not it is considered study-drug related.  
• All requested supplementary documents (e.g., discharge summary, autopsy report) and 
relevant data (e.g., ECGs, laboratory tests, discharge summaries, post mortem results) must 
be faxed or emailed within 24 hours to 
 
The information provided in a SAE or AESI report should be as complete as possible, but 
contain a minimum of the following: 
• A short description of the AE (diagnosis) and the reason why the AE was categorized as an 
SAE or AESI 
• Subject identification and treatment  
• Investigator’s name and telephone number (if applicable) 
• Name of the suspect medicinal product and dates of administration 
• Assessment of causality. 
If any questions or considerations regarding SAE or AESI report requirements or report 
completion arise, the principal investigator/site staff should contact AI Therapeutics. Medically 
related questions or concerns regarding treatment should be directed to the sponsor’s medical 
monitor.  
If all information about the SAE or AESI is not yet known, the investigator will be required to 
report any additional information within 24 hours as it becomes available. SAEs and AESIs must 
be followed and reported upon until the event has completely resolved to Grade 0 or baseline or 
until the event becomes a new stable baseline condition for a subject. 
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All SAEs and AESIs will be evaluated by the sponsor’s medical monitor or designee.  
The investigators must notify their governing IRB of any SAEs in accordance with Section 18.1. 
For any suspected adverse reaction that is both serious and unexpected (not documented in the 
IB or package insert), an Investigational New Drug (IND) safety report or revision to the IB may 
be issued to inform all investigators involved in any study with LAM-002A. 
10.6.1. 
Post-treatment Safety Follow-up 
In this study, all AEs occurring after first treatment will be captured on the eCRF. All subjects 
should be instructed to report AEs or SAEs occurring up to 30 days after the last dose of study 
drug. Unresolved study drug-related AEs and SAEs at the time of treatment discontinuation or 
new study-drug related AEs and SAEs that occur during the 30-day post dose time frame will be 
followed until they have, in the opinion of the investigator, resolved to baseline, have stabilized, 
or are deemed to be irreversible. 
10.7. 
Pregnancy Reporting 
Pregnancy occurring in a subject is not considered an AE. However, the investigator must 
capture pregnancy information for subject and/or subject’s partner (as applicable) on a pregnancy 
report form within 24 hours of learning of the pregnancy. Then the site 
• Completes the pregnancy form with as much information as possible; however, at a 
minimum the subject identification number, name of product, and name of reporter is 
required; 
• Signs Pregnancy Notification form; and 
• FAX the form to AI Therapeutics at 
.  
Subjects determined to be pregnant must be immediately removed from treatment and will be 
followed by the investigator until termination of the pregnancy or delivery of the child. 
Additional information on the course of the pregnancy should be supplied on follow-up forms as 
it becomes available and at minimum at termination or birth.  
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11. 
ASSESSMENT OF EFFICACY
Tumor response will be assessed in the Dose Escalation Stage and Expansion Stage using 
modified Lugano Response Criteria for NHL (Cheson 2014) and revised guidelines for the 
diagnosis and treatment of CLL (Hallek 2008, Cheson 2012) (see Appendix 2). 
Pretreatment tumor assessments will be performed within 30 days of the first dose (bone marrow 
assessment may be performed within 2 months prior to first dose) and will include diagnostic CT 
scans (with intravenous contract) or PET/CT for subjects with lymphoma (CT only for subjects 
with CLL/SLL), bone marrow aspirate/biopsy, complete blood counts and physical examination. 
It is anticipated that in most cases the PET and CT scans will be conducted using a single 
instrument, i.e., as a PET/CT scan (CT scans should be performed using a contiguous 
reconstruction algorithm of ≤ 5 mm). However, MRI is an acceptable alternative method for 
assessing disease in subjects who cannot receive intravenous contrast with CT scans. In such 
subjects MRI and PET scans will have to be obtained separately. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient 
management. 
During treatment, radiology studies will be performed for tumor assessments as indicated in 
Table 8: 
Schedule of Assessments (LAM-002A Continuous Monotherapy Administration), 
Table 9: 
Schedule of Assessments (LAM-002A Intermittent Monotherapy Administration), 
Table 10: Schedule of Assessments (LAM-002A/Rituximab Combination Therapy), and 
Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination Therapy) in 
Section 8.7 until PD or use of alternative antineoplastic therapy. If necessary per applicable 
response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have 
a Complete Response (CR) by imaging and physical examination. Subjects with CLL/SLL who 
achieve CR will require assessment of minimal residual disease (MRD) by flow cytometry of 
bone marrow and peripheral blood. 
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12. 
PHARMOCOKINETIC ASSESSMENTS 
Plasma concentration levels of apilimod and the active metabolites will be measured in the dose-
escalation and dose-expansion stages at each of the specified time points; Table 8: Schedule of 
Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: Schedule of 
Assessments (LAM-002A Intermittent Monotherapy Administration), Table 10: 
Schedule of 
Assessments (LAM-002A/Rituximab Combination Therapy), and Table 11: 
Schedule of 
Assessments (LAM-002A/Atezolizumab Combination Therapy) in Section 8.7. The analytical 
laboratory will measure plasma concentrations of apilimod using a validated analytic method. 
PK parameters will be estimated using standard non-compartmental methods will include: Cmax, 
tmax, AUC0-t, AUCτ; t½, trough concentrations on Days 8 and 15, and a comparison of AUC0-t 
from Days 1 and 8 or Days 1 and Day 10 (as appropriate); additional parameters may be 
determined based on the available data. Accumulation will be assessed by calculating the 
accumulation ratios I for Cmax and AUC when comparing Day 8 to Day 1 for all continuous 
LAM-002A regimens (whether given as monotherapy or in combination) or when comparing 
Day 10 to Day 1 for the intermittent LAM-002A regimen. Dose proportionality for Cmax and 
AUC0-t will be assessed by applying an appropriate power model to the data. Descriptive 
statistics of PK parameters will include minimum, maximum, mean, standard deviation, percent 
coefficient of variation (%CV), and range.  
Pharmacokinetic samples will be collected for determination of plasma apilimod and active 
metabolite concentrations at the time points indicated in Table 13. All subjects must participate 
in PK assessments. Fasting status must be recorded at the time of each PK blood draw. 
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Table 13: 
Pharmacokinetic Sampling Time Points 
Sample 
Study Day 
PK Sampling Time Pointsa  
1b 
1 
Pre-dose (within 30 min prior to dose of LAM-002A) 
2 
1 
0.5 hour (± 10 min) after dosing with LAM-002A 
3 
1 
1 hour (± 10 min) after dosing with LAM-002A 
4 
1 
2 hours (± 10 min) after dosing with LAM-002A 
5 
1 
4 hours (± 10 min) after dosing with LAM-002A  
6 
1 
6 hours (± 10 min) after dosing with LAM-002A 
7 
1 
8 hours (± 10 min) after dosing with LAM-002A 
8b 
8 or 10c 
Pre-dose (within 30 min prior to dose of LAM-002A) 
9 
8 or 10c 
0.5 hour (± 10 min) after dosing with LAM-002A 
10 
8 or 10c 
1 hour (± 10 min) after dosing with LAM-002A 
11 
8 or 10c 
2 hours (± 10 min) after dosing with LAM-002A 
12 
8 or 10c 
4 hours (± 10 min) after dosing with LAM-002A  
13 
8 or 10c 
6 hours (± 10 min) after dosing with LAM-002A 
14 
8 or 10c 
8 hours (± 10 min) after dosing with LAM-002A 
15b 
15 
Pre-dose (within 30 min prior to dose of LAM-002A) 
a Applies to first dose of the day 
b Dosing with LAM-002A should occur after the PK sample has been drawn 
c Sampling to be performed on Day 8 for all continuous LAM-002A regimens (whether given as monotherapy or in 
combination) or on Day 10 for the intermittent LAM-002A dosing regimen 
Abbreviation: PK: Pharmacokinetic  
Comprehensive information on blood sample acquisition, handling, storage and sample 
shipments can be found in the laboratory manual “Procedures for Processing and Shipping PK 
and Biomarker Samples.”. 
On Cycle 1 Day 1, and Cycle 1 Day 8 the dose of LAM-002A should be orally administered (a 
minimum fasting state of 6 to 8 hours) by staff in the clinic immediately after the collection of 
the biomarker samples and after the collection of the first PK sample. Subjects are allowed to eat 
after PK Sample #4 (hour 2) has been collected. Subjects may consume clear liquids during 
fasting periods. 
On Cycle 1 Day 15, the dose of LAM-002A should be orally administered (a minimum fasting 
state of 6 to 8 hours) by staff in the clinic immediately after collection of the pre-dose PK and 
biomarker samples.  
 
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13. 
BIOMARKER ASSESSMENTS 
Plasma will be obtained for pharmacodynamics biomarker analysis on C1D1, C1D15, and at the 
EOT visit. Samples will be analyzed circulating tumor DNA to measure tumor burden and 
mutational changes. 
Plasma pharmacodynamic samples will also be collected for determination of plasma apilimod 
and active metabolite activity at the PK time points indicated in Table 13. The plasma will be 
used in an ex vivo cathepsin activity assay or equivalent to determine level of PIKfyve 
inhibition. 
Plasma will also be collected for evaluation of circulating cytokines (including IL-12 and IL-23) 
predose on each of Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 Day 15 and at the EOT visit. 
Samples will be analyzed using appropriate immune-detection assays. 
For all subjects, PBMCs/B cells will be collected during the prescreening period for 
determination of changes in gene expression that may predict or correlate with anti-lymphoma 
activity and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene 
mutation studies in tumors. 
For subjects with NHL, fresh tumor tissue (preferred) or archival tissue from the most recent 
available biopsy or surgery (within 4 months prior to the start of screening) must be obtained 
pretreatment. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via 
excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core 
needle). Confirmation of tumor in biopsy with fine needle aspirate, touch prep, or FFPE 
processing is requested when possible.  The tumor lesion selected should not have been 
previously irradiated and should not be an index lesion that is followed for response assessment. 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow 
involvement due to NHL (>50% NHL cells). Tissue will be submitted for evaluation of the 
percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor may be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; 
expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, 
and for immune infiltration.  
Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor 
cells or a bone marrow aspirate sample pretreatment. Tissue will be submitted for evaluation of 
the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may 
predict anticancer activity and/or pharmacodynamic activity. In addition, for subjects with 
CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a 
sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, 
FISH panel [chromosome 11q deletion, 13q deletion, 17p deletion and 12 trisomy], DNA 
mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL 
[e.g., Notch]; flow cytometry [for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, 
kappa and lambda light chains and ZAP-70], and/or β2-microglobulin).  
A saliva sample will be obtained during Screening as a normal-tissue control for gene mutation 
studies in tumors. 
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Comprehensive information on tissue acquisition, handling, storage and sample shipments can be 
found in the laboratory manual “Procedures for Processing and Shipping PK and Biomarker 
Samples.” 
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14.
STATISTICS
14.1. 
Determination of Sample Size
14.1.1. 
Dose Escalation Stage (Stage 1) 
The planned sample size for the dose-escalation is not based on a specific statistical hypothesis 
but on experience in the conduct of similar trials in subjects with cancer.  
In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety using 
a standard definition of MTD (ie, a starting dose associated with DLT in <33% of subjects 
during the first cycle of therapy). Based on the planned 3+3 dose-escalation scheme, Table 14 
shows the probability of escalating to the next dose level or proceeding to the next stage, based 
on the true rate of DLT at the current dose level. 
Table 14: 
Statistical Basis for 3+3 Dose-Escalation Paradigm 
True Incidence of DLT 
Probability of Escalating 
10% 
0.91 
20% 
0.71 
30% 
0.49 
40% 
0.31 
50% 
0.17 
60% 
0.08 
Abbreviation: DLT=dose-limiting toxicity 
Thus, if the true underlying proportion of DLT is low (eg, ≤10% at the current dose level, there 
is a high probability (≥0.91) of dose escalation to the next dose level. Conversely, if the true 
underlying proportion of DLT is high (eg, ≥60%) at the current dose level, there is a low 
probability (≤0.08) of escalation to the next dose level.  
14.1.2. 
Cohort Expansion Stage (Stage 2) 
As indicated in Section 6.1.2, expansion cohorts of 6 subjects will be accrued. Enrollment of 
6 subjects per cohort offers the opportunity to determine if there is any antitumor activity 
sufficient to warrant further development in the selected tumor types. An ORR of ≥ 35% is 
considered of potential interest in each of the selected indications. If 0/6 subjects in a cohort 
experience an objective response, then a population ORR of ≥ 35% for that cancer can be 
excluded with > 90% certainty (1-sided exact binomial 90% CI upper bound = 32%). 
Based on the observation of objective responses among study subjects with FL receiving either 
LAM-002A monotherapy or LAM-002A/rituximab, expanded accrual of subjects with relapsed 
FL is planned to evaluate the level of activity with these 2 regimens. Preference will be given to 
enrolling subjects to receive LAM-002A monotherapy before enrolling subjects to receive 
LAM-002A/rituximab.  
Based on historical data with other treatments (Zelenetz 2014), it is known that an ORR of 
< 20% in subjects with relapsed FL receiving LAM-002A monotherapy would be uninteresting 
while achieving a target ORR of ≥ 40% would suggest that further development is warranted. 
Sequential boundaries will be used to continuously monitor that the ORR is ≥ 40% while 
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excluding an ORR of < 20% using a 1-sided test with a significance level of 0.05. A significant 
result with this testing would conclude with 95% confidence that the actual ORR is ≥ 20%. 
Accrual of up to ~20 evaluable subjects will be considered with the potential to stop accrual 
early if the boundary is crossed. Thus, accrual can be considered sufficient if the following n/N 
values are observed: 4/5, 4/6, 4/7, 5/8, 5/9, 5/10, 5/11, 6/11, 6/12, 6/13, 6/14, 7/15, 7/16, 7/17, 
8/18, 8/19, 8/20. For all these values, the ORR is ≥ 40% with a lower 1-sided binomial 
confidence bound of ≥ 20%. 
As noted above, the target ORR with LAM-002A alone is ~40%. Adding rituximab or rituximab 
hyaluronidase human to LAM-002A would be expected to enhance the ORR over that associated 
with single-agent LAM-002A. Thus, the combination of LAM-002A/rituximab could warrant 
further development if an ORR of ≥ 60% could be targeted in preference to an ORR of < 40%.  
Accordingly, for combination therapy, sequential boundaries will be used to continuously 
monitor that the ORR is ≥ 60% while excluding an ORR of 39% using a 1-sided test with a 
significance level of 0.05. A significant result with this testing would conclude with 95% 
confidence that the actual ORR is > 39%. Accrual of up to ~20 evaluable subjects will be 
considered with the potential to stop accrual early if the boundary is crossed. Thus, accrual can 
be considered sufficient if the following n/N values are observed: 7/10, 8/11, 8/12, 9/13, 9/14, 
10/15, 10/16, 11/17, 11/18, 12/19, 12/20. For all these values, the ORR is ≥ 60% with a lower 
1-sided binomial confidence bound of ≥ 39%.
Experience indicates the rates of discontinuations from rituximab or atezolizumab therapy are    
< 5% (Genentech 2016, Genentech 2017). A rate of AE discontinuations of therapy due to 
adverse events of ≥25% in the 2 combination therapy groups of LAM-002A/rituximab (N = 12) 
or LAM-002A/atezolizumab (N = 12) would suggest a potential adverse interaction among the 
components of the combination therapy. Sequential Pocock-type boundaries will be used to 
continuously monitor the rate of AE discontinuations and to test the null hypothesis, after each 
subject, that the event rate is ≥ 0.25 using a 1-sided significance test of ~ 0.05. AE 
discontinuation rates will be considered excessive if the following n/N values are observed: -/1, 
-/2, 3/3, 3/4, 4/5, 4/6, 5/7, 5/8, 5/9, 6/10, 6/11, 7/12. With this method, the probability of 
detecting an AE discontinuation safety signal ranges from 0.091 to >0.820 for true 
discontinuation rates of 25% to ≥ 60%. If excessive levels of AE discontinuation are observed, 
the sponsor, working in collaboration with the cooperating companies and investigators, will 
take appropriate actions (eg, continuation of the cohort with modifications in design or 
monitoring plan, interruption of cohort accrual, cohort therapy discontinuation). 
14.1.3. 
Extension Stage (Stage 3) 
The sample size in the extension stage of the study will be no higher than the total number of 
subjects on study therapy on the data cutoff date that concludes the dose-escalation and 
expansion stages of the clinical trial. 
14.2. 
Statistical and Analytical Plans 
Detailed methodology for summary and statistical analyses of the data collected in this trial will 
be documented in a statistical analysis plan (SAP). The SAP may modify the plans outlined in 
the protocol; any major modifications of the primary endpoint definition and/or its analysis will 
be described in the SAP and the final clinical study report. Additional statistical analyses other 
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than those described in this section may be performed if deemed appropriate and will be 
described in the SAP. Where individual data points are missing because of insufficient samples, 
dropouts, or other reasons, the data will be analyzed based on reduced denominators.  
Results will be summarized by dose cohorts. 
14.3. 
Analysis Sets 
14.3.1. 
Full Analysis Set 
The full analysis set includes all subjects who receive ≥ 1 dose of study drug. This analysis set 
will be used in the analyses of subject characteristics, study drug administration and compliance, 
safety, and categorical and time-to-event efficacy outcomes. In analyses of response rates in the 
full analysis set, subjects who do not have sufficient baseline and on-study tumor assessments to 
characterize response (i.e., have a best overall response of NE) will be counted as failures. 
14.3.2. 
Responding Analysis Set 
The responding analysis set includes subjects in the full analysis set who have measurable 
disease, who can be evaluated for tumor response with both baseline and on-study tumor 
evaluations, and who achieve a CR, CRi, or PR. This analysis set will be used in the analyses of 
time to response and duration of response. 
14.3.3. 
Evaluable Analysis Sets 
The evaluable analysis sets include subjects in the full analysis set who have the necessary 
baseline and on-study measurements to provide interpretable results for specific parameters of 
interest. These analysis sets will be used in the analyses of changes in tumor dimensions, PK 
parameters, and pharmacodynamic parameters.  
14.4. 
Demographics and Baseline Disease Characteristics 
Demographics and other baseline characteristics will be summarized by dose escalation cohorts 
and expanded cohorts. 
14.5. 
Study Drug Exposure 
Study drug exposure information will be summarized using descriptive statistics such as number 
of treatment cycles and total dose.  
14.6. 
Concomitant Medications 
Medications under use at the time of or initiated after enrollment will be summarized by cohorts. 
14.7. 
Safety and Tolerability 
Safety and tolerability of LAM-002A will be assessed based on the following: 
• Incidence, severity of treatment-emergent AEs, SAEs, AEs resulting in permanent 
discontinuation of study drug, and deaths on treatment through approximately 30 days from 
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the last dose of study drug (or immediately before the administration of another anti-cancer 
treatment) 
• Changes in laboratory test results 
• Changes in vital signs including blood pressure, pulse, and temperature 
• Changes in electrocardiogram results 
Adverse events will be coded using the latest available version of the Medical Dictionary for 
Regulatory Activities (MedDRA). Treatment-emergent AEs are defined as AEs that start on or 
after the first dose of study drug and within approximately 30 days of the last administration of 
study drug. Adverse events will be summarized by the number and percentage of subjects who 
experienced the event, according to system organ class and preferred term. A subject reporting 
multiple cases of the same AE will be counted once within each system organ class and similarly 
counted once within each preferred term. 
Unless specified otherwise, the denominator for these calculations will be based on the number 
of subjects in each cohort who received at least one administration of LAM-002A irrespective of 
the total number of doses or treatment cycles administered. These conventions will be 
appropriately modified to calculate AE incidence rates separately for each cycle that study 
therapy is administered.  
AEs will also be summarized by NCI-CTCAE Version 4.0 severity grade and by relationship to 
each study drug. Additional summaries may also be provided for SAEs, and events resulting in 
the permanent discontinuation of therapy. All AEs will be included in individual subject listings. 
The changes in hematology, chemistry, and other laboratory values will be summarized 
descriptively for each scheduled and unscheduled protocol assessment time point. Changes will 
be calculated relative to the values collected at baseline and on the first day of each cycle of 
treatment.  
The incidence of DLT will be provided by treatment cycle and across all treatment cycles. The 
toxicity grades for laboratory tests will be based on NCI-CTCAE Version 4.0 criteria. Subject 
listings of all laboratory data collected during the study will be presented. Laboratory values 
outside normal limits will be identified in the subject listings and will include flags for high and 
low values. 
Vital sign results (blood pressure, pulse, respirations, and temperature) will be summarized 
descriptively for each scheduled and unscheduled protocol time point. Changes will be 
calculated relative to the assessments at baseline and on the first day of each cycle of therapy. 
14.8. 
Biomarkers 
Descriptive statistics will be primarily used to summarize the biomarker and other laboratory 
data generated in this study. For continuous variables, the number of subjects with non-missing 
data, mean, either the standard error or standard deviation, median, 25th percentile (first quartile), 
75th percentile (third quartile), minimum, and maximum will be presented. For discrete data, the 
frequency and percent distribution will be presented. 
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The Wilcoxon signed rank test may be used to identify any statistically significant (p < 0.05) 
changes in biomarker levels. Additionally, correlations may be assessed by calculating 
Spearman’s correlation coefficient between pairs of biomarkers or other parameters. 
14.9. 
Efficacy Analysis 
The tumor response will be assessed by the modified criteria for NHL (Cheson 2014) and revised 
guidelines for the diagnosis and treatment of CLL (Hallek 2008, Cheson 2012) (see Appendix 2). 
The objective response rate will be estimated for each dose escalation cohort and each expanded 
cohort. The estimate of the objective response rate will be calculated based on the maximum 
likelihood estimator (i.e., crude proportion of subjects whose best overall response is CR or 
partial remission [PR]). The estimate of the objective response rate will be accompanied by 
2-sided 95% exact binomial confidence intervals.
The duration of objective response will be calculated for subjects who achieve CR or PR. For 
such subjects, the duration of objective response is defined as the number of days from the start 
date of PR or CR (whichever response is achieved first) to the first date that progressive disease 
is objectively documented. The duration of objective response will be right-censored for subjects 
who achieve CR or PR and meet 1 of the following conditions: 1) non-protocol anticancer 
treatment started before documentation of disease progression, 2) death or documented disease 
progression after more than 1 missed disease assessment visit, or 3) alive and does not have 
documentation of disease progression before a data analysis cutoff date.  
The duration of objective response will be summarized descriptively using the Kaplan-Meier 
method. The 50th percentile of the Kaplan-Meier distribution will be used to estimate the median 
response duration. 
Progression-free survival (PFS) will be measured as from the date of enrollment to the date of 
documented progression or death (whatever the cause). Subjects who are alive and progression 
free at last follow-up (up to a year from first treatment at Cycle 1 day 1) will be censored. Those 
who start another anticancer treatment without evidence of progression will be censored at start 
date of the new therapy. 
The PFS will be summarized descriptively using the Kaplan-Meier method. The 50th percentile 
of the Kaplan-Meier distribution will be used to estimate the median PFS of each cohort of 
subjects. 
14.10. 
Interim Analysis 
Dose escalation decision will be made as outlined based on available safety and available 
PK/pharmacodynamic information. No statistical analyses are planned to aid the dose escalation 
decision. 
14.11. 
Missing Data and Imputation 
Missing data generally will not be imputed except those defined in the SAP. 
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14.12. 
Protocol Deviations 
By-subject listings will be generated for all enrolled subjects’ inclusion and exclusion criteria; 
this includes those subjects who do not meet one or more inclusion criteria, and those subjects 
who meet one or more exclusion criteria. A list of all protocol deviations will be maintained by 
the clinical team and will be included in the clinical study report. The impact of the protocol 
deviation on the efficacy analysis will be evaluated. 
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15. 
DIRECT ACESS TO SOURCE DATA/DOCUMENTS 
A representative of AI Therapeutics will be allowed to conduct site visits to the investigation 
facilities for the purpose of monitoring any aspect of the study. The investigator agrees to allow 
the monitor to inspect the drug storage area, study drug stocks, drug accountability records, 
subject charts and study source documents, and other records relative to study conduct.  
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16. 
STUDY MONITORING 
Before an investigational site can enter a subject into the study, a representative of 
AI Therapeutics will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of AI Therapeutics or its representatives. This 
will be documented in a Clinical Study Agreement between AI Therapeutics and the 
investigator. 
During the study, a monitor from AI Therapeutics or its representative will have regular contacts 
with the investigational site for the following: 
• Provide information and support to the investigator 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol that data are being 
accurately recorded in the eCRFs, and that investigational product accountability checks are 
being performed 
• Perform source data verification. This includes a comparison of the data in the CRFs with the 
subject’s medical records at the hospital or practice, and other records relevant to the study. 
This will require direct access to all original records for each subject (e.g., clinic charts) 
• Record and report any protocol deviations not previously sent to AI Therapeutics 
• Confirm AEs and SAEs have been properly documented on eCRFs, and confirm any SAEs 
have been forwarded to AI Therapeutics and those SAEs that met criteria for reporting have 
been forwarded to the IRB 
The monitor will be available between visits if the investigator or other staff members need 
information or advice. 
Upon conclusion of the Dose-Escalation (Stage 1) and Expansion (Stage 2) stages of the study, 
routine site monitoring by AI Therapeutics or its representatives will be discontinued. 
16.1. 
Audits and Inspections 
Authorized representatives of AI Therapeutics, a regulatory authority, and/or an IRB may visit 
the site to perform audits or inspections, including source data verification. The purpose of a 
AI Therapeutics audit or inspection is to systematically and independently examine all 
study-related activities and documents to determine whether these activities were conducted, and 
data were recorded, analyzed, and accurately reported according to the protocol, Good Clinical 
Practice (GCP) Guidelines of the International Conference on Harmonisation, and any applicable 
regulatory requirements. The investigator should contact AI Therapeutics immediately if 
contacted by a regulatory agency about an inspection. 
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16.2. 
Institutional Review Board 
The investigator must obtain IRB or Ethics Committee (EC) approval for the investigation. 
Initial IRB/EC approval, and all materials approved by the IRB/EC for this study, including the 
subject consent form and recruitment materials, must be maintained by the investigator and made 
available for inspection.  
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17. 
QUALITY CONTROL AND QUALITY ASSURANCE 
Qualified staff of AI Therapeutics or its representative will conduct independent monitoring of 
the clinical study for protocol and GCP compliance periodically. 
The investigator will permit direct access of the study monitors and appropriate regulatory 
authorities to the study data and to the corresponding source data and documents to verify the 
accuracy of this data. 
 
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18. 
ETHICS 
18.1. 
Ethics Review 
The investigator will obtain IRB/EC approval of the clinical protocol and corresponding 
informed consent form(s); modifications to the clinical protocol and corresponding informed 
consent forms; and advertisements (i.e., directed at potential research subjects) for study 
recruitment prior to study implementation. The investigator must submit written approval to 
AI Therapeutics or designee before enrolling any subject into the study. 
The only circumstance in which a deviation from the current IRB/EC approved clinical 
protocol/consent form(s) may be initiated in the absence of prospective IRB/EC approval is to 
eliminate an apparent immediate hazard to the research subject(s). In such circumstances, the 
investigator will promptly notify the IRB/EC of the deviation.  
The investigator is also responsible for providing the IRB/EC with reports of any reportable 
serious adverse drug reactions from any other study conducted with the investigational product. 
AI Therapeutics will provide this information to the investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the 
IRB/EC according to local regulations and guidelines. 
18.2. 
Ethical Conduct of the Study 
The clinical research study will be conducted in accordance with the current IRB/EC approved 
clinical protocol, ICH GCP Guidelines, relevant policies, and requirements of the national 
regulations and laws. 
18.3. 
Written Informed Consent 
The investigator will make certain that an appropriate informed consent process is in place to 
ensure that potential research subjects, or their authorized representatives, are fully informed 
about the nature and objectives of the clinical study, the potential risks and benefits of study 
participation, and their rights as research subjects. The investigator, or a sub-investigator(s) 
designated by the investigator, will obtain the written, signed informed consent of each subject, 
or the subject’s authorized representative, prior to performing any study-specific procedures on 
the subject. Subjects must also be notified that they are free to discontinue from the study at any 
time. The subject (or authorized representative) should be given the opportunity to ask questions 
and allowed time to consider the information provided. The date and time that the subject or the 
subject’s authorized representative signs the informed consent form and a narrative of the issues 
discussed during the informed consent process will be documented in the subject’s case history. 
The investigator will retain the original copy of the signed informed consent form, and a copy 
will be provided to the subject, or to the subject’s authorized representative. 
The investigator will make certain that appropriate processes and procedures are in place to 
ensure that ongoing questions and concerns of enrolled subjects are adequately addressed and 
that subjects are informed of any new information that may affect their decision to continue 
participation in the clinical study. In the event of substantial changes to the clinical study or the 
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benefit: risk ratio of study participation, the investigator will obtain the informed consent of 
enrolled subjects for continued participation in the clinical study. 
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internationally recognized and accepted dictionaries. Additional details are recorded in the 
monitoring and data management documentation. 
19.1. 
Inspection of Records 
AI Therapeutics will be allowed to conduct site visits to the investigation facilities for the 
purpose of monitoring any aspect of the study. The investigator agrees to allow the monitor to 
inspect the drug storage area, study drug stocks, drug accountability records, subject charts and 
study source documents, and other records relative to study conduct. 
19.2. 
Retention of Records 
The investigator will maintain records in accordance with GCP guidelines; to include: 
• Food and Drug Administration (FDA) correspondence related to the IND and clinical 
protocol, including copies of submitted Safety Reports and Annual Reports  
• IRB correspondence (including approval notifications) related to the clinical protocol, 
including copies of AE reports and annual or interim reports 
• Current and past versions of the IRB-approved clinical protocol and corresponding IRB-
approved consent form(s) and, if applicable, subject recruitment advertisements 
• Signed FDA Form 1572 Statement of the investigator 
• Financial disclosure information (i.e., for the investigator and for sub-investigators who will 
be involved in the administration of the study drugs and/or the evaluation of research subjects 
[i.e., who will contribute significantly to the research study data]) 
• Curriculum vitae (i.e., for the investigator)  
• Certificates of required training, e.g., human subject protections, GCP, and so on (i.e., for the 
investigator and for all sub-investigators who will be involved in the administration of the 
study drugs and/or the evaluation of research subjects [i.e., who will contribute significantly 
to the study data]) 
• Listing of printed names/signatures. (i.e., for the investigator and for all sub-investigators 
who will be involved in the administration of the study drugs and/or the evaluation of 
research subjects [i.e., who will contribute significantly to the study data])  
• Normal value(s)/range(s) for medical/laboratory/technical procedures or tests included in the 
clinical protocol  
• Laboratory certification information  
• Instructions for on-site preparation and handling of the investigational drug(s), study 
treatment(s), and other study-related materials (i.e., if not addressed in the clinical protocol) 
• Responsibility delegation log 
• Signed informed consent forms  
• Completed eCRFs, signed and dated by the investigator 
• Source Documents or certified copies of Source Documents  
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• Monitoring visit reports  
• Copies of investigator correspondence (including notifications of safety information) to sub-
investigators 
• Subject screening and enrollment logs 
• Subject identification code list 
• Investigational drug accountability records, including documentation of drug disposal. 
• Final clinical study report. 
The investigator must maintain all documentation relating to the study for a period of 2 years 
after the last marketing application approval or, if not approved, 2 years following the 
discontinuance of the test article for investigation. If it becomes necessary for AI Therapeutics or 
the Regulatory Authority to review any documentation relating to the study, the investigator 
must permit access to such records. 
19.3. 
Data Recording/Case Report Forms 
An eCRF will be completed for each subject enrolled into the clinical study. The investigator 
will review, approve, and sign/date each completed eCRF; the investigator’s signature serves as 
attestation of the investigator’s responsibility for ensuring that all clinical and laboratory data 
entered on the eCRF are complete, accurate, and authentic.  
Source data are the clinical findings and observations, laboratory and test data, and other 
information contained in source documents. Source documents are the original records (and 
certified copies of original records) including, but not limited to, hospital medical records, 
physician or office charts, physician or nursing notes, subject diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, x-rays, and so on. 
When applicable, information recorded on the eCRF shall match the source data recorded on the 
source documents.  
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20. 
PUBLICATION POLICY 
It is the intent of the sponsor to publish the complete study results in a timely manner that is 
appropriate to the project. Contribution to the project will be reflected in authorship. Separate 
publication of a portion of the study results (a sub-study) is discouraged. 
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21. 
STUDY DISCONTINUATION 
Both the investigator and AI Therapeutics reserve the right to terminate the study at any time. 
Should this be necessary, both parties will arrange discontinuation procedures. The investigator 
will be responsible for notifying the relevant study center IRB. AI Therapeutics will be 
responsible for notifying the appropriate regulatory authorities. In terminating the study, the 
investigator and AI Therapeutics will assure that adequate consideration is given to the 
protection of the subjects’ interests. As directed by AI, Therapeutics all study materials must be 
collected and all eCRFs completed to the greatest extent possible. 
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22. 
LIST OF REFERENCES
Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS et al. Distinct types of diffuse large B-cell 
lymphoma identified by gene expression profiling. Nature 2000;403:503–11. 
Asghar A, Naaz S, Agrawal D, Sharma P. Morphometric study of spleen in north Indian adult 
population: CT scan image based study. Journal of Clinical and Diagnostic Research. 2011 Oct; 
5(5):974-7. 
Bezerra AS, D’Ippolito G, Faintuch S, Szejnfeld J, Ahmed M. Determination of splenomegaly 
by CT: is there a place for a single measurement? AJR Am J Roentgenol. 2005 
May;184(5):1510-3. 
Gea-Banacloche JC. Rituximab-associated infections. Semin Hematol. 2010 Apr;47(2):187-98. 
Cai X, Xu Y, Cheung AK, Tomlinson RC, Alcázar-Román A, et al. PIKfyve, a class III PI 
kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-
like receptor signaling. Chem Biol. 2013 Jul 25;20(7):912-21.  
Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the 
evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with 
malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010 May;149(4):578-86. 
Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, et al. Progressive 
multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 
cases from the Research on Adverse Drug Events and Reports project. Blood. 2009 May 
14;113(20):4834-40. 
Cheson BD, Byrd JC, Rai KR, Kay NE, O’Brien SM, et al. Novel targeted agents and the need to 
refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol. 2012 Aug 
10;30(23):2820-2.  
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, et al. Recommendations for 
initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the 
Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. 
Woosley RL, Romero KA. Drugs with known risk of torsades de pointes. 2018 Oct 31. Available 
at: https://www.crediblemeds.org (accessed 2018 Dec 17). 
Cultrera JL, Dalia SM. Diffuse large B-cell lymphoma: current strategies and future directions. 
Cancer Control. 2012 Jul;19(3):204-13. 
Dakhil S, Hermann R, Schreeder MT, Gregory SA, Monte M, Windsor KS, et al. Phase III safety 
study of rituximab administered as a 90-minute infusion in patients with previously untreated 
diffuse large B-cell and follicular lymphoma. Leuk Lymphoma. 2014 Oct;55(10):2335-40. 
De Lartigue J, Polson H, Feldman M, Shokat K, Tooze SA, et al. PIKfyve regulation of 
endosome-linked pathways. Traffic. 2009 Jul;10(7):883-93. 
Erturk SM, Mortelé KJ, Binkert CA, Glickman JN, Oliva MR, Ros PR, Silverman SG. CT 
features of hepatic venoocclusive disease and hepatic graft-versus-host disease in patients after 
hematopoietic stem cell transplantation. AJR Am J Roentgenol. 2006 Jun;186(6):1497-501. 
Clinical Study Report 
16.1 Study Information
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Protocol: LAM-002A-NHL-CLN01 
Version 9, 18 Feb 2020 
AI Therapeutics 
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Flockhart DA. Drug interactions: cytochrome P450 drug interaction table. Indiana University 
School of Medicine. 2007. [Cited 2015 June 12]. Available from: 
http://medicine.iupui.edu/clinpharm/ddis 
Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, et al. Identification of 
apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin 
lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. 
Genentech. Rituxan Hycela® (rituximab and hyaluronidase human) prescribing information. 
2018 Apr. Avaliable at: https://www.gene.com/download/pdf/rituxan_hycela_prescribing.pdf 
(acessed 2018 Dec 18). 
Genentech. Rituxan® (rituximab) prescribing information. 2016 Apr. Available at: 
https://www.gene.com/download/pdf/rituxan_prescribing.pdf (accessed 2017 Aug 3). 
Genentech. TECENTRIQ® (atezolizumab) prescribing information. 2017 Apr. Available at: 
https://www.gene.com/download/pdf/tecentriq_prescribing.pdf (accessed 2017 Aug 3). 
Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, et al. 
Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases 
event-free survival and response duration compared with the standard weekly x 4 schedule. 
Blood. 2004 Jun 15;103(12):4416-23.  
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, et al. Guidelines for the 
diagnosis and treatment of chronic lymphocytic leukemia: a report from the international 
workshop on chronic lymphocytic leukemia updating the national cancer institute-working group 
1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. 
Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, et al. Confirmation of the 
molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a 
tissue microarray. Blood. 2004 Jan 1;103(1):275-82.  
Ikonomov OC, Sbrissa D, Shisheva A. Mammalian cell morphology and endocytic membrane 
homeostasis require enzymatically active phosphoinositide 5-kinase PIKfyve. J Biol Chem. 2001 
Jul 13;276(28):26141-7.  
Ilcus C, Bagacean C, Tempescul A, Popescu C, Parvu A, Cenariu M, Bocsan C, Zdrenghea M. 
Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies. Onco 
Targets Ther. 2017 Apr 28;10:2349-2363. 
Lioté H, Lioté F, Séroussi B, Mayaud C, Cadranel J. Rituximab-induced lung disease: A 
systematic literature review. Eur Respir J. 2010 Mar;35(3):681-7.  
Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, et al. Diffuse large B-cell 
lymphoma. Crit Rev Oncol Hematol. 2013 Aug;87(2):146-71. 
Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, et al. Long-term follow-up of 
patients with follicular lymphoma receiving single-agent rituximab at two different schedules in 
trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4.  
Matsue K, Kimura S, Takanashi Y, Iwama K, Fujiwara H, Yamakura M, Takeuchi M. 
Reactivation of hepatitis B virus after rituximab-containing treatment in patients with CD20-
positive B-cell lymphoma. Cancer. 2010 Oct 15;116(20):4769-76. 
Clinical Study Report 
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Protocol: LAM-002A-NHL-CLN01 
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MD Anderson Cancer Center (MDACC). Tumor lysis in adult patients. 2013 Apr 30. Available 
at: http://www.mdanderson.org/education-and-research/resources-for-professionals/clinical-
tools-and-resources/practice-algorithms/clin-management-tumor-lysis-web-algorithm.pdf 
(accessed 2016 Jan 24). 
National Cancer Institute [homepage on the Internet]. Maryland: Common terminology criteria 
for adverse events, version 4.0; 2009 [updated 2010 June 14; cited 2015 June 12]. Available 
from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. 
National Cancer Institute [homepage on the Internet]. Maryland: Surveillance, epidemiology, 
and end results program: SEER stat fact sheets: non-Hodgkin lymphoma [cited 2015 June 12]. 
Available from: http://seer.cancer.gov/statfacts/html/nhl.html. 
Ning YM, Suzman D, Maher VE, Zhang L, Tang S, Ricks T, et al. FDA approval summary: 
atezolizumab for the treatment of patients with progressive advanced urothelial carcinoma after 
platinum-containing chemotherapy. Oncologist. 2017 Jun;22(6):743-749.  
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, et al. Toxicity and response criteria of 
the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. 
Ram R, Ben-Bassat I, Shpilberg O, Polliack A, Raanani P. The late adverse events of rituximab 
therapy—rare but there! Leuk Lymphoma. 2009 Jul;50(7):1083-95.  
Raut LS, Chakrabarti PP. Management of relapsed-refractory diffuse large B cell lymphoma. 
South Asian J Cancer. 2014 Jan;3(1):66-70. 
Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, et al. Targeting BCL2 with 
venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016 Jan 
28;374(4):311-22. 
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, et al. The use of molecular profiling 
to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002 
Jun 20;346(25):1937-47. 
Rutherford AC, Traer C, Wassmer T, Pattni K, Bujny MV, et al. The mammalian 
phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde 
transport. J Cell Sci. 2006 Oct 1;119(Pt 19):3944-57. 
Salmasi G, Li M, Sivabalasundaram V, Tsang R, Kukreti V, Crump M, Kuruvilla J. A 
retrospective study on the incidence of rituximab-related interstitial pneumonitis in patients 
undergoing immunochemotherapy for non-Hodgkin lymphoma. Blood ASH Annual Meeting 
Abstracts 2010 Nov 19;116(21) Abst 3094). 
Subramanian M, Manjunath R, Kilara N, Mohan Rao KN. Rituximab-induced subacute 
interstitial pneumonitis: a case report and review of literature. J Cancer Res Ther. 2010 Jul-
Sep;6(3):344-6. 
Stern A, Green H, Paul M, Vidal L, Leibovici L. Prophylaxis for Pneumocystis pneumonia 
(PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. 2014 Oct 
1;(10):CD005590. PMID: 25269391. 
Wada Y, Cardinale I, Khatcherian A, Chu J et al. Apilimod inhibits the production of IL-12 and 
IL-23 and reduces dendritic cell infiltration in psoriasis. 2012; PloS ONE 7(4): e35069. 
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Wada Y, Lu R, Zhou D, Chu J, Przewloka T et al. Selective abrogation of Th1 response by 
STA-5326, a potent IL-12/IL-23 inhibitor. Blood 2007;109:1156-1164. 
Walker HK, Hall WD, Hurst JW, editors. Clinical methods: The history, physical, and laboratory 
examinations. 3rd edition. 1990. Boston; Butterworths. 
Weinstock C, Khozin S, Suzman D, Zhang L, Tang S, Wahby S, et al. U.S. Food and Drug 
Administration approval summary: atezolizumab for metastatic non-small cell lung cancer. Clin 
Cancer Res. 2017 Jun 13. 
Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, Andreadis CB, et al. Non 
Hodgkin’s lymphomas, version 4.2014. J Natl Compr Canc Netw. 2014 Sep;12(9):1282 303.  
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Appendix 1. 
Eastern Cooperative Oncology Group (ECOG) Performance 
Status Scale 
Grade 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 
Source: Oken 1982. 
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Appendix 2. 
Criteria for Response Assessment 
1.
LYMPHOMA
1.1. 
Tumor Assessment Criteria 
The determination of response and progression for subject with NHL will be based 
on standardized criteria (Cheson 2014). 
1.2. 
Method of Assessment 
Imaging-based evaluation will be used in this study as the primary basis of lymphoma 
assessment. CT scan is the preferred method for radiographic tumor assessment. Contrast-
enhanced scanning is preferred, but contrast material may be omitted in subjects for whom use of 
a contrast agent becomes medically contraindicated or if CT scanning is done in conjunction 
with PET. If available, PET scan data will be considered in response and progression assessment; 
however, PET scanning will not be a required component of assessment in this study. As 
necessary, bone marrow aspirate/biopsy (e.g., for confirmation of CR) or cytological/histological 
evaluation of lymph nodes, effusions, ascites, or other organ abnormalities) will be also be 
considered. Clinical palpation, chest x-ray, ultrasound, endoscopy, laparoscopy, radionuclide 
scan, or tumor markers will not be considered for response assessment. MRI scanning is not 
advised but may be used at the investigator’s discretion in subjects for whom this becomes a 
necessary alternative to CT scanning. 
For radiographic assessments, the same method of assessment and the same technique (e.g., scan 
type, scanner, subject position, dose of contrast, injection/scan interval) should be used to 
characterize each identified and reported lesion at baseline and during study treatment and 
follow-up. CT of the neck, chest, abdomen, and pelvis should be performed with cuts of 
≤ 0.5 mm in slice thickness contiguously. If performed, whole-body FDG PET-CT scanning 
should be extended from the base of the skull to mid-thigh. 
All relevant radiographic and clinical information required to make each tumor status assessment 
must be made available for source verification as requested by the study sponsor. 
1.3. 
Timing of Assessments 
During screening, clinical and imaging-based tumor assessments should be performed within the 
specified screening period. On-study tumor assessments should be performed as stipulated in 
Section 8.7. An end-of-therapy tumor assessment should be performed unless the subject already 
has radiographic confirmation of disease progression ≤ 4 weeks prior to study drug 
discontinuation. If a subject permanently discontinues treatment prior to objective documentation 
of lymphoma progression, investigators should ideally continue further follow-up of tumor status 
with assessments at ~12-week intervals until disease progression is documented or until the 
initiation of a new post-study therapy for the subject’s lymphoma. 
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1.4. 
Identification and Follow-up of Tumor Lesions and Organomegaly 
1.4.1. 
Index Lesions 
Up to 6 lesions (e.g., lymph nodes, liver or spleen nodules, and/or other circumscribed 
extranodal masses) should be selected as index lesions that will be used to quantitate the status of 
the disease during study treatment. Ideally, the index lesions should be located in disparate 
regions of the body and include mediastinal, abdominal, and retroperitoneal areas of disease 
whenever these sites are involved. For subjects with FDG-avid lymphomas undergoing PET, 
selection of FDG-avid lesions is preferred. 
Index lesions will be measured and recorded at baseline and at the stipulated intervals during 
treatment. The largest cross-sectional dimensions (i.e., the LD × LPD will be recorded (in cm) 
for each index lesion. Using the LD and LPD, the product of the perpendicular diameters (PPD) 
for each index lesion will be calculated. The PPDs and the SPDs for all index lesions will be 
calculated and recorded. The baseline and nadir PPDs of individual lesions and the baseline and 
nadir SPDs will be used as references by which objective tumor response and progression will be 
characterized during treatment. All PPD and SPD measurements will be reported in centimeters 
squared. 
1.4.2. 
Nodal Index Lesions 
A nodal mass may be selected as a nodal index lesion if it is both abnormal and measurable at 
baseline. A lymph node lesion is considered abnormal if it has a single diameter that is > 1.0 cm 
and is considered measurable if it has 2 perpendicular diameters that can be accurately measured 
in cross section with the LD being ≥ 1.0 cm and the LPD also being ≥ 1.0 cm.  
Abnormal, measurable nodal lesions will be subcategorized as either large or small.  
• Large nodal lesions have an LD that is > 1.5 cm and an LPD that is ≥ 1.0 cm.  
• Small nodal lesions have an LD that is > 1.0 cm and ≤ 1.5 cm and an LPD that is 
> 1.0 cm. 
Index lesions measuring > 1.5 cm in the LD, regardless of the measurement of the LPD, will be 
prioritized during baseline index lesion selection. 
At follow-up timepoints, the PPDs for individual nodal lesions and the SPD of all nodal index 
lesions will be considered. Because nodal index lesions that have one or both diameters > 0 cm 
and < 1.0 cm cannot be reliably measured, a default value of 1.0 cm will be assigned for each 
diameter that meets these criteria and the resulting PPD will be used in SPD calculations. Based 
on this convention, a CR may be achieved even if an SPD value is > 0 cm2 (i.e., if all lymph 
nodes measure < 1.0 cm2). 
New or enlarging nodal lesions that are still ≤ 1.0 cm by ≤ 1.0 cm will not be considered to 
represent recurrent or PD. A new node that measures > 1.5 cm in any diameter or a new node 
that measures > 1.0 cm to ≤ 1.5 cm in the LD and measures > 1.0 cm in the LPD will be 
considered PD. 
In cases in which a large lymph node mass has split into multiple components, only those 
elements that are > 1.0 cm in ≥ 1 diameter will be considered abnormal and used in calculating 
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the SPD. Components that are ≤ 1.0 cm in the LD are assumed to be normal lymph node 
structures. PD will not be based on the growth of a lesion sub-component until it meets the 
criteria for abnormal. Lesion sub-components that are abnormal (> 1.0 cm in ≥ 1 diameter) will 
have the true PPDs calculated with the result used only for calculating an accurate nadir. Lesion 
subcomponents that are normal (≤ 1.0 cm in the LD) will have the default PPD of 1.0 cm2 
(1.0 cm x 1.0 cm) stored only for the purposes of calculating the nadir value.  
If lesions merge, a boundary between the lesions will be established so the LD of each individual 
lesion can continue to be measured. If the lesions have merged in a way that they can no longer 
be separated by this boundary, the newly merged lesion will be measured bidimensionally. 
1.4.3. 
Extranodal Index Lesions  
An extranodal mass may be selected as an index lesion if it is both abnormal and measurable at 
baseline. An extranodal mass of any size is considered abnormal. It is considered measurable at 
baseline if it has 2 perpendicular diameters that can be accurately measured in cross section with 
the LD being ≥ 1.0 cm and the LPD also being ≥ 1.0 cm. 
At follow-up timepoints, the PPD of each single extranodal index lesion and the SPD of all 
extranodal index lesions will be considered. Because extranodal index lesions that have one or 
both diameters < 0.5 cm and > 0 cm cannot be reliably measured, a default value of 0.5 cm will 
be assigned for each diameter that meets these criteria and the resulting PPD will be used in SPD 
calculations. If an extranodal lesion is no longer clearly visible, it will be considered resolved 
and its PPD will be defined as 0 cm2.  
If an extranodal lesion that had resolved (i.e., had a PPD of 0 cm2) subsequently reappears, the 
subject will be considered to have PD. A new extranodal lesion of any size that appears at a site 
that was not previously involved with lymphoma and is discernible to the radiologist by CT scan 
will be considered PD. 
1.4.4. 
Non-Index Lesions 
Any other measurable and abnormal nodal or extranodal lesions not selected for quantitation as 
index lesions may be considered non-index lesions. In addition, non-measurable evidence of 
lymphoma such as abnormal, non-measurable nodal lesions, extranodal lesions with both 
diameters < 1.0 cm, bone lesions, leptomeningeal disease, ascites, pleural or pericardial 
effusions, lymphangitis of the skin or lung, abdominal masses that are not confirmed and 
followed by imaging techniques, cystic lesions, previously irradiated lesions, or lesions with 
artifacts may be considered as non-index disease.  
If present at baseline, up to 6 non-index lesions should be recorded. Measurements are not 
required.  
Non-index disease will be used as a general reference to further characterize regression or 
progression of lymphoma during assessments of the objective tumor response during treatment. 
These lesions should be followed as “present” or “absent”. 
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1.4.5. 
Spleen and Liver 
Qualitative assessments of the sizes of the spleen and liver will be performed. In addition, the 
presence or absence of splenic nodules will be recorded.  
At baseline and follow-up timepoints, the spleen and liver size will be reported as normal, 
enlarged not due to lymphoma (no nodules present), enlarged due to lymphoma (≥ 1 nodule 
present), unequivocal increase not due to lymphoma (no nodules present), or unequivocal 
progression (≥ 1 nodule present). For subjects with splenomegaly or hepatomegaly at baseline or 
at the nadirs for assessments of spleen and liver, evaluations will consider only changes relative 
to the enlargement of the organ (i.e., the portion of the LVD that is > 12 cm by imaging for the 
spleen and > 18 cm in LVD for the liver) at baseline or nadir, not changes relative to the total 
splenic LVD. 
By imaging, the spleen will be considered enlarged if it is > 12 cm in LVD (Bezerra 2005, 
Asghar 2011), with the LVD being obtained by multiplying the number of sections on which the 
spleen is visualized by the thickness of the sections (e.g., if the spleen is seen in 14 contiguous 
cross-sectional images with 0.5-cm thickness, the LVD is recorded as 7 cm). An increase in 
splenic enlargement by ≥ 50% (minimum increase of 2 cm) from nadir and the presence of 
≥ 1 splenic nodule is required for declaration of splenic progression. Subjects with a normal 
spleen LVD (i.e., a LVD of ≤ 0 cm by physical examination or ≤ 12 cm by imaging) at nadir will 
only be considered to have progressed if the spleen attains a LVD of > 14 cm by imaging and 
there is ≥ 1 splenic nodule. 
By imaging, the liver will be considered enlarged if it is > 18 cm in LVD (Erturk 2006). An 
increase in liver enlargement by ≥ 50% (minimum increase of 2 cm) from nadir and the presence 
of ≥ 1 hepatic nodule is required for declaration of hepatic progression. Subjects with a normal 
liver LVD (i.e., a LVD of ≤ 18 cm by imaging) at nadir will only be considered to have 
progressed if the liver attains a LVD of > 20 cm by imaging and there is ≥ 1 hepatic nodule. 
1.4.6. 
Bone Marrow 
Bone marrow assessments will be based on morphologic evaluation of bone marrow biopsies. 
Immunohistochemistry may be used to assess response if the sample is indeterminate by 
morphology.  
In a subject who has a baseline bone marrow biopsy showing bone marrow lymphoma or does 
not have a baseline bone marrow examination, declaration of an on-study CR requires bone 
marrow biopsy documentation of the absence of bone marrow lymphoma. In a subject who has a 
baseline bone marrow biopsy showing no evidence of lymphoma, declaration of an on-study CR 
does not require bone marrow examination as long as other criteria for CR are met. Of note, in 
subjects with an FDG-PET avid lymphoma, declaration of an on-study CR can be based on 
FDG-PET documentation of the absence of bone marrow involvement, even if a bone marrow 
biopsy is not performed or not available. 
1.4.7. 
Lymph Node Biopsy 
Lymph node biopsy is not required in the determination of subject eligibility.  
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During study participation, a subject with a more indolent type of disease (e.g., CLL/SLL, FL) 
who has a lymph node biopsy indicating transformation to an aggressive lymphoma will be 
considered to have PD even in the absence of other evidence of PD. If the subject has no earlier 
objective documentation of PD, the date of the lymph node biopsy will be considered the date of 
PD.  
1.5. 
Definitions of Tumor Response and Progression 
Responses will be categorized as complete response (CR), partial response (PR), stable disease 
(SD), or progressive disease (PD). In addition, a response category of nonevaluable (NE) is 
provided for situations in which there is inadequate information to otherwise categorize response 
status.  
The best overall response will be determined. The best overall response is the best on-treatment 
response from baseline recorded from the start of treatment until PD/recurrence. The baseline 
measurement will be taken as a reference for determinations of response. The nadir measurement 
will be taken as a reference for PD; this measurement constitutes the smallest measurement 
recorded, including the baseline measurement if this is the smallest measurement. For FDG-avid 
tumors, metabolic criteria for response by PET-CT will take precedence over anatomic criteria 
for response by contrast CT when assessing CR. 
1.5.1. 
Complete Response 
To satisfy criteria for CR, all of the following conditions must be attained: 
• No evidence of new disease 
• Regression of all index nodal lesions to normal size (≤ 1.5 cm in the LD for nodes 
that were considered large at baseline and ≤ 1.0 cm in the LPD for nodes that were 
considered small at baseline) (see Section 1.4.2 for definitions of large and small 
nodes) 
• Regression to normal of all nodal non-index disease  
• Disappearance of all detectable extranodal index and non-index disease 
• Normal spleen and liver size by imaging studies, no hepatic or splenic lymphoma 
nodules, and no new liver or spleen enlargement 
• Morphologically negative bone marrow based on an adequate unilateral core biopsy 
(> 20 mm unilateral core); if the sample is indeterminate by morphology, it should be 
negative by immunohistochemistry  
• If PET performed, no evidence of residual disease – i.e., score of 1 (no uptake above 
background), 2 (uptake ≤ mediastinum), or 3 (uptake > mediastinum but ≤ liver) on 
the Deauville 5-point scale. 
• Negative for bone marrow involvement by PET for a PET-avid tumor or by an 
adequate unilateral core biopsy (> 20 mm unilateral core); if the bone marrow biopsy 
is indeterminate by morphology, it should be negative by immunohistochemistry. 
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1.5.2. 
Partial Response 
To satisfy criteria for PR, all of the following conditions must be attained: 
• No evidence of new disease 
• A ≥ 50% decrease from baseline in the SPD of the index nodal and extranodal lesions  
• No increase from the nadir in the size of non-index disease 
• No increase from the nadir in the size of the liver or spleen and no new liver or spleen 
enlargement 
• If PET performed: 
− Typically FDG-avid lymphoma: if no baseline PET scan or if the PET scan was 
positive before therapy, the on-treatment PET is positive in ≥ 1 previously 
involved site– i.e., score of 4 (uptake moderately > liver) or score of 5 (uptake 
markedly > liver) on the Deauville 5-point scale but with reduced uptake 
compared with baseline. If baseline PET was performed and was negative, there is 
no new PET evidence of disease. 
− Variably FDG-avid lymphoma/FDG-avidity unknown: if no pretreatment PET 
scan or if the pretreatment PET scan was negative for lymphoma, CT criteria 
should be used in assessing the tumor during treatment. If the PET scan was 
positive before therapy, the on-treatment PET is positive in ≥ 1 previously 
involved site. 
• Persistence of bone marrow involvement in a subject who meets other criteria for CR 
based on the disappearance of all nodal and extranodal masses 
1.5.3. 
Stable Disease 
To satisfy criteria for SD, all of the following conditions must be attained: 
• No evidence of new disease 
• Neither sufficient tumor shrinkage from baseline to qualify for PR nor sufficient 
evidence of tumor growth to qualify for PD 
• If PET-CT performed, the results show a score of 4 (uptake moderately > liver) or 
score of 5 (uptake markedly > liver) on the Deauville 5-point scale with no significant 
change in uptake compared with baseline. 
1.5.4. 
Progressive Disease 
The occurrence of any of the following events indicates progressive disease (PD): 
• Evidence of any new disease that was not present at baseline: 
− A new node that measures > 1.5 cm in any diameter 
− A new node that measures > 1.0 cm to ≤ 1.5 cm in the LD and > 1.0 cm in the 
LPD 
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− Reappearance of an extranodal lesion that had resolved (i.e., had previously been 
assigned a PPD of 0 cm2) 
− A new extranodal lesion of any size 
− New non-index disease (e.g., effusions, ascites, or other organ abnormalities) of 
any size unequivocally attributable to lymphoma (usually requires PET, biopsy, 
cytology, or other non-radiologic confirmation to confirm disease attributable to 
lymphoma). Note: Isolated new effusions, ascites, or bone lesions are not 
sufficient evidence alone of PD unless histologically confirmed. In patients with 
no prior history of pulmonary lymphoma, new lung nodules identified by CT 
are usually benign. Thus, a declaration of PD should not be made if this is the 
only manifestation of an apparently new lesion. 
− New FDG-avid foci consistent with lymphoma rather than another etiology (e.g., 
infection, inflammation). If there is uncertainty regarding the etiology of new 
lesions, biopsy or interval scan may be considered. 
− New or recurrent bone marrow involvement with lymphoma by PET-CT or by 
bone marrow biopsy if prior PET-CT or bone marrow biopsy performed as part of 
the study was negative for lymphoma. 
• Evidence of worsening of nodal or extranodal index lesions: 
− Increase from the nadir by ≥ 50% in the SPD of index lesions 
− Evidence of worsening of individual index lymph nodes or nodal masses:  
 Increase from the nadir by ≥ 50% in the PPD for any individual node if the 
node now has an LD of > 1.5 cm and there is an absolute change from the 
nadir of ≥ 0.5 cm in the LD or LPD and to an absolute dimension of 
≥ 2.0 cm. 
 Increase from the nadir by ≥ 50% in the LD for any individual node if the 
node now has an LD of > 1.5 cm and there is an absolute change from the 
nadir of ≥ 0.5 cm in the LD 
 Increase from the nadir by ≥ 50% in the LPD for any individual node if 
the node now has an LPD of > 1.5 cm and there is an absolute change 
from the nadir of ≥ 0.5 cm in the LPD  
 If a lesion had been classified as a small lymph node, there is an additional 
requirement that the lesion has an LD of > 1.0 cm and an LPD of > 1.0 cm 
− Unequivocal increase in the size of non-index disease 
− Unequivocal worsening in the size of the liver or spleen (with the additional 
condition that there must be ≥ 1 nodule present in the enlarging organ) 
• Transformation to a more aggressive NHL histology as established by lymph node 
biopsy 
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•
If PET performed, there is a score of 4 (uptake moderately > liver) or score of 5
(uptake markedly >liver) on the Deauville 5-point scale with an increase in uptake
compared with the nadir in conjunction with an anatomic increase in lesion size
consistent with PD.
Note: Study subjects undergoing PET for lymphoma assessment can experience transient 
disease flare on imaging before having subsequent therapy-induced tumor regression. 
Worsening of constitutional symptoms or performance status in the absence of objective 
evidence of worsening lymphoma (e.g., due to infection) may not represent definitive disease 
progression. Further, transient worsening of disease during temporary interruptions of study 
therapy (e.g., for drug-related toxicity or inter-current illness) may not indicate definitive 
progressive lymphoma. If there is uncertainty regarding whether there is true lymphoma 
progression and if medically appropriate, the subject may continue or resume study treatment 
and remain under close observation (e.g., evaluated at 3- to 6-week intervals) while relevant 
radiographic, clinical, and/or laboratory assessments are performed to document whether 
tumor control can be maintained or whether disease progression has truly occurred. If 
subsequent evaluations suggest that the subject has experienced persistent definitive disease 
progression, then the date of progression will be the timepoint at which progression was first 
objectively documented.  
1.5.5. 
Nonevaluable 
In a subject who does not have evidence of PD, the occurrence of any of the following conditions 
indicates a response status of NE:  
•
There are no images or inadequate or missing images, defined as the inability to
visualize > 25% of index disease and > 50% of non-index disease.
2.
CHRONIC LYMPHOCYTIC LEUKEMIA/SMALL
LYMPHOCYTIC LYMPHOMA
2.1. 
Tumor Assessment Criteria
The determination of CLL/SLL response and progression will be based on standardized criteria 
(Hallek 2008), as recently updated (Cheson 2012).  
2.2. 
Method of Assessment 
In addition to clinical examination, imaging-based evaluation will be used in this study in all 
subjects enrolled. CT scan is the preferred method for radiographic tumor assessment. MRI 
scanning may be used at the investigator’s discretion in subjects for whom this may be a 
preferred alternative to CT scanning; however, if MRI is performed, a non-contrast CT of the 
chest should be performed. Contrast-enhanced scanning is preferred, but iodine-containing or 
gadolinium contrast material may be omitted in subjects for whom use of a contrast agent would 
be medically contraindicated. Chest x-ray, ultrasound, endoscopy, laparoscopy, PET, 
radionuclide scans, or tumor markers will not be considered for response assessment. 
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For radiographic evaluations, the same method of assessment and the same technique (e.g., scan 
type, scanner, subject position, dose of contrast, injection/scan interval) should be used to 
characterize each identified and reported lesion at baseline and during study treatment and 
follow-up. However, if a subject is imaged without contrast at baseline, subsequent assessments 
should be performed with contrast, unless the subject cannot tolerate the contrast.  
All relevant clinical and radiographic information required to make each tumor status assessment 
must be made available for source verification as requested by the study sponsor. 
2.3. 
Timing of Assessments 
During screening, clinical, laboratory, and imaging-based tumor assessments should be 
performed within the specified screening period. Clinical tumor assessments should be 
performed at each designated clinical visit. On-study CT/MRI tumor assessments should be 
performed as indicated in Section 8.7. An end-of-study CT/MRI tumor assessment should be 
performed unless the subject already has radiographic confirmation of disease progression 
≤ 4 weeks prior. If a subject permanently discontinues study drug prior to objective 
documentation of CLL/SLL progression, investigators should optimally attempt to obtain further 
follow-up at ~12-week intervals until CLL/SLL progression is documented or until the initiation 
of a new post-study therapy for the subject’s CLL/SLL.  
2.4. 
Identification and Measurement of Tumor Lesions and 
Organomegaly 
2.4.1. 
Index Lesions 
At baseline, up to 6 lymph nodes should be selected as index lesions that will be used to 
quantitate the status of the disease during study treatment. Ideally, the index lesions should be 
located in disparate regions of the body. Only peripheral nodes need be selected as index lesions. 
However, it is optimal if mediastinal and retroperitoneal areas of disease are assessed whenever 
these sites are involved. 
Index lesions will be measured and recorded at baseline and at the stipulated intervals. The cross-
sectional dimensions (the largest cross-sectional diameter, i.e., the LD × LPD) will be recorded 
(in cm) for each index lesion. The product of the perpendicular diameters (PPD) (in cm2) for 
each index lesion and SPD (in cm2) for all index lesions will be calculated and recorded. The 
baseline SPD will be used as references by which objective tumor response will be characterized 
during treatment. The nadir LD of individual lesions and the nadir SPD will be used as 
references by which CLL/SLL progression will be characterized. All LD and LPD diameters will 
be reported in centimeters and all PPDs and SPDs will be reported in centimeters squared. 
A nodal mass may be selected as a nodal index lesion if it is both abnormal and measurable at 
baseline. A lymph node lesion is considered abnormal if it has a single diameter that is > 1.5 cm 
and is considered measurable if it has 2 perpendicular diameters that can be accurately measured 
in cross section with the LD being ≥ 1.0 cm and the LPD also being ≥ 1.0 cm. 
Index lesions measuring > 1.5 cm in the LD, regardless of the measurement of the LPD, will be 
prioritized during baseline index lesion selection. 
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At follow-up timepoints, the LDs for individual lesions and the SPD of all nodal index lesions 
will be considered. Because nodal index lesions that have one or both diameters > 0 cm and 
< 1.0 cm cannot be reliably measured, a default value of 1.0 cm will be assigned for each 
diameter that meets these criteria and the resulting PPD will be used in SPD calculations. Based 
on this convention, a CR may be achieved even if an SPD value is > 0 cm2, (i.e., if all lymph 
nodes measure < 1.0 cm2). 
A new node that measures > 1.5 cm in any diameter or a new node that measures > 1.0 cm to 
≤ 1.5 cm in the LD and measures > 1.0 cm in the LPD will be considered progressive disease. 
In cases in which a large lymph node mass has split into multiple components, only those 
elements that are > 1.0 cm in ≥ 1 diameter will be considered abnormal and used in calculating 
the SPD. Progression of the lesion can only be based on the SPD of abnormal sub-components. 
Lesion sub-components that are considered normal but measurable will have the true PPDs 
calculated, with the result used only for calculating an accurate nadir. Similarly, lesion sub-
components that are visible but neither abnormal nor measurable will have the default PPD of 
1.0 cm2 (1.0 cm × 1.0 cm) stored only for the purposes of calculating the nadir SPD value. 
If lesions merge, a boundary between the lesions will be established so the LD of each individual 
lesion can continue to be measured. If the lesions have merged in a way that they can no longer 
be separated by this boundary, the newly merged lesion will be measured bi-dimensionally. 
2.4.2. 
Spleen and Liver 
Both the spleen and liver will be assessed by CT/MRI scan and by physical examination at 
baseline and at the stipulated intervals during treatment. The baseline and nadir values for the 
longest vertical dimension (LVD) of each organ will be used as reference to further characterize 
the objective tumor response of the measurable dimensions of the CLL/SLL during treatment. 
All spleen and liver LVD measurements should be recorded in centimeters. 
Physical examination of the spleen should comprise assessment of its LVD below the left costal 
margin by palpation. By physical examination, the spleen will be considered enlarged if it is 
palpable below the left costal margin. If the spleen is not palpable below the left costal margin, it 
should be assigned a value of 0 cm for physical examination assessment. By imaging, the spleen 
will be considered enlarged if it is > 12 cm in LVD (Bezerra 2005, Asghar 2011), with the LVD 
being obtained by multiplying the number of sections on which the spleen is visualized by the 
thickness of the sections (e.g., if the spleen is seen in 14 contiguous cross-sectional images with 
0.5-cm thickness, the LVD is recorded as 7 cm).  
For subjects with splenomegaly at baseline or at the splenic LVD nadir, respective response and 
progression evaluations of the spleen will consider only changes relative to the enlargement of 
the spleen (i.e., the portion of the LVD that is > 0 cm by physical examination or > 12 cm by 
imaging) at baseline or nadir, not changes relative to the total splenic LVD.  
A 50% decrease from baseline (minimum decrease of 2 cm) in the enlargement of the spleen in 
its LVD or to ≤ 12 cm by imaging, or regression to a spleen LVD of ≤ 0 cm by physical 
examination, is required for declaration of a splenomegaly response. Conversely, an increase in 
splenic enlargement by ≥ 50% (minimum increase of 2 cm) from nadir is required for declaration 
of splenic progression. Subjects with a normal spleen LVD (i.e., a LVD of ≤ 0 cm by physical 
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examination or ≤ 12 cm by imaging) at nadir will only be considered to have progressed if the 
spleen attains a LVD of > 14 cm by imaging or > 2 cm by physical exam. 
Physical examination of the liver should comprise assessment of its LVD at the right 
midclavicular line by percussion. By physical examination, the liver will be considered enlarged 
if it is > 15 cm in LVD as assessed by percussion (Walker 1990). By imaging, the liver will be 
considered enlarged if it is > 18 cm in LVD (Erturk 2006). 
A 50% decrease (minimum decrease of 2 cm) from baseline in the enlargement of the liver in its 
LVD or to ≤ 18 cm by imaging, or regression to a liver LVD of ≤ 15 cm by physical 
examination, is required for declaration of a hepatomegaly response. Conversely, an increase in 
liver enlargement by ≥ 50% (minimum increase of 2 cm) from nadir is required for declaration of 
hepatic progression. Subjects with a normal liver LVD (i.e., a LVD of ≤ 15 cm by physical 
examination or ≤ 18 cm by imaging) at nadir will only be considered to have progressed if the 
liver attains a LVD of > 20 cm by imaging or > 17 cm by physical exam. 
2.4.3. 
Non-Index Lesions 
Any other measurable and abnormal nodal lesions not selected for quantitation as index lesions 
may be considered non-index lesions. In addition, non-measurable evidence of CLL/SLL such as 
nodal lesions with both diameters < 1.0 cm, extranodal lesions, bone lesions, leptomeningeal 
disease, ascites, pleural or pericardial effusions, lymphangitis of the skin or lung, abdominal 
masses that are not confirmed and followed by imaging techniques, cystic lesions, previously 
irradiated lesions, and lesions with artifacts may be considered as non-index disease. 
The presence or absence of non-index disease should be recorded at baseline and at the stipulated 
intervals during treatment. If present at baseline, up to 6 non-index lesions should be recorded. 
The non-index disease at baseline will be used as a general reference to further characterize 
regression or progression of CLL/SLL during assessments of the objective tumor response 
during treatment. Measurements are not required and these lesions should be followed as 
“present” or “absent”. 
2.5. 
Definitions of Tumor Response and Progression 
Responses will be categorized as complete response (CR), partial response (PR), stable disease 
(SD), or progressive disease (PD). In addition, a response category of nonevaluable (NE) is 
provided for situations in which there is inadequate information to otherwise categorize response 
status.  
The best overall response will be determined. The best overall response is the best response 
recorded from the start of treatment until disease/recurrence progression (taking as a reference 
for disease progression the smallest measurements recorded since treatment started). Subjects 
with a best overall response of NE or ND will be counted in the denominators in calculations of 
tumor response rates. Where imaging data are available, these data will supersede physical 
examination data in determining tumor status. 
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2.5.1. 
Complete Response and Complete Response with Incomplete Blood Count 
Recovery 
To satisfy criteria for CR or CRi, all of the following conditions must be attained:  
• No evidence of new disease 
• ALC in peripheral blood of < 4 x 109/L 
• Regression of all index nodal masses to normal size ≤ 1.5 cm in the LD 
• Normal spleen and liver size 
• Regression to normal of all nodal non-index disease and disappearance of all 
detectable non-nodal, non-index disease 
• Morphologically negative bone marrow defined as < 30% of nucleated cells being 
lymphoid cells and no lymphoid nodules in a bone marrow sample that is 
normocellular for age 
• Peripheral blood meeting all of the following criteria: 
− ANC ≥ 1.5 x 109/L without need for exogenous growth factors (e.g., G-CSF) 
− Platelet count ≥ 100 x 109/L without need for exogenous growth factors 
− Hemoglobin ≥ 110 g/L (11.0 g/dL) without red blood cell transfusions or need for 
exogenous growth factors (e.g., erythropoietin) 
Note: Subjects who fulfill all the criteria for a CR (including bone marrow criteria) but who 
have a persistent anemia, thrombocytopenia, or neutropenia or a hypocellular bone marrow 
that is related to prior or ongoing drug toxicity (and not to CLL/SLL) will be considered as a 
CR with incomplete marrow recovery (CRi).  
2.5.2. 
Partial Response 
To satisfy criteria for a PR, all of the following conditions must be attained: 
• No evidence of new disease 
• A change in disease status meeting ≥ 2 of the following criteria, with 2 exceptions in 
which only 1 criterion is needed: (1) Only lymphadenopathy is present at baseline; or 
(2) only lymphadenopathy and lymphocytosis are present at baseline; in these 2 cases, 
only lymphadenopathy must improve to the extent specified below:  
− Decrease in peripheral blood ALC by ≥ 50% from baseline 
− A decrease by ≥ 50% from the baseline in the SPD of the index nodal lesions 
− In a subject with enlargement of the spleen at baseline, a splenomegaly response 
as defined in Section 2.4.2 
− In a subject with enlargement of the liver at baseline, a hepatomegaly response as 
defined in Section 2.4.2 
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− A decrease by ≥ 50% from baseline in the CLL/SLL marrow infiltrate or in 
B-lymphoid nodules 
• No index, splenic, liver, or non-index disease with worsening that meets the criteria 
for definitive PD 
• Peripheral blood meeting ≥ 1 of the following criteria: 
− ANC ≥ 1.5 x 109/L or ≥ 50% increase over baseline without need for exogenous 
growth factors (e.g., G-CSF) 
− Platelet count ≥ 100 x 109/L or ≥ 50% increase over baseline without need for 
exogenous growth factors 
− Hemoglobin ≥ 110 g/L (11.0 g/dL) or ≥ 50% increase over baseline without red 
blood cell transfusions or need for exogenous growth factors (e.g., erythropoietin) 
2.5.3. 
Stable Disease 
To satisfy criteria for SD, the following conditions must be attained: 
• No evidence of new disease 
• There is neither sufficient evidence of tumor shrinkage to qualify for PR nor 
sufficient evidence of tumor growth to qualify for definitive PD 
2.5.4. 
Progressive Disease 
The occurrence of any of the following events indicates PD:  
• Evidence of any new disease: 
− A new node that measures > 1.5 cm in any diameter 
− New splenomegaly as defined in Section 2.4.2 
− New hepatomegaly as defined in Section 2.4.2 
− New non-index disease (e.g., effusions, ascites, or other organ abnormalities 
related to CLL/SLL) 
Note: Isolated new effusions, ascites, or other organ abnormalities are not sufficient evidence 
alone of PD unless histologically confirmed. Thus, a declaration of PD should not be made if 
this is the only manifestation of apparently new disease. 
• Evidence of worsening of index lesions, spleen or liver, or non-index disease:  
− Increase from the nadir by ≥ 50% from the nadir in the SPD of index lesions 
− Increase from the nadir by ≥ 50% in the LD of an individual node or extranodal 
mass that now has an LD of > 1.5 cm and an LPD of > 1.0 cm 
− Splenic progression as defined in Section 2.4.2 
− Hepatic progression as defined in Section 2.4.2 
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− Unequivocal increase in the size of non-index disease (e.g., effusions, ascites, or 
other organ abnormalities related to CLL/SLL)  
− Transformation to a more aggressive histology (e.g., Richter syndrome) as 
established by lymph node biopsy (with the date of the lymph node biopsy being 
considered the date of CLL/SLL progression if the subject has no earlier objective 
documentation of CLL/SLL progression) 
• Decrease in platelet count or hemoglobin that is attributable to CLL/SLL, is not 
attributable to an autoimmune phenomenon, and is confirmed by bone marrow biopsy 
showing an infiltrate of clonal CLL/SLL cells 
− The current platelet count is < 100 x 109/L and there has been a decrease by 
> 50% from the highest on-study platelet count  
− The current hemoglobin is < 110 g/L (11.0 g/dL) and there has been a decrease by 
> 20 g/L (2 g/dL) from the highest on-study hemoglobin  
Note: If there is uncertainty regarding whether there is true progression, the subject should 
continue study treatment and remain under close observation (e.g., evaluated at 4-week 
intervals) pending confirmation of progression status. In particular, worsening of 
constitutional symptoms in the absence of objective evidence of worsening CLL/SLL will not 
be considered definitive disease progression; in such subjects, both CLL/SLL-related and 
non-CLL/SLL-related causes for the constitutional symptoms should be considered. 
Worsening of disease during temporary interruption of study treatment (e.g., for intercurrent 
illness) is not necessarily indicative of resistance to study treatment. In these instances, 
CT/MRI or other relevant evaluations should be considered in order to document whether 
definitive disease progression has occurred. If subsequent evaluations suggest that the subject 
has experienced persistent definitive CLL/SLL progression, then the date of progression 
should be the timepoint at which progression was first objectively documented. 
2.5.5. 
Nonevaluable 
In a subject who does not have evidence of PD, the occurrence of any of the following conditions 
indicates a response status of NE:  
• There are no images or inadequate or missing images 
• Images of the liver and spleen are missing at that timepoint (with the exception that 
absence of splenic images will not result in an NE designation in a subject known to 
have undergone splenectomy). 
2.5.6. 
Lymphocytosis during Therapy 
Lymphocytosis early in therapy may not represent disease progression in subjects who have 
persistent control of other CLL/SLL-related signs and symptoms. In the absence of other 
objective evidence of disease progression, lymphocytosis alone will not preclude subjects from 
meeting the criteria for PR if other criteria for PR are met and will not be considered evidence 
of disease progression if occurring in isolation. Subjects with lymphocytosis should be 
continued on study drug until the occurrence of definitive disease progression (i.e., disease 
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progression that is manifest by worsening CLL/SLL-related signs other than lymphocytosis 
alone), or the occurrence of another reason to discontinue study therapy.  
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Appendix 3. 
Potential Drug Interactions with LAM-002A 
Table 15: 
CYP2C9 and CYP3A Inhibitors and Inducers 
CYP2C9 Inhibitors Z  
Strong 
Moderate 
Weak 
Other 
fluconazole 
amiodarone 
 
efavirenz 
isoniazid 
metronidazole 
paroxetine 
sulfamethoxazole 
voriconazole 
CYP2C9 Inducers 
Strong 
Moderate 
Weak 
Other 
 
 
 
carbamazepine 
nevirapine 
phenobarbital 
rifampin 
St. John’s Wort 
CYP3A Inhibitors 
Strong 
Moderate 
Weak 
Other 
Boceprevir 
Clarithromycin 
Cobicistat 
Conivaptan 
Fluvoxamine 
Grapefruit Juice (in large 
amounts, > 1 liter a day, 
and in high 
concentrations) 
Indinavir 
Itraconazole 
Ketoconazole 
Lopinavir and Ritonavir 
Nefazodone 
Nelfinavir 
Posaconazole 
Quinupristin 
Ritonavir 
 
Aprepitant 
Atazanavir 
Ciprofloxacin 
Darunavir  
Diltiazem 
Dronedarone 
Erythromycin  
Fluconazole 
Fosamprenavir 
Grapefruit Juice (in 
lower concentrations and 
smaller amounts) 
Imatinib 
Verapamil 
Alprazolam 
Amiodarone 
Amlodipine 
Atorvastatin 
Bicalutamide 
Cilostazol 
Cimetidine 
Cyclosporine 
Fluoxetine  
Ginkgo 
Goldenseal 
Imipramine 
Isoniazid 
Nilotinib 
Oral contraceptives 
Ranitidine 
Ranolazine 
Azithromycin 
Bromocriptine 
Chloramphenicol 
Delavirdine 
Desipramine 
Danazol 
Felodipine 
Iloperidone  
Linagliptin 
Nicardipine 
Nifedipine 
Quinidine 
Simeprevir 
Zafirlukast 
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Table 15: 
CYP2C9 and CYP3A Inhibitors and Inducers (Continued) 
CYP3A Inhibitors 
Strong 
Moderate 
Weak 
Other 
Saquinavir  
Telaprevir  
Telithromycin 
Voriconazole 
Tipranavir 
Zileuton 
CYP3A Inducers 
Strong 
Moderate 
Weak 
Other 
Carbamazepine 
Phenobarbital 
Phenytoin  
Rifampin 
St. John’s Wort 
Bosentan 
Efavirenz 
Etravirine 
Modafinil 
Nafcillin 
Aprepitant 
Armodafinil 
Echinacea 
Pioglitazone 
Prednisone 
Rufinamide 
Topiramate 
Dexamethasone 
Felbamate 
Fosamprenavir 
Griseofulvin 
Nevirapine  
Oxcarbazepine  
Rifabutin 
Rifapentine 
Tocilizumab  
Tumor Necrosis Factor 
inhibitors 
Source: Flockhart 2007 
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Table 16: 
Drugs Known to Prolong the QT Interval and/or Cause Torsades De Pointes 
(TDP) 
Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Amiodarone 
Cordarone®, Pacerone®, 
Nexterone® 
Antiarrhythmic 
Abnormal heart rhythm 
Anagrelide 
Agrylin®, Xagrid® 
Phosphodiesterase 3 
inhibitor 
Thrombocythemia 
Arsenic trioxide 
Trisenox® 
Anticancer 
Cancer (leukemia) 
Astemizole (removed 
from market) 
Hismanal® 
Antihistamine 
Allergic rhinitis 
Azithromycin 
Zithromax®, Zmax® 
Antibiotic 
Bacterial infection 
Bepridil (removed 
from market) 
Vascor® 
Antianginal 
Angina Pectoris (heart pain) 
Chloroquine 
Aralen® 
Antimalarial 
Malaria 
Chlorpromazine 
Thorazine®, Largactil®, 
Megaphen® 
Antipsychotic / 
Antiemetic 
Schizophrenia, nausea, many 
others 
Cilostazol 
Pletal® 
Phosphodiesterase 3 
inhibitor 
Intermittent claudication 
Ciprofloxacin 
Cipro®, Cipro-XR®, 
Neofloxin® 
Antibiotic 
Bacterial infection 
Cisapride (removed 
from market) 
Propulsid® 
Gastrointestinal 
stimulant 
Increase gastrointestinal 
motility 
Citalopram 
Celexa®, Cipramil® 
Antidepressant, 
selective serotonin 
reuptake inhibitor 
Depression 
Clarithromycin 
Biaxin®, Prevpac® 
Antibiotic 
Bacterial infection 
Cocaine 
Cocaine 
Local anesthetic 
Anesthesia (topical) 
Disopyramide 
Norpace® 
Antiarrhythmic 
Abnormal heart rhythm 
Dofetilide 
Tikosyn® 
Antiarrhythmic 
Abnormal heart rhythm 
Domperidone (only 
on non-US market) 
Motilium®, Motillium®, 
Motinorm Costi®, 
Nomit® 
Antinausea 
Nausea, vomiting 
Donepezil 
Aricept® 
Cholinesterase 
inhibitor 
Dementia (Alzheimer’s 
Disease) 
Dronedarone 
Multaq® 
Antiarrhythmic 
Abnormal heart rhythm 
Droperidol 
Inapsine®, Droleptan®, 
Dridol®, Xomolix® 
Antipsychotic / 
Antiemetic 
Anesthesia (adjunct), nausea 
Erythromycin 
E.E.S.®, Robimycin®, 
Emycin®, Erymax®, Ery-
Tab®, Eryc Ranbaxy®, 
Erypar®, Eryped®, 
Erythrocin Stearate 
Filmtab®, Erythrocot®, 
E-Base®, Erythroped®, 
Ilosone®, MY-E®, 
Pediamycin®, Zineryt®, 
Abboticin®, Abboticin-
ES®, Erycin®, PCE 
Antibiotic 
Bacterial infection, increase 
gastrointestinal motility 
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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Dispertab®, Stiemycine®, 
Acnasol®, Tiloryth® 
Escitalopram 
Cipralex®, Lexapro®, 
Nexito®, Anxiset-E® 
(India), Exodus® (Brazil), 
Esto® (Israel), Seroplex®, 
Elicea®, Lexamil®, 
Lexam®, Entact® 
(Greece), Losita® 
(Bangladesh), Reposil® 
(Chile), Animaxen® 
(Colombia), Esitalo® 
(Australia), Lexamil® 
(South Africa) 
Antidepressant, 
selective serotonin 
reuptake inhibitor 
Depression (major), anxiety 
disorders 
Flecainide 
Tambocor®, Almarytm®, 
Apocard®, Ecrinal®, 
Flécaine® 
Antiarrhythmic 
Abnormal heart rhythm 
Fluconazole 
Diflucan®, Trican® 
Antifungal 
Fungal infection 
Gatifloxacin 
(removed from 
market) 
Tequin® 
Antibiotic 
Bacterial infection 
Grepafloxacin 
Raxar® 
Antibiotic 
Bacterial infection 
Halofantrine 
Halfan® 
Antimalarial 
Malaria 
Haloperidol 
Haldol® (US & UK), 
Aloperidin®, 
Bioperidolo®, Brotopon®, 
Dozic®, Duraperidol® 
(Germany), Einalon S®, 
Eukystol®, Halosten®, 
Keselan®, Linton®, 
Peluces®, Serenace®, 
Serenase®, Sigaperidol® 
Antipsychotic 
Schizophrenia, agitation 
Ibogaine (only on 
non-US market) 
None 
Psychedelic 
Narcotic addiction, unproven 
Ibutilide 
Corvert® 
Antiarrhythmic 
Abnormal heart rhythm 
Levofloxacin 
Levaquin®, Tavanic® 
Antibiotic 
Bacterial infection 
Levomepromazine 
(methotrimeprazine) 
only on non-US 
market) 
Nosinan®, Nozinan®, 
Levoprome® 
Antipsychotic 
Schizophrenia 
Levosulpiride (only 
on non-US market) 
Lesuride®, Levazeo®. 
Enliva® (with rabeprazole) 
Antipsychotic 
Schizophrenia 
Levomethadyl 
acetate (removed 
from market) 
Orlaam® 
Opioid agonist 
Narcotic dependence 
Mesoridazine 
(removed from 
market) 
Serentil® 
Antipsychotic 
Schizophrenia 
Methadone 
Dolophine®, Symoron®, 
Amidone®, Methadose®, 
Opioid agonist 
Narcotic dependence, pain 
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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Physeptone®, Heptadon® 
Moxifloxacin 
Avelox®, Avalox®, 
Avelon® 
Antibiotic 
Bacterial infection 
Ondansetron 
Zofran®, Anset®, 
Ondemet®, Zuplenz®, 
Emetron®, Ondavell®, 
Emeset®, Ondisolv®, 
Setronax® 
Antiemetic 
Nausea, vomiting 
Oxaliplatin 
Eloxatin® 
Antineoplastic 
Agent 
Cancer 
Papaverine HCl 
none 
Vasodilator, 
Coronary 
Diagnostic adjunct 
Pentamidine 
Pentam® 
Antifungal 
Fungal infection 
(Pneumocystis pneumonia) 
Pimozide 
Orap® 
Antipsychotic 
Tourette’s Disorder 
Probucol (removed 
from market) 
Lorelco® 
Antilipemic 
Hypercholesterolemia 
Procainamide 
Pronestyl®, Procan® 
Antiarrhythmic 
Abnormal heart rhythm 
Propofol 
Diprivan®, Propoven® 
Anesthetic, general 
Anesthesia 
Quinidine 
Quinaglute®, Duraquin®, 
Quinact®, Quinidex®, 
Cin-Quin®, Quinora® 
Antiarrhythmic 
Abnormal heart rhythm 
Roxithromycin (only 
on non-US market) 
Rulide®, Xthrocin®, 
Roxl-150®, Roxo®, 
Surlid®, Rulide®, 
Biaxsig®, Roxar®, 
Roximycinv®, 
Roxomycin®, Rulid®, 
Tirabicin®, Coroxin® 
Antibiotic 
Bacterial infection 
Sevoflurane 
Ulane®, Sojourn® 
Anesthetic, general 
Anesthesia 
Sotalol 
Betapace®, Sotalex®, 
Sotacor® 
Antiarrhythmic 
Abnormal heart rhythm 
Sparfloxacin 
(removed from 
market) 
Zagam® 
Antibiotic 
Bacterial infection 
Sulpiride (only on 
non-US market) 
Dogmatil®, Dolmatil®, 
Eglonyl®, Espiride®, 
Modal®, Sulpor® 
Antipsychotic, 
atypical 
Schizophrenia 
Sultopride (only on 
non-US market) 
Barnetil®, Barnotil®, 
Topral® 
Antipsychotic, 
atypical 
Schizophrenia 
Terfenadine 
(removed from 
market) 
Seldane® 
Antihistamine 
Allergic rhinitis 
Terlipressin (only on 
non-US market) 
Teripress®, Glypressin®, 
Terlipin®, Remestyp®, 
Tresil®, Teriss®, and 
others 
Vasoconstrictor 
Septic shock 
Terodiline (only on 
non-US market) 
Micturin®, Mictrol® (not 
bethanechol) 
Muscle relaxant 
Bladder spasm 
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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Thioridazine 
Mellaril®, Novoridazine®, 
Thioril® 
Antipsychotic 
Schizophrenia 
Vandetanib 
Caprelsa® 
Anticancer 
Cancer (thyroid) 
Note: Includes those drugs known to prolong the cardiac QT interval or cause TdP (Woosley 
2018). 
Abbreviation: QT: Time of start of Q wave until end of T wave in the heart’s electrical cycle; TdP: 
Torsades de Pointes; UK: United Kingdom; US: United States  
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Appendix 4. 
Summary of Protocol Changes 
Changes made in Amendment 1 (17 Jul 2015) 
The primary purpose of this amendment is to reflect a change in manufacturing of Investigational 
Product from a tablet to capsule. Wording throughout the protocol as well as the description of 
the Investigational Product has been amended accordingly. Additional changes have been made 
to provide clarity and consistency and include the following: 
• Provisional Dose Levels Table 2 was revised to correctly reflect the percent increase 
from 200 mg to 275mg (37.5%).  
• A statement has been added to prohibit administration of live vaccines during the study 
due to the potential immunomodulatory effect of apilimod dimesylate.  
• Schedule of Assessments Table 4 has been revised to delete the Day 8 column for Cycle 
3 and Beyond as there are no assessments, other than at home dosing, on this day.  
• Statement(s) regarding self-administered dosing have been amended to clarify that 
subjects must fast for 2 hours prior to and 2 hours after dose administration.  
• Protocol section 12 has been revised to indicate that blood samples for plasma 
concentration (PK) levels of product and metabolites will be collected during Dose 
Expansion as well as Dose Escalation.  
• The PK sample collection window was revised in Table 6 from +/- 1 hr to +/- 10 minutes 
for the 6 hr collection time points on Day 1 and Day 8.  
Changes made in Amendment 2 (14 Oct 2015) 
The primary purpose of this amendment is to update the biomarker / tumor tissue analysis and 
associated time points. Blood smears from treated subjects will be analyzed by microscopy for 
changes in the extent of vacuolation in white blood cells as a phenotypic marker of PIKfyve 
inhibition. Tumor tissue will be examined for the presence of infiltrating immune cells (e.g., 
tumor infiltrating lymphocytes, tumor associated macrophages) as a means to understand the 
potential immunomodulatory effect of LAM-002A. Additionally plasma will be assayed by 
proteomic technology for analytes that may predict anti-lymphoma activity. 
Changes made in Amendment 3 (21 Mar2016) 
This amendment documented a change in the medical monitor for the study. Information 
regarding acquisition of data for exploratory endpoints was clarified or updated. Methods of 
efficacy analysis were updated and were made more complete. Eligibility criteria were updated 
regarding tumor measurability in patients with CLL/SLL, allowed concomitant medications, and 
acquisition of tumor, surrogate, and control samples at baseline. Treatment guidelines and dose-
modification provisions were simplified and clarified. The reasons for discontinuing a subject 
from study therapy were made more specific. Information regarding the disposition and 
destruction of study drug was clarified.  
Changes made in Amendment 4 (07 Nov 2016) 
In this amendment, the description of the drug product was updated with information relating to 
newly introduced 50-mg capsules. Descriptions of emerging safety and efficacy data were 
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provided. Intermediate BID dose levels were added and TID dosing regimens were introduced. 
The maximum number of subjects was increased to accommodate the larger number of dosing 
regimens to be evaluated. Post-treatment follow-up methods were clarified. The types of archival 
or fresh tissue to be collected during screening were clarified. Recommendations regarding 
management of gastrointestinal AEs were updated to reflect the evolving safety profile of the 
study drug. The definitions of analysis sets to be evaluated were clarified. 
Changes made in Amendment 5 (14 Apr 2017) 
In this amendment, medical prophylaxis has been mandated for subjects at intermediate to high 
risk of TLS and a recommendation has been included that subjects at high risk of TLS be 
monitored as inpatients during the first 24 to 48 hours of LAM-002A administration. In addition, 
TLS has been removed as a DLT exclusion. Serum chemistry laboratory monitoring for TLS has 
now been included on Days 2 and 3 of Cycle 1 for subjects at intermediate to high risk of TLS 
(as defined in Section 6.8.1 of the protocol). 
Changes made in Amendment 6 (25 Oct 2017) 
This amendment modified the protocol to evaluate the safety and tolerability of LAM-002A 
when given alone and in combination with rituximab or atezolizumab for the treatment of 
subjects with relapsed or refractory B-cell non-Hodgkin’s lymphoma.  In support of the addition 
of combination therapy to the protocol: 
• Additional information was added to support the rationale for combination therapy with 
LAM-002A and rituximab or atezolizumab. 
• The trial objectives and endpoints were revised to indicate that LAM-002A will be 
evaluated alone and in combination with other drugs and to indicate changes in the types 
of pharmacodynamic assays that were to be performed as a result of evolving experience 
with these exploratory assays. 
• The study design was modified to: 
− include further dose exploration using an intermittent LAM-002A dosing regimen 
with antiemetic and antidiarrheal support as a result of previous findings that nausea, 
vomiting, and diarrhea were treatment-limiting when LAM-002A was given 
continuously at doses ≥150 mg twice per day (BID), 
− identify the disease indications and combination regimens to be administered in the 
expansion stage, 
− include additional information on subject allocation given the plan to explore 
monotherapy and combination therapy and place restrictions of Stage 1 and 2 
enrollment, 
− clarify subject evaluability criteria for the dose-ranging and cohort-expansion 
portions of the study, and 
− revise the number of subjects participating in each portion of the trial. 
• The LAM-002A dose-escalation procedures were revised consistent with the new dose-
escalation and cohort-expansion portions of the study, and additional information on 
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premedications, administration of LAM-002A  in the clinic and on an outpatient basis, 
dose modifications, and supportive care was added. 
• Information (including description, packaging, source, storage and stability, solution 
preparation, and accountability) was added for rituximab and atezolizumab. Instructions 
were added regarding administration, dose modifications, and supportive care for 
rituximab and atezolizumab. 
• A section on study restrictions was added to provide guidance for the investigators with 
regard to breast feeding, contraception, and diet. 
• The duration of study participation was revised to include instructions for administration 
of LAM-002A as monotherapy and as combination therapy. Consistent with intention-to-
treat principles designed to maximize collection of safety and efficacy data, subjects were 
allowed to continue on either of the combination agents even if the other agent were to be 
discontinued due to toxicity. 
• The subject inclusion/exclusion criteria were revised as follows: 
− On mechanistic grounds, primary mediastinal B-cell lymphoma (PMBL) might 
respond to LAM-002A therapy; for this reason, patients with this type of lymphoma 
could be accrued to the dose-ranging portion of the trial. 
− A requirement for prior rituximab therapy was no longer mandated given that some 
patients (eg, those with chronic lymphocytic leukemia/small lymphocytic leukemia 
[CLL/SLL]) might not have received rituximab as prior therapy based on changing 
standards of care. 
− Organ function criteria for hematological function, hepatic function, and renal 
function were updated based on the evolving safety profile of LAM-002A  showing 
that the drug is unlikely to adversely alter these organ systems. 
− The contraception enrollment criteria were made more specific. 
− The requirements for baseline bone marrow collection in patients with lymphoma 
were clarified. 
− Prior therapy prohibitions were now included for study candidates under 
consideration for combination therapy to minimize the likelihood that they would 
have disease that is totally resistant to rituximab or atezolizumab.  
− Restrictions on use of live-virus vaccines, ongoing therapy for hepatitis B virus, 
recent therapy with immunostimulatory agents, ongoing use of immunosuppressive 
therapies, recent serious infection, a history of autoimmunity, or inability to tolerate 
required supportive care were included; these exclusions were intended to enhance 
subject safety and to avoid comorbid conditions that could confuse interpretation of 
safety findings. 
− The requirements relating to baseline serological testing for chronic viral infections 
were clarified. 
• Separate schedules of activities were prepared for LAM-002A continuous monotherapy 
administration, LAM-002A intermittent monotherapy administration, 
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LAM-002A/rituximab combination therapy, and LAM-002A/atezolizumab combination 
therapy.  
• Additional information regarding collection of samples for pharmacokinetic and 
biomarker determinations was added. 
• The statistical section was revised to provide: 
− more detailed information on the statistical basis for the Stage 1 dose-ranging 
approach, and 
− the statistical basis for the planned Stage 2 cohort size.  
In addition to the above, administrative changes in section ordering were made to enhance the 
organization of information in the protocol. 
Changes made in Amendment 7 (14 Jan 2019) 
The following substantive changes were made to the protocol in this amendment: 
• Introductory information regarding LAM-002A efficacy and safety was updated.  
• Information regarding the total potential accrual to the study was updated consistent with 
modifications to the protocol to evaluate single-agent LAM-002A or the 
LAM-002A/rituximab combination in additional patients with FL.  
• A statistical justification for accrual of additional patients with FL to receive LAM-002A 
monotherapy or LAM-002A/rituximab was included. 
• In subjects receiving the LAM-002A/rituximab, combination use of either intravenously 
administered rituximab or subcutaneously administered rituximab hyaluronidase human 
was permitted. Relevant changes were made throughout the protocol to provide necessary 
dosing, administration, and drug product information for rituximab hyaluronidase human. 
The following clarifying changes were made to the protocol in this amendment: 
• The exploratory objectives and endpoints were updated to reflect changes to the 
substrates and parameters being analyzed. 
• Biopsy procedures were clarified.  
• The severity of hypertension warranting exclusion from protocol therapy was clarified. 
• The text was clarified to indicate that past pathology data should be collected as part of 
each subject’s medical history.  
• In the schedules of activities, text regarding the timing of laboratory assessments was 
clarified. 
• Information regarding pharmacovigilance reporting of pregnancies was corrected. 
• Information regarding drugs with known risk of QT prolongation or torsades de pointes 
was updated and the relevant reference was revised accordingly.  
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Changes made in Amendment 8 (18 Feb 2020) 
The following changes were made to the protocol in this amendment: 
• Changes to the company name (from LAM Therapeutics, Inc. to AI Therapeutics, Inc.) 
and modifications to the protocol version and date (from Version 8, dated 14 Jan 2019 to 
Version 9, dated 19 February 2020) were made throughout the document without specific 
notation. 
• Information regarding AI Therapeutics signatories to the protocol was updated. 
• Information regarding LAM-002A efficacy in NHL was updated in the protocol 
introduction.  
• Text was included throughout the protocol consistent with addition of an extension stage 
to the study.  
• In the context of transitioning to the extension stage of the study, site monitoring by the 
contract research organization, Ce3, was discontinued. 
• In the context of transitioning to the extension stage of the study, pharmacovigilance 
monitoring of SAEs and pregnancy was transitioned from the contract research 
organization, Pharmalex, Inc. to the study sponsor, AI Therapeutics. 
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Appendix 5. 
Detailed Protocol Changes 
Changes made in Amendment 1 (17 Jul 2015) 
Changes from Original Protocol (16 Jun 2015) to Amendment 1 (17 Jul 2015) 
Changed to (changes in red): [added text bold, deleted text as strikethrough] 
Throughout protocol, all references — Replaced the word tablets with capsules 
Tablet(s) amended to Capsules 
Page 27, 4.1 Product Summary; Page 56, Table 5 Physical Description — Changed the physical 
description of investigational product 
Physical description of product including size, weight, composition and inactive ingredients 
amended from tablet material to capsule material.  
Page 38, 6.5 Dose Escalation Procedures — Amended the percent increase on dose level 4 from 
27 to 37.5  
Table 2: 
Provisional Dose Levels 
 
Daily LAM-002A Dose  
Percent Increase  
Initial Cohort Size 
-1 
25 mg BID 
-50 
3 
0 
50 mg BID 
Starting dose 
3 
1 
100 mg BID 
100 
3  
2 
150 mg BID 
50 
3  
3 
200 mg BID 
33 
3  
4 
275 mg BID 
2737.5 
3  
 
Page 44, Table 4 Schedule of Assessments — Removed Day 8 column from Cycle 3 and Beyond 
Column deleted from table 
Page 11, synopsis on investigational product and dose administration; Page 48, 7.3.3 LAM002A 
Self-Administration Dosing Diary; Page 57, 9.4 Study Drug Administration — Amended the 
language with regard to fasting around dosing  
They may eat 2 hours before or 2 hours after dose administration  
Subjects should fast for 2 hours before and 2 hours after dose administration, with 
no dietary restrictions otherwise. 
Page 54, 8.6.4 Other Concomitant Medications — Added statement about use of live vaccines 
during study  
Vaccines: Administration of live vaccines is prohibited during the study.  
Page 64, Section 12 Pharmacokinetic Assessments — Added statement about testing in dose 
expansion and changed window for hr 6 assessments 
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Plasma concentration levels of apilimod and the active metabolites will be measured in 
the Dose Escalation and Dose Expansion Stages at each of the specified time points. 
Table 6: 
Pharmacokinetic Sampling Time Points 
Sample 
Study Day 
PK Sampling Time Points*  
1** 
1 
Pre-dose (within 30 min prior to dose of LAM-002A) 
2 
1 
0.5 hour (± 10 min) after dosing with LAM-002A 
3 
1 
1 hour (± 10 min) after dosing with LAM-002A 
4 
1 
2 hours (± 10 min) after dosing with LAM-002A 
5 
1 
4 hours (± 10 min) after dosing with LAM-002A  
6 
1 
6 hours (± 1 hr 10 min) after dosing with LAM-002A 
7 
1 
8 hours (± 10 min) after dosing with LAM-002A 
8** 
8 
Pre-dose (within 30 min prior to dose of LAM-002A) 
9 
8 
0.5 hour (± 10 min) after dosing with LAM-002A 
10 
8 
1 hour (± 10 min) after dosing with LAM-002A 
11 
8 
2 hours (± 10 min) after dosing with LAM-002A 
12 
8 
4 hours (± 10 min) after dosing with LAM-002A  
13 
8 
6 hours (± 1 hr 10 min) after dosing with LAM-002A 
14 
8 
8 hours (± 10 min) after dosing with LAM-002A 
15** 
15 
Pre-dose (within 30 min prior to dose of LAM-002A) 
 
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Changes made in Amendment 2 (14 Oct 2015) 
 
Synopsis: updated dates for accrual 
Estimated date first subject enrolled: Sep Nov 2015 
Estimated date last subject completed: Jan Mar 2018 
 
Synopsis, Exploratory Objectives: Removed reference to PBMCs and added blood smear 
analysis. Added two exploratory objectives. 
 
To evaluate the pharmacodynamic effects of LAM-002A (apilimod dimesylate capsules), 
administered orally, on tumor samples and surrogate tissue (e.g., white blood cells in 
peripheral blood smears mononuclear cells [PBMC]). 
 
To evaluate tumor tissue for infiltrating immune cells in order to determine if LAM-
002A has potential positive benefit through immune modulation 
 
To evaluate plasma for changes in analytes that may predict anti-lymphoma activity. 
 
 
Synopsis, Pharmacokinetic Assessment: updated for addition of analyte analysis by proteomic 
methods. 
 
Pharmacokinetic and Analyte Assessment: 
 
 • 
Blood sampling for determination of the plasma concentrations of apilimod and its 
metabolites will be performed on Cycle 1 Day 1 and Cycle 1 Day 8 as follows: pre-dose, 30 
minutes, 1, 2, 4, 6, 8 hours post-dose. Cycle 1 Day 15 pre-dose only. For analyte 
determination, pharmacokinetic back-up sample will be used from time points: Cycle 1 
Day 1 and Cycle 1 Day 8 pre-dose. 
 
 
Synopsis, Biomarker Assessment: Removed reference to PBMCs and added blood smear 
analysis. 
 
•  Blood smears will be obtained for biomarker analysis on Cycle 1 Day 1 and Cycle 1 
Day 8 as follows: pre-dose, 4 and 8 hours post-dose; and Cycle 1 Day 15 pre-dose only. 
Samples will be analyzed by microscopy for changes in the extent of vacuolation in 
white blood cells as a phenotypic marker of phosphatidylinositol-3-phosphate- 5 kinase 
(PIKfyve) inhibition. PBMCs will be collected for biomarker analysis prior to the first dose, 
at the time of tumor assessment and at the EOT visit. Samples will be analyzed for 
Phosphatidylinositol 3 phosphate  5 kinase (PIKfyve) inhibition by an 
immunohistochemistry assay and/or extent of vacuolation by microscopy. 
 
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•  Tissue from the most recent available biopsy or surgery prior to first dose will be submitted 
for biomarker analysis and determination of immune cell infiltration to determine genetic 
alterations, or gene expression or immune markers that may predict response to apilimod. 
Although tumor samples are not required for enrollment of subjects, obtaining and 
submitting fresh or archival samples is strongly encouraged.  
 
•  A bone marrow aspirate (if positive at baseline) and core tumor biopsy will be obtained at 
the time of the first scheduled tumor assessment (end of Cycle 2). However, the requirement 
for core tumor biopsy may be waived for subjects whose tumor cannot be safely biopsied or 
for whom the investigator deems the procedure inappropriate. These tissues will be analyzed 
for inhibition of PIKfyveby an immunohistochemistry assay and measuring extent of 
vacuolation by microscopy. The biopsy tissue will also be submitted for 
immunohistochemistry to examine for presence of infiltrating immune cells (e.g., tumor 
infiltrating lymphocytes and tumor associated macrophages). Additionally, ribonucleic 
acid (RNA) will be collected from fresh samples for gene expression analysis. 
 
 
Synopsis, Investigational product, dosage and mode of administration: provide clarity on 
consumption of liquids 
 
Subjects will be advised to take the doses at the same time each day, approximately 12 hours 
apart on an empty stomach (no food within 2 hours prior to dose, or within 2 hours after 
dose, only clear liquids allowed in this time window). 
 
 
Section 4.1.1 Pharmacology: Updated with references for immunomodulatory properties of 
LAM-002A. 
 
Apilimod and apilimod dimesylate were originally introduced into clinical trials based on 
apilimod’s immunomodulatory properties (Wada 2007; Wada 2012). Apilimod inhibits the 
production of interleukin-12 (IL-12) and interleukin-23 (IL-23), and was effective in 
preclinical animal models of various autoimmune diseases that are mediated by the 
inappropriate expression of T-helper cell phenotype (Th1) cytokines (Wada 2007). 
 
 
Section 5.3, Exploratory Objectives: Updated for change in biomarker assessment. Added 
exploratory objectives. 
 
To evaluate the pharmacodynamic effects of LAM-002A (apilimod dimesylate capsules), 
administered orally on tumor samples and surrogate tissue (e.g., white blood cells in 
peripheral blood smears mononuclear cells). 
 
To evaluate tumor tissue for infiltrating immune cells in order to determine if LAM-
002A has potential positive benefit through immune modulation. 
 
To evaluate plasma for changes in analytes that may predict anti-lymphoma activity. 
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Section 5.6, Exploratory Endpoints: Updated for change in biomarker assessment 
 
Extent of PIKfyve inhibition and as determined by the extent of vacuole formation in tumor 
tissue and white blood cells in peripheral blood smears mononuclear cells (PBMCs) by 
immunohistochemical and microscopic evaluation. Assay, respectively 
 
Extent of immune cell infiltration as determined by immunohistochemistry in tumor 
tissue. 
 
Correlation between changes in plasma bioanalytes and antilymphoma activity 
following treatment with LAM-002A as determined by proteomic tools. 
 
 
Section 6.9, Schedule of Assessments: time points updated and exploratory biomarkers added in 
table and footnote n, q, r 
 
n For analyte determination, PK back-up sample will be used from time points: Cycle 1 
Day 1 and Cycle 1 Day 8 pre-dose. 
 
q The biopsy tissue will also be examined for presence of infiltrating immune cells. 
 
r PBMCs Blood smears will be collected for biomarker analysismicroscopic evaluation of 
vacuole formation on C1D1 and C1D8 as follows: pre-dose, 4 hrs and 8 hrs post first 
dose of the day. C1D15 pre-dose only. Prior to the first dose, at the time of tumor 
assessment and at the end of treatment visit. 
 
Section 7.3.3., LAM-002A (Apilimod Dimesylate Capsules) Self-Administration Dosing Diary: 
added details regarding pre- and post-dose liquid consumption. 
 
Subjects should not eat within 2 hours prior to taking their dose or within 2 hours after taking 
their dose, with no solid dietary restrictions otherwise. Clear liquids are allowed within the 
+/- 2 hour fasting window.  
 
Section 8.8, Treatment Compliance 
 
Subjects will be asked to bring their study medication container and dosing diary with them at 
each visit. Compliance with protocol-defined study drug intake will be checked by pill count at 
the end of each cycle and compliance decisions will be made by the investigator. 
 
Section 9.4, Study Drug Administration: provide clarity regarding consumption of liquids 
 
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Subjects should not eat within 2 hours of or within 2 hours after dose administration; no solid 
dietary restrictions otherwise. Subjects may consume clear liquids in the 2-hour pre- and 
post-dose window.  
 
Section 9.5, Study Drug Accountability: provide clarity on return of study drug 
 
Subjects should be instructed to bring all bottles, including empty bottles, to each subsequent 
Day 1 or End of Treatment study visit for a compliance and product accountability check. 
 
Section 12, Pharmacokinetic Assessments: provide clarity regarding consumption of liquids 
 
Subjects are allowed to eat after PK Sample #4 (hour 2) has been collected. Subjects may 
consume clear liquids during fasting periods. 
 
Section 13, Biomarker Assessments: updated with exploratory biomarker information. 
 
Blood smears will be obtained for biomarker analysis on C1D1 and C1D8 as follows: 
pre-dose, 4 and 8 hours post-first dose of the day and C1D15 pre-dose only. Samples 
will be analyzed for PIKfyve inhibition as determined by the extent of vacuolation by 
microscopy. PBMCs will be collected for biomarker analysis prior to the first dose, at the 
time of tumor assessment and at the EOT visit. Samples will be analyzed for PIKfyve 
inhibition by an immunohistochemistry assay and/or extent of vacuolation by microscopy. 
 
Tissue from the most recent available biopsy or surgery prior to first dose will be submitted 
for biomarker analysis to determine genetic alterations or gene expression and 
determination of immune cell infiltration that may predict response to LAM-002A 
(apilimod dimesylate capsules). Although tumor samples are not required for enrollment of 
subjects, obtaining and submitting fresh or archival samples is strongly encouraged. Plasma 
bioanalytes will be examined by proteomic technology at Cycle 1 Day 1 and Cycle 1 Day 
8 to determine changes that may predict response to LAM-002A. 
 
These tissues will be analyzed for inhibition of PIKfyve by an immunohistochemistry assay 
and measuring the extent of vacuolation by microscopy. Tissue will also be analyzed by 
immunohistochemistry for determination of the extent of immune cell infiltration 
(tumor infiltrating lymphocytes, tumor associated macrophages).  
 
Section 21, List of References: References added.  
 
Wada Y, Lu R, Zhou D, Chu J, Przewloka T et al. Selective abrogation of Th1 response 
by STA-5326, a potent IL-12/IL-23 inhibitor. Blood 2007;109:1156-1164. 
 
Wada Y, Cardinale I, Khatcherian A, Chu J et al. Apilimod inhibits the production of 
IL-12 and IL-23 and reduces dendritic cell infiltration in psoriasis. 2012; PloS ONE 
7(4): e35069. 
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Section 4.1.1 Pharmacology 
Change:   A paragraph has been added justifying the scientific basis for collection of pre-
treatment tumor biopsy material. 
LAM Therapeutics has also performed research into the mechanism of action of apilimod 
cytotoxicity in cancer cells. Putative genes that confer sensitivity / resistance to apilimod 
have been identified and will be evaluated as potential biomarkers for predicting apilimod 
efficacy.  
Section 5.3 Exploratory Objectives 
Change:  The objectives have been updated to reflect discontinuation of the plan for on-
treatment tumor biopsies and to clarify the types of assessments that will be done in 
surrogate and normal tissues and plasma to assess drug effects. 
•
To evaluate the pharmacodynamic effects of LAM-002A (apilimod dimesylate
capsules), administered orally, on surrogate tissue (e.g., vacuoles in peripheral blood
smears, gene expression in peripheral blood mononuclear cells [PBMCs], and plasma
cytokines [including (IL)-12 and IL-23]).
•
To evaluate tumor for gene expression and genetic alterations (with saliva collection
for germ-line control); and surrogate tissue (PBMC) for gene expression that may
predict anti-lymphoma activity.
•
To evaluate the pharmacodynamic effects of LAM-002A (apilimod dimesylate
capsules), administered orally, on tumor samples and surrogate tissue (e.g., white
blood cells in peripheral blood smears).
•
To evaluate tumor tissue for genetic alterations and/or gene expression that may
predict anti-lymphoma activity.
•
To evaluate tumor tissue for infiltrating immune cells in order to determine if LAM-
002A has potential positive benefit through immune modulation
Section 5.5 Secondary Endpoints 
Change:  A additional citation for a reference describing changes to the Hallek criteria has 
been included 
•
Response as assessed by the investigator according to modified Lugano Response 
Criteria for NHL (Cheson 2014) and revised guidelines for the diagnosis and 
treatment of CLL (Hallek 2008, Cheson 2012).
Section 5.6 Exploratory Endpoints 
Change:  The exploratory endpoints have been updated to match the updated exploratory 
objectives. 
•
Extent of PIKfyve inhibition as determined by the extent of vacuole formation in
tumor tissue and white blood cells in peripheral blood smears by microscopic
evaluation.
•
Changes in gene expression in PBMCs
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• Changes in plasma cytokines (including IL-12 and IL-23). 
• Correlation between genetic alterations as determined by next generation sequencing 
and/or gene expression in tumor tissue or PBMCs and anti-lymphoma activity 
following treatment with LAM-002A (apilimod dimesylate capsules).  
• Extent of immune cell infiltration as determined by immunohistochemistry in tumor 
tissue. 
• Correlation between changes in plasma bioanalytes and antilymphoma activity 
following treatment with LAM-002A as determined by proteomic tools. 
Section 6.2  Number of Subjects 
Change:  The text has been altered for consistency with amendments to the definitions of 
evaluability in other sections of the protocol document. 
Approximately 75 evaluable subjects (evaluable subjects include those who complete Cycle 1 
dosing [administered at least 7580% of doses] and have sufficient safety data, or who are 
withdrawn from the study due to a DLT in Cycle 1) will be enrolled, assuming that: 
Section 6.4 Treatment Assignment 
Change: 
The description of the enrollment procedures has been updated consistent with 
current study procedures. 
Ce3 will conduct a preliminary review of the subject’s eligibility form to and in consultation 
with the medical monitor confirm each subject’s eligibility and will complete the enrollment 
form with treatment cohort, treatment dose and frequency). The enrollment form will be signed 
and a copy sent to the study site. Once the site receives the completed enrollment form, the 
subject will begin treatment accordingly. The treatment will be conducted in an open-label 
manner. Study sites cannot start dosing the subject without receiving the assigned dose on the 
returned Subject Enrollment and Eligibility Formsubject number first.  
Section 6.4.1.2 Treatment Period 
Change:  The text has been updated for consistency with other sections of the protocol that now 
indicate the full list of reasons for treatment discontinuation. 
The subject is treated and monitored for safety (including assessments of AEs, vital signs, ECGs, 
laboratory tests and concomitant medications). Additionally, preliminary anti-tumor activity will 
be assessed and PK and biomarker samples will be collected. In the absence of progressive 
disease (PD) and/or intolerable toxicityprotocol-defined reasons to discontinue therapy, 
subjects may continue to receive study treatment for up to 1 year at the discretion of the 
investigator and beyond 1 year with the agreement of the investigator and the sponsor. 
Section 6.4.1.3 Post-Treatment Period 
Change:  The text has been clarified to separate the end-of-treatment (EOT) visit from the post-
treatment period and to specify the nature of the follow-up required in the post-
treatment period. 
Subjects should be followed until the later of either 30 days after the last dose of study 
treatment or until resolution/stabilization of any ongoing drug-related AEs and/or SAEs. 
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For subjects with events that require follow-up, information regarding concomitant 
medications should be collected. Any necessary follow-up may be obtained in person or by 
telephone contact. 
The subject returns to the study site 30 37 days after the last dose of LAM 002A (apilimod 
dimesylate capsules) for an EOT assessment. All serious treatment emergent AEs and those AEs 
assessed by the investigator as related to study drug should continue to be followed until they 
resolve or stabilize, whichever comes first. 
Section 6.5 Dose Escalation Procedures 
Changes:  The text has been reorganized so as to use a consistent approach in both the synopsis 
and body of the protocol in presenting dose escalation information.  
 
For clarity, additional information regarding the dose levels to be studied is now 
provided.  
 
The DLT criterion relating to the required amount of first-cycle therapy has been 
made more specific to enhance interpretability. 
Subject enrollment will proceed according to a 3 + 3 design. The starting dose of LAM 002A 
(apilimod dimesylate capsules) will be 50 mg administered orally BID. In the absence of DLT, 
subsequent dose levels will increase sequentially according to Table 3, adjusted to accommodate 
available capsule strengths.  
Apilimod dimesylate will be administered on a twice daily (BID) oral dosing regimen with a 
cycle length of 28 days. Subjects will be advised to take the doses at the same time each day, 
approximately 12 hours apart. Less dose intensive schedules may be considered if the initial 
BID regimen’s safety, PK and/or pharmacodynamics suggest that a different schedule would be 
better tolerated and might allow for serum exposures required for anti-lymphoma activity. This 
might include a treatment break such as 3 weeks on/1 week off treatment or 5 days on/2 days off 
over a 4 week cycle or an asymmetric (AM dosing > PM dosing) or once-daily dosing schedule. 
If a less dose-intensive treatment regimen is evaluated, then the initial dose tested on this 
schedule will be a daily dose that has been previously evaluated and tolerated on the more dose-
intensive, BID schedule.  
Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher starting dose 
levels of apilimod dimesylate, as indicated in Table 2.The initial cohort of subjects will be 
prescribed apilimod dimesylate at Dose Level 0 (50 mg BID). Dose level -1 (25 mg BID) is 
provided to permit a dose decrement in subjects experiencing DLT at Dose Level 0. 
Table 2: 
Provisional Dose Levels 
 
Daily LAM-002A Dose  
Percent Increase  
Initial Cohort Size 
-1 
25 mg BID 
-50 
3 
0 
50 mg BID 
Starting dose 
3 
1 
100 mg BID 
100 
3 
2 
150 mg BID 
50 
3 
3 
200 mg BID 
33 
3 
4 
275 mg BID 
37.5 
3 
Abbreviations: BID: Twice daily (or 2 times a day) 
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A 3 + 3 design will be utilized to define an MTD. For cohorts consisting of 3 subjects, dose 
escalation to the next higher dose may proceed if no DLT is observed within the first cycle of the 
3 evaluable subjects accrued to a cohort (See Section 6.1.1). If 1 of 3 subjects in the cohort 
experiences a DLT, up to a total of 6 evaluable subjects will be enrolled. If 2 or more of the 3-6 
evaluable subjects in a cohort experience a DLT, dose escalation will cease, and additional 
subjects will be treated at a lower dose level. If de-escalation to the previous dose cohort is 
undertaken, this cohort will be expanded to 6 subjects. The MTD is defined as the highest dose at 
which no more than 1 of 6 subjects (i.e., < 33%) experiences a DLT in the dose cohort. 
Dose escalation decisions will be evaluated in a DLT evaluable population. The DLT evaluable 
population will include subjects who complete Cycle 1 dosing or who are withdrawn from study 
due to a DLT in Cycle 1. A subject will be deemed non-evaluable for determining DLTs and will 
not be counted toward the total cohort size if the subject did not experience a DLT, did not 
receive at least 75% (42/56) of the 80% of their assignedplanned first-cycle doses or 
discontinued from the study prior to completing necessary safety evaluations through the first 28 
days of study treatment. These subjects may be replaced unless accrual to the cohort has stopped 
due to DLT. 
Section 6.6. Treatment Guidelines 
Changes: Instructions for TLS prophylaxis have been included as a safeguard should this 
appear as a drug-related adverse event.  
 
Information regarding study drug administration has been moved from a later section 
of the protocol to consolidate instructions regarding study treatment in one section of 
the protocol.  
 
Because food does not appreciably influence study drug absorption, subjects will not 
be limited to ingestion of the drug under fasting conditions except on specified days of 
intensive PK monitoring.  
 
Information regarding management of interruptions in scheduling and vomited doses 
is provided in more detail.  
 
The dose modification criteria for the protocol have been clarified. In particular, the 
dose modification rules have been updated to provide consistent practice relating to 
dose modification for DLT in both Cycle 1 and later cycles. This approach permits 
patients the maximal opportunity to derive clinical benefit.  
 
Mandatory discontinuation criteria are removed consistent with other changes to the 
dose modification criteria. These intent is to allow the investigators and medical 
monitor to judge the clinical significance of each event relative to the potential 
clinical benefit being experienced by the patient in determining whether continued 
therapy is appropriate. 
 
Typographical errors in the DLT criteria have been corrected, the criterion for 
neutropenic DLT has been made more stringent by the omission of growth factors 
from the definition, and the hepatic DLT criteria have been made more stringent by 
the addition of substantial elevations in AST as a laboratory event of potential 
concern.  
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Criteria regarding required durations of first-cycle exposure as components of DLT 
have been made more specific for clarity and interpretability. 
6.6.1. 
Tumor Lysis Syndrome (TLS) Prophylaxis 
The risk for TLS should be considered based on established algorithms (Cairo 2010, MDACC 
2013, Roberts 2016): 
• Low-risk: Serum LDH ≤ ULN, all measurable lymph nodes < 5 cm, and absolute 
lymphocyte count (ALC) < 25 × 109/L 
• Intermediate risk: Serum LDH > 1 to ≤ 2 × ULN, ≥ 1 measurable lymph node with an 
LD of ≥ 5 but < 10 cm, or ALC ≥ 25 × 109/L 
• High risk: Serum LDH > 2 × ULN, ≥ 1 measurable lymph node with a LD of ≥ 10 cm, 
or both ≥ 1 measurable lymph node with an LD of ≥ 5 but < 10 cm and 
ALC ≥ 25 × 109/L 
If, during the dose escalation it is observed that the study drug appears to induce TLS, 
subsequent subjects who are at risk should be considered for medical prophylaxis of TLS 
and according to local prevention paradigms. Alternatively, investigators may wish to 
consider the following regimens for prophylaxis in subjects at intermediate or high risk of 
TLS: 
• Intermediate Risk of TLS: These subjects can receive allopurinol, 100 to 300 mg orally 
every 8 hours starting ≥ 24 to 48 hours before the initial administration of apilimod 
dimesylate on Cycle 1-Day 1 of therapy; in addition, subjects who develop 
hyperuricemia should receive rasburicase, 0.2 mg/kg. 
• High Risk of TLS: These subjects can receive allopurinol, 100 to 300 mg orally every 
8 hours starting ≥ 24 to 48 hours before the initial administration of apilimod 
dimesylate on Cycle 1-Day 1 of therapy; in addition, high-risk subjects can receive 
rasburicase, 0.2 mg/kg, administered 3 to 4 hours prior to the first dose of apilimod 
dimesylate. 
Information regarding the management of TLS is provided in Section 8.6.1. 
6.6.2  Description of Study Drug 
LAM-002A (apilimod dimesylate capsule) is intended for oral administration. Each capsule 
will contain 25 mg of apilimod dimesylate (equivalent to 17.1 mg apilimod free base) and 
the total fill weight of each capsule will be 175 mg. LAM-002A is formulated as a blend 
with excipients in Size 0 Swedish Orange gelatin capsules. For additional information, see 
Section 9.1. 
6.6.3 
In-Clinic LAM-002A (Apilimod Dimesylate Capsules) Administration  
On Cycle 1 Day 1, and Cycle 1 Day 8 the dose of LAM-002A (apilimod dimesylate capsules) 
should be orally administered (a minimum fasting state of 6 to 8 hours) by site staff 
immediately after the collection of the biomarker samples and pre-dose PK sample. 
Subjects are allowed to eat after PK Sample #4 (hour 2) has been collected. On Cycle 1 Day 
15, the dose of LAM-002A (apilimod dimesylate capsules) should be orally administered (a 
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minimum fasting state of 6 to 8 hours) by site staff immediately after collection of the pre-
dose PK and biomarker samples.  
6.6.4 
LAM-002A (Apilimod Dimesylate Capsules) Self-Administration  
Except for the days where treatment is administered in the clinic, LAM-002A (apilimod 
dimesylate capsules) will be self-administered orally, BID of each 28-day cycle until disease 
progression or other discontinuation criteria are met. Subjects should be advised to take 
study drug with ≥ 4 oz. (~160 mL) of water at the same time each day, 12 hours apart (e.g., 
8 AM and 8 PM) (+/- 1 hour window). When self-administering the study drug at home, 
subjects may take the drug in the fed or fasted state. On PK days, subjects should come to 
clinic fasted (a minimum fasting state of 6 to 8 hours) and take the dose at the site under 
supervision. All subjects will be required to complete a Dosing Diary, which must be 
returned to the site for review at each site visit. 
6.6.5 Dose Schedule Interruptions and Vomited Doses 
Subjects who have a delay in administration of a dose of apilimod dimesylate of <6 hours 
should take the planned dose as soon as possible after the intended time of administration. 
For subjects who have a delay in administration of apilimod dimesylate of ≥ 6 hours, the 
dose should not be taken. The planned timing of subsequent apilimod dimesylate dosing 
should not be altered.  
For subjects who vomit shortly after taking apilimod dimesylate, the vomited dose should 
not be replaced. The planned timing of subsequent apilimod dimesylate dosing should not 
be altered. 
6.6.6. Dose Modifications 
If a subject experiences an AE that is suspected to be related to apilimod dimesylate, 
appropriate supportive care (e.g., antiemetics, antidiarrheals, therapy for tumor lysis 
syndrome [TLS]) should be instituted consistent with the nature of the event.  
If a subject experiences an apilimod dimesylate-related DLT (reference Table 3), then the 
study drug administration should be interrupted until the toxicity recovers to Grade ≤ 1 or 
baseline. Upon resumption of study drug, the dose of apilimod dimesylate should be 
reduced by 1 dose level (reference Table 3). Successive adjustments to progressively lower 
dose levels can be made. If the subject cannot tolerate apilimod dimesylate after a decrease 
to Dose Level -1 (25 mg BID), then the subject should be discontinued from apilimod 
dimesylate therapy unless continued treatment is permitted by the medical monitor.  
After the apilimod dimesylate dose is reduced, the dose can be maintained at that dose 
level, even if there is minimal or no toxicity with the reduced dose. However, if the subject 
tolerates a reduced dose of apilimod dimesylate for ≥ 4 weeks then the apilimod dimesylate 
dosing regimen may be reescalated to the next higher dose level at the discretion of the 
investigator. Such reescalation may be particularly warranted if the AE comprised TLS or 
if further evaluation reveals that the AE that led to the dose reduction was not related to 
apilimod dimesylate. Successive adjustments to progressively higher dose levels can be 
made. However, the escalated dose cannot exceed the starting dose level for that subject 
during the first 4 cycles of therapy.  
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Individual subjects who initiated treatment at a dose level below the lower of the currently 
established MTD or the RP2D and who have not experienced a DLT after ≥ 4 cycles of 
treatment may have the apilimod dimesylate dose escalated to the next higher dose level if 
both the principal investigator and the medical monitor agree that a dose escalation is 
medically warranted (e.g., for a subject with stable disease who is tolerating the current 
dose level of apilimod dimesylate therapy). In such subjects, successive adjustments to 
progressively higher dose levels can be made at intervals of ≥ 4 weeks with the condition 
that the escalated dose level cannot exceed the lower of the currently established MTD or 
RP2D.  
In a subject who experiences a DLT precluding resumption of apilimod dimesylate therapy 
during a cycle, a new cycle of treatment may begin at the later of Day 29 or when AEs or 
laboratory abnormalities related to apilimod dimesylate have returned to baseline levels. If 
drug-related AEs or laboratory abnormalities precluding further administration of study 
drug are not resolved to baseline by Day 29, week-by-week delays in initiating the new 
cycle of treatment should be instituted. When all drug-related AEs and laboratory 
abnormalities have returned to baseline, the next cycle of therapy can be initiated. Upon 
initiation of a new cycle of therapy, the prior cycle of therapy will be considered completed. 
Investigators are to discuss modifications in the dosing regimen with the medical monitor. 
The appropriate clinic staff should dispense the study drug for the new dose level and 
instruct the subject/caregiver about the change in dose level. 
During a cycle of treatment, study drug should continue to be administered as planned unless a 
DLT has occurred. 
6.6.2 
New Cycle of Therapy Guidelines 
In the absence of otherwise dose limiting toxicity (DLT), in order for a subject to begin a new 
cycle of therapy, the following criteria must be met on Day 1 of the new cycle. 
• Absolute neutrophil count (ANC) must be ≥ 1.0 x109/L (1,000/mm3) 
• Platelet count must be ≥ 75 x 109/L (75,000/mm3) 
• All non-hematologic toxicities considered related to study treatment must be 
≤ Grade 1 (except alopecia) or returned to baseline. 
If the subject does not meet these criteria, dosing will be delayed and the subject should be re
evaluated within 48 
 72 hours. Dosing may resume if these criteria have been met. However, if 
the next cycle is delayed by > 14 days because of insufficient recovery from a treatment related 
toxicity, this will be considered a dose limiting event (See Section Deleled). If the next cycle is 
delayed due to treatment related toxicity by > 21 days, then the subject must be removed from 
study treatment.  
6.6.3 6.6.7  
Definition of Dose-Limiting Toxicity (DLT) 
A DLT will be defined as an AE or abnormal laboratory value meeting the criteria in Table 3 and 
that is assessed as unrelated to disease, a comorbid condition, intercurrent illness, or 
concomitant medications. For the purposes of dose escalation and determination of the MTD, 
DLTs that occur within the first cycle of treatment must be included in decisions regarding dose 
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escalation. DLTs or other clinically significant toxicities that occur after Cycle 1 may also be 
considered when determining the MTD/RP2D. 
If at any time during the study a subject experiences a DLT, the study treatment must be stopped 
and the toxicity in question must be followed until resolution or stabilization. If treatment is to be 
resumed then re initiation criteria must be met and administration must be resumed at a lower 
dose (Section 6.6.4). 
Table 3: 
Criteria for Defining Dose Limiting Toxicities (DLTs) 
Toxicity 
Criteria 
Hematology 
CTCAE Grade 4 neutropenia lasting > 5≥ 7 days despite growth factor support 
CTCAE Grade 4 febrile neutropenia  
CTCAE Grade 3 thrombocytopenia with bleeding that requires transfusion 
therapy 
CTCAE Grade 4 thrombocytopenia  
Gastrointestinal 
≥ CTCAE Grade 3 vomiting or nausea despite the use of optimal anti-emetic 
treatments 
≥ CTCAE Grade 3 diarrhea despite the use of optimal anti-diarrheal treatments 
Renal 
Serum creatinine > 3.0 x ULN 
Hepatic* 
Total bBilirubin ≥ CTCAE Grade 3.0  
Total bBilirubin ≥ CTCAE Grade 2.0 and ALT or AST ≥ CTCAE Grade 2  
or,  
for subjects with liver metastases at baseline, total bBilirubin ≥ 2.0 x ULN and 
ALT or AST ≥ CTCAE Grade 3  
Treatment 
interruption/delays 
Inability to administer ≥ 28/56 planned apilimod dimesylate doses in a 
treatment cycle due to drug-related AEs 
or 
Failure to recover from apilimod-dimesylate-related toxicities to baseline 
within 14 days from the last dose of study drug in a cycleTreatment 
interruption caused by LAM 002A (apilimod dimesylate capsules) related 
toxicity causing > 14 days of missed dosing during a cycle  
or 
Treatment delays by LAM 002A (apilimod dimesylate capsules) related toxicity 
causing > 14 days in the start of a subsequent cycle of treatment 
Other adverse events 
not listed above 
Non-hematologic toxicities of CTCAE ≥ Grade 3 except for the following. 
• 
alopecia 
• 
CTCAE Grade 3 fatigue for < 72 hours  
• 
Asymptomatic Grade 3 elevations in biochemistry laboratory values that 
last for ≤ 7 days that are not deemed to be clinically relevant. This 
includes electrolyte abnormalities that respond to medical intervention 
Any LAM-002A (apilimod dimesylate capsules)-related adverse event that, in the 
opinion of the investigator, requires a dose reduction or discontinuation of 
treatment. 
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* For any dose-limiting hepatic toxicity that does not resolve within 7 days to baseline, an abdominal CT scan must 
be performed to assess whether it is related to disease progression. 
 
Repeat testing of a blood sample or procedure (e.g., ECG) is required to confirm any laboratory abnormality that 
meets the definition of a DLT. 
 
Note: Known oncologic emergencies from NHL (e.g., tumor lysis syndrome, spinal cord compression, ureteric 
obstruction, lymphomatous meningitis, and superior vena cava syndrome) will not be considered as dose-limiting 
toxicities. 
 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CTCAE: Common terminology 
criteria for adverse events; DLT: Dose-limiting toxicity; ECG: Electrocardiogram; NHL: Non-Hodgkin’s 
lymphoma; ULN: Upper limit of normal 
 
6.6.4 6.6.8 Follow-up for DLTs and AEs Leading to Discontinuation 
Subjects who experience a non-laboratory DLT must be evaluated weekly, at a minimum, for 
4 weeks until resolution to ≤ Grade 1 or baseline and then at least monthly until return to 
baseline or stabilization of the event, whichever comes first. For abnormal laboratory values that 
qualify as a DLT, subjects will initially be followed at least twice weekly until values resolve to 
≤ Grade 2 or return to baseline. If not resolved or stabilized within 2 weeks then subjects should 
be followed at least weekly until return to baseline or stabilization, whichever comes first. 
Subjects who discontinue the study for a study-related AE or an abnormal laboratory value must 
be followed at least once a week for 4 weeks, and subsequently at 4-week intervals until 
resolution or stabilization of the AE or laboratory abnormality, whichever comes first.  
QTc: An immediate evaluation by a qualified site physician should be conducted for any subject 
with a new Fridericia correction formula (QTcF) > 500 msec. Following the event, the subject 
should be monitored by the investigator with hourly ECGs until the QTcF is ≤ 500 msec and the 
QTcF has returned to < 30 msec from baseline. A blood sample should be obtained as soon as 
possible following the observation of a QTc > 500 msec to determine levels of potassium and 
magnesium as well as evaluation of circulating apilimod. Management of abnormal potassium 
and magnesium levels as well as other clinical factors such as oxygenation should be addressed 
immediately.  
Upon resolution of the QTc event, the decision to continue treatment at a reduced dose requires 
discussion between the investigator and the subject, and the investigator and the sponsor. 
6.6.5 
Criteria for Re initiation of Therapy Following Occurrence of a DLT After Cycle 1 
Study treatment will be stopped if a subject experiences a DLT (See Section Deleted) at any time 
during the study. Additional AE management is provided in Section 8.6.1. Study treatment may 
resume, except as noted under “Discontinuation of therapy due to treatment related toxicity”, 
with applicable dose adjustments if the following criteria are met: 
• ANC must be ≥ 1.0 x109/L (1,000/mm3) 
• Platelet count must be ≥ 75 x 109/L (75,000/mm3) 
• All other non-hematologic treatment-related toxicities must be ≤ Grade 1 (except 
alopecia) or returned to baseline. 
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6.6.6 
Dose Modification Guidelines 
6.6.6.1 Dose Reductions Following DLTs  
Subjects who experience a DLT (See Section Deleted) in Cycle 1 will be discontinued from 
treatment. However, subjects who develop a DLT in subsequent cycles of treatment may 
continue treatment at a reduced dose level (a minimum reduction of at least one dose level) if the 
following criteria are met: 
• the AE reverts to baseline or ≤ Grade 1 within 21 days, 
• the subject is clearly deriving clinical benefit, and  
• the subject has an otherwise favorable risk/benefit profile 
The decision to continue treatment at a reduced dose requires discussion between the investigator 
and the subject, and the investigator and the sponsor.  
Once a dose level reduction has occurred, subjects will continue to receive this reduced dose. See 
Section 8.6.1 for the management of toxicities. 
6.6.6.2 Discontinuation of Therapy Due to Treatment related Toxicity  
Study treatment should not be resumed in the case of the following treatment related events: 
• Occurrence of a DLT in Cycle 1 (including > 14 day dose delay secondary to 
insufficient recovery from a treatment-related toxicity) 
• ≥ Grade 3 cardiac event 
• Non-hematologic events of Grade 4 severity 
• > 21 day dose delay due to a treatment-related event in Cycle 2 and beyond. 
See Section Deleted for the management of toxicities 
6.6.7 6.6.9 Duration of Subject Participation 
All subjects will be treated for at least 1 cycle unless there is evidence of unacceptable toxicity or 
PD. Although subjects may continue to receive study treatment until experiencing unacceptable 
toxicity or disease progression, it is estimated that each subject will participate for an average of 
6 months of treatment and an additional 1 month of follow-up. Subjects who have discontinued 
study treatment for reasons other than PD will be assessed per Revised Response Criteria for 
NHL or Guidelines for the diagnosis and treatment of CLL at a minimum of every 12 weeks 
until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (Cycle 1 Day 1), whichever comes first.  
Section 6.7. 
Criteria for Study Termination 
Change: 
Treatment withdrawal criteria have been updated for clarity and interpretability. 
The sponsor may terminate this study at any time, provided a written notice is submitted at a 
reasonable time in advance of the intended termination. 
Subjects may be withdrawn from further study treatment for any of the following reasons: 
• Subject withdrawal of informed consent 
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• Disease progression of cancer while receiving study therapy Note: Apparent 
worsening of disease during temporary interruption of study therapy (e.g., for drug-
related toxicity or intercurrent illness) may not indicate true cancer progression. Study 
subjects undergoing PET for lymphoma assessment can experience transient disease 
flare on imaging before having subsequent therapy-induced tumor regression. 
Worsening of constitutional symptoms or performance status in the absence of 
objective evidence of worsening lymphoma (e.g., due to infection) may not represent 
definitive disease progression. For these reasons, if there is uncertainty regarding 
whether there is true disease progression and if medically appropriate, the subject 
may continue or resume study treatment and remain under close observation (e.g., 
evaluated at 4- to 8-week intervals) while relevant radiographic, clinical, and/or 
laboratory assessments are performed to document whether tumor control can be 
maintained or whether disease progression has truly occurred. If subsequent 
evaluations suggest that the subject has experienced persistent definitive disease 
progression, then the date of progression will be the timepoint at which progression 
was first objectively documented.  
• Unacceptable study-drug-related toxicity despite appropriate dose modification 
• Development of intercurrent illness that precludes continued study therapy 
• Physician decision if that continuation is not in the subject’s best interest 
• Treatment of the cancer with another therapeutic regimen 
• Subject becomes pregnant or begins breastfeeding 
• Substantial noncompliance with study drug administration, study procedures, or study 
requirements in circumstances that increase risk or substantially compromise the 
interpretation of study results 
• Termination of the study by the sponsor, relevant regulatory agencies, or the IRB/IEC 
The investigator must determine the primary reason for a subject’s withdrawal from the study 
and record this information on the electronic case report form (eCRF). 
Section 6.9. 
Schedule of Assessment 
Changes: The table has been corrected to include screening viral serology. 
 
The request for an on-study tumor biopsy has been removed. 
 
Confirmation of eligibility need not occur precisely on Day 1; thus, the relevant 
footnote has been changed to indicated that it must occur by Day 1. 
 
The enrollment criteria have been modified to only include subjects with measurable 
lymphadenopathy and so caveats relating to subjects with CLL without adenopathy 
have been removed because they are no longer applicable. 
 
Greater specificity have been provided in the baseline peripheral blood or bone 
marrow aspirate assessments required for subjects with CLL/SLL in order to ensure 
clarity regarding the studies to be performed. 
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The requirements for baseline and follow-up bone marrow analyses have been 
clarified. 
 
The procedures for baseline acquisition of tumor tissue in study candidates have been 
updated and clarified. The request for an on-study tumor biopsy has been removed. 
 
Assessment of changes in circulating cytokines has been added. 
 
One-time, baseline collection of blood or saliva has now been included to obtain a 
normal-tissue control for mutation studies in tumors. 
 
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6.9 
Schedule of Assessments 
Table 4: 
Schedule of Assessments 
 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle 3 and Beyond 
End of 
Treatment 
(EOT) 
Day 
Day 
Day 
-28 to -1 
1 
8 
15 
1 
8 
15-28 
1 
15-28 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Signs and Symptoms, PEb 
X 
Xc 
 
 
X 
 
 
X 
 
X 
ECOG Performance Status 
X 
Xc 
 
 
X 
 
 
X 
 
X 
Vital signs 
X 
Xd 
Xd 
Xd 
X 
 
 
X 
 
X 
ECG 
X 
Xd 
Xd 
Xd 
X 
 
 
X 
 
X 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Serum chemistryf, g 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
Coagulation 
X 
Xc 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
X 
 
 
X 
 
X 
Pregnancy testingi 
X 
Xi 
 
 
X 
 
 
X 
 
X 
PET/CT or CT (or MRI) scans (based on 
indication) for Response Assessment 
Xj 
 
 
 
 
 
Xk 
 
Xk 
Xl 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
PK samplingn + Analyte 
 
X 
X 
X 
 
 
 
 
 
 
Bone marrow aspirate/biopsy 
Xo 
 
 
 
 
 
Xp, q 
 
Xp 
 
Biomarker – tumor tissue 
Xq 
 
 
 
 
 
Xq 
 
 
 
Biomarker – blood smearsr 
 
X 
X 
X 
 
 
 
 
 
 
Biomarker – plasma cytokiness 
 
X 
X 
X 
 
 
 
 
 
 
Biomarker – PBMCt 
 
X 
X 
 
 
 
 
 
 
 
Biomarker – salivau 
 
X 
 
 
 
 
 
 
 
 
Response Assessment 
 
 
 
 
 
 
Xk 
 
Xk 
 
LAM-002A administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Adverse events 
 
Throughout Study 
Concomitant medicationsv 
 
Throughout Study 
a Eligibility will be confirmed byon Cycle 1 Day 1. 
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B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the start of 
each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D 
Obtained on Day 1 prior to dosing for all Cycles. For C1D1 and C1D8 obtained prior to dosing and 1 h (± 15 min after dosing), 2 hrs (± 30 min), 4 hrs (± 
1h), and 8 hrs (± 1h) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F All hematology and chemistry laboratory parameters should be assessed at Screening and Days 1, 8, and 15 of Cycles 1 and 2 and then at least once prior to 
the start of all subsequent cycles (within 72 hrs) and at EOT. These parameters may be obtained within 72 hours prior to the planned day of collection. 
Abnormal test values should be monitored per protocol guidance. 
G 
Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H 
Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be 
obtained within 72 hours prior to the planned day of collection. 
I Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of Day 
1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to screening 
and within 30 days before first dose may be used for baseline tumor assessments 
k Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as appropriate 
for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 months until PD or use of 
alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may be every 6 months. For subjects with 
CLL without nodal disease, splenomegaly or masses on baseline imaging, CT surveillance will not be required except for confirmation of CR. Also sSubjects 
with CLL who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. 
Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict 
anticancer activity and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample to 
be evaluated at a sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q 
deletion, 13q deletion, 17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL 
[e.g., Notch]; flow cytometry [for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], and/or β2-
microglobulin).  Baseline assessments for subjects with CLL include DAT, quantitative immunoglobulins, FISH panel, flow cytometry, and β2 microglobulin. 
All subjects with CLL/SLL must have baseline iImaging (with CT scans [preferred] or MRI scans) and bone marrow biopsy will be performed as 
indicated.  
N 
Blood sampling for determination of the plasma concentrations of apilimod and metabolites will be performed on C1D1 and C1D8 as follows: pre-dose, 
30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. C1D15 pre-dose only. Additional PK samples will be collected, if possible, whenever a subject has a 
study treatment-related SAE or QTc > 500 msec. Subjects are required to come to the study site in a fasting state prior to the collection of certain PK samples. 
For analyte determination, PK back-up sample will be used from time points: Cycle 1 Day 1 and Cycle 1 Day 8 pre-dose. 
O 
Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, 
bBaseline bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management. For subjects with 
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CLL/SLL, a baseline bone marrow aspirate is required unless the presence of sufficient circulating cells in the peripheral blood (e.g., ALC ≥ 10 x 
109/L) permits assessment of baseline parameters as described in Footnote m, above. 
P If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and 
physical examination. Repeat bone marrow aspirate/biopsy is only required to confirm response as applicable. 
Q 
Archival or fresh tumor tissue from the most recent available biopsy or surgery prior to first dose in subjects with NHL must be obtained 
pretreatment. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle 
biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic 
alterations and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, for subjects with NHL, 
tumor may be evaluated for known prognostic characteristics (e.g., for DLBCL:  ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and 
MYC; other mutational status). The baseline biopsy procedure (if required) should be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participation.  
R Blood smears will be collected for microscopic evaluation of vacuole formation on C1D1 and C1D8 as follows: pre-dose, 4 hrs and 8 hrs post first dose of the 
day. C1D15 pre-dose only. 
S Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) predose on each of Cycle 1 Day 1, Cycle 1 Day 8, and 
Cycle 1 Day 15. 
T PBMCs will be collected on Cycle 1, Day 1 pre-treatment; on Cycle 1, Day 1 at 8 hours post-dose; and on Cycle 1, Day 1 at 8 hours post-dose for 
determination of changes in gene expression that may predict or correlate with anti-lymphoma activity and/or pharmacodynamic activity. 
U Saliva will be obtained pre-dose on Cycle 1 Day 1 as a normal-tissue control for gene mutation studies in tumors. 
V Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; CBCs: Complete blood counts; CD: Cluster of 
differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; DAT: Direct antiglobulin test; ECG: 
Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; hrs: Hours; LDH: 
Lactate dehydrogenase; min: Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: 
Progressive disease; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; SAE: 
Serious adverse event; WBC: White blood cell; WCBP: Women of child bearing potential 
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Section 7.1 
Subject Inclusion Criteria 
Changes: Inclusion criteria have been updated to indicate that all study subjects must have 
measurable lymphadenopathy. 
 
In view of the fact that the study drug is not expected to be substantially 
myelosuppressive and that study therapy has the hypothetical potential to improve 
disease-related cytopenias, study candidates who have Grade ≥3 neutropenia or 
thrombocytopenia due to disease infiltration of the bone marrow are permitted to 
enroll. 
 
The study will require that candidates with NHL be willing to provide archival or 
fresh tissue prior to enrollment. 
 
The study will require that candidates with CLL/SLL be willing to provide CLL cells 
from peripheral blood or bone marrow prior to enrollment. 
4.  Subjects must have radiographically measurable lymphadenopathy or extranodal 
lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures ≥ 2.0 cm 
in the longest dimension [LD] and ≥ 1.0 cm in the longest perpendicular dimension 
[LPD] as assessed radiographically). 
Subjects may have measurable or non
measurable disease but to be eligible their disease must be clinically evaluable for 
improvement or progression. 
7. The subject has organ and marrow function as follows: 
c. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1,000/mm3). 
d. Platelets ≥ 75 × 109/L (75,000/mm3). 
e. Total bilirubin ≤ 1.5 x the upper limit of normal (ULN). 
f. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min. 
g. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN 
if no liver involvement, or ≤ 5 x ULN with liver involvement. 
h. Note: Grade ≥3 neutropenia or thrombocytopenia is permitted if the 
abnormality is related to bone marrow involvement with hematological malignancy 
(as documented by bone marrow biopsy/aspirate obtained since the last prior 
therapy). 
11. For subjects with lymphoma: The subject has archived tumor tissue for analysis or 
is willing to undergo a pretreatment core needle, excisional, or incisional biopsy of a 
lymphoma nodal lesion.  
12. For subjects with CLL/SLL: The subject has sufficient circulating cells in the 
peripheral blood (e.g., ALC ≥ 10 x 109/L) or is willing to undergo a pretreatment 
bone marrow aspirate to obtain CLL cells.  
Section 7.2 
Subject Exclusion Criteria 
Changes: Restrictions on immunosuppressive therapy and corticosteroid use have been 
clarified. 
 
The text in Exclusion Criterion 19 was corrected for consistency with other criteria. 
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8. The subject is chronically receiving immunosuppressive therapy, is receiving 
> 10 mg/day of prednisone (or the corticosteroid equivalent), or is using enteric 
corticosteroids. Study candidates using Acute (short term) systemic steroid treatment 
as indicated by standard clinical practice at higher doses will be allowed upon agreement 
between the investigator and sponsor. Ttopical, intra-articular, nasal, and inhaled 
corticosteroids are also allowedare not excluded from study participation. During 
study therapy, subjects may use systemic, enteric, topical, intra-articular, nasal, or 
inhaled corticosteroids as required for treatment-emergent conditions. 
19. The subject has a hHistory of prior cancer (not under study) that has not been in 
remission for at least 3 years. The following are exempt from the 3-year limit: basal cell 
or squamous cell carcinoma of the skin, localized prostate cancer with normal Prostate 
Specific Antigen (PSA), cervical cancer in situ or other in situ carcinomas. 
Section 7.3 
Treatment of Subjects 
Changes: This information was moved from this section and consolidated with other drug 
administration information earlier in the protocol document. 
 
Because food does not appreciably influence study drug absorption, subjects will not 
be limited to ingestion of the drug under fasting conditions except on specified days of 
intensive PK monitoring.  
 
Further information regarding management of interruptions in scheduling is now 
provided in more detail in other sections of the study protocol document. 
7.3.1 
Description of Study Drug 
LAM 002A (apilimod dimesylate capsule) is intended for oral administration. Each capsule will 
contain 25 mg of apilimod dimesylate (equivalent to 17.1 mg apilimod free base) and the total 
fill weight of each capsule will be 175 mg. LAM 002A is formulated as a blend with excipients 
in Size 0 Swedish Orange gelatin capsules. For additional information, see Section 9.1. 
7.3.2 
In-Clinic LAM-002A (Apilimod Dimesylate Capsules) Administration  
On Cycle 1 Day 1, and Cycle 1 Day 8 the dose of LAM 002A (apilimod dimesylate capsules) 
should be orally administered (a minimum fasting state of 6 to 8 hours) by site staff immediately 
after the collection of the biomarker samples and pre dose PK sample. Subjects are allowed to 
eat after PK Sample #4 (hour 2) has been collected. On Cycle 1 Day 15, the dose of LAM 002A 
(apilimod dimesylate capsules) should be orally administered (a minimum fasting state of 6 to 8 
hours) by site staff immediately after collection of the pre dose PK and biomarker samples.  
7.3.3 
LAM-002A (Apilimod Dimesylate Capsules) Self-Administration Dosing Diary 
Except for the days where treatment is administered in the clinic, LAM 002A (apilimod 
dimesylate capsules) will be self administered orally, BID every 12 hours (e.g., 8 AM and 8 PM) 
of each 28 day cycle until disease progression or other discontinuation criteria are met.  
Administration guidelines: Subjects should be advised to take study drug with 12 oz. water at the 
same time each day, 12 hours apart +/  1 hour window. Subjects should not take drug if > 3 
hours from scheduled dose and the +/  window. Subjects should not eat within 2 hours prior to 
taking their dose or within 2 hours after taking their dose, with no solid diet restrictions 
otherwise. Clear liquids are allowed within the +/  2 hour fasting window. On PK days, subjects 
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should come to clinic fasted (a minimum fasting state of 6 to 8 hours) and take the dose at the 
site under supervision. If the subject forgets to take a dose by > 3 hours then the dose should not 
be taken and will be reported as ‘missed’ in the subject’s dosing diary. If the subject vomits after 
taking a dose, that dose should not be taken again. 
Dosing should occur at the same time each day whenever possible. All subjects will be required 
to complete a Dosing Diary, which must be returned to the site for review at each site visit.  
Section 8.1.2 Inclusion and Exclusion Criteria 
Changes: Confirmation of eligibility need not occur precisely on Day 1; thus this provision has 
been changed. 
At During Screening, inclusion and exclusion criteria will be reviewed for each potential subject 
and confirmed on by Day 1 of Cycle 1.  
Section 8.1.5 Disease Status Assessment for Subjects with NHL 
Changes: The requirements for baseline imaging and bone marrow analyses have been 
clarified. 
 
The procedures for baseline acquisition of tumor tissue in study candidates with 
lymphoma have been updated and clarified.  
Pretreatment tumor assessments will be performed within 30 days of the first dose of study 
treatment and will include diagnostic CT scans (with intravenous contrast) or Positron 
Emission Tomography (PET)/Computerized Tomography Scans (CT scan) for patients with 
lymphoma (CT for subjects with CLL/SLL), bone marrow aspirate/biopsy, complete blood 
counts and physical examination. It is anticipated that in most cases the PET/ and (CT scans) will 
be conducted using a single instrument, i.e., as a PET/CT scan (CT scans should be performed 
using a contiguous reconstruction algorithm of ≤ 5 mm). However, MRI is an acceptable 
alternative method for assessing disease in subjects who cannot receive intravenous contrast with 
CT scans. In such subjects MRI and PET scans will have to be obtained separately. 
Suitable scans performed prior to screening and within 30 days before first dose may be used for 
baseline tumor assessments. Similarly bone marrow biopsies/aspirates performed within 
2 months prior to first dose may be used for baseline assessments. For subjects with NHL, 
baseline bone marrow biopsies/aspirates may be omitted if not deemed essential for 
response assessment or patient management. For subjects with CLL/SLL, a baseline bone 
marrow aspirate is required unless the presence of sufficient circulating cells in the 
peripheral blood (e.g., ALC ≥ 10 x 109/L) permits assessment of baseline parameters for 
gene expression and prognosis. Baseline bone marrow biopsies/aspirates may be omitted if not 
deemed essential for response assessment or patient management. Details of assessments will be 
collected on the eCRF and must be filed in the subject’s medical record. 
Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue must 
be obtained pretreatment. For subjects undergoing a biopsy, adequate tumor tissue should 
be acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes 
using a 16-gauge core needle). Tissue will be submitted for evaluation of the percentage of 
tumor cells and analysis of genetic alterations and/or gene expression that may predict 
anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor may be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; 
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expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status). The baseline 
biopsy procedure (if required) should ideally be performed after the study candidate has 
undergone the baseline radiology examination and is otherwise considered eligible for 
study participation. 
Section 8.1.6. Disease Status Baseline Assessments for Subjects with CLL/SLL 
Changes: Greater specificity have been provided in the baseline imaging and peripheral blood 
assessments for subjects with CLL/SLL in order to ensure clarity regarding the 
studies to be performed. 
All subjects with CLL must have baseline imaging (with CT scans [preferred] or MRI 
scans). 
Subjects with CLL/SLL must provide either a fresh blood sample containing circulating 
tumor cells or a bone marrow aspirate sample pretreatment. Tissue will be submitted for 
evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene 
expression that may predict anticancer activity and/or pharmacodynamic activity. In 
addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample 
to be evaluated at a sponsor-specified laboratory for known prognostic markers (e.g., 
quantitative immunoglobulins, FISH panel [chromosome 11q deletion, 13q deletion, 
17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-
21], and other genes of interest in CLL [e.g., Notch]; flow cytometry [for CD5, CD10, 
CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], 
and/or β2-microglobulin). Subjects with CLL will have the following baseline assessments 
performed direct antiglobulin test (DAT), quantitative immunoglobulins, Fluorescence in Situ 
Hybridization (FISH) panel, flow cytometry and β2 microglobulin. Imaging and bone marrow 
aspirate/biopsy will be conducted as above at Screening/Baseline, Each Cycle and End of 
Treatment. 
Section 8.3.1 Clinical Laboratory Tests 
Change: 
Information regarding the locations for clinical laboratory testing has been clarified. 
Clinical laboratory tests during the first 2 cycles will be performed by the investigative site’s 
local laboratory. Samples will be collected from subjects at scheduled study visits before the 
administration of study drug unless otherwise noted, and more frequently if clinically indicated. 
Clinical laboratory tests may be performed up to 72 hours prior to the scheduled visits (See 
Section Deleted for Schedule of Assessments). Upon completion of Cycle 2, subjects may use 
the investigative site’s laboratory or their local laboratory for clinical laboratory assessments. 
Accredited certification, such as College of American Pathologists (CAP) and Clinical 
Laboratory Improvement Amendments (CLIA), and valid reference ranges must be collected for 
all clinical laboratories used by subjects. 
Section 8.3.1.1  
Hematology 
Change: 
The text has been edited to allow reporting of either aPTT or PTT depending upon 
the type of test done at the site. Text regarding on-study tumor biopsies is no longer 
applicable because the on-study tumor biopsies have been removed as components of 
this study.  
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Hemoglobin, hematocrit, WBC count with differential, red blood cell (RBC) count, and platelet 
count will be collected at Screening and Days 1, 8, and 15 of Cycles 1 and 2 then at least once 
prior to start of all subsequent cycles and at EOT. 
Coagulation parameters (aPTT [or PTT] and INR) should be performed at Screening. 
Additionally these labs should be repeated per institutional guidelines prior to any on study 
tumor biopsies. 
Section 8.3.1.2  
Blood Chemistry 
Change: 
The text has been edited to match the plan for reporting of bilirubin on the case 
report forms. Total bilirubin should be recorded and direct bilirubin should be 
reported if available. If necessary, the indirect bilirubin will be calculated 
programmatically.  
Albumin, alkaline phosphatase (ALP), total bilirubin, calcium, carbon dioxide, chloride, 
creatinine, glucose, inorganic phosphorus, potassium, total protein, ALT, AST, lactate 
dehydrogenase (LDH), sodium, BUN, and uric acid will be collected at Screening and Days 1, 8, 
and 15 of Cycles 1 and 2 then at least once prior to start of all subsequent cycles and at EOT. If 
the total bilirubin concentration is > 1.5 times the upper normal limit, total bilirubin should be 
differentiated and the total and direct bilirubin should be reported.into the direct and indirect 
reacting bilirubin.  
Section 8.3.1.3 
PK and Biomarker Assessments 
Change: 
The text has been edited for accuracy. 
Biomarker samples will be obtained at time points indicated in Section 13. Comprehensive 
information on tissue acquisition, handling, storage, and sample shipments can be found in the 
biomarker sample process documents. Laboratory manual. 
Section 8.5 
Adverse Events 
Change: 
Information that is already described in other sections of the protocol has been 
deleted in order to avoid redundancy and/or inconsistency. 
The frequency of AE monitoring increases for subjects who experience a DLT as outlined below 
and in Section Deleted. See Section 6.6.5 for dosing adjustment/termination criteria. Subjects 
who experience a DLT (See Section Deleted) in Cycle 1 will be discontinued from treatment. 
If at any time during the study a subject experiences a DLT, the study treatment must be stopped 
and the toxicity in question must be followed until resolution or stabilization. Subjects who 
experience a non laboratory DLT must be evaluated weekly, at a minimum, for 4 weeks until 
resolution to ≤ Grade 1 or baseline and then at least monthly until return to baseline or 
stabilization of the event, whichever comes first. For abnormal laboratory values that qualify as a 
DLT, subjects will initially be followed at least twice weekly until values resolve to ≤ Grade 2 or 
return to baseline. If not resolved or stabilized within 2 weeks then subjects should be followed 
at least weekly until return to baseline or stabilization, whichever comes first. 
For patients who discontinue study treatment due to a study related AE, the reporting time period 
may be extended. These patients must be followed at least once a week for 4 weeks, and 
subsequently at 4 week intervals until resolution or stabilization of the AE or laboratory 
abnormality, whichever comes first.  
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Section 8.6. Concomitant Medications and Supportive Care and Section 8.6.1 TLS 
Management 
Change: 
Recommendations for TLS management have been included for completeness. 
Information regarding TLS prophylaxis is provided in Section 6.8.1. 
Subjects who develop TLS may experience hyperkalemia, hypocalcemia, hyperuricemia, 
hyperphosphatemia, cardiac dysrhythmias, and acute renal failure; thus, close monitoring 
of electrolytes is important after initial therapy.  
Subjects with TLS should receive intravenous hydration, rapid reversal of hyperkalemia, 
antihyperuricemic agents, and appropriate cardiac and renal support, including dialysis as 
indicated. Upon recovery to baseline functioning and as medically appropriate, such 
subjects should continue with protocol therapy to maintain tumor control. 
Section 8.6.4 8.6.5 
Other Concomitant Medications 
Change: 
The text has been changed to allow more latitude regarding the implementation of 
bisphosphonates under circumstances in which the occurrence of disease progression 
is not certain.  
 
Instructions on the concomitant administration of corticosteroids during study 
therapy are now provided. 
Bisphosphonates: Bisphosphonates are permitted if a subject was receiving ongoing 
bisphosphonate therapy at time of screening and will continue on a stable regimen throughout 
protocol therapy. The need to start bisphosphonates while on therapy may be an indication of 
disease progression and should be discussed with the sponsor prior to implementationwill 
be seen as an indication of disease progression and the subject should be withdrawn from 
therapy. 
Corticosteroids: Subjects may be using topical, intra-articular, nasal, or inhaled 
corticosteroids at study entry and may use such drugs during therapy. The use of systemic 
or enteric corticosteroids is precluded at study entry because such drugs may confound 
interpretation of pharmacodynamic, immunological, or toxic responses in subjects on this 
study. However, such drugs are permitted if a subject develops intercurrent conditions that 
require corticosteroid therapy. 
Section 8.7 
Drug Interactions 
Change: 
Restrictions on coadministration of drugs that may alter apilimod dimesylate 
disposition have been updated. 
Drug Interactions: No information is available regarding interactions of LAM-002A (apilimod 
dimesylate capsules) with therapeutic agents or other substances in humans. In vitro data 
suggest that concomitant administration of potent inhibitors or inducers of CYP3A4 or 
CYP2C9 might alter apilimod dimesylate clearance and lead to clinically significant 
increases or decreases in apilimod dimesylate exposure. Consequently, the concomitant use 
of strong inhibitors or inducers of CYP3A4 or CYP2C9 (see Table 15) should be avoided 
when possible.  
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Based on these considerations, protocol candidates who require therapy with CYP3A4 or 
CYP2C9 inhibitors or inducers listed in Table 15 should not be enrolled into the study.  
During study participation, coadministration of apilimod dimesylate with CYP3A4 or 
CYP2C9 inhibitors or inducers (see Table 15) should be avoided, if possible. However, a 
subject who develops a condition that may require use of such drugs is not required to 
permanently discontinue apilimod dimesylate if the subject is experiencing clinical benefit 
and other options for treating the subject’s cancer are limited. If medically appropriate, 
investigators may wish to use a therapeutic alternative that would not be expected to affect 
these enzymes. For subjects who require temporary use of a drug that does affect these 
enzymes (e.g., treatment with a systemic antifungal agent), apilimod dimesylate can be 
interrupted (or the doses reduced) during use of the other medication and then resumed 
after completion of the other drug. For subjects who require initiation of chronic therapy 
with a drug that potently affects these enzymes, investigators must consult with the medical 
monitor to consider the best course of action. However, theoretically interactions may occur 
with medications metabolized in the following pathways: CYP3A4 and CYP2C9. Subjects will 
be excluded from concomitantly receiving strong inducers or inhibitors of CYP2C9 and 
CYP3A4 (Table 15). Investigators are also advised that subjects should not be treated with 
moderate inducers/inhibitors of these enzymes if alternative treatment is available. If such 
treatments are required, concomitant medications should be started at the lowest effective dose 
level.  
Section 8.8 
 
Treatment Compliance 
Change: 
Consistent with other sections of the protocol document, this DLT criterion has been 
made more specific to enhance interpretability. 
A subject is considered to be DLT-evaluable if he/she has taken 80% at least 75% (42/56) of 
the planned first-cycle doses and has sufficient safety data, or has experienced a DLT in the 
first cycle.  
Section 9 Study Drug Materials and Management 
Changes: The text has been clarified to indicate that drug dispensing must conform to legal, 
regulatory, or site requirements.  
 
Information that is already described in other sections of the protocol has been 
deleted in order to avoid redundancy and/or inconsistency. 
 
Information regarding disposition of study drug has been updated and clarified.  
9.1 
Study Drug 
LAM-002A drug description is provided in Table 12. 
Table 5: 
LAM-002A Drug Description 
Product Name: 
LAM-002A 
Dosage Form: 
Capsule 
Unit Dose 
25 mg (50 mg pending future development) 
Route of Administration 
Oral 
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Product Name: 
LAM-002A 
Physical Description 
Each capsule will contain 25 mg of apilimod dimesylate (equivalent 
to 17.1 mg of apilimod free base) and the total fill weight of each 
capsule will be 175 mg. The claimed dosage strength of the active 
ingredient will be expressed in the free base form of apilimod. 
Manufacture of a 50 mg capsule is planned as part of the ongoing 
development program. 
Inactive components in active capsules are microcrystalline 
cellulose Avicell PH102, silicified microcrystalline cellulose, 
anhydrous lactose, croscarmellose sodium (Ac-Di-Sol), colloidal 
silicon dioxide, and magnesium stearate.  
Manufacturer 
Patheon 
Abbreviation: mg: Milligram 
 
9.2 
Study Drug Packaging and Labeling 
Study drug will be provided in bulk bottles to each investigational pharmacy for dispensing. The 
pharmacist will dispense capsules into bottles for each subject (based on Cohort assignment) 
following applicable state and federal laws and site policies. Details on the labeling, 
dispensing, and administration of study drug are provided in the Pharmacy Manual. 
9.4 
Study Drug Administration 
Except for the days where treatment is administered in the clinic, LAM 002A will be self
administered orally, BID every 12 hours (e.g., 8 AM and 8 PM) of each 28 day cycle until 
disease progression or other discontinuation criteria are met.  
Administration guidelines: Subjects should be advised to take study drug with 12 oz. water at the 
same time each day, 12 hours apart +/  1 hour window. Subjects should not eat within 2 hours of 
or within 2 hours after dose administration; no solid diet restrictions otherwise. Subjects may 
consume clear liquids in the 2 hour pre  and post dose window. On PK days, subjects should 
come to clinic fasted and take dose in the clinic under supervision.  
Missed Dose: Dosing should occur at the same time each day whenever possible. If the subject 
forgets to take a dose by > 3 hours then the dose should not be taken and will be reported as 
‘missed’ in the subject’s diary. The next dose should be taken on schedule.  
If the subject vomits after taking a dose, that dose should not be taken again. 
Dosing Diary: All subjects will be required to complete a Dosing Diary, which must be returned 
to the clinic for review at each clinic visit.  
9.5 9.4 Study Drug Accountability 
Study drug will be dispensed to subjects in labeled bottles at the beginning of each cycle. 
Subjects should be instructed to bring all bottles, including empty bottles, to each Day 1 or End 
of Treatment study visit for a compliance and product accountability check. Returned study drug 
should be retained for monitor review prior to destruction at the sitereturn to the drug depot, 
unless contraindicated by site standard operating procedures (SOPs). If contraindicated by the 
site SOP, approval of site process by the sponsor must be obtained and filed in the pharmacy file 
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and/or regulatory binder. The investigational pharmacy must maintain contemporary and 
accurate records on product receipt, storage temperature, stock, dispensation, return and disposal. 
These records should be available for review during monitoring visits and copies available for 
retrieval for the Trial Master File.  
9.6 9.5 Study Drug Handling and Disposal 
Study drug accountability and inventory records will be inspected by the sponsor/Ce3 prior to 
final disposition. Instructions will be provided by the sponsor/Ce3 for shipment to and 
destruction of unused study drug product by the designated packaging depot, to include 
unopened bulk bottlesunused product returned by study subjects, unused stock product at the 
end of the study and expired product. Unused product returned by study subjects or opened 
bulk bottles will be destroyed by each site per site SOPs. Study drug should only be shipped 
or destroyed upon written authorization from the sponsor/Ce3. Documentation of return of 
shipment, including a packing list and copy of the tracking label, should be retained in the 
Pharmacy and/or regulatory files.  
Section 11 Assessment of Efficacy 
Changes: Citations have been updated and associated references in the bibliography have been 
corrected. 
Following subjects with diagnostic CT scans to evaluate efficacy is now also 
permitted. 
Patients with CLL must have lymphadenopathy to be enrolled in the study. 
Tumor response will be assessed in the Dose Escalation Stage and Expansion Stage using 
modified Lugano Response Criteria for NHL (Cheson 2014 NCCN 1 2015) and revised 
gGuidelines for the diagnosis and treatment of CLL (HallekBlood 2008, Cheson 2012) (See 
Appendix 2). 
Pretreatment tumor assessments will be performed within 30 days of the first dose (bone marrow 
assessment may be performed within 2 months prior to first dose) and will include diagnostic 
CT scans (with intravenous contract) or PET/CT for subjects with lymphoma (CT only for 
subjects with CLL/SLL), bone marrow aspirate/biopsy, complete blood counts and physical 
examination. It is anticipated that in most cases the PET and CT scans will be conducted using a 
single instrument, i.e., as a PET/CT scan (CT scans should be performed using a contiguous 
reconstruction algorithm of ≤ 5 mm). However, MRI is an acceptable alternative method for 
assessing disease in subjects who cannot receive intravenous contrast with CT scans. In such 
subjects MRI and PET scans will have to be obtained separately. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient 
management. 
During treatment, radiology studies PET/CT scans will be performed for tumor assessments 
within 7 days prior to Day 1 of Cycles 3, 5, 7 and then every 3 months thereafter until PD or use 
of alternative antineoplastic therapy. If necessary per applicable response criteriaAdditionally, 
a repeat bone marrow biopsy or aspirate will be required for subjects with bone marrow 
infiltration at baseline who have a Complete Response (CR) by imaging and physical 
examination. For subjects with CLL without nodal disease, splenomegaly or masses on baseline 
imaging, CT surveillance will not be required except for confirmation of CR. Also subjects with 
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IgHV3-21], and other genes of interest in CLL [e.g., Notch]; flow cytometry [for CD5, 
CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and 
ZAP-70]), and serum β2-microglobulin.  
A saliva sample will be obtained on Cycle 1 Day 1 as a normal-tissue control for gene 
mutation studies in tumors. 
Tissue from the most recent available biopsy or surgery prior to first dose will be submitted for 
biomarker analysis to determine genetic alterations or gene expression and determination of 
immune cell infiltration that may predict response to LAM 002A (apilimod dimesylate capsules). 
Although tumor samples are not required for enrollment of subjects, obtaining and submitting 
fresh or archival samples is strongly encouraged. Plasma bioanalytes will be examined by 
proteomic technology at Cycle 1 Day 1 and Cycle 1 Day 8 to determine changes that may predict 
response to LAM 002A. 
Additionally, a bone marrow aspirate (if positive at baseline) and core tumor biopsy will be 
obtained at the time of the first scheduled tumor assessment (end of Cycle 2). However, the 
requirement for core tumor biopsy may be waived for subjects whose tumor cannot be safely 
biopsied or for whom the investigator deems the procedure inappropriate. These tissues will be 
analyzed for inhibition of PIKfyve by measuring the extent of vacuolation by microscopy. Tissue 
will also be analyzed by immunohistochemistry for determination of the extent of immune cell 
infiltration (tumor infiltrating lymphocytes, tumor associated macrophages). Additionally, 
ribonucleic acid (RNA) will be collected from fresh samples for gene expression analysis. 
Comprehensive information on tissue acquisition, handling, storage and sample shipments can be 
found in the biomarker sample process documents laboratory manual. 
Section 14.3.4  
DLT Evaluable Population 
Change: 
The text has been altered for consistency with amendments to the definitions of DLT 
evaluability in other sections of the protocol document 
Dose escalation decisions will be evaluated in DLT evaluable population. The DLT evaluable 
population will include subjects who complete Cycle 1 dosing (administered at least 7580% of 
doses) and have sufficient safety data, or who are withdrawn from study due to a DLT in 
Cycle 1. 
Section 14.9  
Efficacy Analysis 
Change: 
Citations and references in the bibliography have been corrected. 
The tumor response will be assessed by the modified Lugano Response Ccriteria for NHL 
(NCCN 1 2015 Cheson 2014) and revised gGuidelines for the diagnosis and treatment of CLL 
(Hallek 2008, Cheson 2012) (See Appendix 2). 
Section 21  
List of References 
Change: 
References in the bibliography have been updated consistent with other additions or 
changes to the protocol document. 
Asghar A, Naaz S, Agrawal D, Sharma P. Morphometric study of spleen in north Indian 
adult population: CT scan image based study. Journal of Clinical and Diagnostic Research. 
2011 Oct; 5(5):974-7. 
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Bezerra AS, D’Ippolito G, Faintuch S, Szejnfeld J, Ahmed M. Determination of 
splenomegaly by CT: is there a place for a single measurement? AJR Am J Roentgenol. 
2005 May;184(5):1510-3. 
Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the 
evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children 
with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010 
May;149(4):578-86. 
Cheson BD, Byrd JC, Rai KR, Kay NE, O’Brien SM, et al. Novel targeted agents and the 
need to refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol. 2012 Aug 
10;30(23):2820-2.  
Erturk SM, Mortelé KJ, Binkert CA, Glickman JN, Oliva MR, Ros PR, Silverman SG. CT 
features of hepatic venoocclusive disease and hepatic graft-versus-host disease in patients 
after hematopoietic stem cell transplantation. AJR Am J Roentgenol. 2006 
Jun;186(6):1497-501. 
MD Anderson Cancer Center (MDACC). Tumor lysis in adult patients. 2013 Apr 30. 
Available at: http://www.mdanderson.org/education-and-research/resources-for-
professionals/clinical-tools-and-resources/practice-algorithms/clin-management-tumor-
lysis-web-algorithm.pdf (accessed 2016 Jan 24). 
Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, et al. Targeting BCL2 with 
venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016 Jan 
28;374(4):311-22. 
Walker HK, Hall WD, Hurst JW, editors. Clinical methods: The history, physical, and 
laboratory examinations. 3rd edition. 1990. Boston; Butterworths. 
Appendix 2. 
Criteria for Response Assessment 
Changes: A more comprehensive description of the criteria for response assessment in 
lymphoma has been provided to ensure appropriate evaluation of patients with both 
FDG-avid and FDG-non-avid lymphoma subtypes and patients who are followed by 
PET/CT or by diagnostic CT. The criteria are consistent with Cheson 2014. 
 
The criteria for response assessment in CLL have been updated and clarified 
consistent with both the Hallek 2008 and Cheson 2012 references. 
Table 7: 
Revised Criteria for Response Assessment 
Response and Site 
PET CT Based Response 
CT Based Response 
Complete 
Complete metabolic response 
Complete radiologic response (all of the 
following) 
Lymph nodes and 
extralymphatic sites 
Score 1, 2, or 3* with or without a residual mass on 5PS† 
Target nodes/nodal masses must regress to 
≤ 1.5 cm in Ldi 
It is recognized that in Waldeyer’s ring or extranodal sites with 
high physiologic uptake or with activation within spleen or 
marrow (e.g., with chemotherapy or myeloid colony stimulating 
factors), uptake may be greater than normal mediastinum and/or 
liver. In this circumstance, complete metabolic response may be 
inferred if uptake at sites of initial involvement is no greater 
than surrounding normal tissue even if the tissue has high 
No extralymphatic sites of disease 
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Response and Site 
PET CT Based Response 
CT Based Response 
physiologic uptake 
Nonmeasured lesion 
Not applicable 
Absent 
Organ enlargement 
Not applicable 
Regress to normal 
New lesions 
None 
None 
Bone marrow 
No evidence of FDG avid disease in marrow 
Normal by morphology; if indeterminate, 
IHC negative 
Partial 
Partial metabolic response 
Partial remission (all of the following) 
Lymph nodes and 
extralymphatic sites 
Score 4 or 5† with reduced uptake compared with baseline and 
residual mass(es) of any size 
≥ 50% decrease in SPD of up to 6 target 
measurable nodes and extranodal sites 
  
At interim, these findings suggest responding disease 
When a lesion is too small to measure on 
CT, assign 5 mm × 5 mm as the default 
value 
  
At end of treatment, these findings indicate residual disease 
When no longer visible, 0 × 0 mm 
  
  
For a node > 5 mm × 5 mm, but smaller 
than normal, use actual measurement for 
calculation 
Nonmeasured lesions 
Not applicable 
Absent/normal, regressed, but no increase 
Organ enlargement 
Not applicable 
Spleen must have regressed by > 50% in 
length beyond normal 
New lesions 
None 
None 
Bone marrow 
Residual uptake higher than uptake in normal marrow but 
reduced compared with baseline (diffuse uptake compatible with 
reactive changes from chemotherapy allowed). If there are 
persistent focal changes in the marrow in the context of a nodal 
response, consideration should be given to further evaluation 
with MRI or biopsy or an interval scan 
Not applicable 
No response or stable disease 
No metabolic response 
Stable disease 
Target nodes/nodal masses, 
extranodal lesions 
Score 4 or 5 with no significant change in FDG uptake from 
baseline at interim or end of treatment 
< 50% decrease from baseline in SPD of 
up to 6 dominant, measurable nodes and 
extranodal sites; no criteria for progressive 
disease are met 
Nonmeasured lesions 
Not applicable 
No increase consistent with progression 
Organ enlargement 
Not applicable 
No increase consistent with progression 
New lesions 
None 
None 
Bone marrow 
No change from baseline 
Not applicable 
Progressive disease 
Progressive metabolic disease 
Progressive disease requires at least 1 of 
the following 
Individual target 
nodes/nodal masses 
Score 4 or 5 with an increase in intensity of uptake from 
baseline and/or 
PPD progression: 
Extranodal lesions 
New FDG avid foci consistent with lymphoma at interim or 
end of treatment assessment 
An individual node/lesion must be 
abnormal with: 
Ldi > 1.5 cm and 
Increase by ≥ 50% from PPD nadir and 
An increase in Ldi or Sdi from nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
In the setting of splenomegaly, the splenic 
length must increase by > 50% of the 
extent of its prior increase beyond baseline 
(e.g., a 15 cm spleen must increase to > 16 
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Response and Site 
PET CT Based Response 
CT Based Response 
cm). If no prior splenomegaly, must 
increase by at least 2 cm from baseline 
New or recurrent splenomegaly 
Nonmeasured lesions 
None 
New or clear progression of preexisting 
nonmeasured lesions 
New lesions 
New FDG avid foci consistent with lymphoma rather than 
another etiology (e.g., infection, inflammation). If uncertain 
regarding etiology of new lesions, biopsy or interval scan may 
be considered 
Regrowth of previously resolved lesions 
A new node > 1.5 cm in any axis 
A new extranodal site > 1.0 cm in any 
axis; if < 1.0 cm in any axis, its presence 
must be unequivocal and must be 
attributable to lymphoma 
Assessable disease of any size 
unequivocally attributable to lymphoma 
Bone marrow 
New or recurrent FDG avid foci 
New or recurrent involvement 
* A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an 
interim scan. However, in trials involving PET where de escalation is investigated, it may be preferable to consider 
a score of 3 as inadequate response (to avoid under treatment). Measured dominant lesions: Up to 6 of the largest 
dominant nodes, nodal masses, and extranodal lesions selected to be clearly measurable in 2 diameters. Nodes 
should preferably be from disparate regions of the body and should include, where applicable, mediastinal and 
retroperitoneal areas. Non nodal lesions include those in solid organs (e.g., liver, spleen, kidneys, lungs), GI 
involvement, cutaneous lesions, or those noted on palpation. Nonmeasured lesions: Any disease not selected as 
measured, dominant disease and truly assessable disease should be considered not measured. These sites include any 
nodes, nodal masses, and extranodal sites not selected as dominant or measurable or that do not meet the 
requirements for measurability but are still considered abnormal, as well as truly assessable disease, which is any 
site of suspected disease that would be difficult to follow quantitatively with measurement, including pleural 
effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other lesions that cannot be 
confirmed and followed by imaging. In Waldeyer’s ring or in extranodal sites (e.g.,, GI tract, liver, bone marrow), 
FDG uptake may be greater than in the mediastinum with complete metabolic response, but should be no higher than 
surrounding normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy or myeloid growth 
factors).  
† PET 5PS: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 4, 
uptake moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of uptake unlikely 
to be related to lymphoma. 
Abbreviations: 5PS, 5 point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC, 
immunohistochemistry; Ldi, longest transverse diameter of a lesion; MRI, magnetic resonance imaging; PET, 
positron emission tomography; PPD, cross product of the Ldi and perpendicular diameter; Sdi, shortest axis 
perpendicular to the Ldi; SPD, sum of the product of the perpendicular diameters for multiple lesions.  
 
Source: Cheson 2014. 
 
Response Assessment of CLL (Source: Hallek 2008) 
The World Health Organization (WHO) classification of hematopoietic neoplasias describes 
CLL as leukemic, lymphocytic lymphoma, being only distinguishable from small lymphocytic 
lymphoma (SLL) by its leukemic appearance. In the World Health Organization classification, 
CLL is always a disease of neoplastic B cells, whereas the entity formerly described as T cell 
chronic lymphocytic leukemia (T CLL) is now called T cell prolymphocytic leukemia. 
It is important to verify that the subject has CLL and not some other lymphoproliferative disease 
that can masquerade as CLL, such as hairy cell leukemia, or leukemic manifestations of mantle 
cell lymphoma, marginal zone lymphoma, splenic marginal zone lymphoma with circulating 
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villous lymphocytes, or follicular lymphoma. To achieve this, it is essential to evaluate the blood 
count, blood smear, and the immune phenotype of the circulating lymphoid cells. 
Definition of Response 
Assessment of response should include a careful physical examination and evaluation of the 
blood and marrow (See **). To define a CR, the marrow sample must be at least normocellular 
for age, with less than 30% of nucleated cells being lymphocytes. Lymphoid nodules should be 
absent. 
Complete remission (CR) 
CR requires all of the following criteria as assessed at least 2 months after completion of 
therapy: 
• Peripheral blood lymphocytes (evaluated by blood and differential count) below 
4 × 109/L (4,000/μL). 
13. In clinical trials, the presence of MRD after therapy should be assessed. The sensitivity of 
the method used to evaluate for MRD should be reported. 
14. Absence of significant lymphadenopathy (e.g, lymph nodes > 1.5 cm in diameter) by 
physical examination. In clinical trials, a CT scan of the abdomen, pelvis, and thorax is 
desirable if previously abnormal. Lymph nodes should not be larger than 1.5 cm in 
diameter. 
15. No hepatomegaly or splenomegaly by physical examination. In clinical trials, a CT scan 
of the abdomen should be performed at response assessment if found to be abnormal 
before therapy or if physical examination is inconclusive at the time of evaluation. 
16. Absence of constitutional symptoms. 
17. Blood counts above the following values: 
• Neutrophils More Than 1.5 × 109/L (1500/µL) without need for Exogenous Growth 
Factors. 
• Platelets More Than 100 × 109/L (100,000/µL) without need for Exogenous Growth 
Factors. 
• Hemoglobin More Than 110 G/L (11.0 g/dL) without Red Blood Cell Transfusion or 
need for Exogenous Erythropoietin. 
• For subjects in clinical trials a marrow aspirate and biopsy should be performed at 
least 2 months after the last treatment and if clinical and laboratory results above 
demonstrate that a CR has been achieved 
Partial remission (PR) 
PR is defined by the criteria described in Sections 1, 2, or 3 below (if abnormal before therapy), 
as well as one or more of the features listed in Section 4. To define a PR, these parameters need 
to be documented for a minimal duration of 2 months (See Table 8). Constitutional symptoms 
persisting for more than 1 month should be recorded. 
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1. A decrease in the number of blood lymphocytes by 50% or more from the value before 
therapy. 
18. Reduction in lymphadenopathy (by CT scans in clinical trials or by palpation in general 
practice) as defined by the following: 
• A decrease in lymph node size by 50% or more either in the sum products of up to 6 
lymph nodes, or in the largest diameter of the enlarged lymph node(s) detected prior 
to therapy. 
• No increase in any lymph node, and no new enlarged lymph node. In small lymph 
nodes (< 2 cm), an increase of less than 25% is not considered to be significant. 
19. A reduction in the noted pretreatment enlargement of the spleen or liver by 50% or more, 
as detected by CT scan (in clinical trials) or palpation (in general practice). 
20. The blood count should show one of the following results: 
•  Neutrophils more than 1.5 x 109/L (1,500/µL) without need for exogenous growth 
factors. 
• Platelet counts greater than 100 × 109/L (100,000/µL) or 50% improvement over 
baseline without need for exogenous growth factors. 
• Hemoglobin greater than 110 g/L (11.0 g/dL) or 50% improvement over baseline 
without requiring red blood cell transfusions or exogenous erythropoietin. 
Stable disease (SD) 
Patients who have not achieved a CR or a PR, and who have not exhibited progressive disease, 
will be considered to have stable disease (which is equivalent to a nonresponse). 
Progressive Disease 
Progressive disease during or after therapy is characterized by at least one of the following: 
1. Lymphadenopathy. 
Progression of lymphadenopathy is often discovered by physical examination and should 
be recorded. In CLL, the use of CT scans usually does not add much information for the 
detection of progression or relapse. Therefore, the use of imaging methods to follow CLL 
progression is at the discretion of the treating physician. Disease progression occurs if 
one of the following events is observed: 
Appearance of any new lesion, such as enlarged lymph nodes (> 1.5 cm), splenomegaly, 
hepatomegaly, or other organ infiltrates. 
An increase by 50% or more in greatest determined diameter of any previous site. 
21. An increase in the previously noted enlargement of the liver or spleen by 50% or more or 
the de novo appearance of hepatomegaly or splenomegaly. 
22. An increase in the number of blood lymphocytes by 50% or more with at least 5,000 B 
lymphocytes per microliter. 
23. Transformation to a more aggressive histology (e.g., Richter syndrome). Whenever 
possible, this diagnosis should be established by lymph node biopsy. 
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Table 8: 
Response Definition After Chronic Lymphocytic Leukemia Treatment 
Parameter 
CR* 
PR* 
PD* 
Group A 
  
  
  
 
 
 
 
Lymphadenopathy† 
None > 1.5 cm 
Decrease ≥ 50% 
Increase ≥ 50% 
 
 
 
 
Hepatomegaly 
None 
Decrease ≥ 50% 
Increase ≥ 50% 
 
 
 
 
Splenomegaly 
None 
Decrease ≥ 50% 
Increase ≥ 50% 
 
 
 
 
Blood lymphocytes 
< 4000/μL 
Decrease ≥ 50% 
from baseline 
Increase ≥ 50% over 
baseline 
 
 
 
 
Marrow‡ 
Normocellular, < 30% 
lymphocytes, no 
B-lymphoid nodules. 
Hypocellular marrow 
defines CRi. 
50% reduction in 
marrow infiltrate, or 
B lymphoid nodules 
  
Group B 
  
  
  
 
 
 
 
Platelet count 
> 100 000/μL 
> 100 000/μL or 
increase ≥ 50% over 
baseline 
Decrease of ≥ 50% 
from baseline 
secondary to CLL 
 
 
 
 
Hemoglobin 
> 11.0 g/dL 
> 11 g/dL or 
increase ≥ 50% over 
baseline 
Decrease of > 2 g/dL 
from baseline 
secondary to CLL 
 
 
 
 
Neutrophils‡ 
> 1500/μL 
> 1500/μL or > 50% 
improvement over 
baseline 
  
• Note: Group A criteria define the tumor load, Group B criteria define the function of the 
hematopoietic system (or marrow). 
* CR (complete remission): all of the criteria have to be met, and patients have to lack disease related constitutional 
symptoms; PR (partial remission): at least 2 of the criteria of group A plus one of the criteria of group B have to be 
met; SD is absence of progressive disease (PD) and failure to achieve at least a PR; PD: at least one of the above 
criteria of group A or group B has to be met. 
† Sum of the products of multiple lymph nodes (as evaluated by CT scans in clinical trials, or by physical 
examination in general practice). 
‡ These parameters are irrelevant for some response categories. 
Abbreviations: cm: Centimeter; Cri: CR with incomplete marrow recovery; dL: Deciliter; g: Gram; μL: Microliter 
Source: Hallek 2008. 
1 
LYMPHOMA 
1.1 
Tumor Assessment Criteria 
The determination of response and progression for subject with NHL will be based on 
standardized criteria [Cheson 2014]. 
1.2 
Method of Assessment 
Imaging-based evaluation will be used in this study as the primary basis of lymphoma 
assessment. CT scan is the preferred method for radiographic tumor assessment. Contrast-
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enhanced scanning is preferred, but contrast material may be omitted in subjects for whom 
use of a contrast agent becomes medically contraindicated or if CT scanning is done in 
conjunction with PET. If available, PET scan data will be considered in response and 
progression assessment; however, PET scanning will not be a required component of 
assessment in this study. As necessary, bone marrow aspirate/biopsy (e.g., for confirmation 
of CR) or cytological/histological evaluation of lymph nodes, effusions, ascites, or other 
organ abnormalities) will be also be considered. Clinical palpation, chest x-ray, ultrasound, 
endoscopy, laparoscopy, radionuclide scan, or tumor markers will not be considered for 
response assessment. MRI scanning is not advised but may be used at the investigator’s 
discretion in subjects for whom this becomes a necessary alternative to CT scanning. 
For radiographic assessments, the same method of assessment and the same technique 
(e.g., scan type, scanner, subject position, dose of contrast, injection/scan interval) should 
be used to characterize each identified and reported lesion at baseline and during study 
treatment and follow-up. CT of the neck, chest, abdomen, and pelvis should be performed 
with cuts of ≤ 0.5 mm in slice thickness contiguously. If performed, whole-body FDG PET-
CT scanning should be extended from the base of the skull to mid-thigh. 
All relevant radiographic and clinical information required to make each tumor status 
assessment must be made available for source verification as requested by the study 
sponsor. 
1.3 
Timing of Assessments 
During screening, clinical and imaging-based tumor assessments should be performed 
within the specified screening period. On-study tumor assessments should be performed as 
stipulated in Section Changed. An end-of-therapy tumor assessment should be performed 
unless the subject already has radiographic confirmation of disease progression ≤ 4 weeks 
prior to study drug discontinuation. If a subject permanently discontinues treatment prior 
to objective documentation of lymphoma progression, investigators should ideally continue 
further follow-up of tumor status with assessments at ~12-week intervals until disease 
progression is documented or until the initiation of a new post-study therapy for the 
subject’s lymphoma. 
1.4 
Identification and Follow-up of Tumor Lesions and Organomegaly 
1.4.1 
Index Lesions 
Up to 6 lesions (e.g., lymph nodes, liver or spleen nodules, and/or other circumscribed 
extranodal masses) should be selected as index lesions that will be used to quantitate the 
status of the disease during study treatment. Ideally, the index lesions should be located in 
disparate regions of the body and include mediastinal, abdominal, and retroperitoneal 
areas of disease whenever these sites are involved. For subjects with FDG-avid lymphomas 
undergoing PET, selection of FDG-avid lesions is preferred. 
Index lesions will be measured and recorded at baseline and at the stipulated intervals 
during treatment. The largest cross-sectional dimensions (i.e., the LD × LPD will be 
recorded (in cm) for each index lesion. Using the LD and LPD, the product of the 
perpendicular diameters (PPD) for each index lesion will be calculated. The PPDs and the 
SPDs for all index lesions will be calculated and recorded. The baseline and nadir PPDs of 
individual lesions and the baseline and nadir SPDs will be used as references by which 
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objective tumor response and progression will be characterized during treatment. All PPD 
and SPD measurements will be reported in centimeters squared. 
1.4.2 
Nodal Index Lesions 
A nodal mass may be selected as a nodal index lesion if it is both abnormal and measurable 
at baseline. A lymph node lesion is considered abnormal if it has a single diameter that is 
> 1.0 cm and is considered measurable if it has 2 perpendicular diameters that can be 
accurately measured in cross section with the LD being ≥ 1.0 cm and the LPD also being 
≥ 1.0 cm.  
Abnormal, measurable nodal lesions will be subcategorized as either large or small.  
• Large nodal lesions have an LD that is > 1.5 cm and an LPD that is ≥ 1.0 cm.  
• Small nodal lesions have an LD that is > 1.0 cm and ≤ 1.5 cm and an LPD that is 
> 1.0 cm. 
Index lesions measuring > 1.5 cm in the LD, regardless of the measurement of the LPD, will 
be prioritized during baseline index lesion selection. 
At follow-up timepoints, the PPDs for individual nodal lesions and the SPD of all nodal 
index lesions will be considered. Because nodal index lesions that have one or both 
diameters > 0 cm and < 1.0 cm cannot be reliably measured, a default value of 1.0 cm will 
be assigned for each diameter that meets these criteria and the resulting PPD will be used 
in SPD calculations. Based on this convention, a CR may be achieved even if an SPD value 
is > 0 cm2 (i.e., if all lymph nodes measure < 1.0 cm2). 
New or enlarging nodal lesions that are still ≤ 1.0 cm by ≤ 1.0 cm will not be considered to 
represent recurrent or PD. A new node that measures > 1.5 cm in any diameter or a new 
node that measures > 1.0 cm to ≤ 1.5 cm in the LD and measures > 1.0 cm in the LPD will 
be considered PD. 
In cases in which a large lymph node mass has split into multiple components, only those 
elements that are > 1.0 cm in ≥ 1 diameter will be considered abnormal and used in 
calculating the SPD. Components that are ≤ 1.0 cm in the LD are assumed to be normal 
lymph node structures. PD will not be based on the growth of a lesion sub-component until 
it meets the criteria for abnormal. Lesion sub-components that are abnormal (> 1.0 cm in 
≥ 1 diameter) will have the true PPDs calculated with the result used only for calculating an 
accurate nadir. Lesion subcomponents that are normal (≤ 1.0 cm in the LD) will have the 
default PPD of 1.0 cm2 (1.0 cm x 1.0 cm) stored only for the purposes of calculating the 
nadir value.  
If lesions merge, a boundary between the lesions will be established so the LD of each 
individual lesion can continue to be measured. If the lesions have merged in a way that they 
can no longer be separated by this boundary, the newly merged lesion will be measured 
bidimensionally. 
1.4.3 
Extranodal Index Lesions  
An extranodal mass may be selected as an index lesion if it is both abnormal and 
measurable at baseline. An extranodal mass of any size is considered abnormal. It is 
considered measurable at baseline if it has 2 perpendicular diameters that can be 
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accurately measured in cross section with the LD being ≥ 1.0 cm and the LPD also being 
≥ 1.0 cm. 
At follow-up timepoints, the PPD of each single extranodal index lesion and the SPD of all 
extranodal index lesions will be considered. Because extranodal index lesions that have one 
or both diameters < 0.5 cm and > 0 cm cannot be reliably measured, a default value of 
0.5 cm will be assigned for each diameter that meets these criteria and the resulting PPD 
will be used in SPD calculations. If an extranodal lesion is no longer clearly visible, it will 
be considered resolved and its PPD will be defined as 0 cm2.  
If an extranodal lesion that had resolved (i.e., had a PPD of 0 cm2) subsequently reappears, 
the subject will be considered to have PD. A new extranodal lesion of any size that appears 
at a site that was not previously involved with lymphoma and is discernible to the 
radiologist by CT scan will be considered PD. 
1.4.4 
Non-Index Lesions 
Any other measurable and abnormal nodal or extranodal lesions not selected for 
quantitation as index lesions may be considered non-index lesions. In addition, non-
measurable evidence of lymphoma such as abnormal, non-measurable nodal lesions, 
extranodal lesions with both diameters < 1.0 cm, bone lesions, leptomeningeal disease, 
ascites, pleural or pericardial effusions, lymphangitis of the skin or lung, abdominal masses 
that are not confirmed and followed by imaging techniques, cystic lesions, previously 
irradiated lesions, or lesions with artifacts may be considered as non-index disease.  
If present at baseline, up to 6 non-index lesions should be recorded. Measurements are not 
required.  
Non-index disease will be used as a general reference to further characterize regression or 
progression of lymphoma during assessments of the objective tumor response during 
treatment. These lesions should be followed as “present” or “absent”. 
1.4.5 
Spleen and Liver 
Qualitative assessments of the sizes of the spleen and liver will be performed. In addition, 
the presence or absence of splenic nodules will be recorded.  
At baseline and follow-up timepoints, the spleen and liver size will be reported as normal, 
enlarged not due to lymphoma (no nodules present), enlarged due to lymphoma (≥ 1 nodule 
present), unequivocal increase not due to lymphoma (no nodules present), or unequivocal 
progression (≥ 1 nodule present). For subjects with splenomegaly or hepatomegaly at 
baseline or at the nadirs for assessments of spleen and liver, evaluations will consider only 
changes relative to the enlargement of the organ (i.e., the portion of the LVD that is 
> 12 cm by imaging for the spleen and > 18 cm in LVD for the liver) at baseline or nadir, 
not changes relative to the total splenic LVD. 
By imaging, the spleen will be considered enlarged if it is > 12 cm in LVD [Bezerra 2005, 
Asghar 2011], with the LVD being obtained by multiplying the number of sections on 
which the spleen is visualized by the thickness of the sections (e.g., if the spleen is seen in 
14 contiguous cross-sectional images with 0.5-cm thickness, the LVD is recorded as 7 cm). 
An increase in splenic enlargement by ≥ 50% (minimum increase of 2 cm) from nadir and 
the presence of ≥ 1 splenic nodule is required for declaration of splenic progression. 
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Subjects with a normal spleen LVD (i.e., a LVD of ≤ 0 cm by physical examination or 
≤ 12 cm by imaging) at nadir will only be considered to have progressed if the spleen 
attains a LVD of > 14 cm by imaging and there is ≥ 1 splenic nodule. 
By imaging, the liver will be considered enlarged if it is > 18 cm in LVD [Erturk 2006]. An 
increase in liver enlargement by ≥ 50% (minimum increase of 2 cm) from nadir and the 
presence of ≥ 1 hepatic nodule is required for declaration of hepatic progression. Subjects 
with a normal liver LVD (i.e., a LVD of ≤ 18 cm by imaging) at nadir will only be 
considered to have progressed if the liver attains a LVD of > 20 cm by imaging and there is 
≥ 1 hepatic nodule. 
1.4.6 
Bone Marrow 
Bone marrow assessments will be based on morphologic evaluation of bone marrow 
biopsies. Immunohistochemistry may be used to assess response if the sample is 
indeterminate by morphology.  
In a subject who has a baseline bone marrow biopsy showing bone marrow lymphoma or 
does not have a baseline bone marrow examination, declaration of an on-study CR requires 
bone marrow biopsy documentation of the absence of bone marrow lymphoma. In a 
subject who has a baseline bone marrow biopsy showing no evidence of lymphoma, 
declaration of an on-study CR does not require bone marrow examination as long as other 
criteria for CR are met. Of note, in subjects with an FDG-PET avid lymphoma, declaration 
of an on-study CR can be based on FDG-PET documentation of the absence of bone 
marrow involvement, even if a bone marrow biopsy is not performed or not available. 
1.4.7 
Lymph Node Biopsy 
Lymph node biopsy is not required in the determination of subject eligibility.  
During study participation, a subject with a more indolent type of disease (e.g., CLL/SLL, 
FL) who has a lymph node biopsy indicating transformation to an aggressive lymphoma 
will be considered to have PD even in the absence of other evidence of PD. If the subject 
has no earlier objective documentation of PD, the date of the lymph node biopsy will be 
considered the date of PD.  
1.5 
Definitions of Tumor Response and Progression 
Responses will be categorized as complete response (CR), partial response (PR), stable 
disease (SD), or progressive disease (PD). In addition, a response category of nonevaluable 
(NE) is provided for situations in which there is inadequate information to otherwise 
categorize response status.  
The best overall response will be determined. The best overall response is the best on-
treatment response from baseline recorded from the start of treatment until 
PD/recurrence. The baseline measurement will be taken as a reference for determinations 
of response. The nadir measurement will be taken as a reference for PD; this measurement 
constitutes the smallest measurement recorded, including the baseline measurement if this 
is the smallest measurement. For FDG-avid tumors, metabolic criteria for response by 
PET-CT will take precedence over anatomic criteria for response by contrast CT when 
assessing CR. 
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1.5.1 
Complete Response 
To satisfy criteria for CR, all of the following conditions must be attained: 
• No evidence of new disease 
• Regression of all index nodal lesions to normal size (≤ 1.5 cm in the LD for nodes that 
were considered large at baseline and ≤ 1.0 cm in the LPD for nodes that were 
considered small at baseline) (see Section 1.4.2 for definitions of large and small nodes) 
• Regression to normal of all nodal non-index disease  
• Disappearance of all detectable extranodal index and non-index disease 
• Normal spleen and liver size by imaging studies, no hepatic or splenic lymphoma 
nodules, and no new liver or spleen enlargement 
• Morphologically negative bone marrow based on an adequate unilateral core biopsy 
(> 20 mm unilateral core); if the sample is indeterminate by morphology, it should be 
negative by immunohistochemistry  
• If PET performed, no evidence of residual disease – i.e., score of 1 (no uptake above 
background), 2 (uptake ≤ mediastinum), or 3 (uptake > mediastinum but ≤ liver) on the 
Deauville 5-point scale. 
• Negative for bone marrow involvement by PET for a PET-avid tumor or by an 
adequate unilateral core biopsy (> 20 mm unilateral core); if the bone marrow biopsy is 
indeterminate by morphology, it should be negative by immunohistochemistry. 
1.5.2 
Partial Response 
To satisfy criteria for PR, all of the following conditions must be attained: 
• No evidence of new disease 
• A ≥ 50% decrease from baseline in the SPD of the index nodal and extranodal lesions  
• No increase from the nadir in the size of non-index disease 
• No increase from the nadir in the size of the liver or spleen and no new liver or spleen 
enlargement 
• If PET performed: 
o Typically FDG-avid lymphoma: if no baseline PET scan or if the PET scan was 
positive before therapy, the on-treatment PET is positive in ≥ 1 previously involved 
site– i.e., score of 4 (uptake moderately > liver) or score of 5 (uptake markedly 
> liver) on the Deauville 5-point scale but with reduced uptake compared with 
baseline. If baseline PET was performed and was negative, there is no new PET 
evidence of disease. 
o Variably FDG-avid lymphoma/FDG-avidity unknown: if no pretreatment PET scan 
or if the pretreatment PET scan was negative for lymphoma, CT criteria should be 
used in assessing the tumor during treatment. If the PET scan was positive before 
therapy, the on-treatment PET is positive in ≥ 1 previously involved site. 
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• Persistence of bone marrow involvement in a subject who meets other criteria for CR 
based on the disappearance of all nodal and extranodal masses 
1.5.3 
Stable Disease 
To satisfy criteria for SD, all of the following conditions must be attained: 
• No evidence of new disease 
• Neither sufficient tumor shrinkage from baseline to qualify for PR nor sufficient 
evidence of tumor growth to qualify for PD 
• If PET-CT performed, the results show a score of 4 (uptake moderately > liver) or score 
of 5 (uptake markedly > liver) on the Deauville 5-point scale with no significant change 
in uptake compared with baseline. 
1.5.4 Progressive Disease 
The occurrence of any of the following events indicates progressive disease (PD): 
• Evidence of any new disease that was not present at baseline: 
o A new node that measures > 1.5 cm in any diameter 
o A new node that measures > 1.0 cm to ≤ 1.5 cm in the LD and > 1.0 cm in the LPD 
o Reappearance of an extranodal lesion that had resolved (i.e., had previously been 
assigned a PPD of 0 cm2) 
o A new extranodal lesion of any size 
o New non-index disease (e.g., effusions, ascites, or other organ abnormalities) of any 
size unequivocally attributable to lymphoma (usually requires PET, biopsy, 
cytology, or other non-radiologic confirmation to confirm disease attributable to 
lymphoma). Note: Isolated new effusions, ascites, or bone lesions are not sufficient 
evidence alone of PD unless histologically confirmed. In patients with no prior history 
of pulmonary lymphoma, new lung nodules identified by CT are usually benign. Thus, 
a declaration of PD should not be made if this is the only manifestation of an 
apparently new lesion. 
o New FDG-avid foci consistent with lymphoma rather than another etiology (e.g., 
infection, inflammation). If there is uncertainty regarding the etiology of new 
lesions, biopsy or interval scan may be considered. 
o New or recurrent bone marrow involvement with lymphoma by PET-CT or by bone 
marrow biopsy if prior PET-CT or bone marrow biopsy performed as part of the 
study was negative for lymphoma. 
• Evidence of worsening of nodal or extranodal index lesions: 
o Increase from the nadir by ≥ 50% in the SPD of index lesions 
o Evidence of worsening of individual index lymph nodes or nodal masses:  
 Increase from the nadir by ≥ 50% in the PPD for any individual node if the node 
now has an LD of > 1.5 cm and there is an absolute change from the nadir of 
≥ 0.5 cm in the LD or LPD and to an absolute dimension of ≥ 2.0 cm. 
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 Increase from the nadir by ≥ 50% in the LD for any individual node if the node 
now has an LD of > 1.5 cm and there is an absolute change from the nadir of 
≥ 0.5 cm in the LD 
 Increase from the nadir by ≥ 50% in the LPD for any individual node if the node 
now has an LPD of > 1.5 cm and there is an absolute change from the nadir of 
≥ 0.5 cm in the LPD  
 If a lesion had been classified as a small lymph node, there is an additional 
requirement that the lesion has an LD of > 1.0 cm and an LPD of > 1.0 cm 
o Unequivocal increase in the size of non-index disease 
o Unequivocal worsening in the size of the liver or spleen (with the additional 
condition that there must be ≥ 1 nodule present in the enlarging organ) 
• Transformation to a more aggressive NHL histology as established by lymph node 
biopsy 
• If PET performed, there is a score of 4 (uptake moderately > liver) or score of 5 (uptake 
markedly > liver) on the Deauville 5-point scale with an increase in uptake compared 
with the nadir in conjunction with an anatomic increase in lesion size consistent with 
PD. 
Note: Study subjects undergoing PET for lymphoma assessment can experience transient 
disease flare on imaging before having subsequent therapy-induced tumor regression. 
Worsening of constitutional symptoms or performance status in the absence of objective 
evidence of worsening lymphoma (e.g., due to infection) may not represent definitive disease 
progression. Further, transient worsening of disease during temporary interruptions of study 
therapy (e.g., for drug-related toxicity or inter-current illness) may not indicate definitive 
progressive lymphoma. If there is uncertainty regarding whether there is true lymphoma 
progression and if medically appropriate, the subject may continue or resume study treatment 
and remain under close observation (e.g., evaluated at 3- to 6-week intervals) while relevant 
radiographic, clinical, and/or laboratory assessments are performed to document whether 
tumor control can be maintained or whether disease progression has truly occurred. If 
subsequent evaluations suggest that the subject has experienced persistent definitive disease 
progression, then the date of progression will be the timepoint at which progression was first 
objectively documented.  
1.5.5 
Nonevaluable 
In a subject who does not have evidence of PD, the occurrence of any of the following 
conditions indicates a response status of NE:  
• There are no images or inadequate or missing images, defined as the inability to 
visualize > 25% of index disease and > 50% of non-index disease. 
2 
Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma 
2.1 
Tumor Assessment Criteria 
The determination of CLL/SLL response and progression will be based on standardized 
criteria [Hallek 2008], as recently updated [Cheson 2012].  
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2.2 
Method of Assessment 
In addition to clinical examination, imaging-based evaluation will be used in this study in 
all subjects enrolled. CT scan is the preferred method for radiographic tumor assessment. 
MRI scanning may be used at the investigator’s discretion in subjects for whom this may 
be a preferred alternative to CT scanning; however, if MRI is performed, a non-contrast 
CT of the chest should be performed. Contrast-enhanced scanning is preferred, but iodine-
containing or gadolinium contrast material may be omitted in subjects for whom use of a 
contrast agent would be medically contraindicated. Chest x-ray, ultrasound, endoscopy, 
laparoscopy, PET, radionuclide scans, or tumor markers will not be considered for 
response assessment. 
For radiographic evaluations, the same method of assessment and the same technique (e.g., 
scan type, scanner, subject position, dose of contrast, injection/scan interval) should be 
used to characterize each identified and reported lesion at baseline and during study 
treatment and follow-up. However, if a subject is imaged without contrast at baseline, 
subsequent assessments should be performed with contrast, unless the subject cannot 
tolerate the contrast.  
All relevant clinical and radiographic information required to make each tumor status 
assessment must be made available for source verification as requested by the study 
sponsor. 
2.3 
Timing of Assessments 
During screening, clinical, laboratory, and imaging-based tumor assessments should be 
performed within the specified screening period. Clinical tumor assessments should be 
performed at each designated clinical visit. On-study CT/MRI tumor assessments should 
be performed as indicated in Section Changed. An end-of-study CT/MRI tumor assessment 
should be performed unless the subject already has radiographic confirmation of disease 
progression ≤ 4 weeks prior. If a subject permanently discontinues study drug prior to 
objective documentation of CLL/SLL progression, investigators should optimally attempt 
to obtain further follow-up at ~12-week intervals until CLL/SLL progression is 
documented or until the initiation of a new post-study therapy for the subject’s CLL/SLL.  
2.4 
Identification and Measurement of Tumor Lesions and Organomegaly 
2.4.1 
Index Lesions 
At baseline, up to 6 lymph nodes should be selected as index lesions that will be used to 
quantitate the status of the disease during study treatment. Ideally, the index lesions should 
be located in disparate regions of the body. Only peripheral nodes need be selected as index 
lesions. However, it is optimal if mediastinal and retroperitoneal areas of disease are 
assessed whenever these sites are involved. 
Index lesions will be measured and recorded at baseline and at the stipulated intervals. The 
cross-sectional dimensions (the largest cross-sectional diameter, i.e., the LD × LPD) will be 
recorded (in cm) for each index lesion. The product of the perpendicular diameters (PPD) 
(in cm2) for each index lesion and SPD (in cm2) for all index lesions will be calculated and 
recorded. The baseline SPD will be used as references by which objective tumor response 
will be characterized during treatment. The nadir LD of individual lesions and the nadir 
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SPD will be used as references by which CLL/SLL progression will be characterized. All 
LD and LPD diameters will be reported in centimeters and all PPDs and SPDs will be 
reported in centimeters squared. 
A nodal mass may be selected as a nodal index lesion if it is both abnormal and measurable 
at baseline. A lymph node lesion is considered abnormal if it has a single diameter that is 
> 1.5 cm and is considered measurable if it has 2 perpendicular diameters that can be 
accurately measured in cross section with the LD being ≥ 1.0 cm and the LPD also being 
≥ 1.0 cm. 
Index lesions measuring > 1.5 cm in the LD, regardless of the measurement of the LPD, will 
be prioritized during baseline index lesion selection. 
At follow-up timepoints, the LDs for individual lesions and the SPD of all nodal index 
lesions will be considered. Because nodal index lesions that have one or both diameters 
> 0 cm and < 1.0 cm cannot be reliably measured, a default value of 1.0 cm will be assigned 
for each diameter that meets these criteria and the resulting PPD will be used in SPD 
calculations. Based on this convention, a CR may be achieved even if an SPD value is 
> 0 cm2, (i.e., if all lymph nodes measure < 1.0 cm2). 
A new node that measures > 1.5 cm in any diameter or a new node that measures > 1.0 cm 
to ≤ 1.5 cm in the LD and measures > 1.0 cm in the LPD will be considered progressive 
disease. 
In cases in which a large lymph node mass has split into multiple components, only those 
elements that are > 1.0 cm in ≥ 1 diameter will be considered abnormal and used in 
calculating the SPD. Progression of the lesion can only be based on the SPD of abnormal 
sub-components. Lesion sub-components that are considered normal but measurable will 
have the true PPDs calculated, with the result used only for calculating an accurate nadir. 
Similarly, lesion sub-components that are visible but neither abnormal nor measurable will 
have the default PPD of 1.0 cm2 (1.0 cm × 1.0 cm) stored only for the purposes of 
calculating the nadir SPD value. 
If lesions merge, a boundary between the lesions will be established so the LD of each 
individual lesion can continue to be measured. If the lesions have merged in a way that they 
can no longer be separated by this boundary, the newly merged lesion will be measured bi-
dimensionally. 
2.4.2 
Spleen and Liver 
Both the spleen and liver will be assessed by CT/MRI scan and by physical examination at 
baseline and at the stipulated intervals during treatment. The baseline and nadir values for 
the longest vertical dimension (LVD) of each organ will be used as reference to further 
characterize the objective tumor response of the measurable dimensions of the CLL/SLL 
during treatment. All spleen and liver LVD measurements should be recorded in 
centimeters. 
Physical examination of the spleen should comprise assessment of its LVD below the left 
costal margin by palpation. By physical examination, the spleen will be considered 
enlarged if it is palpable below the left costal margin. If the spleen is not palpable below the 
left costal margin, it should be assigned a value of 0 cm for physical examination 
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assessment. By imaging, the spleen will be considered enlarged if it is > 12 cm in LVD 
[Bezerra 2005, Asghar 2011], with the LVD being obtained by multiplying the number of 
sections on which the spleen is visualized by the thickness of the sections (e.g., if the spleen 
is seen in 14 contiguous cross-sectional images with 0.5-cm thickness, the LVD is recorded 
as 7 cm).  
For subjects with splenomegaly at baseline or at the splenic LVD nadir, respective response 
and progression evaluations of the spleen will consider only changes relative to the 
enlargement of the spleen (i.e., the portion of the LVD that is > 0 cm by physical 
examination or > 12 cm by imaging) at baseline or nadir, not changes relative to the total 
splenic LVD.  
A 50% decrease from baseline (minimum decrease of 2 cm) in the enlargement of the 
spleen in its LVD or to ≤ 12 cm by imaging, or regression to a spleen LVD of ≤ 0 cm by 
physical examination, is required for declaration of a splenomegaly response. Conversely, 
an increase in splenic enlargement by ≥ 50% (minimum increase of 2 cm) from nadir is 
required for declaration of splenic progression. Subjects with a normal spleen LVD (i.e., a 
LVD of ≤ 0 cm by physical examination or ≤ 12 cm by imaging) at nadir will only be 
considered to have progressed if the spleen attains a LVD of > 14 cm by imaging or > 2 cm 
by physical exam. 
Physical examination of the liver should comprise assessment of its LVD at the right 
midclavicular line by percussion. By physical examination, the liver will be considered 
enlarged if it is > 15 cm in LVD as assessed by percussion [Walker 1990]. By imaging, the 
liver will be considered enlarged if it is > 18 cm in LVD [Erturk 2006]. 
A 50% decrease (minimum decrease of 2 cm) from baseline in the enlargement of the liver 
in its LVD or to ≤ 18 cm by imaging, or regression to a liver LVD of ≤ 15 cm by physical 
examination, is required for declaration of a hepatomegaly response. Conversely, an 
increase in liver enlargement by ≥ 50% (minimum increase of 2 cm) from nadir is required 
for declaration of hepatic progression. Subjects with a normal liver LVD (i.e., a LVD of 
≤ 15 cm by physical examination or ≤ 18 cm by imaging) at nadir will only be considered to 
have progressed if the liver attains a LVD of > 20 cm by imaging or > 17 cm by physical 
exam. 
2.4.3 
Non-Index Lesions 
Any other measurable and abnormal nodal lesions not selected for quantitation as index 
lesions may be considered non-index lesions. In addition, non-measurable evidence of 
CLL/SLL such as nodal lesions with both diameters < 1.0 cm, extranodal lesions, bone 
lesions, leptomeningeal disease, ascites, pleural or pericardial effusions, lymphangitis of the 
skin or lung, abdominal masses that are not confirmed and followed by imaging 
techniques, cystic lesions, previously irradiated lesions, and lesions with artifacts may be 
considered as non-index disease. 
The presence or absence of non-index disease should be recorded at baseline and at the 
stipulated intervals during treatment. If present at baseline, up to 6 non-index lesions 
should be recorded. The non-index disease at baseline will be used as a general reference to 
further characterize regression or progression of CLL/SLL during assessments of the 
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objective tumor response during treatment. Measurements are not required and these 
lesions should be followed as “present” or “absent”. 
2.5 
Definitions of Tumor Response and Progression  
Responses will be categorized as complete response (CR), partial response (PR), stable 
disease (SD), or progressive disease (PD). In addition, a response category of nonevaluable 
(NE) is provided for situations in which there is inadequate information to otherwise 
categorize response status.  
The best overall response will be determined. The best overall response is the best response 
recorded from the start of treatment until disease/recurrence progression (taking as a 
reference for disease progression the smallest measurements recorded since treatment 
started). Subjects with a best overall response of NE or ND will be counted in the 
denominators in calculations of tumor response rates. Where imaging data are available, 
these data will supersede physical examination data in determining tumor status. 
2.5.2 
Complete Response and Complete Response with Incomplete Blood Count 
Recovery 
To satisfy criteria for CR or CRi, all of the following conditions must be attained:  
• No evidence of new disease 
• Absolute lymphocyte count (ALC) in peripheral blood of < 4 x 109/L 
• Regression of all index nodal masses to normal size ≤ 1.5 cm in the LD 
• Normal spleen and liver size 
• Regression to normal of all nodal non-index disease and disappearance of all detectable 
non-nodal, non-index disease 
• Morphologically negative bone marrow defined as < 30% of nucleated cells being 
lymphoid cells and no lymphoid nodules in a bone marrow sample that is normocellular 
for age 
• Peripheral blood meeting all of the following criteria: 
o ANC ≥ 1.5 x 109/L without need for exogenous growth factors (e.g., G-CSF) 
o Platelet count ≥ 100 x 109/L without need for exogenous growth factors 
o Hemoglobin ≥ 110 g/L (11.0 g/dL) without red blood cell transfusions or need for 
exogenous growth factors (e.g., erythropoietin) 
Note: Subjects who fulfill all the criteria for a CR (including bone marrow criteria) but who 
have a persistent anemia, thrombocytopenia, or neutropenia or a hypocellular bone marrow 
that is related to prior or ongoing drug toxicity (and not to CLL/SLL) will be considered as a 
CR with incomplete marrow recovery (CRi).  
2.5.3 
Partial Response 
To satisfy criteria for a PR, all of the following conditions must be attained: 
• No evidence of new disease 
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• A change in disease status meeting ≥ 2 of the following criteria, with 2 exceptions in 
which only 1 criterion is needed: (1) Only lymphadenopathy is present at baseline; or 
(2) only lymphadenopathy and lymphocytosis are present at baseline; in these 2 cases, 
only lymphadenopathy must improve to the extent specified below:  
o Decrease in peripheral blood ALC by ≥ 50% from baseline 
o A decrease by ≥ 50% from the baseline in the SPD of the index nodal lesions 
o In a subject with enlargement of the spleen at baseline, a splenomegaly response as 
defined in Section 2.4.2 
o In a subject with enlargement of the liver at baseline, a hepatomegaly response as 
defined in Section 2.4.2 
o A decrease by ≥ 50% from baseline in the CLL/SLL marrow infiltrate or in 
B-lymphoid nodules 
• No index, splenic, liver, or non-index disease with worsening that meets the criteria for 
definitive PD 
• Peripheral blood meeting ≥ 1 of the following criteria: 
o ANC ≥ 1.5 x 109/L or ≥ 50% increase over baseline without need for exogenous 
growth factors (e.g., G-CSF) 
o Platelet count ≥ 100 x 109/L or ≥ 50% increase over baseline without need for 
exogenous growth factors 
o Hemoglobin ≥ 10 g/L (11.0 g/dL) or ≥ 50% increase over baseline without red blood 
cell transfusions or need for exogenous growth factors (e.g., erythropoietin) 
2.5.3 
Stable Disease 
To satisfy criteria for SD, the following conditions must be attained: 
• No evidence of new disease 
• There is neither sufficient evidence of tumor shrinkage to qualify for PR nor sufficient 
evidence of tumor growth to qualify for definitive PD 
2.5.4 
Progressive Disease 
The occurrence of any of the following events indicates PD:  
• Evidence of any new disease: 
o A new node that measures > 1.5 cm in any diameter 
o New splenomegaly as defined in Section 2.4.2 
o New hepatomegaly as defined in Section 2.4.2 
o New non-index disease (e.g., effusions, ascites, or other organ abnormalities related 
to CLL/SLL) 
Note: Isolated new effusions, ascites, or other organ abnormalities are not sufficient 
evidence alone of PD unless histologically confirmed. Thus, a declaration of PD 
should not be made if this is the only manifestation of apparently new disease. 
• Evidence of worsening of index lesions, spleen or liver, or non-index disease:  
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o Increase from the nadir by ≥ 50% from the nadir in the SPD of index lesions 
o Increase from the nadir by ≥ 50% in the LD of an individual node or extranodal 
mass that now has an LD of > 1.5 cm and an LPD of > 1.0 cm 
o Splenic progression as defined in Section 2.4.2 
o Hepatic progression as defined in Section 2.4.2 
o Unequivocal increase in the size of non-index disease (e.g., effusions, ascites, or other 
organ abnormalities related to CLL/SLL)  
o Transformation to a more aggressive histology (e.g., Richter syndrome) as 
established by lymph node biopsy (with the date of the lymph node biopsy being 
considered the date of CLL/SLL progression if the subject has no earlier objective 
documentation of CLL/SLL progression) 
• Decrease in platelet count or hemoglobin that is attributable to CLL/SLL, is not 
attributable to an autoimmune phenomenon, and is confirmed by bone marrow biopsy 
showing an infiltrate of clonal CLL/SLL cells 
o The current platelet count is < 100 x 109/L and there has been a decrease by > 50% 
from the highest on-study platelet count  
o The current hemoglobin is < 110 g/L (11.0 g/dL) and there has been a decrease by 
> 20 g/L (2 g/dL) from the highest on-study hemoglobin  
Note: If there is uncertainty regarding whether there is true progression, the subject should 
continue study treatment and remain under close observation (e.g., evaluated at 4-week 
intervals) pending confirmation of progression status. In particular, worsening of 
constitutional symptoms in the absence of objective evidence of worsening CLL/SLL will not 
be considered definitive disease progression; in such subjects, both CLL/SLL-related and 
non-CLL/SLL-related causes for the constitutional symptoms should be considered. 
Worsening of disease during temporary interruption of study treatment (e.g., for intercurrent 
illness) is not necessarily indicative of resistance to study treatment. In these instances, 
CT/MRI or other relevant evaluations should be considered in order to document whether 
definitive disease progression has occurred. If subsequent evaluations suggest that the subject 
has experienced persistent definitive CLL/SLL progression, then the date of progression 
should be the timepoint at which progression was first objectively documented. 
2.5.5 
Nonevaluable 
In a subject who does not have evidence of PD, the occurrence of any of the following 
conditions indicates a response status of NE:  
• There are no images or inadequate or missing images 
• Images of the liver and spleen are missing at that timepoint (with the exception that 
absence of splenic images will not result in an NE designation in a subject known to 
have undergone splenectomy). 
2.5.6 
Lymphocytosis during Therapy 
Lymphocytosis early in therapy may not represent disease progression in subjects who 
have persistent control of other CLL/SLL-related signs and symptoms. In the absence of 
other objective evidence of disease progression, lymphocytosis alone will not preclude subjects 
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from meeting the criteria for PR if other criteria for PR are met and will not be considered 
evidence of disease progression if occurring in isolation. Subjects with lymphocytosis should 
be continued on study drug until the occurrence of definitive disease progression (i.e., 
disease progression that is manifest by worsening CLL/SLL-related signs other than 
lymphocytosis alone), or the occurrence of another reason to discontinue study therapy.  
Changes made in Amendment 4 (07 Nov 2016) 
Title Page 
Change: The protocol version and date have been updated. 
Protocol Version and Date: 
 
Version 5.0, 07 Nov 2016 
Version 4.0; 21 Mar 2016  
Investigator’s Agreement 
Change: The date has been updated. 
I have read the attached Protocol entitled “A Phase 1 Dose Escalation Study of the Safety and 
Pharmacokinetics of LAM-002A (apilimod dimesylate capsules) Administered Orally in 
Subjects with Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma” dated 07 Nov 201621 
Mar 2016.  
Synopsis 
Changes:  All changes to the synopsis also occur in the body of the protocol. Thus, changes to 
the synopsis are not described; instead, changes to the body of the protocol are 
described. 
Abbreviations 
Change:  An abbreviation has been added. 
TID 
Thrice per day 
Section 4.1 
Product Summary 
Change: 
The description of the drug product has been updated with information relating to the 
newly introduced 50-mg capsule. 
LAM-002A (apilimod dimesylate capsule) is intended for oral administration. Each capsule 
will contain 25 mg or 50 of apilimod dimesylate (equivalent to 17.1 mg or 34.3 mg of 
apilimod free base, respectively). The 25-mg capsule is Swedish orange and the 50-mg 
capsule is white. Both the 25- and 50-mg capsules are Size 0 and both have a total fill 
weight of 175 mg. 
Inactive components in active capsules are microcrystalline cellulose Avicell PH102, 
silicified microcrystalline cellulose, anhydrous lactose, croscarmellose sodium (Ac-Di-Sol), 
colloidal silicon dioxide, and magnesium stearate.  
LAM 002A (apilimod dimesylate capsule) is intended for oral administration. LAM 002A is 
formulated as a blend with excipients in Size 0 Swedish Orange gelatin capsules. Each capsule 
will contain 25 mg of apilimod dimesylate (equivalent to 17.1 mg of apilimod free base) and the 
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total fill weight of each capsule will be 175 mg. The claimed dosage strength of the active 
ingredient will be expressed in the free base form of apilimod. Manufacture of a 50 mg capsule is 
planned as part of the ongoing development program.  
Inactive components in active capsules are anticipated to be microcrystalline cellulose Avicell 
PH102, silicified microcrystalline cellulose, anhydrous lactose, croscarmellose sodium 
(Ac Di Sol), colloidal silicon dioxide and magnesium stearate.  
Section 4.1.4.2 
Efficacy 
Change: 
The description of drug efficacy has been updated. 
Efficacy data in patients with hematological malignancies are pending. One patient, a 
60-year-old male with GCB-DLBCL who was had experienced minimal or no response to 
multiple prior chemoimmunotherapy regimens (including R-CHOP), received apilimod 
dimesylate at 100 mg/dose BID for 6 weeks before enlarging right axillary 
lymphadenopathy required cessation of study drug and intervention with local radiation 
therapy. A follow-up PET-CT, obtained approximately 2 weeks later, showed a substantial 
systemic decrease in DLBCL lesions in non-irradiated lymph nodes, liver, spleen, and bone 
(C4 vertebra); these improvements in disease burden were attributed by the investigator to 
the study drug. There is no efficacy data in patients with NHL or other malignancies. 
Section 4.1.4.3 
Safety  
Change: 
The description of drug safety has been updated. 
Apilimod dimesylate has been generally well tolerated in humans. In patient populations with 
Crohn’s disease or psoriasis, more frequent (> 10%) AEs experienced to date included headache, 
upper respiratory tract infection, and nausea; less frequent (> 5% to 10%) AEs included 
dizziness, fatigue, and nasopharyngitis; and rare (2% to 5%) AEs included diarrhea, arthralgia, 
fever, abdominal pain, peripheral edema, and vomiting. In general, most AEs were assessed as 
mild in severity. In the ongoing trial of apilimod dimesylate in patients with hematological 
cancers, dose-dependent gastrointestinal events of nausea, vomiting, and diarrhea have 
been observed. 
No renal insufficiency has been observed in completed clinical trials to date and no clinically 
significant safety signals in laboratory, physical examination, or vital sign findings have been 
noted. One patient with a hematological malignancy receiving the drug at 150 mg BID 
developed asymptomatic Grade 3 hyponatremia that was attributed to the combined effects 
of a apilimod-dimesylate-induced diarrhea and hydrochlorothiazide administration. 
Cardiac monitoring in clinical studies to date has not revealed any major issues. However in a 
thorough QT/QTc study, apilimod dimesylate at doses of 50 mg and 150 mg was associated with 
repolarization findings in excess of those deemed negative by International Conference on 
Harmonisation (ICH) E14 guidance. The magnitude of the change was modest (~8.5 msec) and 
the root-mean-square based analyses did not demonstrate as large an increase in cardiac 
repolarization time (≤ 1.22 msec) as that identified using the Fridericia method. Therefore the 
significance of this finding is unclear. Preliminary QTc observations in the ongoing study in 
patients with hematological malignancies suggest the potential for dose- and 
exposure-dependent Grade 1 or 2 QT prolongation. 
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In totality, the nonclinical and clinical data collected to date support the exploration of apilimod 
dimesylate in patients with NHL. 
Section 4.1.6. 
Previous Clinical Experience with Apilimod and Apilimod Dimesylate in 
Nonmalignant Conditions 
Change: 
The title of the section has been clarified, as noted above. 
SECTION 6 
INVESTIGATIONAL PLAN 
Changes: Information in Subsections 6.1, 6.2, and 6.5 regarding the dose-escalation and 
sample sizes has been updated to reflection inclusion of additional dose levels and 
schedules. 
 
Subsection 6.4.3,1 has been clarified to indicate that all subjects will be followed for 
survival and to provide additional information regarding out how that follow-up will 
be performed. 
6.1 
Overall Study Design 
This is a Phase 1, single-arm, open-label, dose-escalation study of safety and PK of apilimod 
administered to subjects with refractory or relapsed B-cell NHL. This study consists of 2 stages: 
6.1.1 
Dose Escalation Stage 
The maximum tolerated dose (MTD) will be determined during the Dose Escalation Stage. 
Subjects will accrue using a 3 + 3 design. During this stage, the decision to open a new cohort at 
a higher or lower dose level will be made by the participating clinical investigators and sponsor 
when all subjects in the current cohort have been treated through at least Week 4 or once 2 DLTs 
have occurred in that dose cohort. All available safety and PK data will be considered in a 
decision by the medical monitor in collaboration with the investigators to dose escalate, de-
escalate, or expand the current cohort or explore an alternate schedule of drug 
administration. The MTD will be determined based primarily on DLTs observed through 
Week 4 in at least 6 subjects.  
6.1.2 
Expansion Stage 
Once the MTD and/or Recommended Phase 2 Dose (RP2D) and schedule is determined, the 
study will enter the Expansion Stage, in which 3 cohorts of 15 subjects each will be accrued in 
order to obtain additional information on safety, tolerability, preliminary anti-tumor activity, PK, 
and pharmacodynamic data at the RP2D and schedule. The eligibility criteria will remain the 
same as in escalation but each cohort will be specific to subjects with DLBCL, FL, and 
CLL/SLL, respectively. The treatment regimen in each of the expansion cohorts will be single 
agent LAM-002A (apilimod dimesylate capsules) according to the RP2D and schedule. 
6.2 
Number of Subjects 
Approximately 115 75 evaluable subjects (evaluable subjects include those who complete Cycle 
1 dosing [administered at least 75% of doses] and have sufficient safety data, or who are 
withdrawn from the study due to a DLT in Cycle 1) will be enrolled, assuming that: 
• In the Dose Escalation Stage of the study, the total number of subjects will depend 
upon the numbers of subjects accrued to each dose level and the number of dose 
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levels evaluated. If 6 subjects are enrolled at all 9 possible starting dose levels and 
6 additional subjects are enrolled at the MTD or RD, as many as 60 subjects could be 
enrolled. To allow for the possibility that some subjects may not be fully evaluable 
for DLT or that an intermediate dose level might be evaluated, up to ~70 subjects 
may be enrolled5 dose levels will be studied and a maximum of 6 subjects will be 
enrolled per dose level, for an estimated total of 18 to 30 evaluable subjects.  
• In the Expansion Stage of the study, if all 3 potential expansion cohorts of 
15 evaluable subjects are accrued, as many as 45 subjects could be enrolled. To allow 
for the possibility that some subjects may not be fully evaluable for efficacy, up to 
~55 subjects may be enrolled. Up to an additional 45 evaluable subjects (3 cohorts of 
15 subjects) will be enrolled in the Expansion Stage of the study. Subjects will be 
treated at the RP2D and schedule determined in the Dose Escalation Stage of the 
study. 
6.4.3.1 
Post-Treatment Period 
Subjects should be followed until the later of either 30 days after the last dose of study treatment 
or until resolution/stabilization of any ongoing drug-related AEs and/or SAEs. For subjects with 
events that require follow-up, information regarding concomitant medications should be 
collected. Any necessary follow-up may be obtained in person or by telephone contact. 
Subjects who have discontinued study treatment for reasons other than PD will be assessed per 
Revised Response Criteria for NHL or Guidelines for the diagnosis and treatment of CLL at a 
minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for 
up to 1 year from the last enrolled subject’s first treatment (Cycle 1 Day 1) whichever comes 
first. Long-term follow-up survival information will be obtained in all surviving subjects 
who permanently discontinue study therapy. Such information may be collected at ~3- to 6-
month intervals at the sponsor’s discretion through 3 years. This long-term follow-up 
information will be gathered during routine clinic visits, other study site contact with the 
subjects, or via telephone or e-mail with the subjects/caregivers or referring physician 
offices.Survival of all subjects will be followed by the investigator via telephone contact every 
3 months. 
6.5 
Dose Escalation Procedures 
Apilimod dimesylate will be administered on a twice daily (BID) or thrice daily (TID) oral 
dosing regimen with a cycle length of 28 days. Subjects on a BID schedule will be advised to 
take the doses at the same time each day, approximately ~12 hours apart. Subjects on a TID 
schedule will be advised to take the doses at the same time each day at intervals of ~6 to 
8 hours. On PK days, subjects on a TID schedule should receive the morning dose and 
complete the blood collections through 8 hours thereafter before taking the second dose on 
that day.  
Other drug administration Less dose intensive schedules may be considered if the initial BID 
or TID regimen’s safety, PK and/or pharmacodynamics suggest that a different schedule would 
be better tolerated and might allow for serum exposures required for anti-lymphoma activity. 
This might include a treatment break such as 3 weeks on/1 week off treatment or 5 days on/2 
days off over a 4-week cycle or an asymmetric (AM dosing > PM dosing) or once-daily dosing 
schedule. If a less dose intensiveanother treatment regimen is evaluated, then the initial dose 
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tested on this schedule will be no higher than the totala daily dose that has been previously 
evaluated and tolerated on the more dose intensive, BID schedule.  
Cohorts of 3 to 6 subjects will be sequentially enrolled at progressively higher starting dose 
levels of apilimod dimesylate, as indicated in Table 2. The initial cohort of subjects will be 
prescribed apilimod dimesylate at Dose Level 0 (50 mg BID). Dose level -1 (25 mg BID) is 
provided to permit a dose decrement in subjects experiencing DLT at Dose Level 0. 
Table 2: 
LAM-002A Provisional Starting Dose Levels 
Dose  
Level 
Apilimod Dimesylate Dose  
mg/dose 
Apilimod Dimesylate Dose 
mg/day 
-1  
25 mg BID 
50 
0 (Initial Dose Level) 
50 mg BID 
100 
1 
100 mg BID 
200 
1a 
125 mg BID 
250 
1b 
75 mg TID 
225 
1c 
100 mg TID 
300 
1d 
125 mg TID 
375 
2 
150 mg BID 
300 
3 
200 mg BID 
400 
4 
275 mg BID 
550 
Abbreviations: BID: Twice daily (or 2 times per day); TID: Thrice daily (or 3 times per day) 
 
 
Daily LAM 002A Dose  
Percent Increase  
Initial Cohort Size 
1 
25 mg BID 
50 
3 
0 
50 mg BID 
Starting dose 
3 
1 
100 mg BID 
100 
3 
2 
150 mg BID 
50 
3 
3 
200 mg BID 
33 
3 
4 
275 mg BID 
37.5 
3 
Abbreviations: BID: Twice daily (or 2 times a day) 
A 3 + 3 design will be utilized to define an MTD. For cohorts consisting of 3 subjects, dose 
escalation to the next higher dose may proceed if no DLT is observed within the first cycle of the 
3 evaluable subjects accrued to a cohort (See Section 6.1.1). If 1 of 3 subjects in the cohort 
experiences a DLT, up to a total of 6 evaluable subjects will be enrolled. If 2 or more of the 3-6 
evaluable subjects in a cohort experience a DLT, dose escalation will cease, and additional 
subjects will be treated at a lower dose level or with another schedule. If de-escalation to the 
previous dose cohort is undertaken, this cohort will be expanded to ≥6 subjects. Additional 
subjects (up to 12 total per cohort) may be evaluated to refine the estimation of the MTD 
and RP2D at the planned dose levels or at an intermediate dose level between the highest 
previously tolerated total dose and the next planned total daily dose. The MTD is defined as 
the highest dose at which no more than 1 of 6 subjects (i.e., < 33% of subjects) experiences a 
DLT in the total dose cohort. 
Dose escalation decisions will be evaluated in a DLT evaluable population. The DLT evaluable 
population will include subjects who complete Cycle 1 dosing or who are withdrawn from study 
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due to a DLT in Cycle 1. A subject will be deemed non-evaluable for determining DLTs and will 
not be counted toward the total cohort size if the subject did not experience a DLT, did not 
receive at least 75% (42/56 BID schedule; 63/84 TID schedule) of the planned first-cycle doses 
or discontinued from the study prior to completing necessary safety evaluations through the first 
28 days of study treatment. These subjects may be replaced unless accrual to the cohort has 
stopped due to DLT. 
Following the above guidelines, the participating investigators and sponsor will review available 
data including toxicity, PK and anti-tumor activity data to reach consensus on dose levels and 
determination of the MTD. This group will review available safety data for each cohort and will 
determine whether the MTD has been reached and decide upon further subject enrollment. Any 
detected cumulative toxicity may require later dose reductions or other action as appropriate, and 
may also have an effect onbe evaluated in determining the RP2D and schedule.  
The RP2D and schedule will be determined in discussion between the sponsor and participating 
investigators. Observations related to PK, pharmacodynamics and any drug-related toxicities 
may be included in the rationale supporting the RP2D and schedule. 
Once the RP2D and schedule are established, additional subjects will be treated in 
3 histologically distinct dose expansion cohorts designed to better characterize the safety, 
tolerability, preliminary anti-tumor activity, PK, and pharmacodynamics of the study drug when 
provided at the MTD (or lower dose per agreement of the investigators and sponsor) in a specific 
B-cell NHL subtype. Up to 15 subjects will be treated in each expansion cohort. 
Section 6.6.2 Description of Study Drug 
Change: 
The description of the drug product has been updated with information relating to the 
newly introduced 50-mg capsule. 
LAM-002A (apilimod dimesylate capsule) is intended for oral administration. Each capsule 
will contain 25 mg or 50 of apilimod dimesylate (equivalent to 17.1 mg or 34.3 mg of 
apilimod free base, respectively). The 25-mg capsule is Swedish orange and the 50-mg 
capsule is white. Both the 25- and 50-mg capsules are Size 0 and both have a total fill 
weight of 175 mg. LAM 002A (apilimod dimesylate capsule) is intended for oral administration. 
Each capsule will contain 25 mg of apilimod dimesylate (equivalent to 17.1 mg apilimod free 
base) and the total fill weight of each capsule will be 175 mg. LAM 002A is formulated as a 
blend with excipients in Size 0 Swedish Orange gelatin capsules. For additional information, see 
Section 9.1. 
Section 6.6.4 LAM-002A (Apilimod Dimesylate Capsules) Self-Administration 
Change: 
Information has been updated to reflection inclusion of additional dose levels and 
schedules. 
Except for the days where treatment is administered in the clinic, LAM-002A (apilimod 
dimesylate capsules) will be self-administered orally, BID or TID of each 28-day cycle until 
disease progression or other discontinuation criteria are met. When taking the drug at home, 
sSubjects should be advised to take study drug with ≥ 4 oz. (~160 mL) of water at the same times 
each day,. Subjects on a BID schedule will be advised to take the doses at approximately 
12 hours apart (e.g., 8 AM and 8 PM) (+/- 1 hour window). Subjects on a TID schedule will be 
advised to take the doses at intervals of ~6 to 8 hours. When self-administering the study drug 
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at home, subjects may take the drug in the fed or fasted state. On PK days, subjects should come 
to clinic fasted (a minimum fasting state of 6 to 8 hours) and take the dose at the site under 
supervision. All subjects will be required to complete a Dosing Diary, which must be returned to 
the site for review at each site visit. 
Section 6.6.5 
Dose Schedule Interruptions and Vomited Doses 
Change: 
Information has been updated to reflection inclusion of additional dose levels and 
schedules. 
Subjects on a BID schedule who have a delay in administration of a dose of apilimod dimesylate 
of <6 hours should take the planned dose as soon as possible after the intended time of 
administration. For subjects who have a delay in administration of apilimod dimesylate of 
≥6 hours, the dose should not be taken. The planned timing of subsequent apilimod dimesylate 
dosing should not be altered.  
Subjects on a TID schedule who inadvertently have a delay in administration of a dose of 
the study drug of ≤1 hour, the planned dose should be taken with no changes to the 
subsequent dose schedule. For subjects who have a delay of >1 hour but ≤4 hours, the 
planned dose should be taken; however, all future doses for that day should be shifted later 
by a corresponding amount. It is recommended that subjects take the last dose of study 
medication no later than 12:00 midnight on any study treatment day.  For example, if the 
07:00 AM dose is taken at 10:00 AM, the next dose should be taken ≥6 hours later (after 
5:00 PM), and the last dose should be taken ≥6 hours thereafter (between 11:00PM and 
12:00 midnight). For subjects on a TID schedule who have a delay in administration of 
study drug of >4 hours, the dose should not be taken. Study drug administration may 
continue but the missed dose should not be made up and the planned timing of subsequent 
study drug dosing should not be altered. 
For subjects who vomit shortly after taking apilimod dimesylate, the vomited dose should not be 
replaced. The planned timing of subsequent apilimod dimesylate dosing should not be altered. 
Section 6.6.6 
Dose Modifications 
Change: 
Information has been updated to reflection inclusion of additional dose levels and 
schedules. 
If a subject experiences an AE that is suspected to be related to apilimod dimesylate, appropriate 
supportive care (e.g., antiemetics, antidiarrheals, therapy for tumor lysis syndrome [TLS]) should 
be instituted consistent with the nature of the event.  
If a subject experiences an apilimod dimesylate-related DLT (reference Section Deleted) or 
other AE requiring a dose modification, then the study drug administration should be 
interrupted until the toxicity recovers to Grade ≤ 1 or baseline. Upon resumption of study drug, 
the total daily dose of apilimod dimesylate should be reduced using an appropriate by 1 dose 
level or schedule (reference Section Deleted) as agreed between the investigator and medical 
monitor. Successive adjustments to progressively lower total daily dose levels can be made. If 
the subject cannot tolerate apilimod dimesylate after a decrease to Dose Level -1 (25 mg BID), 
then the subject should be discontinued from apilimod dimesylate therapy unless continued 
treatment is permitted by the medical monitor.  
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After the apilimod dimesylate dose is reduced, the dose can be maintained at that dose level or 
schedule, even if there is minimal or no toxicity with the reduced dosing regimen. However, if 
the subject tolerates a reduced total daily dose of apilimod dimesylate for ≥ 4 weeks then the 
apilimod dimesylate dosing regimen may be reescalated to the nexta higher total daily dose 
level at the discretion of the investigator and with the concurrence of the medical monitor. 
Such reescalation may be particularly warranted if the AE comprised TLS or if further evaluation 
reveals that the AE that led to the dose reduction was not related to apilimod dimesylate. 
Successive adjustments to progressively higher total daily dose levels can be made. However, 
the escalated dose cannot exceed the total daily starting dose level for that subject during the 
first 4 cycles of therapy.  
Individual subjects who initiated treatment at a total daily dose level below the lower of the 
currently established MTD or the RP2D and who have not experienced a DLT after ≥ 4 cycles of 
treatment may have the apilimod dimesylate total daily dose escalated to the next higher dose 
level if both the principal investigator and the medical monitor agree that a dose escalation is 
medically warranted (e.g., for a subject with stable disease who is tolerating the current dose 
level of apilimod dimesylate therapy). In such subjects, successive adjustments to progressively 
higher total daily dose levels can be made at intervals of ≥ 4 weeks with the condition that the 
escalated total daily dose level cannot exceed the lower of the currently established MTD or 
RP2D.  
In a subject who experiences a DLT precluding resumption of apilimod dimesylate therapy 
during a cycle, a new cycle of treatment may begin at the later of Day 29 or when AEs or 
laboratory abnormalities related to apilimod dimesylate have returned to baseline levels. If drug-
related AEs or laboratory abnormalities precluding further administration of study drug are not 
resolved to baseline by Day 29, week-by-week delays in initiating the new cycle of treatment 
should be instituted. When all drug-related AEs and laboratory abnormalities have returned to 
baseline, the next cycle of therapy can be initiated. Upon initiation of a new cycle of therapy, the 
prior cycle of therapy will be considered completed. 
Investigators are to discuss modifications in the dosing regimen with the medical monitor. The 
appropriate clinic staff should dispense the study drug for the new dose level or schedule and 
instruct the subject/caregiver about the change in dose levelthe dosing regimen. 
Section 6.6.7 
Definition of Dose-Limiting Toxicity (DLT) 
Change: 
Information has been updated to reflection inclusion of additional schedules. 
Table 3: 
Criteria for Defining Dose-Limiting Toxicities (DLTs) 
Toxicity 
Criteria 
Treatment 
interruption/delays 
Inability to administer ≥28/56 (BID schedule) or ≥42/84 (TID schedule) 
planned apilimod dimesylate doses in a treatment cycle due to drug-related AEs 
or 
Failure to recover from apilimod-dimesylate-related toxicities to baseline within 
14 days from the last dose of study drug in a cycle 
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Section 6.6.9 
Duration of Subject Participation 
Change: 
The section has been clarified to indicate that all subjects will be followed for 
survival and to provide additional information regarding out how that follow-up will 
be performed. 
All subjects will be treated for at least 1 cycle unless there is evidence of unacceptable toxicity or 
PD. Although subjects may continue to receive study treatment until experiencing unacceptable 
toxicity or disease progression, it is estimated that each subject will participate for an average of 
6 months of treatment and an additional 1 month of follow-up. Subjects who have discontinued 
study treatment for reasons other than PD will be assessed per Revised Response Criteria for 
NHL or Guidelines for the diagnosis and treatment of CLL at a minimum of every 12 weeks 
until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (Cycle 1 Day 1), whichever comes first. Long-term follow-up 
survival information will be obtained in all surviving subjects who permanently 
discontinue study therapy. Such information may be collected at ~3- to 6-month intervals 
at the sponsor’s discretion through 3 years. This long-term follow-up information will be 
gathered during routine clinic visits, other study site contact with the subjects, or via 
telephone or e-mail with the subjects/caregivers or referring physician offices. 
Section 6.9 
Schedule of Assessments 
Changes: In Table 4 (Schedule of Assessments), it has been clarified that the pretherapy 
collection of blood for coagulation parameters is only required during Screening. 
This clarification removes an inconsistency with protocol text. 
 
An extra column and extra row have been added consistent with existing instructions 
in protocol indicating that long-term follow-up is requested. In an addition, an 
explanatory footnote (Footnote w) has now been included to indicate how that follow-
up will be performed. 
 
In Footnote q, information has been included to note that a bone marrow aspirate 
may be substituted for archival or fresh biopsy tissues in subjects with bone marrow 
involvement due to NHL. 
Assessment 
Screenin
g 
Cycle 1 
Cycle 2 
Cycle ≥3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
-28 to -1 
1 
8 
15 
1 
8 
15-28 
1 
15-28 
Coagulation 
X 
Xc 
 
 
 
 
 
 
 
 
 
Long-term follow-up (F/U)w 
 
 
 
 
 
 
 
 
 
 
X 
q Archival or fresh tumor tissue from the most recent available biopsy or surgery prior to first dose in subjects with 
NHL must be obtained pretreatment. For subjects undergoing a biopsy, adequate tumor tissue should be acquired 
via excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow 
involvement due to NHL. Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics 
activity. In addition, for subjects with NHL, tumor may be evaluated for known prognostic characteristics (e.g., for 
DLBCL:  ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status). 
The baseline biopsy procedure (if required) should be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participation.  
W Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised 
Response Criteria for NHL or Guidelines for the diagnosis and treatment of CLL at a minimum of every 12 
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weeks until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last enrolled 
subject’s first treatment (Cycle 1 Day 1) whichever comes first. Long-term follow-up survival information 
will be obtained in all surviving subjects who permanently discontinue study therapy. Such information 
may be collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This long-term 
follow-up information will be gathered during routine clinic visits, other study site contact with the subjects, 
or via telephone or e-mail with the subjects/caregivers or referring physician offices. 
Section 8.1.5. 
Disease Status Assessment for Subjects with NHL 
Change: 
Information has been included to note that a bone marrow aspirate may be 
substituted for archival or fresh biopsy tissues in subjects with bone marrow 
involvement due to NHL. 
Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue must be 
obtained pretreatment. For subjects undergoing a biopsy, adequate tumor tissue should be 
acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 
16-gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in 
subjects with bone marrow involvement due to NHL. Tissue will be submitted for evaluation 
of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that 
may predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor may 
be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; 
expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status). The baseline 
biopsy procedure (if required) should ideally be performed after the study candidate has 
undergone the baseline radiology examination and is otherwise considered eligible for study 
participation. 
Section 8.6.2 
Medications for AE Management – Gastrointestinal AEs 
Change: 
Recommendations regarding management of gastrointestinal AEs have been updated 
to reflect the evolving safety profile of the study drug. 
While prophylactic antiemetics can be considered, it is preferred that antiemetics not be 
given prophylactically before initial study drug administration on Cycle 1, Day 1.  
It is recommended that, if prophylactic or therapeutic antiemetics are required, subjects be 
offered 2 mg of the serotonin antagonist, granisetron (Kytril®, Granisol®), as an oral 
tablet or solution every 6 hours as needed. If subjects have persistent nausea or vomiting, 
consideration can be given to application of a 31.3 mg granisetron transdermal patch 
(Sancuso®) every 3 to 7 days. For transdermal prophylaxis, 24 to 48 hours may be 
necessary to allow a sufficient period to achieve effective granisetron systemic 
concentrations. Use of the serotonin antagonists, ondansetron (Zofran®, Zuplenz®) or 
dolasetron (Anzemet®), is discouraged due to the possibility that such agents could prolong 
the cardiac QT interval.   
Based on currently available information regarding LAM-002A metabolism, the 
neurokinin 1 receptor antagonist, rolapitant (Varubi®), can be considered, but aprepitant 
(Emend®) or netupitant+palonosetron (Akynzeo®) should be avoided because these drugs 
may inhibit CYP3A4 and/or CYP2C9 activity.   
Other classes of antiemetic medications that may be employed include dopamine 
antagonists or benzodiazepines if such drugs do not pose risks of QT prolongation or drug-
drug interactions. Given the possibility that LAM-002A may alter immunological 
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mechanisms, use of systemic corticosteroids (e.g., dexamethasone) should be minimized to 
avoid immunocompromise; however, corticosteroids can be introduced if other types of 
antiemetic agents are not sufficiently effective.   
Management of nausea and/or vomiting: Prophylactic anti emetic therapy will not be used in this 
study. However, it may be implemented if it is demonstrated that LAM 002A (apilimod 
dimesylate capsules) clearly causes acute nausea and vomiting. If prophylactic anti emetic 
therapy is needed, 5 HT3 receptor antagonists and benzodiazepines should be tried first. 
Additionally, anti emetic therapy may be used as needed in the individual management of 
subjects who develop nausea and/or vomiting. 
For mManagement of diarrhea, it is recommended that s: Subjects should be instructed to take 
loperamide, 4 mg, at the occurrence of the first loose stool and then 2 mg every 2 hours until 
they are diarrhea-free for at least 12 hours. More aggressive loperamide administration or 
titration of loperamide dosing for each loose bowel movement may be considered. During 
the night, subjects may take 4 mg of loperamide every 4 hours. Subjects should be advised to 
avoid dehydration through adequate fluid intake.  Drugs such as 5HT3 antagonists or 
octreotide may be considered for their anti-secretory effects: 
As with any AE, sSites should consider providing study participants with antiemetics and 
antidiarrheals so that these supportive care medications are readily available in case 
gastrointestinal symptoms develop. Subjects who develop nausea, vomiting or diarrhea should 
be monitored closely until the event is resolved/stabilized. 
Section 8.8 
Treatment Compliance 
Change: 
Information has been updated to reflection inclusion of additional schedules. 
The investigator will dispense the study medication only for use by subjects enrolled in the study 
as described in this protocol. The study medication is not to be used for reasons other than those 
described in this protocol. 
The investigator or other study staff will supervise study drug treatment given at the site and 
instruct the subject on study medication self-administration. Subjects will be asked to bring their 
dosing diary with them at each visit. Compliance with protocol-defined study drug intake will be 
checked by pill count at the end of each cycle and compliance decisions will be made by the 
investigator. 
A subject is considered to be DLT-evaluable if he/she has taken at least 75% (42/56 BID 
schedule; 63/84 TID schedule) of the planned first-cycle doses and has sufficient safety data, or 
has experienced a DLT in the first cycle.  
Section 9.1 
Study Drug 
Change: 
The description of the drug product has been updated with information relating to the 
newly introduced 50-mg capsule. 
LAM-002A drug description is provided in Table 5. 
Table5: 
LAM-002A Drug Description 
Product Name: 
LAM-002A 
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Product Name: 
LAM-002A 
Dosage Form: 
Capsule 
Unit Dose 
25 mg or (50 mg pending future development) 
Route of Administration 
Oral 
Physical Description 
Each capsule will contain 25 mg or 50 of apilimod dimesylate 
(equivalent to 17.1 mg or 34.3 mg of apilimod free base, 
respectively). The 25-mg capsule is Swedish orange and the 50-
mg capsule is white. Both the 25- and 50-mg capsules are Size 0 
and both have a total fill weight of 175 mg. 
Inactive components in active capsules are microcrystalline 
cellulose Avicell PH102, silicified microcrystalline cellulose, 
anhydrous lactose, croscarmellose sodium (Ac-Di-Sol), colloidal 
silicon dioxide, and magnesium stearate. Each capsule will 
contain 25 mg of apilimod dimesylate (equivalent to 17.1 mg of 
apilimod free base) and the total fill weight of each capsule will be 
175 mg. The claimed dosage strength of the active ingredient will 
be expressed in the free base form of apilimod. Manufacture of a 50 
mg capsule is planned as part of the ongoing development program. 
Inactive components in active capsules are microcrystalline 
cellulose Avicell PH102, silicified microcrystalline cellulose, 
anhydrous lactose, croscarmellose sodium (Ac Di Sol), colloidal 
silicon dioxide, and magnesium stearate.  
Manufacturer 
Patheon 
Abbreviation: mg: Milligram 
Section 14.1 
Determination of Sample Size 
Change: 
Information regarding the sample sizes has been updated to reflect inclusion of 
additional dose levels and schedules. 
This Phase 1 trial is being conducted primarily to assess the safety and tolerability of LAM-002A 
(apilimod dimesylate capsules) when administered in subjects with relapsed or refractory B-cell 
NHL and to determine the MTD and RP2D of LAM-002A. No formal sample-size estimation 
was performed. The choice of the number of subjects was based on the standard 3 + 3 design that 
is commonly used in Phase 1 trials of anti-cancer investigational drugs. For the Dose Escalation 
Stage of the study, the maximum sample size will be approximately 6030 subjects if 6 subjects 
are assigned at to each of the 9 potential dose levels 0 to 4 and an additional 6 patients are 
accrued at the RP2D. However, additional subjects may be added if exploration of intermediate 
dose level(s) of LAM-002A is warranted.  
Up to 45 additional evaluable subjects (3 cohorts of 15 subjects) may be enrolled at the RP2D 
and schedule in the Expansion Stage of the study. The safety population will consist of all 
subjects receiving at least 1 dose of LAM-002A. The assessment of DLT and MTD will involve 
only those subjects completing the first cycle of therapy, unless the subject discontinuation in 
first cycle was due to a DLT. 
Section 14.3 
Analysis Sets 
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Change: 
The definitions of the analysis sets have been clarified and simplified. 
14.3.1  Full Analysis Sets 
The full analysis set includes all subjects who receive ≥1 dose of study drug. This analysis 
set will be used in the analyses of subject characteristics, study drug administration and 
compliance, safety, and categorical and time-to-event efficacy outcomes. In analyses of 
response rates in the full analysis set, subjects who do not have sufficient baseline and on-
study tumor assessments to characterize response (i.e., have a best overall response of NE) 
will be counted as failures. 
14.3.2  Responding Analysis Set 
The responding analysis set includes subjects in the full analysis set who have measurable 
disease, who can be evaluated for tumor response with both baseline and on-study tumor 
evaluations, and who achieve a CR, CRi, or PR. This analysis set will be used in the 
analyses of time to response and duration of response. 
14.3.3  Evaluable Sets 
The evaluable analysis sets include subjects in the full analysis set who have the necessary 
baseline and on-study measurements to provide interpretable results for specific 
parameters of interest. These analysis sets will be used in the analyses of changes in tumor 
dimensions, PK parameters, and pharmacodynamic parameters.  
14.3.1 Pharmacokinetic Evaluable Population 
The primary analysis of PK will use the PK Evaluable Population, which consists of enrolled 
subjects who have all of their PK samples collected in Cycle 1, who did not have any major 
protocol deviations and who are evaluable for Cmax or AUC0 t analysis. 
14.3.2 Pharmacodynamic Evaluable Population 
The population of subjects evaluable for pharmacodynamics will include all subjects who have 
tissue or PBMCs available for analysis at baseline and during treatment, and for which an 
assessment of changes (e.g., gene expression, vacuolation, PIKfyve inhibition) is technically 
feasible.  
14.3.3 Safety Population 
For safety analyses, the Safety Population will be used. This population consists of subjects who 
have taken at least one dose of LAM 002A. 
14.3.4 DLT Evaluable Population 
Dose escalation decisions will be evaluated in DLT evaluable population. The DLT evaluable 
population will include subjects who complete Cycle 1 dosing (administered at least 75% of 
doses) and have sufficient safety data, or who are withdrawn from study due to a DLT in 
Cycle 1.  
14.3.5 Full Analysis Data Set 
The Full Analysis Set (FAS) will serve as the primary population for the analysis of tumor 
response and other efficacy related data. Subjects will be excluded from the FAS for the 
following reasons: 
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•
No baseline data
•
Failure to receive at least one dose of LAM-002A
•
No post-baseline endpoint data subsequent to at least 1 dose of study drug.
Changes made in Amendment 5 (14 Apr 2017) 
Title Page 
Change: The protocol version and date have been updated. 
Protocol Version and Date: 
Version 6.0, 14 Apr 2017 
Version 5.0; 07 Nov 2016 
Investigator’s Agreement 
Change: The date has been updated. 
I have read the attached Protocol entitled “A Phase 1 Dose Escalation Study of the Safety and 
Pharmacokinetics of LAM-002A (apilimod dimesylate capsules) Administered Orally in 
Subjects with Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma” dated 14 Apr 2017 07 
Nov 2016.  
Section 6.6.1 Tumor Lysis Syndrome (TLS) Prophylaxis 
Change: 
Medical prophylaxis has been mandated for subjects at intermediate to high risk of 
TLS and a recommendation has been included that subjects at high risk of TLS be 
monitored as inpatients during the first 24 to 48 hours of LAM-002A administration. 
The risk for TLS should must be considered based on established algorithms (Cairo 2010, 
MDACC 2013, Roberts 2016): 
•
Low-risk: Serum LDH ≤ ULN, all measurable lymph nodes < 5 cm, and absolute
lymphocyte count (ALC) < 25 × 109/L
•
Intermediate risk: Serum LDH > 1 to ≤ 2 × ULN, ≥ 1 measurable lymph node with an
LD of ≥ 5 but < 10 cm, or ALC ≥ 25 × 109/L
•
High risk: Serum LDH > 2 × ULN, ≥ 1 measurable lymph node with a LD of
≥ 10 cm, or both ≥ 1 measurable lymph node with an LD of ≥ 5 but < 10 cm and ALC
≥ 25 × 109/L
Subjects who are at intermediate or high risk of TLS must receive medical prophylaxis 
according to the following prophylaxis regimens or similar institutional regimens: 
If, during the dose escalation it is observed that the study drug appears to induce TLS, 
subsequent subjects who are at risk should be considered for medical prophylaxis of TLS and 
according to local prevention paradigms. Alternatively, investigators may wish to consider the 
following regimens for prophylaxis in subjects at intermediate or high risk of TLS: 
•
Intermediate Risk of TLS: These subjects shouldcan receive allopurinol, 100 to
300 mg orally every 8 hours starting ≥ 24 to 48 hours before the initial administration
of apilimod dimesylateLAM-002A on Cycle 1-Day 1 of therapy; of note, the
maximum daily allopurinol dose is 800 mg, doses ≤ 300 mg need not be divided
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(but may be insufficient for high-risk subjects), and doses should be reduced by 
≥ 50% in subjects with renal insufficiency. In addition, subjects who develop 
hyperuricemia should receive rasburicase, 0.2 mg/kg. 
• High Risk of TLS: These subjects can should receive allopurinol, 100 to 300 mg 
orally every 8 hours starting ≥ 24 to 48 hours before the initial administration of 
apilimod dimesylateLAM-002A on Cycle 1-Day 1 of therapy; of note, the 
maximum daily allopurinol dose is 800 mg, doses ≤ 300 mg need not be divided 
(but may be insufficient for high-risk subjects), and doses should be reduced by 
≥ 50% in subjects with renal insufficiency. In addition, high-risk subjects can 
should receive rasburicase, 0.2 mg/kg, administered 3 to 4 hours prior to the first 
dose of apilimod dimesylate. 
In addition, subjects who are at high risk of TLS should be considered for in-hospital 
monitoring during the first 24 to 48 hours of LAM-002A administration. 
Section 6.6.7 Definition of Dose-Limiting Toxicity (DLT) – Footnote to Table 3. Criteria for 
Defining Dose Limiting Toxicities (DLTs) 
Change: 
TLS has been removed as a DLT exclusion. 
Note: Known oncologic emergencies from NHL (e.g., tumor lysis syndrome, spinal cord compression, ureteric 
obstruction, lymphomatous meningitis, and superior vena cava syndrome) will not be considered as dose-limiting 
toxicities. 
Section 6.9 Schedule of Assessments – Table 4 Schedule of Assessments 
Change: 
Serum chemistry laboratory monitoring for TLS has now been included on Days 2 
and 3 of Cycle 1 for subjects at intermediate to high risk of TLS (as defined in 
Section 6.8.1 of the protocol). 
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Table 4: 
Schedule of Assessments 
 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
-28 to -1 
1 
2 
3 
8 
15 
1 
8 
15-28 
1 
15-28 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Signs and Symptoms, PEb 
X 
Xc 
 
 
 
 
X 
 
 
X 
 
X 
 
ECOG Performance Status 
X 
Xc 
 
 
 
 
X 
 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
X 
 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
X 
 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
X 
X 
X 
 
X 
 
Coagulation 
X 
- 
 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
X 
 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
X 
 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based 
on indication) for response assessment 
Xj 
 
 
 
 
 
 
 
Xk 
 
Xk 
Xl 
 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK samplingn + Analyte 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
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Table 4: 
Schedule of Assessments (Continued) 
 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
-28 to -1 
1 
2 
3 
8 
15 
1 
8 
15-28 
1 
15-28 
Bone marrow aspirate/biopsy 
Xo 
 
 
 
 
 
 
 
Xp, q 
 
Xp 
 
 
Biomarker – tumor tissue 
Xq 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – blood smearsr 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
Biomarker – PBMCt 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Biomarker – salivau 
 
X 
 
 
 
 
 
 
 
 
 
 
 
LAM-002A administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Adverse events 
 
Throughout Study 
Concomitant medicationsv 
 
Throughout Study 
Long-term follow-up (F/U)w 
 
 
 
 
 
 
 
 
 
 
 
 
X 
a Eligibility will be confirmed by Cycle 1 Day 1. 
B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the start of 
each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D 
Obtained on Day 1 prior to dosing for all Cycles. For C1D1 and C1D8 obtained prior to dosing and 1 h (± 15 min after dosing), 2 hrs (± 30 min), 4 hrs (± 
1h), and 8 hrs (± 1h) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F All hematology and chemistry laboratory parameters should be assessed at Screening and Days 1, 8, and 15 of Cycles 1 and 2, and then at least once prior to 
the start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of Cycle 1 is only required in subjects 
with intermediate or high risk of TLS (per the risk definition in Section 6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, t These parameters may be 
obtained within 72 hours prior to the planned day of collection. Abnormal test values should be monitored per protocol guidance. 
G 
Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H 
Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained 
within 72 hours prior to the planned day of collection. 
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I Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to screening 
and within 30 days before first dose may be used for baseline tumor assessments. 
K 
Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as appropriate 
for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 months until PD or use of 
alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may be every 6 months. Subjects with CLL 
who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. Tissue 
will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anticancer activity 
and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a 
sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q deletion, 13q deletion, 
17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL [e.g., Notch]; flow cytometry 
[for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], and/or β2-microglobulin). The baseline bone 
marrow aspiration procedure (if required) should be performed after the study candidate has undergone the baseline radiology examination and is otherwise 
considered eligible for study participation. All subjects with CLL/SLL must have baseline imaging (with CT scans [preferred] or MRI scans).  
N 
Blood sampling for determination of the plasma concentrations of apilimod and metabolites will be performed on C1D1 and C1D8 as follows: pre-dose, 
30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. C1D15 pre-dose only. Additional PK samples will be collected, if possible, whenever a subject has a 
study treatment-related SAE or QTc > 500 msec. Subjects are required to come to the study site in a fasting state prior to the collection of certain PK samples. 
For analyte determination, PK back-up sample will be used from time points: Cycle 1 Day 1 and Cycle 1 Day 8 pre-dose. 
O 
Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, 
baseline bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management. For subjects with CLL/SLL, a 
baseline bone marrow aspirate is required unless the presence of sufficient circulating cells in the peripheral blood (e.g., absolute lymphocyte count [ALC] ≥ 10 
x 109/L) permits assessment of baseline parameters as described in Footnote m, above. 
P 
If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and physical 
examination. 
Q Archival or fresh tumor tissue from the most recent available biopsy or surgery prior to first dose in subjects with NHL must be obtained pretreatment. For 
subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 
16-gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL. Tissue will 
be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anti-lymphoma 
activity and/or pharmacodynamics activity. In addition, for subjects with NHL, tumor may be evaluated for known prognostic characteristics (e.g., for 
DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status). The baseline biopsy procedure (if required) 
should be performed after the study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation.  
R Blood smears will be collected for microscopic evaluation of vacuole formation on C1D1 and C1D8 as follows: pre-dose, 4 hrs and 8 hrs post first dose of the 
day. C1D15 pre-dose only. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) predose on each of Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 
Day 15. 
T  PBMCs will be collected on Cycle 1, Day 1 pre-treatment; on Cycle 1, Day 1 at 8 hours post-dose; and on Cycle 1, Day 8 at 8 hours post-dose for 
determination of changes in gene expression that may predict or correlate with anti-lymphoma activity and/or pharmacodynamic activity.  
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U  Saliva will be obtained pre-dose on Cycle 1 Day 1 as a normal-tissue control for gene mutation studies in tumors.  
V  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
W Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised Response Criteria for NHL or Guidelines for the 
diagnosis and treatment of CLL at a minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (Cycle 1 Day 1) whichever comes first. Long-term follow-up survival information will be obtained in all surviving subjects 
who permanently discontinue study therapy. Such information may be collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This 
long-term follow-up information will be gathered during routine clinic visits, other study site contact with the subjects, or via telephone or e-mail with the 
subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; CBCs: Complete blood counts; CD: Cluster of 
differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; DAT: Direct antiglobulin test; ECG: 
Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; hrs: Hours; LDH: 
Lactate dehydrogenase; min: Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: 
Progressive disease; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; SAE: 
Serious adverse event; WBC: White blood cell; WCBP: Women of child bearing potential 
 
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Changes made in Amendment 6 (25 Oct 2017) 
In preparing this amendment of the protocol document, the following changes were made. 
Explanations of the changes are provided in italics as “Changes.” Inserted text is indicated by 
red bold font. Deleted text is indicated by red strikeout font. Changes to the synopsis also 
appear in the body of the protocol; thus, changes to the synopsis are not described and only 
changes to the body of the protocol are described. 
General Change 
Change: 
Where applicable and as appropriate for the context, the name “apilimod 
dimesylate” was redesignated as LAM-002A. Similarly, to provide clarity, the term 
“study drug” was modified to “LAM-002A,” when appropriate. 
Title Page 
Change: 
The protocol version and date were updated. 
Protocol Version and Date: 
 
Version 7.0, 25 Oct 2017 
Version 6.0; 14 Apr 2017 
Investigator’s Agreement 
Change: The date was updated. 
I have read the attached Protocol entitled “A Phase 1 Dose Escalation Study of the Safety and 
Pharmacokinetics of LAM-002A (apilimod dimesylate capsules) Administered Orally in 
Subjects with Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma” dated 25 Oct 2017 
14 Apr 2017.  
 
Section 4.1.1. Pharmacology 
Change: 
An additional reference was added to replace a former reference to unpublished data, 
and all references were hyperlinked to the bibliography. 
Apilimod and apilimod dimesylate were originally introduced into clinical trials based on 
apilimod’s immunomodulatory properties (Wada 2007; Wada 2012). Apilimod inhibits the 
production of interleukin-12 (IL-12) and interleukin-23 (IL-23), and was effective in preclinical 
animal models of various autoimmune diseases that are mediated by the inappropriate expression 
of T-helper cell phenotype (Th1) cytokines (Wada 2007).  
Recently published data (and LAM Therapeutics unpublished data in cancer cells) have shown 
that apilimod is a potent and highly selective first-in-class phosphatidylinositol-3-phosphate- 5 
kinase (PIKfyve) inhibitor (Cai 2013, Gayle 2017). In total, LAM has tested 456 kinases, 
including disease-relevant kinases, for their ability to bind to apilimod. The screening 
concentration of apilimod was 1 µM, a concentration that is > 12,000 times greater than the Kd 
(81 picomolar) for apilimod against PIKfyve. The results showed that apilimod did not bind to 
any of the 456 kinases tested. 
Inhibition of PIKfyve by pharmacological methods as well as RNA interference (RNAi) 
produces swollen vacuoles and disruption of endomembrane dynamics. In cell culture, the 
pharmacological disruption of PIKfyve with apilimod induces selective lethality of specific 
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Section 4.1.4.2. 
Efficacy 
Change: 
Efficacy information from the study in patients with hematological malignancies was 
updated to reflect data as of 30 Sep 2017. 
Efficacy data in patients with hematological malignancies are evolvingpending. As of 30 Sep 
2017, positron emission tomography (PET) demonstrated systemic partial metabolic 
responses in nodal and extranodal lesions in 3 patients with refractory DLBCL (treated at 
100 mg BID, 75 mg TID, and 125 mg BID) (1 of whom also received radiation for bulky 
axillary adenopathy); concomitant computed tomography (CT) demonstrated anatomic 
shrinkage of many lesions. One additional subject with transformed, refractory DLBCL 
(treated at 125 mg BID) experienced tumor lysis syndrome (TLS). One patient with 
marginal zone lymphoma (MZL) (treated at 125 mg BID) has had a metabolic response by 
PET together with a 43% decrease in the sum of the products of the perpendicular 
diameters (SPD) of index lesions by CT. Another patient with MZL and a patient with 
chronic lymphocytic leukemia (CLL) (both receiving 100 mg BID) experienced prolonged 
stable disease through 11+ and 14 cycles, respectively.One patient, a 60 year old male with 
GCB DLBCL who was had experienced minimal or no response to multiple prior 
chemoimmunotherapy regimens (including R CHOP), received apilimod dimesylate at 
100 mg/dose BID for 6 weeks before enlarging right axillary lymphadenopathy required 
cessation of study drug and intervention with local radiation therapy. A follow up PET CT, 
obtained approximately 2 weeks later, showed a substantial systemic decrease in DLBCL lesions 
in non irradiated lymph nodes, liver, spleen, and bone (C4 vertebra); these improvements in 
disease burden were attributed by the investigator to the study drug. 
Section 4.1.4.3. 
Safety 
Change: 
Safety data in the second paragraph were updated. 
No renal insufficiency has been observed in completed clinical trials to date except in 1 patient 
with DLBCL who acutely developed transient elevations in serum creatinine and blood-
urea nitrogen (BUN) due to tumor lysis syndrome (TLS) shortly after starting LAM-002A 
at a dose of 125 mg BID. And no clinically significant safety signals in laboratory, physical 
examination, or vital sign findings have been notedOne patient with a hematological malignancy 
receiving the drug at 150 mg BID developed asymptomatic Grade 3 hyponatremia that was 
attributed to the combined effects of a apilimod dimesylate induced LAM-002A-induced 
diarrhea and hydrochlorothiazide administration. No other clinically significant safety signals 
in laboratory, physical examination, or vital sign findings have been noted. 
Section 4.1.5. Overview of Indication 
Change: 
Background information was added to the fourth paragraph to support the 
combination of LAM-002A with rituximab or atezolizumab. 
Patients with DLBCL who relapse after, or who are not candidates for ASCT, as well as patients 
with relapsed MCL, MZL, FL, and CLL/SLL are not considered curative curable with 
conventional therapies. Therefore, management of relapsed and refractory NHL remains an 
unmet medical need.  Patients with recurrent disease are commonly given sequential 
regimens of chemotherapeutic, immunotherapeutic, or investigational agents in an attempt 
to control disease manifestations. Rituximab is commonly employed in combination with 
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other agents (Zelentz 2014). Newer immunopotentiating approaches using anti-PD1/PDL1 
inhibitors (including atezolizumab [https://clinicaltrials.gov/ct2/show/NCT031206761]) are 
being explored and have shown evidence of activity in patients with recurrent NHL 
(Ilcus 2017). However, despite use of agents with differing mechanisms of action, 
progressive resistance to treatment typically develops. Patients with refractory or multiply 
relapsed progressive disease have poor prognoses and are ultimately likely to die of their 
cancers. Novel mechanisms of action are needed that can be administered alone or in 
combination with existing chemoimmunotherapeutic approaches to offer additional 
treatment options for patients with hematological cancers who have experienced disease 
progression. 
Section 5. TRIAL OBJECTIVES AND PURPOSE 
Change: 
The section was updated to indicate that LAM-002A will be evaluated alone and in 
combination with other drugs and to indicate changes in the types of 
pharmacodynamic assays that will be performed based on evolving experience with 
these exploratory endpoints. Only the sections in which changes were made are 
shown. 
5. 
TRIAL OBJECTIVES AND PURPOSE 
The overall purpose of this Phase 1 study is to explore the safety and tolerability of LAM-002A 
when given alone and in combination for the treatment of subjects with relapsed or refractory 
B-cell NHL.  
5.3. 
Exploratory Objectives 
• To evaluate the pharmacodynamic effects of LAM-002A, administered orally, in 
plasma assays and on surrogate tissue (e.g., vacuoles in peripheral blood smears, 
gene expression in peripheral blood mononuclear cells [PBMCs]/B cells, and plasma 
cytokines [including (IL)-12 and IL-23]).  
• To evaluate tumor for gene expression and genetic alterations (with saliva and/or 
B-cell-depleted PBMC collection for germ-line control) and surrogate tissue 
(PBMC/B cells) for gene expression that may predict anti-lymphoma activity. 
• To evaluate plasma for changes in analytes or tumor for protein expression that 
may predict anti-lymphoma activity. 
5.6. 
Exploratory Endpoints 
• Extent of PIKfyve inhibition as determined by plasma inhibitory assaysthe extent of 
vacuole formation in white blood cells in peripheral blood smears by microscopic 
evaluation 
• Changes in gene expression in PBMCs 
• Changes in plasma cytokines (including IL-12 and IL-23) 
• Correlation between genetic alterations as determined by next generation sequencing 
and/or gene expression in tumor tissue, circulating tumor DNA, or PBMCs/B cells 
and anti-lymphoma activity following treatment with LAM-002A  
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• Correlation between changes in plasma bioanalytes or tumor protein expression and 
anti-lymphoma activity following treatment with LAM-002A as determined by 
proteomic tools 
 
Section 6.1.1. LAM-002A Dose Escalation Stage 
Change: 
Based on findings that nausea, vomiting, and diarrhea were treatment-limiting when 
LAM-002A was given continuously at a dose ≥150 mg twice per day (BID), a plan for 
further dose exploration using an intermittent LAM-002A dosing regimen with  
antiemetic and antidiarrheal support was defined (see also Section 6.6). The section 
was modified accordingly. 
The maximum tolerated dose (MTD) will be determined during the dose-escalation stage, 
evaluating both continuous and intermittent dosing regimens. Subjects will accrue using a 3 
+ 3 design. During this stage, the decision to open a new cohort at a higher or lower dose level 
will be made by the participating clinical investigators and sponsor when all subjects in the 
current cohort have been treated through at least Week 4 or once 2 DLTs have occurred in that 
dose cohort. All available safety and PK data will be considered in a decision by the medical 
monitor in collaboration with the investigators to dose escalate, de-escalate, expand the current 
cohort or explore an alternate regimens scheduleof drug administration. The MTD will be 
determined based primarily on DLTs observed through Week 4 in at least≥ 6 subjects.  
 
Section 6.1.2. Expansion Stage 
Change: 
Based on emerging clinical data, the disease indications to be evaluated in the 
expansion stage of the study were established. In addition, based on emerging 
nonclinical data, the combination regimens to be evaluated in the expansion stage 
were defined. The section was modified accordingly. 
Once the MTD and/or recommended phase 2 dose (RP2D) and schedule is determined, the study 
will enter the expansion stage, in which 3 cohorts of 15 subjects each will be accrued in order to 
obtain additional information on safety, tolerability, preliminary anti-tumor activity, PK, and 
pharmacodynamic data at the RP2D and schedule when LAM-002A is administered alone or 
in combination with rituximab or atezolizumab. Expansion-stage cohorts will comprise 
groups of subjects with specific types of previously treated, relapsed, progressive, and 
measurable NHL who will receive LAM-002A monotherapy or LAM-002A-containing 
combination therapy as shown in Table 2. For both monotherapy and combination cohorts, 
the starting dose of LAM-002A will be 125 mg BID administered continuously.The 
eligibility criteria will remain the same as in escalation but each cohort will be specific to 
subjects with DLBCL, FL, and CLL/SLL, respectively. The treatment regimen in each of the 
expansion cohorts will be single agent LAM 002A (apilimod dimesylate capsules) according to 
the RP2D and schedule.  
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Table 2: 
Expansion Stage Disease Types and Therapies 
Cohort 
Number 
NHL Type 
Investigational  
Drug 
Combination  
Drug 
Evaluable  
Subjects, n 
1 
FL 
LAM-002A 
-- 
6 
2 
MZL 
LAM-002A 
-- 
6 
3 
DLBCL-GCB 
LAM-002A 
-- 
6 
4 
DLBCL-ABC 
LAM-002A 
-- 
6 
5 
FL or MZL 
LAM-002A 
Rituximab 
6 
6 
DLBCL-GCB or DLBCL-
ABC 
LAM-002A 
Rituximab 
6 
7 
FL or MZL 
LAM-002A 
Atezolizumab 
6 
8 
DLBCL-GCB or DLBCL-
ABC 
LAM-002A 
Atezolizumab 
6 
Abbreviations: ABC: activated B-cell (subtype); DLBCL: diffuse large B-cell lymphoma; FL: follicular 
lymphoma; GCB: germinal center B-cell (subtype); MZL: marginal zone lymphoma; NHL: non-Hodgkin 
lymphoma 
 
Section 6.1.3. Subject Allocation (Stages 1 and 2) 
Change: 
Consistent with the plan to perform dose-ranging evaluation of intermittent 
LAM-002A administration and to assess monotherapy and combination therapy 
cohorts using continuous LAM-002A administration, this section was added to 
provide information on subject allocation and to describe restrictions to enrollment 
in Stage 1 and Stage 2 enrollment to enhance study safety. 
Subjects will be allocated to the cohorts by the study sponsor working in collaboration with 
each investigator considering the availability of openings for enrollment in Stage 1 or 2, 
disease type (i.e., FL, MZL, DLBCL-GCB, DLBCL-ABC, or other indications), therapy 
history (e.g., prior use of anti-CD20 or anti-PD1/PDL1 antibodies), and current disease 
status (e.g., potential to benefit from rituximab treatment based on past responses to anti-
CD20 antibody therapy).  
During Stage 1 dose ranging with LAM-002A monotherapy, allocation will be performed 
according to a 3+3 dose-escalation procedure with the requirement that each cohort of 3 
subjects be observed for ≥4 weeks before another cohort is enrolled (as detailed in 
Section 6.6). During Stage 2 cohort expansion evaluating LAM-002A monotherapy, 
allocation will be performed as subjects present to the accruing clinics and there will be no 
specific restrictions on the cadence of enrollment.  During Stage 2 cohort-expansion of 
LAM-002A combinations with rituximab and atezolizumab, enrollment of the first 3 
subjects in each combination cohort will be restricted such that each subject must be 
enrolled sequentially and observed for ≥3 weeks before the next subject is enrolled. 
Beginning with the 4th patient in each combination group, further enrollment may proceed 
without restriction as long as the continuous reassessment boundaries for toxic drug 
discontinuations are not met (as detailed in Section 6.8.2.5 and Section 6.12). 
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Section 6.1.4 Subject Evaluability 
Change: 
This section was added to clarify subject evaluability for the dose-ranging and 
cohort-expansion portions of the study. 
A Stage 1 subject will be considered evaluable if the subject meets the definition for 
evaluability of Cycle 1 DLT as described in Section 6.6. A Stage 2 subject will be considered 
evaluable if the subject has both baseline and ≥1 on-study tumor assessments sufficient to 
allow a determination of response to study therapy. 
 
Section 6.2. 
 
Number of Subjects 
Change: 
The number of subjects was updated to reflect the new dose-escalation and 
cohort-expansion plans. 
As many as 110 Approximately 115 evaluable subjects (evaluable subjects include those who 
complete Cycle 1 dosing [administered at least 75% of doses] and have sufficient safety data, or 
who are withdrawn from the study due to a DLT in Cycle 1) will be enrolled, assuming that: 
• In the dose-escalation stage of the study, the total number of subjects will depend 
upon the numbers of subjects accrued to each dose level and the number of dose 
levels evaluated. If 6 subjects are enrolled at all 9 possible open starting dose levels 
(Dose Levels 5, 6, 7, and 8) and 6 additional subjects are enrolled at the MTD or RD, 
as many as 60 30 subjects could be enrolled. To allow for the possibility that some 
subjects may not be fully evaluable for DLT or that an intermediate dose level might 
be evaluated, up to ~70 45 subjects may be enrolled.  
• In the expansion stage of the study, if all 3 8 potential expansion cohorts of 15 
6 evaluable subjects are accrued, as many as 45 48 subjects could be enrolled. To 
allow for the possibility that some subjects may not be fully evaluable for efficacy, up 
to ~55 65 subjects may be enrolled. Subjects will be treated at the RP2D and schedule 
determined in the Dose Escalation Stage of the study. 
 
Section 6.6. 
 
LAM-002A Dose-Escalation Procedures 
Change: 
Table 3 was updated consistent with the new dose-escalation and cohort-expansion 
plans. The initial dose level of the 150 mg BID to be explored with intermittent dosing 
represented a modest increment over the recommended Phase 2 continuous dosing 
regimen of 125 mg BID. The text definition of “DLT evaluable” was updated to 
include the minimum required dosing.   
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Table 3: 
LAM-002A Provisional Starting Dose Levels 
Continuous Administration 
Dose Level 
LAM-002A Dose and Schedule 
Apilimod Dimesylate Dose  
mg/dose 
LAM-002A Total Daily Dose 
Apilimod Dimesylate Dose 
mg/day 
-1 
  25 mg BID 
50 mg 
0 (Initial Dose Level) 
  50 mg BID 
100 mg 
1 
100 mg BID 
200 mg 
1a 
125 mg BID 
250 mg 
1b 
  75 mg TID 
225 mg 
1c 
100 mg TID 
300 mg 
1d 
125 mg TID 
375 mg 
2 
150 mg BID 
300 mg 
3 
200 mg BID 
400 mg 
4 
275 mg BID 
550 mg 
Intermittent Administration 
Dose Level 
LAM-002A Dose and Schedule 
LAM-002A Total Daily Dose 
5 
150 mg BID 
300 mg 
6 
200 mg BID 
400 mg 
7 
250 mg BID 
500 mg 
8 
 300 mg BID 
600 mg 
Abbreviations: BID: Twice daily (or 2 times per day); TID: Thrice daily (or 3 times per day) 
Dose escalation decisions will be evaluated in a DLT-evaluable population. The DLT-evaluable 
population will include subjects who complete Cycle 1 dosing or who are withdrawn from study 
due to a DLT in Cycle 1. A subject will be deemed non-evaluable for determining DLTs and will 
not be counted toward the total cohort size if the subject did not experience a DLT, did not 
receive at least 75% (42/56 BID schedule; 63/84 TID schedule, 18/24 intermittent schedule) of 
the planned first-cycle doses or discontinued from the study prior to completing necessary safety 
evaluations through the first 28 days of study treatment. These subjects may be replaced unless 
accrual to the cohort has stopped due to DLT. 
Section 6.7. 
 
Definition of LAM-002A Dose-Limiting Toxicity (DLT) 
Change: 
Information regarding DLT definitions was moved to this section (previously in 
Section 6.7.2.5) to provide an easier flow of concepts. No changes to the substance of 
the DLT definitions were made except that the inability to administer the required 
minimum number of doses on the intermittent schedule due to drug-related AEs was 
added as a necessary new DLT criterion. 
A DLT will be defined as an AE or abnormal laboratory value meeting the criteria in 
Table 3 and that is assessed as unrelated to disease, a comorbid condition, intercurrent 
illness, or concomitant medications (see Table 4). For the purposes of dose escalation and 
determination of the LAM-002A MTDs, DLTs that occur within the first cycle of treatment 
must be included in decisions regarding dose escalation. DLTs or other clinically significant 
toxicities that occur after Cycle 1 may also be considered when determining the RP2D. 
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Table 4: 
Criteria for Defining Dose-Limiting Toxicities (DLTs) 
Toxicity 
Criteria 
Hematology 
CTCAE Grade 4 neutropenia lasting ≥ 7 days 
CTCAE Grade 4 febrile neutropenia  
CTCAE Grade 3 thrombocytopenia with bleeding that requires transfusion 
therapy 
CTCAE Grade 4 thrombocytopenia  
Toxicity 
Criteria 
Gastrointestinal 
≥ CTCAE Grade 3 vomiting or nausea despite the use of optimal anti-emetic 
treatments 
≥ CTCAE Grade 3 diarrhea despite the use of optimal anti-diarrheal 
treatments 
Renal 
Serum creatinine > 3.0 x ULN 
Hepatica 
Total bilirubin ≥ CTCAE Grade 3 
Total bilirubin ≥ CTCAE Grade 2 and ALT or AST ≥ CTCAE Grade 2 
or,  
for subjects with liver metastases at baseline, total bilirubin ≥ 2.0 x ULN and 
ALT or AST ≥ CTCAE Grade 3  
Treatment 
interruption/delays 
Inability to administer ≥28/56 (BID schedule) or ≥42/84 (TID schedule) or 
≥12/24 (intermittent schedule) planned LAM-002A doses in a treatment 
cycle due to drug-related AEs 
or 
Failure to recover from apilimod-dimesylate-related toxicities to baseline 
within 14 days from the last dose of LAM-002A  in a cycle 
Other adverse 
events not listed 
above 
Non-hematologic toxicities of CTCAE ≥ Grade 3 except for the following. 
• 
alopecia 
• 
CTCAE Grade 3 fatigue for < 72 hours  
• 
Asymptomatic Grade 3 elevations in biochemistry laboratory values 
that last for ≤ 7 days that are not deemed to be clinically relevant. 
This includes electrolyte abnormalities that respond to medical 
intervention. 
Any LAM-002A-related adverse event that, in the opinion of the 
investigator, requires a dose reduction or discontinuation of treatment. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; CTCAE: Common 
terminology criteria for adverse events; DLT: Dose-limiting toxicity; ECG: Electrocardiogram; NHL: Non-
Hodgkin lymphoma; ULN: Upper limit of normal 
Once the RP2D and schedule are established, additional subjects will be treated in 
3 histologically distinct dose expansion cohorts designed to better characterize the safety, 
tolerability, preliminary anti tumor activity, PK, and pharmacodynamics of the study drug when 
provided at the MTD (or lower dose per agreement of the Investigators and Sponsor) in a 
specific B cell NHL subtype. Up to 15 subjects will be treated in each expansion cohort. 
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Section 6.8.1. Tumor Lysis Syndrome Prophylaxis and Therapy 
Change: 
The heading of the section was changed, as shown above, and information on TLS 
management was condensed under a single section within the protocol document. 
6.8.2 
TLS Management 
Information regarding TLS prophylaxis is provided in Section 6.6.1. 
Subjects who develop TLS may experience hyperkalemia, hypocalcemia, hyperuricemia, 
hyperphosphatemia, cardiac dysrhythmias, and acute renal failure; thus, close monitoring 
of electrolytes is important after initial therapy.  
Subjects with TLS should receive intravenous hydration, rapid reversal of hyperkalemia, 
antihyperuricemic agents, and appropriate cardiac and renal support, including dialysis as 
indicated. Upon recovery to baseline functioning and as medically appropriate, such 
subjects should continue with protocol therapy to maintain tumor control. 
 
Section 6.8.2. LAM-002A 
Change: 
Information regarding LAM-002A administration, dose modifications, and supportive 
care was consolidated in one location in the protocol text, and this section was 
updated consistent with the new dose-escalation and cohort-expansion plans. The 
description of the study drug was removed from Section 6.8 and consolidated in a 
single location in Section 9.1 to avoid redundancy. The types of adverse events 
typically requiring LAM-002A dose modification were described.  Given that 
LAM-002A has no obvious cumulative toxicity, allowance was made for dose 
escalation after Cycle 2 of therapy if such an escalation might be medically 
appropriate considering subject tolerance and antitumor efficacy. More detailed and 
protocol-specific guidelines for antiemetic prophylaxis and antidiarrheal prophylaxis 
were included based on current ASCO guidelines. 
6.8.2.1. 
Premedications 
Subjects taking LAM-002A by continuous administration may be offered antiemetics and 
antidiarrheals as necessary to control gastrointestinal symptoms as described in 
Section 6.8.2.6.1 For subject who do develop such adverse effects, sites should consider 
providing study participants with antiemetics and antidiarrheals so that these supportive 
care medications are readily available in case gastrointestinal symptoms related to 
LAM-002A recur or persist.  
Subjects taking LAM-002A by intermittent administration are required to receive 
prophylactic antiemetic supportive care as described in Section 6.8.2.6.2. 
6.7.2. 
Description of Study Drug 
LAM 002A (apilimod dimesylate capsule) is intended for oral administration. Each capsule will 
contain 25 mg or 50 of apilimod dimesylate (equivalent to 17.1 mg or 34.3 mg of apilimod free 
base, respectively). The 25 mg capsule is Swedish orange and the 50 mg capsule is white. Both 
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the 25  and 50 mg capsules are Size 0 and both have a total fill weight of 175 mg. For additional 
information, see Section 9.1 
6.8.2.2. 
In-Clinic LAM-002A Administration 
For subjects receiving the continuous LAM-002A regimen, On Cycle 1 Day 1, and Cycle 1 
Day 8 the morning dose of LAM-002A should be orally administered on Cycle 1 Day 1 and 
Cycle 1 Day 8 (after a minimum fasting state of 6 to 8 hours) by site staff immediately after the 
collection of the biomarker samples and pre-dose PK sample. Subjects are allowed to eat after 
PK Sample #4 (Hour 2) has been collected. On Cycle 1 Day 15, the morning dose of 
LAM-002A should be orally administered (after a minimum fasting state of 6 to 8 hours) by site 
staff immediately after collection of the pre-dose PK and biomarker samples.  
For subjects receiving the intermittent LAM-002A regimen, prophylactic antiemetics are a 
required component of the regimen as described in Section 6.8.2.5.2. After initiation of the 
antiemetic regimen, the morning dose of LAM-002A should be orally administered on 
Cycle 1 Day 1 and Cycle 1 Day 10 (after a minimum fast of 6 hours) by site staff after the 
collection of the biomarker samples and pre-dose PK sample. Subjects are allowed to eat 
after PK Sample #4 (Hour 2) has been collected. Similarly, on Cycle 1 Day 8 and Cycle 1 
Day 15, the antiemetic regimen should be initiated and the morning dose of LAM-002A 
should be orally administered (after a minimum fast of 6 hours) by site staff immediately 
after collection of the pre-dose samples.  
When given as a component of combination therapy with rituximab, LAM-002A will be 
started on Cycle 1 Day 1 with a BID schedule. LAM-002A will be administered after 
administration of premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the 
start of the initial rituximab infusion.  On Cycle 1 Day 8, the morning dose of LAM-002A 
will be administered after premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior 
to the rituximab infusion. 
When given as a component of combination therapy with atezolizumab, LAM-002A will be 
started on Cycle 1 Day 1 with a BID schedule. LAM-002A will be administered ~15 to 
30 minutes prior to the start of the initial atezolizumab infusion.  On Cycle 1 Day 8, the 
morning dose of LAM-002A will be administered ~15 to 30 minutes prior to the 
atezolizumab infusion. 
6.8.2.3. 
LAM-002A Self-Administration 
Except for the days where treatment is administered in the clinic, LAM-002A will be self-
administered orally, BID or TID of each 28-day cycle until disease progression or other 
discontinuation criteria are met. When taking the drug at home, subjects should be advised to 
take LAM-002A with ≥ 4 oz. (~160 mL) of water at the same times each day. Subjects on a BID 
schedule will be advised to take the doses at ~12 hours apart (e.g., 8:00 AM and 8:00 PM) (+/-
 1-hour window). Subjects on a TID schedule will be advised to take the doses at intervals of ~6 
to 8 hours. When self-administering LAM-002A at home, subjects may take the drug in the fed 
or fasted state. On PK days, subjects should come to clinic fasted (a minimum fasting state of 6 
to 8 hours) and take the dose at the site under supervision. All subjects will be required to 
complete a dosing diary, which must be returned to the site for review at each site visit.   
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For those subjects taking LAM-002A with continuous administration, the drug should be 
taken according the prescribed BID or TID schedule without interruption unless toxicity or 
intercurrent illness requires a modification to the dosing regimen (see Section 6.8.2.5).  
For those subjects taking LAM-002A with intermittent administration, the drug should be 
taken in repeated 7-day sequences comprising BID self-administration for 3 days (6 doses) 
followed by 4 days without dosing. If the cadence of the on-off periods is interrupted due to 
toxicity, intercurrent illness, or other reasons, the medical monitor should be consulted 
regarding the timing of therapy resumption and dose modification (see Section 6.8.2.5).  
6.8.2.4. 
LAM-002A Dose Schedule Interruptions and Vomited Doses 
No changes were made to this section. 
6.8.2.5. 
LAM-002A Dose Modifications 
The AEs associated with LAM-002A administration have included gastrointestinal 
toxicities of nausea, vomiting, and diarrhea, typically beginning shortly after initiation of 
drug administration.  
If a subject experiences an AE that is suspected to be related to LAM-002A, appropriate 
supportive care (e.g., antiemetics, antidiarrheals, therapy for tumor lysis syndrome [TLS]) should 
be instituted consistent with the nature of the event.  
If a subject experiences an LAM-002A-related DLT (reference Table 3) or other AE requiring a 
dose modification, then the LAM-002A administration should be interrupted until the toxicity 
recovers to Grade ≤ 1 or baseline. Upon resumption of LAM-002A, the total daily dose of 
LAM-002A should be reduced using an appropriate dose level or schedule (reference Table 3) as 
agreed between the investigator and medical monitor. Successive adjustments to progressively 
lower total daily dose levels can be made. If the subject cannot tolerate LAM-002A after a 
decrease to Dose Level -1 (25 mg BID), then the subject should be discontinued from 
LAM-002A therapy unless continued treatment is permitted by the medical monitor.  
After the LAM-002A dose is reduced, the dose can be maintained at that dose level or schedule, 
even if there is minimal or no toxicity with the reduced dosing regimen. However, if the subject 
tolerates a reduced total daily dose of LAM-002A for ≥ 4 weeks then the LAM-002A dosing 
regimen may be reescalated to a higher total daily dose level at the discretion of the investigator 
and with the concurrence of the medical monitor. Such reescalation may be particularly 
warranted if the AE comprised TLS or if further evaluation reveals that the AE that led to the 
dose reduction was not related to LAM-002A. Successive adjustments to progressively higher 
total daily dose levels can be made. However, the escalated dose cannot exceed the total daily 
starting dose level for that subject during the first 4 2 cycles of therapy.  
Individual subjects who initiated treatment at a total daily dose level at or below the lower of the 
currently established MTD or the RP2D and who have not experienced a DLT after ≥ 4 2 cycles 
of treatment may have the LAM-002A total daily dose escalated to the next higher dose level if 
both the principal investigator and the medical monitor agree that a dose escalation is medically 
warranted (e.g., for a subject with stable disease who is tolerating the current dose level of 
LAM-002A therapy). In such subjects, successive adjustments to progressively higher total daily 
dose levels can be made at intervals of ≥ 4 weeks with the condition that the escalated total daily 
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dose level cannot exceed a LAM-002A dose of 150 mg BID when administered continuously 
or the lower of the currently established MTD or RP2D of LAM-002A when given 
intermittently.  
In a subject who experiences a DLT precluding resumption of LAM-002A therapy during a 
cycle, a new cycle of treatment may begin at the later of Day 29 or when AEs or laboratory 
abnormalities related to LAM-002A have returned to baseline levels. If drug-related AEs or 
laboratory abnormalities precluding further administration of study drug are not resolved to 
baseline by Day 29, week-by-week delays in initiating the new cycle of treatment should be 
instituted. When all drug-related AEs and laboratory abnormalities have returned to baseline, the 
next cycle of therapy can be initiated. Upon initiation of a new cycle of therapy, the prior cycle 
of therapy will be considered completed. 
Investigators are to discuss modifications in the dosing regimen with the medical monitor. The 
appropriate clinic staff should dispense the LAM-002A for the new dose level or schedule and 
instruct the subject/caregiver about the change in the dosing regimen. 
6.6.2.6. 
LAM-002A Supportive Care 
6.8.2.6.1. Antiemetics for Subjects Taking LAM-002A by Continuous Administration 
For subjects taking LAM-002A via continuous administration, sites should consider 
providing study participants with antiemetics and antidiarrheals so that these supportive 
care medications are readily available in case gastrointestinal symptoms related to 
LAM-002A develop.  
For subjects taking LAM-002A via continuous administration, it is recommended that, if 
prophylactic or therapeutic antiemetics are required, subjects be offered 2 mg of the 
serotonin antagonist, granisetron (Kytril®, Granisol®), as an oral tablet or solution every 6 
hours as needed. If subjects have persistent nausea or vomiting, consideration can be given 
to a 10-mg subcutaneous injection of the extended release form of granisetron (Sustol®). 
Alternatively, application of a 31.3 mg granisetron transdermal patch (Sancuso®) every 3 
to 7 days can be offered. For transdermal prophylaxis, 24 to 48 hours may be necessary to 
allow a sufficient period to achieve effective granisetron systemic concentrations. Use of the 
serotonin antagonists, ondansetron (Zofran®, Zuplenz®) or dolasetron (Anzemet®), is 
discouraged due to the possibility that such agents could prolong the cardiac QT interval.  
The dopamine antagonist, olanzapine (Zyprexa®), at doses of 2.5 to 10 mg, may be 
considered alone or in conjunction with serotonin antagonists or other types of antiemetic 
agents. Olanzapine doses of 10 mg may be sedating, which could be helpful for certain 
subjects, but may represent a concern for others, particularly for those who are elderly.  
Based on currently available information regarding LAM-002A metabolism, the 
neurokinin 1 receptor antagonist, rolapitant (Varubi®), can be considered, but aprepitant 
(Emend®) or netupitant+palonosetron (Akynzeo®) should be avoided because these drugs 
may inhibit CYP3A4 and/or CYP2C9 activity. 
Other classes of antiemetic medications that may be employed include dopamine 
antagonists or benzodiazepines if such drugs do not pose risks of QT prolongation or drug-
drug interactions. Given the possibility that LAM-002A may alter immunological 
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mechanisms, use of systemic corticosteroids (e.g., dexamethasone) should be minimized 
(particularly when coadministered with atezolizumab) to avoid immunocompromise; 
however, corticosteroids can be introduced if other types of antiemetic agents are not 
sufficiently effective.  
6.8.2.6.2. Antiemetics for Subjects Taking LAM-002A by Intermittent Administration 
Because LAM-002A induces dose-dependent nausea and vomiting, subjects who are taking 
LAM-002A by intermittent administration are required to receive antiemetic supportive 
care.  The following prophylaxis regimen should be started ≥30 minutes before initiation of 
each LAM-002A 3-day treatment sequence: 
• Dexamethasone 12 mg PO on Day 1 and then 8 mg PO on Day 2 and Day 3 
• Granisetron 2 mg PO on Day 1 and then 1 mg PO BID on Days 2 and 3 
• Olanzapine, 10 mg PO on Day 1 and then 10 mg PO on Days 2 and 3 
The study subject must be sent home from the clinic with sufficient dexamethasone, 
granisetron, and olanzapine to ensure that the supportive care medications are readily 
available to the subject for each of the four 3-day courses of LAM-002A therapy during 
each 28-day cycle.   
Doses of dexamethasone and olanzapine may be adjusted to tolerance.  Other antiemetic 
drugs (eg, neurokinin 1 receptor antagonists, dopamine antagonists, or benzodiazepines) 
may be considered in consultation with the medical monitor. 
6.8.2.6.3. Antidiarrheals 
For management of diarrhea related to LAM-002A, it is recommended that subjects take 
loperamide, 4 mg, at the occurrence of the first loose stool and then 2 mg every 2 hours 
until they are diarrhea-free for at least 12 hours. More aggressive loperamide prophylactic 
or therapeutic administration and titration of loperamide dosing for each loose bowel 
movement may be considered. During the night, subjects may take 4 mg of loperamide 
every 4 hours. Subjects should be advised to avoid dehydration through adequate fluid 
intake. Drugs such as 5HT3 antagonists or octreotide may be considered for their anti-
secretory effects.  For subjects who develop diarrhea while also receiving atezolizumab, the 
possibility of atezolizumab-induced colitis should be considered (see Section 6.8.4.4). 
Section 6.8.3. Rituximab 
Change: 
Consistent with the plan to evaluate the combination of LAM-002A and rituximab in 
this study, instructions for administration, dose modifications, and supportive care 
relating to rituximab were added to the protocol. 
6.8.3.1. 
Premedications 
In accordance with rituximab prescribing information (Genentech 2016), subjects should 
be premedicated with an antipyretic and an antihistamine to reduce the incidence and 
severity of infusion reactions. A recommended regimen is diphenhydramine, 25 mg orally, 
and acetaminophen (paracetamol), 650 mg orally, both given ~30 minutes prior to each 
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rituximab administration. Intravenous corticosteroids may also be administered as a 
premedication. Local practices and guidelines may be followed. 
6.8.3.2. 
Rituximab Administration 
Based on past experience with this regimen (Ghielmini 2004, Martinelli 2010), rituximab 
will be administered intravenously in the clinic for a total of 8 infusions: 
• Four induction infusions will be administered weekly on Cycle 1 Day 1, 
Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 22.  
• Four subsequent maintenance infusions will be administered every 8 weeks on 
Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.  
The dose for each infusion will be 375 mg/m2 of body surface area. The dose calculation of 
body surface area will be based on the subject’s height and actual body weight prior to 
therapy. Once established based on the pretreatment body weight, the total dose of 
rituximab for the subject should not be altered during therapy based on fluctuations in 
body weight unless required by institutional policy. 
At Cycle 1 Day 1, ~30 minutes after administration of the required antipyretic and 
antihistamine premedications and ~15 to 30 minutes after administration of the first dose 
of LAM-002A, the first infusion of rituximab will be administered via an infusion pump. 
For the initial infusion, the recommended infusion rate is 50 mg/hour. In the absence of 
infusion toxicity, the infusion rate can be increased in 50-mg/hour increments every 
30 minutes, to a maximum of 400 mg/hour. 
For subsequent infusions, the required antipyretic and antihistamine premedications will 
be given and the rituximab will be infused via an infusion pump. For these infusions, the 
infusion can be initiated at 100 mg/hour. In the absence of infusion toxicity, the infusion 
rate can be increased in 100-mg/hour increments every 30 minutes, to a maximum of 
400 mg/hour. Alternatively, for subjects who tolerate the first infusion with Grade ≤3 
infusion toxicity, subsequent infusions can be administered over a planned infusion time of 
90 minutes, with ~20% of the total dose administered in the first 30 minutes and the 
remaining 80% of the total protein dose administered in the subsequent 60 minutes 
(Dakhil 2014, Genentech 2016).  
6.8.3.3. 
Management of Rituximab Infusion Toxicity 
Rituximab can cause severe, including fatal, infusion reactions (Genentech 2016). Patients 
with pre-existing cardiac or pulmonary conditions, those who experienced prior 
cardiopulmonary adverse reactions to rituximab, and those with high numbers of 
circulating malignant cells (≥25 x 109/L) may be at particular risk. Severe reactions 
typically occur during the first infusion and are generally less frequent and less severe with 
subsequent infusions. The time to onset of infusion toxicity ranges from 30 to 120 minutes. 
Rituximab-induced infusion reactions and sequelae include urticaria, hypotension, 
angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress 
syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and/or 
anaphylactoid events. 
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Rituximab infusions should be interrupted or slowed in subjects experiencing Grade ≥3 
rituximab-related infusion reactions. Medical management (eg, oxygen, epinephrine, 
bronchodilators, and/or glucocorticoids) should be instituted, as needed. Upon 
improvement of symptoms, the infusion may be continued at 50% of the previous rate. At 
the discretion of the investigator, rituximab therapy may be permanently discontinued in 
subjects with Grade 4 infusion reactions or with reactions requiring substantial 
intervention. 
6.8.3.4. 
Rituximab Dose Modifications and Supportive Care 
Rituximab-related noninfectious pneumonitis has been described (Subramanian 2010) with 
an incidence of ~4.3% (Salmasi 2010). In patients developing rituximab-associated 
pneumonitis, the mean time from the first rituximab infusion to the onset of respiratory 
symptoms was 3 months, with a peak incidence after administration of a mean cumulative 
dosage of 1600 mg/m2 (Lioté 2010). 
Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab 
during infusion or at later timepoints. Non-infusion related events have included 
paraneoplastic pemphigus, Stevens Johnson syndrome, lichenoid dermatitis, 
vesiculobullous dermatitis, and toxic epidermal necrolysis (Genentech 2016). The onset of 
these reactions has varied from 1 to 13 weeks following initiation of rituximab exposure. 
Among patients receiving rituximab in combination with chemotherapy, rare instances of 
life-threatening bowel obstruction or perforation has been observed [Ram 2009], primarily 
in patients with NHL. In post-marketing reports, the mean time to documented 
gastrointestinal perforation was 6 (range 1–77) days from start of chemoimmunotherapy.  
Fulminate and fatal HBV infection and reactivation can occur during or after treatment 
with rituximab (Genentech 2016). The risk is very low among patients with negative anti-
HBc serology (Matsue 2010) and/or undetectable HBV DNA as assessed by quantitative 
PCR. Because subjects with such evidence of persistent HBV infection are excluded from 
this study, reactivation is not anticipated. Other serious bacterial, fungal, and new or 
reactivated viral infections have also occurred during and for ~1 year following rituximab-
based therapy (Gea-Banacloche 2010). Other new or reactivated viral infections in patients 
receiving rituximab have included CMV, herpes simplex virus, parvovirus B19, varicella 
zoster virus, West Nile virus, and HCV. Progressive multifocal leukoencephalopathy 
(PML) due to polyomavirus JC has been observed in patients who have received rituximab 
therapy for hematologic malignancies (Carson 2009).  
No dose reductions of rituximab are recommended. If a subject experiences an AE that is 
suspected to be related to rituximab and is of sufficient severity to warrant modification of 
therapy, administration of the drug should be interrupted or discontinued. Protocol-
recommended management of selected adverse events and appropriate supportive care is 
described in Table 5. 
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Table 5: 
Recommended Rituximab Modifications and Supportive Care 
Adverse 
Event 
Rituximab Interuption 
and Resumption 
Rituximab 
Permanent 
Discontinuation 
Supportive Care 
Pneumonitis 
Interrupt for Grade 2; 
resume when Grade ≤ 1 
Grade ≥3 
For Grade ≥2, 
corticosteroids, 
1-2 mg/kg of prednisone 
equivalents  
Rash 
Interrupt for Grade 3; 
resume when Grade ≤ 1 
Grade 4 
For Grade 2, topical 
corticosteroids. For 
Grade ≥ 3, 
corticosteroids, 
1-2 mg/kg of prednisone 
equivalents 
Hepatitis 
Grade ≥3 elevations of 
serum AST or ALT (> 5 
x ULN); resume when 
Grade ≤ 1 
-- 
Evaluate for HBV 
positivity; if HBV 
reactivation, treat with 
appropriate antiviral 
considering any 
potential for drug-drug 
interaction with 
LAM-002A. 
Bowel 
obstruction 
or 
perforation 
-- 
Any grade 
Provide appropriate 
antibiotic therapy and 
surgical supportive care. 
Infection 
Grade ≥3; resume when 
control of infection 
achieved 
-- 
Treat with appropriate 
systemic antibiotics for 
suspected or confirmed 
infections 
Abbreviations: ALT=alanine aminotransferase, AST=aspirate aminotransferase, ULN=upper 
limits of normal 
Section 6.8.4. Atezolizumab 
Change: 
Consistent with the plan to evaluate the combination of LAM-002A and atezolizumab 
in this study, instructions for administration, dose modifications, and supportive care 
relating to atezolizumab were added to the protocol.  
6.8.4.1. 
Premedications 
No specific premedications are recommended for administration prior to atezolizumab 
administration. Given the potential for interference with desired atezolizumab 
immunopotentiation, systemic corticosteroid administration should be avoided. 
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6.8.4.2. 
Atezolizumab Administration 
Atezolizumab will be administered intravenously in the clinic every 3 weeks.  The dose for 
each infusion will be 1200 mg. 
Using an infusion pump, atezolizumab should be administered through an intravenous line 
with or without a sterile, non-pyrogenic, low-protein binding in-line filter (pore size of 0.2 
to 0.22 μm). Other drugs should not be coadministered with atezolizumab through the 
same intravenous line. 
At Cycle 1 Day 1, ~15 to 30 minutes after administration of the first dose of LAM-002A, the 
first infusion of atezolizumab will be administered over 60 minutes. If the first infusion is 
tolerated, all subsequent infusions may be delivered over 30 minutes. Atezolizumab should 
not be administered as an intravenous push or bolus.  
6.8.4.3. 
Management of Atezolizumab Infusion Toxicity 
While infrequent (incident <2%), severe infusion reactions have occurred in clinical trial 
subjects receiving atezolizumab. For subjects with Grade 1 or 2 infusion reactions, the 
atezolizumab infusion should be interrupted or slowed. For subjects with Grade ≥3 
infusion reactions, atezolizumab therapy should be permanently discontinued. 
6.8.4.4. 
Atezolizumab Dose Modifications and Supportive Care 
In clinical trials supporting its approval as therapy for patients with previously treated 
advanced non-small cell lung cancer and metastatic bladder cancer (Weinstock 2017, 
Ning 2017), atezolizumab administration has been associated with immune-related AEs of 
pneumonitis, hepatitis, pancreatitis, colitis, endocrinopathies (hypophysitis, thyroiditis, 
adrenal insufficiency, diabetes mellitus), and neurological toxicity (meningitis/encephalitis, 
motor/sensory neuropathies, myasthenic syndrome/myasthenia gravis, Guillain-Barré 
syndrome). Immune-related AEs can be observed within days to months after starting 
atezolizumab therapy (Genentech 2017). 
Severe infections, including pneumonias, urinary tract infections, sepsis, herpes 
encephalitis, and mycobacterial infection have occurred.  
Systemic immune activation is a rare condition characterized by an excessive immune 
response.  Given the mechanism of action of atezolizumab, systemic immune activation is 
considered a potential risk when atezolizumab is given in combination with other 
immunomodulating agents.  Systemic immune activation should be included in the 
differential diagnosis for study subjects who, in the absence of an alternative etiology, 
develop a sepsis-like syndrome after administration of atezolizumab.  The initial evaluation 
should include: 
• CBC with peripheral smear 
• PT, PTT, fibrinogen, and D-dimer 
• Ferritin 
• Triglycerides 
• AST, ALT, and total bilirubin 
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• LDH 
• Complete neurologic and abdominal examination (assessing for 
hepatosplenomegaly) 
If systemic immune activation is suspected after the initial evaluation, the medical monitor 
should be contacted in consultation.  
Reference should be made to Section 6 of the atezolizumab investigator brochure for a 
detailed description of anticipated safety risks for atezolizumab. 
No dose reductions of atezolizumab are recommended. If a subject experiences an AE that 
is suspected to be related to atezolizumab and is of sufficient severity to warrant 
modification of therapy, administration of the drug should be interrupted or discontinued. 
Protocol-recommended management of selected adverse events is described in Table 6. 
Table 6: 
Recommended Atezolizumab Modifications and Supportive Care 
Adverse 
Event 
Atezolizumab  
Interruption and 
Resumption 
Atezolizumab  
Permanent 
Discontinuation 
Supportive Care 
Pneumonitis 
Interrupt for Grade 2; 
resume when Grade ≤ 1 
Grade ≥3 
For Grade ≥2, 
corticosteroids, 
1-2 mg/kg of prednisone 
equivalents  
Hepatitis 
Interrupt for Grade 2 
elevations of serum AST 
or ALT (> 3-5 x ULN) or 
total bilirubin (> 1.5-3 x 
ULN); resume when 
Grade ≤ 1 
Grade ≥3 elevations of 
serum AST or ALT (> 5 x 
ULN) or total bilirubin 
(> 3 x ULN) 
For Grade ≥2, 
corticosteroids, 
1-2 mg/kg of prednisone 
equivalents  
Colitis 
Interrupt for Grade 2 or 
3; resume if Grade ≤ 1 
within 12 weeks on 
≤ 10 mg oral prednisone 
equivalents 
Grade 4 
For Grade 2 recurrent 
or persistent (> 5 days), 
corticosteroids, 
1-2 mg/kg of prednisone 
equivalents; For Grade 
≥3, methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
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Pancreatitis 
Interrupt for Grade 2 or 
3 pancreatitis or Grade 
≥3 increases in serum 
amylase or lipase levels 
(>2 x ULN); resume if 
Grade ≤ 1 within 
12 weeks on ≤ 10 mg oral 
prednisone equivalents 
Grade 4 pancreatitis or 
any grade of recurrent 
pancreatitis 
For Grade ≥2, 
methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
Hypophysitis 
Interrupt for symptoms; 
resume when Grade ≤ 1 
-- 
Administer 
corticosteroids and 
hormone replacement as 
clinically indicated 
Thyroid 
disorders 
Interrupt for symptoms; 
resume when Grade ≤ 1 
-- 
For symptomatic hypo- 
or hyperthyroidism, 
initiate hormone 
replacement or anti-
thyroid drug, as needed 
Adrenal 
insufficiency 
Interrupt for symptoms; 
resume if Grade ≤ 1 
within 12 weeks on 
≤ 10 mg oral prednisone 
equivalents 
-- 
For symptoms, 
methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
Diabetes 
mellitus 
Interrupt for Grade ≥3 
hyperglycemia (serum 
glucose ≥ 250 mg/dL; 
resume when blood sugar 
control achieved 
-- 
Insulin for Type 1 
diabetes mellitus 
Meningitis, 
encephalitis, 
myasthenic 
syndrome, 
myasthenia 
gravis, or 
Guillain-
Barré 
syndrome 
-- 
Any grade 
Methylprednisolone 
1-2 mg/kg intravenous 
→ oral corticosteroid 
taper over ≥ 1 month 
Rash 
Interrupt for Grade 3; 
resume when Grade ≤ 1 
Grade 4 
For Grade 2, topical 
corticosteroids. For 
Grade ≥ 3, 
corticosteroids, 
1-2 mg/kg of prednisone 
equivalents 
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Infection 
Grade 3 or 4; resume 
when control of infection 
achieved 
-- 
Treat with appropriate 
systemic antibiotics for 
suspected or confirmed 
infections 
Abbreviations: ALT=alanine aminotransferase, AST=aspirate aminotransferase, ULN=upper limits of 
normal 
 
Section 6.9 
Other Supportive Care Recommendations 
Change: 
General supportive care recommendations were updated and consolidated in this 
section of the protocol. 
6.9 
Other Supportive Care Recommendations 
Consistent with subject safety and comfort, administration of any prescription or over-the-
counter drug products other than study medication will be minimized during the study 
period. Subjects should be discouraged from use of herbal remedies, self-prescribed drugs, 
tobacco products, or street drugs during their participation in the clinical study and should 
be counseled to minimize use of alcohol or nonmedical marijuana. 
If considered necessary for the subject’s well-being, drugs for concomitant medical 
conditions or for symptom management may be given at the discretion of the investigator. 
The investigator’s decision to authorize the use of any drug other than study drug will take 
into account subject safety, the medical need, the potential for drug interactions, the 
possibility for masking symptoms of a more significant underlying event, and whether use 
of the drug will compromise the outcome or integrity of the study. 
Subjects will be instructed about the importance of the need to inform the clinic staff of the 
use of any drugs or remedies (whether prescribed, over-the-counter, or illicit) before and 
during the study.  
Recommendations regarding specific types of concomitant therapies, supportive care, diet, 
and other interventions are provided below. To minimize variations in supportive care, the 
recommended supportive care agents (eg, loperamide, granisetron) should be used unless 
there is a medical rationale in a specific subject for use of an alternative product. 
6.9.1. 
Antibiotics, Antifungals, and Antivirals 
Care should be taken to avoid or minimize concomitant administration of prophylactic or 
therapeutic antibacterial, antifungal, or antiviral, agents that are moderate or strong 
CYP3A4 or CY2C9 inhibitors or inducers (see Section 6.96 and Appendix 3).  
For subjects with a history of recurrent infections, prophylaxis with intravenous 
gammglobulin may be offered and consideration may be given to initiation of antibiotic 
prophylaxis against pneumocystis infection (eg, with trimethoprim-sulfamethoxazole, 
dapsone, aerosolized pentamidine, or atovaquone) beginning prior to study drug 
administration. Such support also offers the benefit of reducing the risk for other bacterial 
infections (Stern 2014). Local practices or guidelines regarding infection prophylaxis may 
be followed.  
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Subjects developing an intercurrent infection during study drug treatment may receive 
therapeutic antibacterial, antiviral, or antifungal drugs for intercurrent infections as 
needed. Continuation of study therapy during treatment for an intercurrent infection is at 
the discretion of the investigator but guidance in Section 6.8.3.4 and Section 6.8.4.4 should 
be considered in subjects receiving combination therapy. 
6.9.2. 
Anticancer Therapies Other than the Study Drugs 
No systemic anticancer therapies (including chemotherapy, antibody therapy, hormonal 
therapy, immunotherapy, or other experimental therapies) for the subject’s cancer are 
permitted while the subject is receiving study treatment. Subjects are not allowed to 
participate concurrently in any other therapeutic clinical or imaging study. 
The use of palliative radiotherapy should be minimized given the potential of such 
treatment to confuse assessments of study drug safety or therapeutic effect. However, 
administration of limited-fraction radiotherapy is permitted to control local tumor-related 
symptoms if irradiation is unlikely to induce major organ toxicity or affect target lesions 
being followed for tumor response and progression. 
If required to maintain disease control, study drugs may be continued with caution during 
radiotherapy administration. 
6.9.3. 
Anticoagulants 
Use of local anticoagulation or antithrombotic agents to maintain a venous access catheter 
is permitted. While not prohibited, use of systemic anticoagulants (eg, unfractionated 
heparin, low-molecular-weight heparin, fractionated heparin, warfarin or other oral 
anticoagulants, aspirin) after a subject is on study should be avoided unless necessary for 
development of a serious intercurrent thrombotic or embolic condition. Subjects who 
develop conditions that require anticoagulant therapy are permitted to receive such drugs 
and are not required to discontinue study participation if they appear to be safely 
benefiting from study therapy. Subjects should be closely monitored for bleeding events 
when on systemic anticoagulant therapy. 
6.9.4. 
Antihistamine, Antiinflammatory, or Antipyretic, Drugs 
Antihistamines (eg, cetirizine, diphenhydramine), and antiinflammatory/antipyretic drugs 
(eg, acetaminophen [paracetamol], nonsteroidal anti-inflammatory drugs [NSAIDs]), may 
be used during the study, as medically warranted. The potential for adverse hepatic effects 
with acetaminophen and platelet inhibitory effects with NSAIDs should be considered in 
the selection of the appropriate drug for the clinical situation. 
6.9.5. 
Corticosteroids 
At study entry, subjects may not be using systemic or enteric corticosteroids but may be 
receiving inhaled or topical corticosteroids. During study therapy, subjects may use 
systemic, enteric, topical or enteric corticosteroids as required by protocol or for 
treatment-emergent conditions. Use of systemic or enteric corticosteroids as 
premedications or for other reasons should be minimized but can be considered after 
consultation with the medical monitor.  
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6.9.6. 
Drugs with Potential for Drug-Drug Interactions with LAM-002A 
No information is available regarding interactions of LAM-002A with therapeutic agents 
or other substances in humans. In vitro data suggest that concomitant administration of 
potent inhibitors or inducers of CYP3A4 or CYP2C9 might alter LAM-002A clearance and 
lead to clinically significant increases or decreases in LAM-002A exposure. Consequently, 
the concomitant use of strong inhibitors or inducers of CYP3A4 or CYP2C9 (see Table 14) 
should be avoided when possible.  
Based on these considerations, protocol candidates who require therapy with strong 
CYP3A4 or CYP2C9 inhibitors or inducers listed in Table 14 should not be enrolled into 
the study.  
During study participation, coadministration of LAM-002A with CYP3A4 or CYP2C9 
inhibitors or inducers (see Table 14) should be avoided, if possible. However, a subject who 
develops a condition that may require use of such drugs is not required to permanently 
discontinue LAM-002A if the subject is experiencing clinical benefit and other options for 
treating the subject’s cancer are limited. If medically appropriate, investigators may wish 
to use a therapeutic alternative that would not be expected to affect these enzymes. For 
subjects who require temporary use of a drug that does affect these enzymes (e.g., 
treatment with a systemic antifungal agent), LAM-002A can be interrupted (or the doses 
reduced) during use of the other medication and then resumed after completion of the 
other drug. For subjects who require initiation of chronic therapy with a drug that potently 
affects these enzymes, investigators must consult with the medical monitor to consider the 
best course of action.  
6.9.7. 
Drugs Known to Prolong the QT Interval 
In a thorough QTc study, apilimod dimesylate at doses of 50 mg and 150 mg was associated 
with repolarization findings in excess of those deemed negative by regulatory guidance. 
The magnitude of the change was modest (~8.5 msec), peaked at 4 hours and did not 
demonstrate a dose trend. Preliminary QTc observations in the ongoing study in patients 
with hematological malignancies suggest the potential for dose- and exposure dependent 
Grade 1 or 2 QT prolongation. 
As a precaution, the clinical potential of LAM-002A to prolong the QT interval will be 
assessed in this study. Accordingly, co-administration of LAM-002A and known QT-
prolonging drugs is to be minimized because use of such drugs might confound 
interpretation of QT data from the trial.  
Based on these considerations, protocol candidates who require therapy with drugs known 
to prolong the QT interval (as listed in Table 15) should not be enrolled into the study. If 
medically justified, protocol candidates may be enrolled if such drugs can be discontinued 
or alternative drugs that do not affect QT can be substituted >7 days before the first dose 
of study drug.  
After the subject is enrolled to the protocol, use of drugs known to prolong the QT interval 
should be minimized but is not prohibited if administration of such drug is necessary and 
the subject appears to be benefiting from protocol therapy. 
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6.9.8. 
Hematopoietic Support 
Granulocyte colony-stimulating factor (G-CSF) (eg, filgrastim, filgrastim snd, 
pegfilgrastim, lenograstim) may be administered in response to Grade ≥3 neutropenia or 
neutropenic complications. 
Granulocyte-macrophage colony-stimulating factor (GM-CSF) should not be administered 
given the potential for GM-CSF-related inflammatory symptoms.  
Use of erythropoietic agents (eg, erythropoietin or darbepoetin) is not recommended. 
Red blood cell or platelet transfusions may be administered as medically indicated. 
6.9.9. 
Immunization 
There is no information regarding the effects of LAM-002A or atezolizumab on the safety 
or response to immunization against infectious pathogens.  
In randomized clinical trials, rituximab has been shown to reduce the antibody response to 
pneumococcal vaccination (a T-cell-independent antigen) or to anti-keyhole limpet 
hemocyanin antibodies (a novel protein antigen) (Genentech 2016). Response to tetanus 
toxoid vaccine (a T‑cell-dependent antigen with existing immunity) or maintenance of a 
positive Candida skin test (as a measure of T-cell-mediated delayed-type hypersensitivity) 
was not altered. The specific clinical relevance of these findings is unknown.  
For subjects who are at substantial risk of an infection (eg, influenza) that might be 
prevented by immunization, consideration should be given to providing the vaccine prior to 
initiation of study therapy. Vaccination with live virus vaccines during study treatment is 
not recommended. 
6.9.10. 
Procedures/Surgery 
The extent to which LAM-002A or other study drugs may affect wound healing or the risk 
of would infection is unknown. Investigators may use clinical discretion in deciding 
whether to interrupt protocol therapy before and after surgery or other invasive 
procedures.  
6.9.11. 
Skeletal Event Prophylaxis 
Bisphosphonates or denosumab are permitted if a subject was receiving such therapy at the 
time of screening and will continue on a stable regimen throughout protocol therapy. The 
need to start such drugs while on therapy may be an indication of disease progression and 
should be discussed with the sponsor prior to implementation. 
 
Section 6.10. Study Restrictions 
Change: 
A study restrictions section was added to provide guidance to the investigator. 
6.10.1. 
Breast Feeding 
There is no information regarding the presence of LAM-002A or its metabolites in animal 
or human breast milk and the effects of the drug on the breastfed infant or on milk 
production are unknown. 
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Rituximab is secreted in the milk of lactating cynomolgus monkeys, but it is not specifically 
known whether rituximab is secreted into human milk (Genentech 2016). There is similarly 
no information regarding the presence of atezolizumab in human milk (Genentech 2017). 
However, because human IgG is excreted in human milk, there is a hypothetical potential 
for absorption and harm to an infant from administration of these types of therapeutic 
antibodies.  
For these reasons, women who are nursing are not eligible to participate in this study. 
Lactating women who do participate in this clinical trial must discontinue nursing during 
protocol therapy and should avoid nursing for ≥2 months after LAM-002A and for ≥5 
months after the last dose of rituximab or atezolizumab.  
6.10.2. 
Contraception 
Animal studies have been conducted to assess the effects of apilimod on fertility and 
organogenesis. In studies conducted to date, apilimod or apilimod dimesylate did not affect 
fertility or cause reproductive harm. One patient receiving the drug for Crohn disease 
conceived during therapy; a normal pregnancy was carried to term and a healthy infant 
was born. However, no other experience is available with the drug in pregnant patients.  
Reproduction studies of rituximab in cynomolgus monkeys at maternal exposures similar 
to human therapeutic exposures have shown no teratogenic effects (Genentech 2016). 
However, B-cell lymphoid tissue was reduced in the offspring of these animals; B-cell 
counts returned to normal levels and immunologic function was restored within 6 months 
of birth. In humans, B-cell lymphocytopenia generally lasting <6 months can occur 
postnatally in infants exposed to rituximab in utero. 
Animal reproduction studies have not been conducted with atezolizumab to evaluate its 
effect on reproduction and fetal development. A literature-based assessment of the effects 
on reproduction demonstrated that a central function of the PD-L1/PD-1 pathway is to 
preserve pregnancy by maintaining maternal immune tolerance to a fetus (Genentech 
2017). Blockage of PD-L1 signaling has been shown in murine models of pregnancy to 
disrupt tolerance to a fetus and to result in an increase in fetal loss; therefore, potential 
risks of administering atezolizumab during pregnancy include increased rates of abortion 
or stillbirth. As reported in the literature, there were no malformations related to the 
blockade of PD-L1/PD-1 signaling in the offspring of these animals; however, immune-
mediated disorders occurred in PD-L1 and PD-1 knockout mice. Based on its mechanism of 
action, fetal exposure to atezolizumab may increase the risk of developing immune-
mediated disorders or altering the normal immune response. 
Accordingly, sexually active females of childbearing potential must agree to use a protocol-
recommended method of contraception during heterosexual intercourse from the start of 
the screening period until ≥5 months days after the final dose of study therapy. 
In the context of this protocol, a female subject is considered to be of childbearing potential 
unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has 
medically documented ovarian failure (with serum follicle stimulating hormone (FSH) level 
> 35 mIU/mL and a negative serum or urine beta βHCG); or is menopausal (amenorrhea 
for ≥12 months).  
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Sexually active male subjects who can father a child and are having intercourse with 
females of childbearing potential who are not using adequate contraception must agree to 
use a protocol-recommended method of contraception from the start of study therapy until 
≥5 months days after the final dose of the study therapy and to refrain from sperm 
donation from the start of study therapy until ≥5 months after administration of the final 
dose of study therapy. 
In the context of this protocol, a male subject is considered able to father a child unless he 
has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy. 
Protocol-recommended contraceptive methods are described in Table 7. 
Table 7: 
Protocol-Recommended Contraceptive Methods 
Individual Methods 
Combination Methods 
Hormonal Methods 
(One method to be used  
with a barrier method) 
Barrier Methods 
(Both methods to be used OR one 
method to be used with one 
hormonal method) 
IUD (eg, Copper T380A, LNg20) Estrogen and progesterone 
Diaphragm with spermicide 
Tubal sterilization 
Oral contraceptives 
Male condom (with spermicide) 
Hysterectomy 
Transdermal patch 
 
Vasectomy 
Vaginal ring 
 
 
Progesterone injection or implant 
 
Abbreviation: IUD=intrauterine device 
6.10.3. 
Diet 
Because LAM-002A is a substrate of CYP3A4, subjects should be advised to avoid 
ingestion of grapefruit, grapefruit juice, or Seville oranges (which contains a potent 
CYP3A4 inhibitor) and should not use St. John’s wort, which is a potent CYP3A4 inducer. 
No other specific dietary restrictions are required. 
 
Section 6.11. Duration of Subject Participation 
Change: 
Information regarding the duration of subject participation was updated to include 
instructions for administration of both LAM-002A monotherapy and 
LAM-002A-based combination therapy. Consistent with intention-to-treat principles 
designed to maximize collection of safety and efficacy data, it was noted that subjects 
could continue on either of the combination agents even if the other agent were to be 
discontinued due to toxicity. 
All subjects will be treated for at least 1 cycle unless there is evidence of unacceptable toxicity or 
PD. Although subjects may continue to receive study treatment until  experiencing unacceptable 
toxicity or disease progression, it is estimated that each subject will participate for an average of 
6 months of treatment and an additional 1 month of follow up.  
Subjects may continue receiving LAM-0002A until the occurrence of any events requiring 
treatment discontinuation as defined in Section 6.8.2.5 and Section 6.12. 
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Subjects allocated to LAM-0002A/rituximab may continue to receive rituximab until the 
earliest of a maximum of 8 infusions or the occurrence of any events requiring treatment 
discontinuation as defined in Section 6.8.3.4 and Section 6.12. 
Subjects allocated to LAM-0002A/atezolizumab may continue to receive atezolizumab until 
the earliest of any events requiring treatment discontinuation as defined in Section 6.8.4.4 
or Section 6.12. 
Note: If medically appropriate, subjects allocated to combination doublet therapy may 
continue with protocol-specified therapy for the therapeutic agent (LAM-002A, rituximab, or 
atezolizumab) that continues to be tolerated, even if the other agent need to be discontinued 
due to drug-specific toxicity. 
Subjects who have discontinued study treatment for reasons other than PD will be assessed per 
Revised Response Criteria for NHL or Guidelines for the diagnosis and treatment of CLL at a 
minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for 
up to 1 year from the last enrolled subject’s first treatment (Cycle 1 Day 1), whichever comes 
first. Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month 
intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will 
be gathered during routine clinic visits, other study site contact with the subjects, or via 
telephone or e-mail with the subjects/caregivers or referring physician offices. 
 
Section 6.12. Criteria for Subject Withdrawal from Study Treatment or Study Participation 
Study Termination 
Change: 
This section of the protocol was modified to focus on potential reasons for subject 
withdrawal from study treatment or study participation.  A later section dealing with 
potential study termination was updated. 
The sponsor may terminate this study at any time, provided a written notice is submitted at a 
reasonable time in advance of the intended termination. 
Subjects may be withdrawn from further study treatment for any of the following reasons: 
• Subject withdrawal of informed consent 
• Disease progression of cancer while receiving study therapy Note: Apparent worsening 
of disease during temporary interruption of study therapy (e.g., for drug-related toxicity 
or intercurrent illness) may not indicate true cancer progression. Study subjects 
undergoing PET for lymphoma assessment can experience transient disease flare on 
imaging before having subsequent therapy-induced tumor regression. Worsening of 
constitutional symptoms or performance status in the absence of objective evidence of 
worsening lymphoma (e.g., due to infection) may not represent definitive disease 
progression. For these reasons, if there is uncertainty regarding whether there is true 
disease progression and if medically appropriate, the subject may continue or resume 
study treatment and remain under close observation (e.g., evaluated at 4- to 8-week 
intervals) while relevant radiographic, clinical, and/or laboratory assessments are 
performed to document whether tumor control can be maintained or whether disease 
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progression has truly occurred. If subsequent evaluations suggest that the subject has 
experienced persistent definitive disease progression, then the date of progression will 
be the timepoint at which progression was first objectively documented.  
• Unacceptable study-drug-related toxicity despite appropriate dose modification 
• Development of intercurrent illness that precludes continued study therapy 
• Physician decision that continuation is not in the subject’s best interest 
• Treatment of the cancer with another therapeutic regimen 
• Subject becomes pregnant or begins breastfeeding 
• Substantial noncompliance with study drug administration, study procedures, or study 
requirements in circumstances that increase risk or substantially compromise the 
interpretation of study results 
• Termination of the study by the sponsor, relevant regulatory agencies, or the IRB/IEC 
The investigator must determine the primary reason for a subject’s withdrawal from the study 
and record this information on the electronic case report form (eCRF). 
Unless they withdraw consent for further follow-up, subjects who discontinue study 
therapy will continue on study for acquisition of safety information through ≥30 days after 
the last dose of study treatment, and for further collection of long-term information 
regarding survival. 
 
Section 6.13. Replacement of Subjects 
Change: 
Because Stage 1 focuses on DLT evaluability and Stage 2 focuses on efficacy 
evaluability, the information in this section was updated and cross-referenced to 
relevant sections of the protocol. 
6.13. 
Replacement of Subjects 
Subjects not meeting the criteria for evaluability defined in Section 6.1.3 may be replaced 
at the discretion of the sponsor. Subjects who are withdrawn from study treatment prior to 
completing Cycle 1 dosing for reasons other than DLT will be replaced so that a full cohort of 
subjects completes Cycle 1 safety evaluations. If a subject needs to be replaced, the site will 
notify the Sponsor for the need of a replacement; the associated subject ID will not be used. 
 
Section 7. SELECTION AND WITHDRAWAL OF SUBJECTS 
Changes: The description of withdrawal of subjects was moved to Section 6.12.  Subject 
selection criteria were updated as follows: 
• On mechanistic grounds, PMBL may respond to LAM-002A therapy; for this reason, 
patients with this type of lymphoma were permitted to be accrued to the dose-ranging 
portion of the trial. 
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• A requirement for prior rituximab therapy was no longer mandated given that some 
patients (eg, those with CLL/SLL) may not have received rituximab as prior therapy 
based on changing standards of care. 
• Organ function criteria for hematological function, hepatic function, and renal 
function were updated based on the evolving safety profile of LAM-002A  showing 
that the drug is unlikely to adversely alter these organ systems. 
• The contraception enrollment criteria were made more specific, referencing protocol-
recommended contraceptive measures now described in Section 6.10.2. 
• The requirements for disease biopsy timing and baseline bone marrow collection in 
patients with lymphoma were clarified. 
• Prior therapy prohibitions were included for study candidates under consideration 
for combination therapy to minimize the likelihood that they have disease that might 
be totally resistant to rituximab or atezolizumab.  
• Included were restrictions on use of live virus vaccines, ongoing therapy for HBV, 
recent therapy with immunostimulatory agents, ongoing use of immunosuppressive 
therapies, recent serious infection, a history of autoimmunity, or inability to tolerate 
required supportive care; these exclusions were intended to enhance subject safety 
and to avoid comorbid conditions that could confuse interpretation of safety findings. 
• The requirements relating to baseline serological testing for chronic viral infections 
were clarified. 
7.1. 
Subject Inclusion Criteria 
1. The subject is capable of understanding and complying with the protocol requirements 
and has signed the informed consent document. The subject is able to provide signed and 
dated informed consent prior to initiation of any study-specific procedures. 
2. Subjects must have a histologically confirmed diagnosis of B-cell NHL limited to FL, 
DLBCL, MCL, MZL, primary mediastinal B-cell lymphoma (PMBL), or CLL/SLL 
according to the World Health Organization (WHO) classification, that has progressed 
and for which standard curative measures do not exist or are no longer effective. Prior 
therapy must have included a rituximab based chemoimmunotherapy regimen.  
3. Subjects with DLBCL must have progressed after transplant, or be unwilling, unable or 
not an appropriate candidate for an autologous stem cell or bone marrow transplant. 
4. Subjects must have radiographically measurable lymphadenopathy or extranodal 
lymphoid malignancy (defined as the presence of ≥ 1 lesion that measures ≥ 2.0 cm in the 
longest dimension [LD] and ≥ 1.0 cm in the longest perpendicular dimension [LPD] as 
assessed radiographically). 
5. The subject is ≥ 18 years old. 
6. The subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 
≤ 2. 
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7. The subject has organ and marrow function as follows: 
a. Absolute neutrophil count (ANC) ≥ 1.0 × 109/L (1,000/mm3) without hematopoietic-
stimulating factor support 
b. Platelets ≥ 75 50 × 109/L (5075,000/mm3) 
c. Total bilirubin ≤ 1.5 x the upper limit of normal (ULN) except for subjects with 
known Gilbert disease (total bilirubin ≤ 3 x ULN permitted) 
d. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 60 mL/min (based 
on the Cockcroft-Gault formula) 
e. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN 
if no liver involvement, or ≤ 5 x ULN with liver involvement 
f. Albumin ≥ 2 g/dL 
Note: Grade ≥ 3 neutropenia or thrombocytopenia is permitted if the abnormality is 
related to bone marrow involvement with hematological malignancy (as documented by 
bone marrow biopsy/aspirate obtained since the last prior therapy). 
8. The subject has the ability to swallow oral capsules without difficulty. 
9. Sexually active subjects (men and women), even if on oral contraceptives, must agree to 
remain abstinent (refrain from heterosexual intercourse) or use appropriate 
contraceptive methods (see Section 6.10.2) during the treatment period and for 
5 months after the last dose of study therapy use medically accepted barrier methods 
of contraception (e.g., male condom, female condom, or diaphragm with spermicidal gel) 
during the course of the study and for 3 months after the last dose of study drug.  
10. Women of childbearing potential (WCBP) must have a negative serum or urine 
pregnancy test at screening. WCBP include any woman who has experienced menarche 
and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal 
ligation, or bilateral oophorectomy) or is not postmenopausal. Postmenopausal is defined 
as: 
a. Amenorrhea ≥ 12 consecutive months without another cause or  
b. For women with irregular menstrual periods and on hormone replacement therapy, a 
documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL 
11. For subjects with lymphoma: The subject has archived tumor tissue for analysis that was 
obtained within 4 months prior to the start of screening; or is willing to undergo a 
pretreatment core needle, excisional, or incisional biopsy of a lymphoma nodal lesion; or 
is willing to undergo a pretreatment bone marrow aspirate if there is known bone 
marrow involvement (≥ 50% NHL cells).  
12. For subjects with CLL/SLL: The subject has sufficient circulating cells in the peripheral 
blood (e.g., ALC ≥ 10 x 109/L) or is willing to undergo a pretreatment bone marrow 
aspirate to obtain CLL cells.  
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7.2 
Subject Exclusion Criteria 
1. 
Subjects with central nervous system (CNS) lymphoma are not eligible for the trial 
unless the disease had been treated and the subject remained asymptomatic (for at 
least 6 months) with no active CNS lymphoma, as determined by lumbar puncture, 
computed tomography scan (CT), or magnetic resonance imaging (MRI). 
2. 
The subject has received cytotoxic chemotherapy (including investigational cytotoxic 
chemotherapy) within 3 weeks, or nitrosoureas/ mitomycin C within 6 weeks before 
the first dose of study treatment. 
3. 
The subject has received treatment with a therapeutic antibody less than 4 weeks 
before the first dose of study treatment. For subjects with rapidly progressive or 
aggressive subtypes of lymphoma, a minimum period of 2 weeks between the last 
treatment with a therapeutic antibody and the first dose of study treatment may be 
permitted following discussion with the medical monitor. 
4. 
The subject has received radioimmunotherapy within 6 weeks of the first dose of 
study treatment. 
5. 
The subject has received radiation therapy within 14 days of the first dose of study 
treatment. 
6. 
The subject has received prior treatment with a small-molecule kinase inhibitor or 
other small-molecule investigational agent within 14 days or 5 half-lives of the 
compound or active metabolites, whichever is greater, before the first dose of study 
treatment. 
7. 
Stage 2 (study candidates being considered for LAM-002A/rituximab 
combination therapy): Best overall response with the last regimen containing an 
anti-CD20 antibody (eg, rituximab, ofatumumab, obinutuzumab) was disease 
progression. 
8. 
Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy): Prior exposure to a CD137 agonist or an immune 
checkpoint inhibitor, including an anti-PD1, anti-PDL1, or anti-CTLA4 
therapeutic antibody. 
9. 
Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy):  treatment with a live, attenuated vaccine within 4 weeks 
prior to initiation of study treatment, or anticipation of need for such a vaccine 
during atezolizumab treatment or within 5 months after the last dose of 
atezolizumab. 
10. 
Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy):  Current treatment with anti-viral therapy for hepatitis B 
virus (HBV). 
11. 
Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy):  Treatment with systemic immunostimulatory agents 
(including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks 
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or 5 half-lives of the drug (whichever is longer) prior to initiation of study 
treatment. 
12. 
The subject is currently receiving treatment with strong inhibitors or inducers of 
CYP450 2C9 or 3A4 enzymes. 
13. 
The subject is chronically receiving immunosuppressive therapy (eg, with 
cyclophosphamide, azathioprine, thalidomide, lenalidomide, methotrexate, or 
anti-TNF-α agents) within 2 weeks prior to initiation of study treatment or 
requires systemic or enteric corticosteroidsat the time of starting study therapy. 
Study candidates using systemic low-dose corticosteroids for orthostatic 
hypotension or adrenal insufficiency or topical, intra-articular, nasal, or inhaled 
corticosteroids are not excluded from study participation. Note: During study 
therapy, subjects may use systemic, enteric, topical, intraarticular, nasal, or inhaled 
corticosteroids as required by protocol or for treatment-emergent conditions. 
14. 
The subject has not recovered from toxicity due to all prior therapies (i.e., return to 
pre-therapy baseline or to Grade 0 or 1). Persistent > Grade 1 toxicity from prior 
therapy will be considered by the sponsor for inclusion if there is no evidence of an 
overlapping apilimod toxicity.  
15. 
The subject has uncontrolled significant intercurrent illness including, but not limited 
to, ongoing or active infection, history of congestive heart failure within 6 months, 
hypertension, unstable angina pectoris within 6 months, stroke within 6 months, 
myocardial infarction within 6 months, or cardiac arrhythmias. (Controlled chronic 
atrial fibrillation will not be excluded). 
16. 
Severe uncontrolled infection within 2 weeks prior to initiation of study treatment, 
including hospitalization for complications of infection, bacteremia, or severe 
pneumonia or treatment with therapeutic oral or IV antibiotics. Note: subjects 
receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or 
chronic obstructive pulmonary disease exacerbation) are not excluded.   
17. 
Stage 2 (study candidates being considered for LAM-002A/atezolizumab 
combination therapy): Active or history of autoimmune disease or immune 
deficiency, including, but not limited to, myasthenia gravis, myositis, 
autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, 
inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener 
granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple 
sclerosis (with the following exceptions: history of autoimmune-related 
hypothyroidism and receiving thyroid-replacement hormone; controlled Type 1 
diabetes mellitus on an insulin regimen; eczema, psoriasis, lichen simplex 
chronicus, or vitiligo with dermatologic manifestations if rash covers covers 
< 10% of body surface area, disease is well controlled at baseline and requires 
only low-potency topical corticosteroids, there is no occurrence of acute 
exacerbations of the underlying condition requiring psoralen plus ultraviolet A 
radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or 
high-potency or oral corticosteroids within the previous 12 months, and the 
subject does not have extra-cutaneous disease [e.g., psoriatic arthritis]).  
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18. 
The subject has a history of malabsorption or other GI disease that may significantly 
alter the absorption of apilimod (e.g., ≥ Grade 2 nausea, vomiting or diarrhea). 
19. 
The subject has undergone major surgery within 28 days prior to first dose of study 
drug. 
20. 
The subject has a QTcF > 470 msec on screening ECG or has a history or risk factors 
for, or use of medications known to prolong QTc interval or that may be associated 
with Torsades de Pointes within 7 days of treatment start. 
21. 
The subject has past history of tuberculosis (TB) or active infection with TB, human 
immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). 
Note: Subjects must have negative human immunodeficiency virus (HIV) antibody, 
negative hepatitis B surface antigen (HbsAg) and negative hepatitis B core (HBc) 
antibody or undetectable HBV deoxyribonucleic acid (DNA) by quantitative 
polymerase chain reaction (PCR) testing, and negative HCV antibody or negative 
HCV ribonucleic acid (RNA) by quantitative PCR. 
22. 
The subject is lactating and breast feeding. 
23. 
The subject has a previously identified allergy or hypersensitivity to components of 
the study treatment formulation. 
24. 
Stage 1 (study candidates being considered for LAM-002A intermittent 
administration): Known inability to tolerate the protocol-specified antiemetic 
and antidiarrheal supportive care regimen. 
25. 
The subject is unable or unwilling to abide by the study protocol or cooperate fully 
with the investigator or designee. 
26. 
The subject has a history of other medical or psychiatric illness or organ dysfunction 
which, in the opinion of the investigator, would either compromise the subject’s 
safety or interfere with the evaluation of the safety of the study agent. 
27. 
The subject has a history of prior cancer (not under study) that has not been in 
remission for at least 3 years. The following are exempt from the 3-year limit: basal 
cell or squamous cell carcinoma of the skin, localized prostate cancer with normal 
Prostate Specific Antigen (PSA), cervical cancer in situ or other in situ carcinomas. 
 
Section 8. METHODS OF ASSESSMENT AND ENDPOINTS 
Change: 
The following changes were made: 
• Information regarding pretreatment tumor tissue assessment was updated. 
• All schedules of assessment tables were consolidated into Section 8.   
• Methods of assessment were updated in text, tables, and table footnotes to enhance 
clarity and to ensure consistency with the updated exploratory endpoints described in 
Section 5. Schedules of assessment specific for LAM-002A continuous monotherapy, 
LAM-002A intermittent monotherapy, LAM-002A/rituximab combination therapy, 
and LAM-002A/atezolizumab combination therapy were included.   
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• Information regarding concomitant medications and supportive care was removed 
from Section 8 and updated and consolidated in Section 6.9.  
Only the sections in which changes were made are displayed below. 
8. 
METHODS OF ASSESSMENT AND ENDPOINTS 
All trial data will be recorded on the eCRFs. Timing of study procedures are listed in Section 
Deleted: Schedule of Assessments. All trial data will be recorded on the eCRFs. Timing of 
study procedures are listed in schedules of assessments tables – Table 8: Schedule of 
Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: Schedule of 
Assessments (LAM-002A Intermittent Monotherapy Administration), Table 10: Schedule 
of Assessments (LAM-002A/Rituximab Combination Therapy), and Table 11: Schedule of 
Assessments (LAM-002A/Atezolizumab Combination Therapy) in Section 8.7. 
8.1.5. 
Disease Status Assessment for Subjects with NHL 
Pretreatment tumor assessments will be performed within 30 days of the first dose of study 
treatment and will include diagnostic CT scans (with intravenous contrast) or Positron Emission 
Tomography (PET)/Computerized Tomography Scans (CT scan) for patients with lymphoma, 
bone marrow aspirate/biopsy, complete blood counts and physical examination. It is anticipated 
that in most cases the PET/CT scans will be conducted using a single instrument, i.e., as a 
PET/CT scan (CT scans should be performed using a contiguous reconstruction algorithm of 
≤ 5 mm). However, MRI is an acceptable alternative method for assessing disease in subjects 
who cannot receive intravenous contrast with CT scans. In such subjects MRI and PET scans 
will have to be obtained separately. 
Suitable scans performed prior to screening and within 30 days before first dose may be used for 
baseline tumor assessments. Similarly bone marrow biopsies/aspirates performed within 
2 months prior to first dose may be used for baseline assessments. For subjects with NHL, 
baseline bone marrow biopsies/aspirates may be omitted if not deemed essential for response 
assessment or patient management and there is another source of tumor tissue for 
pretreatment evaluation of gene expression and prognosis. For subjects with CLL/SLL, a 
baseline bone marrow aspirate is required unless the presence of sufficient circulating cells in the 
peripheral blood (e.g., ALC ≥ 10 x 109/L) permits assessment of baseline parameters for gene 
expression and prognosis. Details of assessments will be collected on the eCRF and must be filed 
in the subject’s medical record. 
Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue 
(preferred) must be obtained pretreatment for nucleic acid extraction. For subjects undergoing 
a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or 
core needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Alternatively, cells from a 
bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL 
(≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and 
analysis of genetic alterations and/or gene expression that may predict anti-lymphoma activity 
and/or pharmacodynamics activity.  
In addition, tumor tissue from the most recently availably biopsy or surgery willmay be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; 
expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, 
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and for immune infiltration. The baseline biopsy procedure (if required) should ideally be 
performed after the study candidate has undergone the baseline radiology examination and is 
otherwise considered eligible for study participation.. 
8.2.4. 
Electrocardiogram 
A 12-lead ECG with subject resting for 5 minutes will be done at Screening. Additional ECGs 
will be conducted Table 8: Schedule of Assessments (LAM-002A Continuous Monotherapy 
Administration), Table 9: Schedule of Assessments (LAM-002A Intermittent Monotherapy 
Administration), Table 10: Schedule of Assessments (LAM-002A/Rituximab Combination 
Therapy), and Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination 
Therapy) in Section 8.7 prior to the start of each cycle, prior to each PK time point (except for 
30 minutes and 6 hours) on Day 1 and Day 8, at the End of Treatment, and more often if 
clinically indicated. Parameters measured will include heart rate, PR, QRS, QT, and QTc 
intervals (calculated by the Fridericia correction formula. Bazett’s correction is acceptable if 
institutional policy). See Section 12 for PK time points. The ECGs will be reviewed and signed 
by the investigator. 
8.3.1.1 
Hematology 
Hemoglobin, hematocrit, WBC count with differential, red blood cell (RBC) count, and platelet 
count will be collected at Screening and Days 1, 8, and 15 of Cycles 1 and 2 then at least once 
prior to start of all subsequent cycles and at EOTaccording to the relevant schedule of events; 
see Table 8: Schedule of Assessments (LAM-002A Continuous Monotherapy 
Administration), Table 9: Schedule of Assessments (LAM-002A Intermittent Monotherapy 
Administration), Table 10: Schedule of Assessments (LAM-002A/Rituximab Combination 
Therapy), and Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination 
Therapy) in Section 8.7. 
Coagulation parameters (aPTT [or PTT] and INR) should be performed at Screening. 
8.3.1.2 
Blood Chemistry 
Albumin, alkaline phosphatase (ALP), total bilirubin, calcium, carbon dioxide, chloride, 
creatinine, glucose, inorganic phosphorus, potassium, total protein, ALT, AST, lactate 
dehydrogenase (LDH), sodium, BUN, and uric acid will be collected according to the relevant 
schedule of events; see Table 8: Schedule of Assessments (LAM-002A Continuous 
Monotherapy Administration), Table 9: Schedule of Assessments (LAM-002A Intermittent 
Monotherapy Administration), Table 10: Schedule of Assessments (LAM-002A/Rituximab 
Combination Therapy), and Table 11: Schedule of Assessments (LAM-002A/Atezolizumab 
Combination Therapy) in Section 8.7. at Screening and Days 1, 8, and 15 of Cycles 1 and 2 
then at least once prior to start of all subsequent cycles and at EOT.  If the total bilirubin 
concentration is > 1.5 times the upper normal limit, total bilirubin should be differentiated and 
the total and direct bilirubin should be reported. 
8.6 
Concomitant Medications and Supportive Care 
Information on concomitant medications and other treatments will be collected from 14 days 
prior to informed consent through 30 
 37 days after the last dose of study drug. 
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8.6.1. 
Antineoplastic Medications/Therapy  
Antineoplastic Therapy: Other chemotherapy, investigational agents or biologic therapy will not 
be permitted during the study. 
Palliative radiotherapy for local peripheral metastases not being used as target lesions is allowed. 
However, the need for such therapy may be an indication of disease progression and should be 
discussed with the Sponsor prior to implementation. Radiotherapy for central metastases (e.g., 
vertebral, mediastinal) will not be allowed; the need for such radiotherapy while on therapy will 
be seen as an indication of disease progression and the subject should be withdrawn from 
therapy. 
8.6.2. 
Growth Factors  
Hematopoietic Growth Factors: Subjects receiving hematopoietic growth factors such as 
erythropoietin prior to study start may continue to receive pre treatment doses.  
The use of erythropoietic and granulocyte growth factors in accordance with American Society 
of Clinical Oncology (ASCO) guidelines may be implemented during study treatment at the 
discretion of the treating physician. 
8.6.3. 
Other Concomitant Medications  
Bisphosphonates: Bisphosphonates are permitted if a subject was receiving ongoing 
bisphosphonate therapy at time of screening and will continue on a stable regimen throughout 
protocol therapy. The need to start bisphosphonates while on therapy may be an indication of 
disease progression and should be discussed with the Sponsor prior to implementation. 
Anticoagulants: Apilimod is highly protein bound; therefore, the Investigator is cautioned about 
the use of therapeutic doses of sodium warfarin. 
Corticosteroids: Subjects may be using topical, intra articular, nasal, or inhaled corticosteroids at 
study entry and may use such drugs during therapy. The use of systemic or enteric 
corticosteroids is precluded at study entry because such drugs may confound interpretation of 
pharmacodynamic, immunological, or toxic responses in subjects on this study. However, such 
drugs are permitted if a subject develops intercurrent conditions that require corticosteroid 
therapy. 
Medications for the treatment of AEs or cancer symptoms, e.g., packed red blood cells and pain 
medications, are allowed. Measures to prevent potential tumor lysis syndrome are allowed per 
institutional guidelines. Additionally, medications (not addressed above) used to treat underlying 
medical conditions at study entry (including anti emetics and anti diarrheals) will be allowed to 
continue.  
Vaccines: Administration of live vaccines is prohibited during the study.  
8.7. 
Drug Interactions 
Drug Interactions: No information is available regarding interactions of LAM 002A (apilimod 
dimesylate capsules) with therapeutic agents or other substances in humans. In vitro data suggest 
that concomitant administration of potent inhibitors or inducers of CYP3A4 or CYP2C9 might 
alter apilimod dimesylate clearance and lead to clinically significant increases or decreases in 
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apilimod dimesylate exposure. Consequently, the concomitant use of strong inhibitors or 
inducers of CYP3A4 or CYP2C9 (see Table 7) should be avoided when possible.  
Based on these considerations, protocol candidates who require therapy with strong CYP3A4 or 
CYP2C9 inhibitors or inducers listed in Table 7 should not be enrolled into the study.  
During study participation, coadministration of apilimod dimesylate with CYP3A4 or CYP2C9 
inhibitors or inducers (see Table 7) should be avoided, if possible. However, a subject who 
develops a condition that may require use of such drugs is not required to permanently 
discontinue apilimod dimesylate if the subject is experiencing clinical benefit and other options 
for treating the subject’s cancer are limited. If medically appropriate, investigators may wish to 
use a therapeutic alternative that would not be expected to affect these enzymes. For subjects 
who require temporary use of a drug that does affect these enzymes (e.g., treatment with a 
systemic antifungal agent), apilimod dimesylate can be interrupted (or the doses reduced) during 
use of the other medication and then resumed after completion of the other drug. For subjects 
who require initiation of chronic therapy with a drug that potently affects these enzymes, 
investigators must consult with the medical monitor to consider the best course of action.  
Medications that prolong QTC and/or cause Torsades de pointes should be avoided (See Table 8).  
See Appendix 3 for additional information.  
8.6. 
Treatment Compliance 
Change: The minimum requirement for DLT evaluability was included for subjects taking 
LAM-002A on the intermittent schedule. 
The investigator will dispense the study medication only for use by subjects enrolled in the study 
as described in this protocol. The study medication is not to be used for reasons other than those 
described in this protocol. 
The investigator or other study staff will supervise LAM-002A treatment given at the site and 
instruct the subject on study medication self-administration. Subjects will be asked to bring their 
dosing diary with them at each visit. Compliance with protocol-defined LAM-002A intake will 
be checked by pill count at the end of each cycle and compliance decisions will be made by the 
investigator. 
A subject is considered to be DLT-evaluable if he/she has taken at least 75% (42/56 BID 
schedule; 63/84 TID schedule, 18/24 intermittent schedule) of the planned first cycle doses and 
has sufficient safety data, or has experienced a DLT in the first cycle. 
 
Section 8.7 
Schedules of Assessments 
Change: 
Previous schedule of assessments (Table 6, previously in Section 6) was deleted and 
separate tables were included that were specific for LAM-002A continuous monotherapy, 
LAM-002A intermittent monotherapy, LAM-002A/rituximab combination therapy, and 
LAM-002A/atezolizumab. 
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Table 6: 
Schedule of Assessments 
 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long
Term 
F/U 
Day 
Day 
Day 
28 to 1 
1 
2 
3 
8 
15 
1 
8 
15 28 
1 
15 28 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Signs and Symptoms, PEb 
X 
Xc 
 
 
 
 
X 
 
 
X 
 
X 
 
ECOG Performance Status 
X 
Xc 
 
 
 
 
X 
 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
X 
 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
X 
 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
X 
X 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
X 
 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
X 
 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based 
on indication) for response assessment 
Xj 
 
 
 
 
 
 
 
Xk 
 
Xk 
Xl 
 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK samplingn + Analyte 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
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Table 6:: 
Schedule of Assessments (Continued) 
 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long
Term 
F/U 
Day 
Day 
Day 
28 to 1 
1 
2 
3 
8 
15 
1 
8 
15 28 
1 
15 28 
Bone marrow aspirate/biopsy 
Xo 
 
 
 
 
 
 
 
Xp, q 
 
Xp 
 
 
Biomarker  tumor tissue 
Xq 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarker  blood smearsr 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
Biomarker  plasma cytokiness 
 
X 
 
 
X 
X 
 
 
 
 
 
 
 
Biomarker  PBMCt 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
Biomarker  salivau 
 
X 
 
 
 
 
 
 
 
 
 
 
 
LAM 002A administration 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Adverse events 
 
Throughout Study 
Concomitant medicationsv 
 
Throughout Study 
Long term follow up (F/U)w 
 
 
 
 
 
 
 
 
 
 
 
 
X 
a Eligibility will be confirmed by Cycle 1 Day 1. 
B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the start of 
each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D 
Obtained on Day 1 prior to dosing for all Cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 min after dosing), 2 hours (± 30 min), 4 
hours (± 1h), and 8 hours (± 1h) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F All hematology and chemistry laboratory parameters should be assessed at Screening and Days 1, 8, and 15 of Cycles 1 and 2, and then at least once prior to 
the start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of Cycle 1 is only required in subjects with 
intermediate or high risk of TLS (per the risk definition in Section 6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters may be obtained within 
72 hours prior to the planned day of collection. Abnormal test values should be monitored per protocol guidance. 
G 
Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H 
Urinalysis includes appearance, specific gravity and pH as well as a semi quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained 
within 72 hours prior to the planned day of collection. 
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I Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each Cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to screening 
and within 30 days before first dose may be used for baseline tumor assessments. 
K 
Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as appropriate 
for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 months until PD or use of 
alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may be every 6 months. Subjects with CLL 
who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. Tissue 
will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anticancer activity 
and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a 
sponsor specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q deletion, 13q deletion, 
17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3 21], and other genes of interest in CLL [e.g., Notch]; flow cytometry 
[for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP 70], and/or β2 microglobulin). The baseline bone 
marrow aspiration procedure (if required) should be performed after the study candidate has undergone the baseline radiology examination and is otherwise 
considered eligible for study participation. All subjects with CLL/SLL must have baseline imaging (with CT scans [preferred] or MRI scans).  
N 
Blood sampling for determination of the plasma concentrations of apilimod and metabolites will be performed on C1D1 and C1D8 as follows: pre dose, 
30 minutes, 1, 2, 4, 6, 8 hours post first dose of the day. C1D15 pre dose only. Additional PK samples will be collected, if possible, whenever a subject has a 
study treatment related SAE or QTc > 500 msec. Subjects are required to come to the study site in a fasting state prior to the collection of certain PK samples. 
For analyte determination, PK back up sample will be used from time points: Cycle 1 Day 1 and Cycle 1 Day 8 pre dose. 
O 
Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, 
baseline bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management. For subjects with CLL/SLL, a 
baseline bone marrow aspirate is required unless the presence of sufficient circulating cells in the peripheral blood (e.g., absolute lymphocyte count [ALC] ≥ 10 
x 109/L) permits assessment of baseline parameters as described in Footnote m, above. 
P 
If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and physical 
examination. 
Q Archival or fresh tumor tissue from the most recent available biopsy or surgery prior to first dose in subjects with NHL must be obtained pretreatment. For 
subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 
16 gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to NHL. Tissue will 
be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anti lymphoma 
activity and/or pharmacodynamics activity. In addition, for subjects with NHL, tumor may be evaluated for known prognostic characteristics (e.g., for 
DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki 67, CD20, and MYC; other mutational status). The baseline biopsy procedure (if required) 
should be performed after the study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation.  
R Blood smears will be collected for microscopic evaluation of vacuole formation on C1D1 and C1D8 as follows: pre dose, 4 hours and 8 hours post first dose 
of the day. C1D15 pre dose only. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL 12 and IL 23) predose on each of Cycle 1 Day 1, Cycle 1 Day 8, and Cycle 1 
Day 15. 
T  PBMCs will be collected on Cycle 1, Day 1 pre treatment; on Cycle 1, Day 1 at 8 hours post dose; and on Cycle 1, Day 8 at 8 hours post dose for 
determination of changes in gene expression that may predict or correlate with anti lymphoma activity and/or pharmacodynamic activity.  
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U  Saliva will be obtained pre dose on Cycle 1 Day 1 as a normal tissue control for gene mutation studies in tumors.  
V  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30 37 days after the last dose 
of study drug. 
W Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised Response Criteria for NHL or Guidelines for the 
diagnosis and treatment of CLL at a minimum of every 12 weeks until documentation of PD, start of new anti cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (Cycle 1 Day 1) whichever comes first. Long term follow up survival information will be obtained in all surviving subjects 
who permanently discontinue study therapy. Such information may be collected at ~3  to 6 month intervals at the sponsor’s discretion through 3 years. This 
long term follow up information will be gathered during routine clinic visits, other study site contact with the subjects, or via telephone or e mail with the 
subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; CBCs: Complete blood counts; CD: Cluster of 
differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; ECG: Electrocardiogram; ECOG: Eastern 
Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; hrs: Hours; LDH: Lactate dehydrogenase; min: 
Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: Progressive disease; PE: 
Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; SAE: Serious adverse event; 
WBC: White blood cell; WCBP: Women of child bearing potential 
 
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Table 8: 
Schedule of Assessments (LAM-002A Continuous Monotherapy Administration) 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
-28 to -1 
1 
2 
3 
8 
15 
18 
15-28 
1 
15-28 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
Xc 
 
 
 
 
X 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
XX 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
XX 
X 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
X 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
X 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xj 
 
 
 
 
 
 
Xk 
 
Xk 
Xl 
 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
 
 
PK/PD plasma samplingn + analyte 
 
X 
 
 
X 
X 
 
 
 
 
 
 
Bone marrow aspirate/biopsy 
Xo 
 
 
 
 
 
 
Xp, q 
 
Xp 
 
 
Biomarker – tumor tissue 
Xq 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAblood 
smears r 
 
X 
 
 
X 
X 
 
 
 
 
X 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
 
 
 
 
 
 
Biomarker – PBMC/B cellt 
X 
X 
 
 
X 
 
 
 
 
 
 
 
Biomarker – salivau 
X 
X 
 
 
 
 
 
 
 
 
 
 
LAM-002A administration in clinicv 
 
X 
X 
X 
X 
X 
XX 
X 
X 
X 
 
 
 
Adverse events 
 
Throughout Study 
 
Concomitant medicationsw 
 
Throughout Study 
 
Long-term follow-up (F/U)x 
 
 
 
 
 
 
 
 
 
 
 
 
X 
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a 
Eligibility will be confirmed by C1D1. 
B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the start of 
each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 prior to dosing for all cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F 
All hematology and chemistry laboratory parameters should be assessed at Screening and Days 1, 8, and 15 of Cycles 1 and 2, and then at least once prior to 
the start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of Cycle 1 is only required in subjects with 
intermediate or high risk of TLS (per the risk definition in Section 6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters may be obtained within 
72 hours prior to the planned day of collection. Abnormal test values should be monitored per protocol guidance. 
G Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic phosphorus, 
potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, leukocytes, 
and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be obtained within 
72 hours prior to the planned day of collection. 
I 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 hours of 
Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first dose. 
J 
Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to 
screening and within 30 days before first dose may be used for baseline tumor assessments. 
K Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as appropriate 
for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 months until PD or use 
of alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may be every 6 months. Subjects with 
CLL who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. Tissue 
will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict anticancer activity 
and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample to be evaluated at a 
sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q deletion, 13q deletion, 
17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in CLL [e.g., Notch]; flow cytometry 
[for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], and/or β2-microglobulin). The baseline bone 
marrow aspiration procedure (if required) should be performed after the study candidate has undergone the baseline radiology examination and is otherwise 
considered eligible for study participation. All subjects with CLL/SLL must have baseline imaging (with CT scans [preferred] or MRI scans).  
N Blood sampling for determination of the plasma concentrations and activity of apilimod LAM-002A and metabolites will be performed on C1D1 and C1D8 
as follows: pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D15 will be pre-dose only. Additional PK samples will be 
collected, if possible, whenever a subject has a study treatment related SAE or QTc > 500 msec. Subjects are required to come to the study site in a fasting 
state prior to the collection of certain PK samples. For analyte determination, PK back up sample will be used from time points: Cycle 1 Day 1 and Cycle 1 
Day 8 pre dose. 
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O Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, baseline 
bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of 
tumor tissue for pretreatment evaluation of gene expression and prognosis. For subjects with CLL/SLL, a baseline bone marrow aspirate is required 
unless the presence of sufficient circulating cells in the peripheral blood (e.g., absolute lymphocyte count [ALC] ≥ 10 x 109/L) permits assessment of baseline 
parameters as described in Footnote m, above. 
P 
If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and physical 
examination. 
Q  Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for nucleic acid 
extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., 
≥ 3 passes using a 16-gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due to 
NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that 
may predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor tissue from the most recently availably biopsy or surgery 
willmay be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki-67, CD20, and MYC; 
other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if required) should ideally be performed after the 
study candidate has undergone the baseline radiology examination and is otherwise considered eligible for study participation.  
R Plasma will be collected on C1D1 pretreatment, on C1D15 pretreatment, and at EOT visit for evaluation of circulating tumor DNA to measure 
tumor burden and mutational changes. Blood smears will be collected for microscopic evaluation of vacuole formation on C1D1 and C1D8 as follows: 
pre dose, 4 hours and 8 hours post first dose of the day. C1D15 pre dose only. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) predose on each of C1D1, C1D8, and C1D15 and at EOT. 
T  PBMCs/B-cells will be collected during Screening, on C1D1 pre treatment; on C1D1 at 8 hours post dose; and on C1D8 at 8 hours post dose for 
determination of changes in gene expression that may predict or correlate with anti-lymphoma activity and/or pharmacodynamic activity and will also serve 
as normal-tissue controls for gene mutation studies in tumors.  
U  Saliva will be obtained during Screening pre dose on C1D1 as a normal-tissue control for gene mutation studies in tumors.  
V LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). 
W  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the last dose 
of study drug. 
X Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised Response Criteria for NHL or Guidelines for the 
diagnosis and treatment of CLL at a minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for up to 1 year from the last 
enrolled subject’s first treatment (C1D1) whichever comes first. Long-term follow-up survival information will be obtained in all surviving subjects who 
permanently discontinue study therapy. Such information may be collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This long-
term follow-up information will be gathered during routine clinic visits, other study site contact with the subjects, or via telephone or e-mail with the 
subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID, twice per day; BUN: Blood urea nitrogen; CBCs: Complete blood 
counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; hrs: Hours; 
LDH: Lactate dehydrogenase; min: Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; 
PD: Progressive disease; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; 
SAE: Serious adverse event; TLS: tumor lysis syndrome; WBC: White blood cell; WCBP: Women of child bearing potential 
 
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Table 9: 
Schedule of Assessments (LAM-002A Intermittent Monotherapy Administration) 
Assessment 
Screening 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
End of 
Treatment 
(EOT) 
Long-
Term 
F/U 
Day 
Day 
Day 
 
-28 to -1 
1 
2 
3 
8 
10 
15 
1 
15-28 
1 
15-28 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
X 
 
ECOG performance status 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
X 
Xd 
Xd 
X 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
X 
Xd 
 
X 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
 
X 
X 
 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
 
X 
X 
 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
 
X 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xj 
 
 
 
 
 
 
 
Xk 
 
Xk 
Xl 
 
CLL baseline assessmentsm 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PK/PD plasma samplingn  
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
Bone marrow aspirate/biopsy 
Xo 
 
 
 
 
 
 
 
Xp 
 
Xp 
 
 
Biomarker – tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAr 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
X 
 
 
 
 
X 
 
Biomarker – PBMC/B cellt 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Biomarker – salivau 
X 
 
 
 
 
 
 
 
 
 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
X 
 
 
 
 
 
 
Adverse events 
 
Throughout Study 
 
Concomitant medicationsw 
 
Throughout Study 
 
Long-term follow-up (F/U)x 
 
 
 
 
 
 
 
 
 
 
 
 
X 
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a 
Eligibility will be confirmed by C1D1. 
B Complete physical examination (PE) will be performed at screening. A directed PE, including weight, will be performed within 72 hours prior to the 
start of each cycle and EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 for all cycles. For C1D1 and C1D10 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D8 and C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F All hematology and chemistry laboratory parameters should be assessed at Screening and Days 1, 8, and 15 of Cycles 1 and 2, and then at least once 
prior to the start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of Cycle 1 is only required 
in subjects with intermediate or high risk of TLS (per the risk definition in Section 6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters 
may be obtained within 72 hours prior to the planned day of collection. Abnormal test values should be monitored per protocol guidance. 
G Chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic 
phosphorus, potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be 
obtained within 72 hours prior to the planned day of collection. 
I 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 
hours of Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first 
dose. 
J 
Imaging as appropriate for disease indication will be conducted within 30 days of the first dose of study treatment. Suitable scans performed prior to 
screening and within 30 days before first dose may be used for baseline tumor assessments. 
K Assessment of disease status will be conducted with standard clinical measurements: PE, CBCs, bone marrow aspirates/biopsies, and imaging as 
appropriate for indication. During treatment, scans will be repeated for tumor assessment within 7 days of Day 1, Cycles 3, 5, and 7 then every 3 
months until PD or use of alternative antineoplastic therapy. For subjects still in response after 1 year, intervals for radiographic surveillance may 
be every 6 months. Subjects with CLL who achieve CR will require assessment of MRD by flow cytometry of bone marrow and peripheral blood. 
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 30 days of EOT visit. 
M Subjects with CLL/SLL must provide either a fresh blood sample containing circulating tumor cells or a bone marrow aspirate sample pretreatment. 
Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene expression that may predict 
anticancer activity and/or pharmacodynamic activity. In addition, for subjects with CLL/SLL, the sponsor may arrange for a portion of the sample 
to be evaluated at a sponsor-specified laboratory for known prognostic markers (e.g., quantitative immunoglobulins, FISH panel [chromosome 11q 
deletion, 13q deletion, 17p deletion and 12 trisomy], DNA mutational analysis for p53, IgHV [including IgHV3-21], and other genes of interest in 
CLL [e.g., Notch]; flow cytometry [for CD5, CD10, CD11c, CD19, CD20, CD23, CD38, CD45, kappa and lambda light chains and ZAP-70], and/or 
β2-microglobulin). The baseline bone marrow aspiration procedure (if required) should be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participation. All subjects with CLL/SLL must have baseline imaging 
(with CT scans [preferred] or MRI scans).  
N Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D10 
as follows: pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D8 and C1D15 will be pre-dose only. Subjects are 
required to come to the study site in a fasting state prior to the collection of certain PK samples.  
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O Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. For subjects with NHL, 
baseline bone marrow biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another 
source of tumor tissue for pretreatment evaluation of gene expression and prognosis. For subjects with CLL/SLL, a baseline bone marrow aspirate 
is required unless the presence of sufficient circulating cells in the peripheral blood (e.g., absolute lymphocyte count [ALC] ≥ 10 x 109/L) permits 
assessment of baseline parameters as described in Footnote m, above. 
P If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and 
physical examination. 
Q Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for nucleic acid 
extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle biopsy 
(e.g., ≥ 3 passes using a 16-gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow 
involvement due to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations 
and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor tissue from the most 
recently availably biopsy or surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of 
BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if 
required) should ideally be performed after the study candidate has undergone the baseline radiology examination and is otherwise considered 
eligible for study participation. 
R Plasma will be collected on C1D1 (predose), on C1D15 (predose), and at EOT visit for evaluation of circulating tumor DNA to measure tumor 
burden and mutational changes. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) on C1D1 (predose), C1D8 (predose), C1D10 (predose), 
and C1D15 (predose) and at EOT. 
T  PBMCs/B-cells will be collected during Screeningfor determination of changes in gene expression that may predict or correlate with anti-lymphoma 
activity and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors.  
U  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors.  
V LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). 
W  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the 
last dose of study drug. 
X Subjects who have discontinued study treatment for reasons other than PD will be assessed per Revised Response Criteria for NHL or Guidelines for 
the diagnosis and treatment of CLL at a minimum of every 12 weeks until documentation of PD, start of new anti-cancer therapy or for up to 1 year 
from the last enrolled subject’s first treatment (C1D1) whichever comes first. Long-term follow-up survival information will be obtained in all 
surviving subjects who permanently discontinue study therapy. Such information may be collected at ~3- to 6-month intervals at the sponsor’s 
discretion through 3 years. This long-term follow-up information will be gathered during routine clinic visits, other study site contact with the 
subjects, or via telephone or e-mail with the subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID, twice per day; BUN: Blood urea nitrogen; CBCs: Complete 
blood counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; h: Hour; 
hrs: Hours; LDH: Lactate dehydrogenase; min: Minutes; MRD: Minimal residual disease; MRI: Magnetic Resonance Imaging; PBMC: Peripheral 
blood mononuclear cell; PD: Progressive disease; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected 
QT interval; RBC: Red blood cell; SAE: Serious adverse event; TLS: tumor lysis syndrome; WBC: White blood cell; WCBP: Women of child bearing 
potential 
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Table 10: Schedule of Assessments (LAM-002A/Rituximab Combination Therapy) 
Assessment 
Screening 
Cycle 1 
Cycles ≥2 
End of 
Treatment 
(EOT) 
Long-Term 
F/U 
Day 
Day 
 
-28 to -1 
1 
2 
3 
8 
15 
22 
1 
22-28 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
ECOG performance Status 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
X 
 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
Urinalysish 
X 
Xc 
 
 
 
 
 
X 
 
X 
 
Pregnancy testingi 
X 
Xi 
 
 
 
 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xj 
 
 
 
 
 
 
 
Xk 
Xl 
 
PK/PD samplingm 
 
X 
 
 
X 
X 
 
 
 
 
 
Bone marrow aspirate/biopsy 
Xn 
 
 
 
 
 
 
 
Xo 
 
 
Biomarker – tumor tissuep 
X 
 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAq 
 
X 
 
 
 
X 
 
 
 
X 
 
Biomarker – plasma cytokinesr 
 
X 
 
 
X 
X 
 
 
 
X 
 
Biomarker – PBMC/B cells 
X 
 
 
 
 
 
 
 
 
 
 
Biomarker – salivat 
X 
 
 
 
 
 
 
 
 
 
 
Premedicationu 
 
X 
 
 
X 
X 
X 
 Xu 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
 
 
 
 
 
Rituximab infusionw 
 
X 
 
 
X 
X 
X 
 Xw 
 
 
 
Adverse events 
 
Throughout study 
 
Concomitant medicationsx 
 
Throughout study 
 
Long-term F/Uy 
 
 
 
 
 
 
 
 
 
 
X 
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a 
Eligibility will be confirmed by C1D1. 
B Complete PE will be performed at Screening. A directed PE, including weight, will be performed within 72 hours prior to the start of each cycle and 
EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
D Obtained on Day 1 for all cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F All hematology and chemistry laboratory parameters should be assessed at Screening, on C1D1, C1D8, C1D15, C≥2D1 (all subsequent cycles), and 
at EOT. Obtaining a chemistry laboratory parameter on C1D2 and C1D3 is only required in subjects with intermediate or high risk of TLS (per the 
risk definition in Section 6.8.1).  Except for C1D1, C1D2, and C1D3, these parameters may be obtained within 72 hours prior to the planned day of 
collection.  
G Serum chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic 
phosphorus, potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be 
obtained within 72 hours prior to the planned day of collection. 
I 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 
hours of Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first 
dose. 
J 
Imaging as appropriate for disease indication will be conducted within 30 days before C1D1. Suitable scans performed prior to Screening and within 
30 days before first dose may be used for baseline tumor assessments. 
K Assessment of disease status will be conducted with standard imaging as appropriate for indication. During treatment, scans will be repeated for 
tumor assessment within 7 days before C3D1, C5D1, C7D1, and then every 3 cycles (12 weeks) until PD or use of alternative antineoplastic therapy.  
L Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 4 weeks of EOT visit. 
M Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D8 as 
follows: pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D15 will be pre-dose only. Subjects are required to come to 
the study site in a fasting state prior to the collection of certain PK samples.  
N Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of tumor tissue 
for pretreatment evaluation of gene expression and prognosis.  
O If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and 
PE. 
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P Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for nucleic acid 
extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle biopsy 
(e.g., ≥ 3 passes using a 16-gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow 
involvement due to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations 
and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor tissue from the most 
recently availably biopsy or surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of 
BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if 
required) should ideally be performed after the study candidate has undergone the baseline radiology examination and is otherwise considered 
eligible for study participation. 
Q Plasma will be collected on C1D1 (predose), on C1D15 (predose), and at EOT visit for evaluation of circulating tumor DNA to measure tumor 
burden and mutational changes. 
R  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) on C1D1 (predose), C1D8 (predose), C1D15 (predose), 
C2D1, and at EOT. 
S  PBMCs/B-cells will be collected during Screening for determination of changes in gene expression that may predict or correlate with anti-lymphoma 
activity and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors. 
T  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors. 
U Oral antipyretic, oral or intravenous antihistamine, and intravenous corticosteroid (at investigator discretion) (see Section 6.8.3.1) to be 
administered to the subject ~30 minutes prior to each rituximab infusion (see Footnote w). 
v 
LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). On C1D1, 
LAM-002A will be started on a BID schedule after administration of premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of 
the initial rituximab infusion. On C1D8, the morning dose of LAM-002A will be administered after premedications (see Section 6.8.3.1) and ~15 to 
30 minutes prior to the rituximab infusion 
w Rituximab, 375 mg/m2, will be administered by intravenous infusion ~30 after premedication weekly on C1D1, C1D8, C1D15, and C1D22 and then 
every 8 weeks on C4D1, C6D1, C8D1, and C10D1 for a total of 8 infusions. 
X  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the 
last dose of study drug. 
Y Subjects who have discontinued study treatment for reasons other than PD will be assessed at a minimum of every 12 weeks until documentation of 
PD, start of new anti-cancer therapy or for up to 1 year from the last enrolled subject’s first treatment (C1D1) whichever comes first. Long-term 
follow-up survival information will be obtained in all surviving subjects who permanently discontinue study therapy. Such information may be 
collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will be gathered during 
routine clinic visits, other study site contact with the subjects, or via telephone or e-mail with the subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID: twice per day; BUN: Blood urea nitrogen; CBCs: Complete 
blood counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; F/U: 
Follow-up; LDH: Lactate dehydrogenase; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: Progressive disease; 
PDL1: programmed death ligand-1; PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; 
RBC: Red blood cell; SAE: Serious adverse event; TLS: tumor lysis syndrome; WBC: White blood cell; WCBP: Women of child-bearing potential. 
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Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination Therapy) 
Assessment 
Screening 
Cycle 1 
Cycles ≥2 
End of 
Treatment 
(EOT) 
Long-Term 
F/U 
Day 
Day 
 
-28 to -1 
1 
2 
3 
8 
15 
1 
15-22 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
Xa 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
Signs and symptoms, PEb 
X 
Xc 
 
 
 
 
X 
 
X 
 
ECOG performance Status 
X 
Xc 
 
 
 
 
X 
 
X 
 
Vital signs 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
ECG 
X 
Xd 
 
 
Xd 
Xd 
X 
 
X 
 
HIV, HBV, and HCV serology 
X 
 
 
 
 
 
 
 
 
 
Hematologye, f 
X 
X 
 
 
X 
X 
X 
 
X 
 
Serum chemistryf, g 
X 
X 
Xf 
Xf 
X 
X 
X 
 
X 
 
Serum thyroid functionh 
X 
 
 
 
 
 
X 
 
 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
Urinalysisi 
X 
Xc 
 
 
 
 
X 
 
X 
 
Pregnancy testing 
X 
Xj 
 
 
 
 
X 
 
X 
 
PET/CT or CT (or MRI) scans (based on 
indication) for response assessment 
Xk 
 
 
 
 
 
 
Xl 
Xm 
 
PK/PD samplingn 
 
X 
 
 
X 
X 
 
 
 
 
Bone marrow aspirate/biopsy 
Xo 
 
 
 
 
 
 
Xp 
 
 
Biomarker – tumor tissueq 
X 
 
 
 
 
 
 
 
 
 
Biomarker – plasma tumor DNAr 
 
X 
 
 
 
X 
 
 
X 
 
Biomarker – plasma cytokiness 
 
X 
 
 
X 
X 
X 
 
X 
 
Biomarker – PBMC/B cellst 
X 
 
 
 
 
 
 
 
 
 
Biomarker – salivau 
X 
 
 
 
 
 
 
 
 
 
LAM-002A administration in clinicv 
 
X 
 
 
X 
X 
 
 
 
 
Atezolizumab infusionw 
 
X 
 
 
 
 
 Xw 
 
 
 
Adverse events 
 
Throughout study 
 
Concomitant medicationsx 
 
Throughout study 
 
Long-term F/Uy 
 
 
 
 
 
 
 
 
 
X 
a 
Eligibility will be confirmed by C1D1. 
B Complete PE will be performed at Screening. A directed PE, including weight, will be performed within 72 hours prior to the start of each cycle and 
EOT. 
C Assessment/test does not need to be repeated on C1D1 if baseline was within normal limits and conducted within 72 hours of first dose. 
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D Obtained on Day 1 for all cycles. For C1D1 and C1D8 obtained prior to dosing and 1 hour (± 15 minutes after dosing), 2 hours (± 30 minutes), 
4 hours (± 1 hour), and 8 hours (± 1 hour) postdose. For C1D15, obtained prior to dosing. 
E Hematology includes hemoglobin, hematocrit, RBC count, platelet count, WBC and differential. 
F All hematology and chemistry laboratory parameters should be assessed at Screening, on C1D1, C1D8, C1D15, C≥2D1 (all subsequent cycles), and 
at EOT. Obtaining a chemistry laboratory parameter on C1D2 and C1D3 is only required in subjects with intermediate or high risk of TLS (per the 
risk definition in Section 68.1).  Except for C1D1, C1D2, and C1D3, these parameters may be obtained within 72 hours prior to the planned day of 
collection.  
G Serum chemistry includes albumin, alkaline phosphatase, total bilirubin, BUN, calcium, carbon dioxide, chloride, creatinine, glucose, inorganic 
phosphorus, potassium, total protein, LDH, ALT, AST, sodium, and uric acid. 
H Serum thyroid function tests include TSH, free T3, and free T4 at C3D1, C5D1, C7D1, C9D1, and then every 4 cycles (12 weeks). 
I 
Urinalysis includes appearance, specific gravity and pH as well as a semi-quantitative “dipstick” evaluation of glucose, protein, bilirubin, ketones, 
leukocytes, and blood. Microscopic examination of sediment will be performed if urinalysis is positive for WBC, proteins or blood. Urinalysis may be 
obtained within 72 hours prior to the planned day of collection. 
J 
Pregnancy testing (serum or urine) will be required for women of childbearing potential (WCBP) only. Testing is required at Screening; within 72 
hours of Day 1 of each cycle and at EOT. Test does not need to be repeated on C1D1 if baseline was negative and conducted within 72 hours of first 
dose. 
K Imaging as appropriate for disease indication will be conducted within 30 days before C1D1. Suitable scans performed prior to Screening and within 
30 days before first dose may be used for baseline tumor assessments. 
L Assessment of disease status will be conducted with standard imaging as appropriate for indication. During treatment, scans will be repeated for 
tumor assessment within 7 days before C3D1, C5D1, C7D1, C9D1, and then every 4 cycles (12 weeks) until PD or use of alternative antineoplastic 
therapy.  
M Imaging at EOT is not required if PD has already been radiographically documented or last imaging was within 4 weeks of EOT visit. 
N Blood sampling for determination of the plasma concentrations and activity of LAM-002A and metabolites will be performed on C1D1 and C1D8 as 
follows: pre-dose, 30 minutes, 1, 2, 4, 6, 8 hours post-first dose of the day. Sampling on C1D15 will be pre-dose only. Subjects are required to come to 
the study site in a fasting state prior to the collection of certain PK samples.  
O Bone marrow aspirates/biopsies performed within 2 months prior to first dose may be used for clinical baseline assessments. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient management and there is another source of tumor tissue 
for pretreatment evaluation of gene expression and prognosis.  
P If necessary per applicable response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have a CR by imaging and 
PE. 
Q Archival tissue from the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for nucleic acid 
extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core needle biopsy 
(e.g., ≥ 3 passes using a 16-gauge core needle). Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow 
involvement due to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of genetic alterations 
and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics activity. In addition, tumor tissue from the most 
recently availably biopsy or surgery will be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of 
BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure (if 
required) should ideally be performed after the study candidate has undergone the baseline radiology examination and is otherwise considered 
eligible for study participation. 
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R Plasma will be collected on C1D1 (predose), on C1D15 (predose), and at EOT visit for evaluation of circulating tumor DNA to measure tumor 
burden and mutational changes. 
S  Plasma will be collected for evaluation of circulating cytokines (including IL-12 and IL-23) on C1D1 (predose), C1D8 (predose), and C1D15 
(predose) and at EOT. 
T PBMCs/B-cells will be collected during Screening for determination of changes in gene expression that may predict or correlate with anti-lymphoma 
activity and/or pharmacodynamic activity and will also serve as normal-tissue controls for gene mutation studies in tumors. 
U  Saliva will be obtained during Screening as a normal-tissue control for gene mutation studies in tumors. 
V LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the LAM-002A administration). On C1D1, 
LAM-002A will be started on a BID schedule after administration of premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of 
the initial atezolizumab infusion. On C1D8, the morning dose of LAM-002A will be administered after premedications (see Section 6.8.3.1) and ~15 
to 30 minutes prior to the atezolizumab infusion 
w Atezolizumab, 1200 mg, will be administered by intravenous infusion ~30 every 3 weeks. 
X  Information on concomitant medications and other treatments will be collected from 14 days prior to informed consent through 30-37 days after the 
last dose of study drug. 
Y Subjects who have discontinued study treatment for reasons other than PD will be assessed at a minimum of every 12 weeks until documentation of 
PD, start of new anti-cancer therapy or for up to 1 year from the last enrolled subject’s first treatment (C1D1) whichever comes first. Long-term 
follow-up survival information will be obtained in all surviving subjects who permanently discontinue study therapy. Such information may be 
collected at ~3- to 6-month intervals at the sponsor’s discretion through 3 years. This long-term follow-up information will be gathered during 
routine clinic visits, other study site contact with the subjects, or via telephone or e-mail with the subjects/caregivers or referring physician offices. 
Abbreviations: ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; BID: twice per day; BUN: Blood urea nitrogen; CBCs: Complete 
blood counts; CD: Cluster of differentiation; CLL: Chronic lymphocytic leukemia; CR: Complete response; CT: Computerized tomography; 
ECG: Electrocardiogram; ECOG: Eastern Cooperative Oncology Group; EOT: End of treatment; FISH: Fluorescence in situ hybridization; F/U: 
Follow-up; LDH: Lactate dehydrogenase; MRI: Magnetic Resonance Imaging; PBMC: Peripheral blood mononuclear cell; PD: Progressive disease; 
PE: Physical exam; PET: Positron emission tomography; PK: Pharmacokinetics; QTc: Corrected QT interval; RBC: Red blood cell; SAE: Serious 
adverse event; T3: triiodothyronine; T4: thyroxine; TLS: tumor lysis syndrome; TSH: thyroid-stimulating hormone; WBC: White blood cell; WCBP: 
Women of child-bearing potential 
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Section 9. STUDY DRUG MATERIALS AND MANAGEMENT 
Change: 
Pharmaceutical information regarding LAM-002A was updated and information for 
rituximab and atezolizumab was added.  
9.1. 
LAM-002A  
9.1.1. 
Description 
LAM-002A drug description is provided in Table 12. 
Table 12: 
LAM-002A Drug Description 
Product Name: 
LAM-002A 
Dosage Form: 
Capsule 
Unit Dose 
25 mg or 50 mg 
Route of Administration 
Oral 
Physical Description 
Each capsule will contain 25 mg or 50 of apilimod dimesylate (equivalent 
to 17.1 mg or 34.3 mg of apilimod free base, respectively). The 25-mg 
capsule is Swedish orange and the 50-mg capsule is white. Both the 25- and 
50-mg capsules are Size 0 and both have a total fill weight of 175 mg. 
Inactive components in active capsules are microcrystalline cellulose 
Avicell PH102, silicified microcrystalline cellulose, anhydrous lactose, 
croscarmellose sodium (Ac-Di-Sol), colloidal silicon dioxide, and 
magnesium stearate.   
Manufacturer 
Patheon 
Abbreviation: mg: Milligram 
9.1.2. 
LAM-002A  Packaging and Labeling 
LAM-002 will be provided in bulk bottles to each investigational pharmacy for dispensing. The 
pharmacist will dispense capsules into bottles for each subject (based on Cohort assignment) 
following applicable state and federal laws and site policies. Details on the labeling, dispensing, 
and administration of LAM-002A  are provided in the Pharmacy Manual. 
9.1.3. 
Source 
LAM-002A will be provided by the sponsor. 
9.1.4. 
Storage 
The LAM-002A  must be stored in a secure storage area, with limited access, under 
environmental conditions appropriate for the product. LAM-002A capsules should be stored at 2 
to 8°C. 
9.1.5. 
Accountability 
LAM-002A  will be dispensed to subjects in labeled bottles at the beginning of each cycle. 
Subjects should be instructed to bring all bottles, including empty bottles, to each Day 1 or End 
of Treatment study visit for a compliance and product accountability check. Returned 
studyLAM-002A should be retained for monitor review prior to destruction at the site, unless 
contraindicated by site standard operating procedures (SOPs). If contraindicated by the site SOP, 
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approval of site process by the sponsor must be obtained and filed in the pharmacy file and/or 
regulatory binder. The investigational pharmacy must maintain contemporary and accurate 
records on product receipt, storage temperature, stock, dispensation, return and disposal. These 
records should be available for review during monitoring visits and copies available for retrieval 
for the Trial Master File.  
9.1.6. 
Handling and Disposal 
LAM-002A  accountability and inventory records will be inspected by the sponsor/Ce3 prior to 
final disposition. Instructions will be provided by the sponsor/Ce3 for shipment to and 
destruction of unused LAM-002A  product by the designated packaging depot, to include 
unopened bulk bottles at the end of the study and expired product. Unused product returned by 
study subjects or opened bulk bottles will be destroyed by each site per site SOPs. LAM-002A  
should only be shipped or destroyed upon written authorization from the sponsor/Ce3. 
Documentation of return of shipment, including a packing list and copy of the tracking label, 
should be retained in the Pharmacy and/or regulatory files.  
9.2. 
Rituximab 
9.2.1. 
Description 
Rituximab (Rituxan, MabThera) is a genetically engineered chimeric murine/human 
monoclonal IgG1 kappa antibody directed against the CD20 antigen found on pre-B and 
mature B cells (Genentech 2016). Rituximab is produced by mammalian Chinese hamster 
ovary cells. The protein has an approximate molecular weight of 145 kD. 
The drug is provided as a clear, colorless, preservative-free liquid concentrate containing 
10 mg/mL of rituximab. The product is formulated in 9 mg/mL sodium chloride, 
7.35 mg/mL sodium citrate dihydrate, 0.7 mg/mL polysorbate 80, and water for injection 
with a pH of 6.5. 
9.2.2. 
Packaging 
Rituximab is supplied in 100-mg (10-mL) or 500-mg (50-mL) single-use vials. 
9.2.3. 
Source 
Unless otherwise instructed by the sponsor, the rituximab to be used in this study may be 
obtained from available commercial supplies.  
9.2.4. 
Storage and Stability 
Rituximab vials are stable at 2°C–8°C (36°F–46°F). Vials should be protected from direct 
sunlight and should not be frozen or shaken. 
Diluted rituximab solutions for infusion may be stored at 2°C–8°C (36°F–46°F) for 
24 hours and are known to be stable for an additional 24 hours at room temperature. 
However, since rituximab solutions do not contain a preservative, diluted solutions should 
be stored refrigerated (2°C–8°C). 
No incompatibilities between rituximab and polyvinylchloride or polyethylene bags have 
been observed. 
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9.2.6. 
Solution Preparation 
Before use, the rituximab vials should be inspected for particulate matter or discoloration. 
Any vial with evidence of particulates or discoloration should not be used. 
Using aseptic technique, the necessary amount of rituximab should be withdrawn from the 
vial and diluted to a final concentration of 1 to 4 mg/mL in an infusion bag containing 
either 0.9% Sodium Chloride, USP or 5% Dextrose in Water, USP. The bag should be 
gently inverted to mix the solution. The infusion solution should not be mixed or diluted 
with other drugs. Any unused portion of rituximab remaining in the vial should be 
discarded. 
9.2.7. 
Accountability 
Acquisition, storage, control, and disposal of rituximab used in the study should be 
performed according to institutional procedures and policies. 
The investigator and/or the responsible site personnel must maintain accurate records of 
the source, dates of administration, quantities of administration, and lot numbers of the 
rituximab dispensed for this study. 
9.3. 
Atezolizumab 
9.3.1. 
Description 
Atezolizumab (TECENTRIQ) is an Fc-engineered, humanized, monoclonal antibody that 
binds to PD-L1 and blocks interactions with the PD-1 and B7.1 receptors (Genentech 
2017). Atezolizumab is a non-glycosylated IgG1 kappa immunoglobulin that has a 
calculated molecular mass of 145 kDa. 
The drug is provided as a sterile, preservative-free, colorless to slightly yellow solution in 
single-dose vials. Each mL of TECENTRIQ contains 60 mg of atezolizumab and is 
formulated in glacial acetic acid (16.5 mg), L-histidine (62 mg), sucrose (821.6 mg), 
polysorbate 20 (8 mg). The solution has a pH of 5.8. 
9.3.2. 
Packaging 
Atezolizumab is supplied in a carton containing one 1200-mg/20-mL single-dose vial. 
9.3.3. 
Source 
The atezolizumab to be used in this study will be supplied by Genentech, Inc. via the study 
sponsor (LAM Therapeutics, Inc.).  
9.3.4. 
Storage and Stability 
Atezolizumab vials are stable at 2°C–8°C (36°F–46°F). Vials should be stored in the 
original cartons protected from light and should not be frozen or shaken. 
Atezolizumab does not contain a preservative; thus, diluted solutions should be 
administered as soon as possible after preparation.  If the diluted atezolizumab solution is 
not used immediately, it may be stored or maintained at room temperature (e.g., 20°C–
25°C; 68°F–77°F). for ≤6 hours from the time of preparation, including time for 
administration of the infusion. Alternatively, it may be stored under refrigeration at 2°C–
8°C (36°F–46°F) for ≤24 hours. 
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9.3.5. 
Solution Preparation 
Before use, the atezolizumab vials should be inspected for particulate matter or 
discoloration. Any vial with evidence of particulates or discoloration should not be used.  
The vial should not be shaken. 
Using aseptic technique, 20 mL of atezolizumab should be withdrawn from the vial and 
diluted into a 250-mL polyvinyl chloride, polyethylene, or polyolefin infusion bag 
containing 0.9% Sodium Chloride Injection, USP. The bag should be gently inverted to mix 
the solution. Shaking of the bag must be avoided. The infusion solution should not be mixed 
or diluted with other drugs. Used or empty vials of atezolizumab should be discarded. 
The intravenous solution should be prepared and dispensed by the study center pharmacist 
and should be infused by a qualified nurse with experience in monitoring the 
administration of chemotherapeutic agents. 
9.3.6 
Accountability 
Acquisition, storage, control, and disposal of atezolizumab used in the study should be 
performed according to institutional procedures and policies. 
The investigator and/or the responsible site personnel must maintain accurate records of 
the source, dates of administration, quantities of administration, and lot numbers of the 
atezolizumab dispensed for this study. 
 
Section 10.1.1.4 Adverse Event of Special Interest 
Change: 
A definition of adverse events of special interest has now been added. 
Adverse events of special interest (AESIs) comprise TLS occurring in any study subject. 
Among study subjects receiving atezolizumab the following treatment-emergent AEs will 
be considered AESIs: 
• AE suggestive of hypersensitivity, infusion-related reactions, cytokine-release 
syndrome, influenza-like illness, systemic inflammatory response syndrome, or 
systemic immune activation 
• Autoimmune hemolytic anemia 
• Cardiac disorders Grade ≥ 2: atrial fibrillation, myocarditis, pericarditis 
• Colitis 
• Cutaneous reactions: Stevens-Johnson syndrome, bullous dermatitis, toxic 
epidermal necrolysis 
• Drug-induced liver injury (Grade ≥ 3 serum ALT or AST increase in 
combination with a Grade ≥ 2 serum total bilirubin) 
• Endocrinopathy: diabetes mellitus, pancreatitis, adrenal insufficiency, 
hyperthyroidism, or hypophysitis 
• Hepatitis (Grade ≥3 serum ALT or AST increase) 
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must be followed and reported upon until the event has completely resolved to Grade 0 or 
baseline or until the event becomes a new stable baseline condition for a subject. 
All SAEs and AESIs will be evaluated by the sponsor’s medical monitor or designee.  
The investigators must notify their governing IRB of any SAEs in accordance with Section 18.1. 
For any suspected adverse reaction that is both serious and unexpected (not documented in the 
IB or package insert), an Investigational New Drug (IND) safety report or revision to the IB may 
be issued to inform all investigators involved in any study with LAM-002A. 
 
Section 11. 
ASSESSMENT OF EFFICACY 
Changes: References to the schedules of assessment tables were included to clarify where 
information regarding the timing of efficacy assessments could be found. 
11. 
ASSESSMENT OF EFFICACY 
Tumor response will be assessed in the Dose Escalation Stage and Expansion Stage using 
modified Lugano Response Criteria for NHL (Cheson 2014) and revised guidelines for the 
diagnosis and treatment of CLL (Hallek 2008, Cheson 2012) (see Appendix 2). 
Pretreatment tumor assessments will be performed within 30 days of the first dose (bone marrow 
assessment may be performed within 2 months prior to first dose) and will include diagnostic CT 
scans (with intravenous contract) or PET/CT for subjects with lymphoma (CT only for subjects 
with CLL/SLL), bone marrow aspirate/biopsy, complete blood counts and physical examination. 
It is anticipated that in most cases the PET and CT scans will be conducted using a single 
instrument, i.e., as a PET/CT scan (CT scans should be performed using a contiguous 
reconstruction algorithm of ≤ 5 mm). However, MRI is an acceptable alternative method for 
assessing disease in subjects who cannot receive intravenous contrast with CT scans. In such 
subjects MRI and PET scans will have to be obtained separately. Baseline bone marrow 
biopsies/aspirates may be omitted if not deemed essential for response assessment or patient 
management. 
During treatment, radiology studies will be performed for tumor assessments within 7 days prior 
to Day 1 of Cycles 3, 5, 7 and then every 3 months thereafter as indicated in Table 8: Schedule 
of Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: Schedule 
of Assessments (LAM-002A Intermittent Monotherapy Administration), Table 10: 
Schedule of Assessments (LAM-002A/Rituximab Combination Therapy), and 
Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination Therapy) in 
Section 8.7.  until PD or use of alternative antineoplastic therapy. If necessary per applicable 
response criteria, a repeat bone marrow biopsy or aspirate will be required for subjects who have 
a Complete Response (CR) by imaging and physical examination. Subjects with CLL/SLL who 
achieve CR will require assessment of minimal residual disease (MRD) by flow cytometry of 
bone marrow and peripheral blood. 
 
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Section 12. 
PHARMACOKINETIC ASSESSMENTS 
Changes: Additional information regarding the timing of pharmacokinetic assessments was 
provided, and references to the schedules of assessment tables were included to 
clarify where information regarding the timing of pharmacokinetic assessments can 
be found. Collection of unscheduled pharmacokinetic samples was removed because 
it is difficult to manage and provided little incremental information over the frequent 
pharmacokinetic samples that were already planned. 
12. 
PHARMACOKINETIC ASSESSMENTS 
Plasma concentration levels of apilimod and the active metabolites will be measured in the 
dose-escalation and dose-expansion stages at each of the specified time points; Table 8: 
Schedule of Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: 
Schedule of Assessments (LAM-002A Intermittent Monotherapy Administration), 
Table 10: Schedule of Assessments (LAM-002A/Rituximab Combination Therapy), and 
Table 11: Schedule of Assessments (LAM-002A/Atezolizumab Combination Therapy) in 
Section 8.7  The analytical laboratory will measure plasma concentrations of apilimod using a 
validated analytic method. PK parameters that will be estimated on Day 1 and Day 8 using 
standard non-compartmental methods as follows will include: Cmax, tmax, AUC0-t, AUCτ; t½, 
trough concentrations on Days 8 and 15, and a comparison of AUC0-t from Days 1 and 8 or 
Days 1 and Day 10 (as appropriate); additional parameters may be determined based on the 
available data. Accumulation will be assessed by calculating the Day 15/Day 1 accumulation 
ratios I for Cmax and AUC when comparing Day 8 to Day 1 for all continuous LAM-002A 
regimens (whether given as monotherapy or in combination) or when comparing Day 10 to 
Day 1 for the intermittent LAM-002A regimen. Dose proportionality for Cmax and AUC0-t will 
be assessed by applying an appropriate power model to the data. Descriptive statistics of PK 
parameters will include minimum, maximum, mean, standard deviation, percent coefficient of 
variation (%CV), and range.  
Metabolite concentrations at the time points indicated in Table 13. All subjects must participate 
in PK assessments. Fasting status must be recorded at the time of each PK blood draw. 
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Table 13: 
Pharmacokinetic Sampling Time Points 
Sample 
Study Day 
PK Sampling Time Pointsa  
1b 
1 
Pre-dose (within 30 min prior to dose of LAM-002A) 
2 
1 
0.5 hour (± 10 min) after dosing with LAM-002A 
3 
1 
1 hour (± 10 min) after dosing with LAM-002A 
4 
1 
2 hours (± 10 min) after dosing with LAM-002A 
5 
1 
4 hours (± 10 min) after dosing with LAM-002A  
6 
1 
6 hours (± 10 min) after dosing with LAM-002A 
7 
1 
8 hours (± 10 min) after dosing with LAM-002A 
8b 
8 or 10c 
Pre-dose (within 30 min prior to dose of LAM-002A) 
9 
8 or 10c 
0.5 hour (± 10 min) after dosing with LAM-002A 
10 
8 or 10c 
1 hour (± 10 min) after dosing with LAM-002A 
11 
8 or 10c 
2 hours (± 10 min) after dosing with LAM-002A 
12 
8 or 10c 
4 hours (± 10 min) after dosing with LAM-002A  
13 
8 or 10c 
6 hours (± 10 min) after dosing with LAM-002A 
14 
8 or 10c 
8 hours (± 10 min) after dosing with LAM-002A 
15b 
15 
Pre-dose (within 30 min prior to dose of LAM-002A) 
a Applies to first dose of the day 
b Dosing with LAM-002A should occur after the PK sample has been drawn. 
c Sampling to be performed on Day 8 for all continuous LAM-002A regimens (whether given as monotherapy 
or in combination) or on Day 10 for the intermittent LAM-002A dosing regimen. 
Abbreviations: min: Minutes; PK: Pharmacokinetic  
Comprehensive information on blood sample acquisition, handling, storage and sample 
shipments can be found in the pharmacokinetic laboratory manual.  
On Cycle 1 Day 1, and Cycle 1 Day 8 the dose of LAM-002A should be orally administered (a 
minimum fasting state of 6 to 8 hours) by staff in the clinic immediately after the collection of 
the biomarker samples and after the collection of the first PK sample. Subjects are allowed to eat 
after PK Sample #4 (hour 2) has been collected. Subjects may consume clear liquids during 
fasting periods. 
On Cycle 1 Day 15, the dose of LAM-002A should be orally administered (a minimum fasting 
state of 6 to 8 hours) by staff in the clinic immediately after collection of the pre-dose PK and 
biomarker samples.  
In addition, PK samples may be collected, if possible and deemed appropriate by the Investigator 
and Sponsor, whenever a subject has a study treatment related SAE or QTc > 500 msec. 
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A saliva sample will be obtained on Cycle 1 Day 1 during Screening as a normal-tissue control 
for gene mutation studies in tumors. 
Comprehensive information on tissue acquisition, handling, storage and sample shipments can be 
found in the biomarker sample process documents. 
Section 14. 
STATISTICS 
Changes: The Stage 1 dose-ranging approach and a statistical basis for the planned Stage 2 
cohort sizes were provided.  A method for continuous reassessment of safety created a 
framework for risk assessments associated with the investigational combination 
therapies to be explored in the study. This safety method complemented the 
restrictions on the pace of Stage 2 combination therapy enrollment detailed in 
Section 6.1.3 of the protocol. 
14.1. 
Determination of Sample Size 
14.1.1. 
Stage 1 (Dose Escalation) 
The planned sample size for the dose-escalation is not based on a specific statistical 
hypothesis but on experience in the conduct of similar trials in subjects with cancer.  
In the dose escalation, the cohort sizes of 3 to 6 subjects allow evaluation of regimen safety 
using a standard definition of MTD (ie, a starting dose associated with DLT in <33% of 
subjects during the first cycle of therapy). Based on the planned 3+3 dose-escalation 
scheme, Table 14 shows the probability of escalating to the next dose level or proceeding to 
the next stage, based on the true rate of DLT at the current dose level. 
Table 14: 
Statistical Basis for 3+3 Dose-Escalation Paradigm 
True Incidence of DLT 
Probability of Escalating 
10% 
0.91 
20% 
0.71 
30% 
0.49 
40% 
0.31 
50% 
0.17 
60% 
0.08 
Abbreviation: DLT=dose-limiting toxicity 
Thus, if the true underlying proportion of DLT is low (eg, ≤10% at the current dose level, 
there is a high probability (≥0.91) of dose escalation to the next dose level. Conversely, if 
the true underlying proportion of DLT is high (eg, ≥60%) at the current dose level, there is 
a low probability (≤0.08) of escalation to the next dose level.  
14.1.2. 
Stage 2 (Cohort Expansion) 
As indicated in Section 6.1.2, expansion cohorts of 6 subjects will be accrued. Enrollment of 
6 subjects per cohort offers the opportunity to determine if there is any antitumor activity 
sufficient to warrant further development in the selected tumor types. An ORR of ≥ 35% is 
considered of potential interest in each of the selected indications. If 0/6 subjects in a cohort 
experience an objective response, then a population ORR of ≥ 35% for that cancer can be 
excluded with > 90% certainty (1-sided exact binomial 90% CI upper bound = 32%). 
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Experience indicates the rates of discontinuations from rituximab or atezolizumab therapy 
are < 5% (Genentech 2016, Genentech 2017). A rate of AE discontinuations of therapy due 
to adverse events of ≥25% in the 2 combination therapy groups of LAM-002A/rituximab 
(N = 12) or LAM-002A/atezolizumab (N = 12) would suggest a potential adverse interaction 
among the components of the combination therapy. Sequential Pocock-type boundaries will 
be used to continuously monitor the rate of AE discontinuations and to test the null 
hypothesis, after each subject, that the event rate is ≥ 0.25 using a 1-sided significance test 
of ~ 0.05. AE discontinuation rates will be considered excessive if the following n/N values 
are observed: -/1, -/2, 3/3, 3/4, 4/5, 4/6, 5/7, 5/8, 5/9, 6/10, 6/11, 7/12. With this method, the 
probability of detecting an AE discontinuation safety signal ranges from 0.091 to >0.820 for 
true discontinuation rates of 25% to ≥ 60%. If excessive levels of AE discontinuation are 
observed, the sponsor, working in collaboration with the cooperating companies and 
investigators, will take appropriate actions (eg, continuation of the cohort with 
modifications in design or monitoring plan, interruption of cohort accrual, cohort therapy 
discontinuation). 
This Phase 1 trial is being conducted primarily to assess the safety and tolerability of LAM 002A 
(apilimod dimesylate capsules) when administered in subjects with relapsed or refractory B cell 
NHL and to determine the MTD and RP2D of LAM 002A. No formal sample size estimation 
was performed. The choice of the number of subjects was based on the standard 3 + 3 design that 
is commonly used in Phase 1 trials of anti cancer investigational drugs. For the Dose Escalation 
Stage of the study, the maximum sample size will be approximately 60 subjects if 6 subjects are 
assigned to each of the 9 potential dose levels and an additional 6 patients are accrued at the 
RP2D. However, additional subjects may be added if exploration of intermediate dose level(s) of 
LAM 002A is warranted.  
Up to 45 additional evaluable subjects (3 cohorts of 15 subjects) may be enrolled at the RP2D 
and schedule in the Expansion Stage of the study. The safety population will consist of all 
subjects receiving at least 1 dose of LAM 002A. The assessment of DLT and MTD will involve 
only those subjects completing the first cycle of therapy, unless the subject discontinuation in 
first cycle was due to a DLT. 
Section 21. 
 
STUDY DISCONTINUATION 
Change: 
This section was added to separate it from Sections 6.11 and 6.12, which relate to 
duration of therapy and discontinuation of participation for individual subjects. 
12. 
STUDY DISCONTINUATION 
Both the investigator and LAM reserve the right to terminate the study at any time. Should 
this be necessary, both parties will arrange discontinuation procedures. The investigator 
will be responsible for notifying the relevant study center IRB. LAM will be responsible for 
notifying the appropriate regulatory authorities. In terminating the study, the investigator 
and LAM will assure that adequate consideration is given to the protection of the subjects’ 
interests. As directed by LAM, all study materials must be collected and all eCRFs 
completed to the greatest extent possible. 
 
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Section 22. 
LIST OF REFERENCES 
Change: 
The reference list was updated to include additional relevant references. 
22. 
LIST OF REFERENCES
Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS et al. Distinct types of diffuse large B-cell 
lymphoma identified by gene expression profiling. Nature 2000;403:503–11. 
Asghar A, Naaz S, Agrawal D, Sharma P. Morphometric study of spleen in north Indian adult 
population: CT scan image based study. Journal of Clinical and Diagnostic Research. 2011 Oct; 
5(5):974-7. 
Bezerra AS, D’Ippolito G, Faintuch S, Szejnfeld J, Ahmed M. Determination of splenomegaly 
by CT: is there a place for a single measurement? AJR Am J Roentgenol. 2005 
May;184(5):1510-3. 
Gea-Banacloche JC. Rituximab-associated infections. Semin Hematol. 2010 
Apr;47(2):187-98. 
Cai X, Xu Y, Cheung AK, Tomlinson RC, Alcázar-Román A, et al. PIKfyve, a class III PI 
kinase, is the target of the small molecular IL-12/IL-23 inhibitor apilimod and a player in Toll-
like receptor signaling. Chem Biol. 2013 Jul 25;20(7):912-21.  
Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the 
evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with 
malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010 May;149(4):578-86. 
Carson KR, Evens AM, Richey EA, Habermann TM, Focosi D, Seymour JF, et al. 
Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative 
patients: a report of 57 cases from the Research on Adverse Drug Events and Reports 
project. Blood. 2009 May 14;113(20):4834-40. 
Cheson BD, Byrd JC, Rai KR, Kay NE, O’Brien SM, et al. Novel targeted agents and the need to 
refine clinical end points in chronic lymphocytic leukemia. J Clin Oncol. 2012 Aug 
10;30(23):2820-2.  
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, et al. Recommendations for 
initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the 
Lugano classification. J Clin Oncol. 2014 Sep 20;32(27):3059-68. 
CredibleMeds. [homepage on the Internet]. Arizona: Combined list of drugs that prolong QC 
and/or cause tosrades de pointes (TDP). [Updated 2014 May 32; Cited 2015 June 12]. Available 
from: https://www.crediblemeds.org/pdftemp/pdf/CompositeList.pdf 
Cultrera JL, Dalia SM. Diffuse large B-cell lymphoma: current strategies and future directions. 
Cancer Control. 2012 Jul;19(3):204-13. 
Dakhil S, Hermann R, Schreeder MT, Gregory SA, Monte M, Windsor KS, et al. Phase III 
safety study of rituximab administered as a 90-minute infusion in patients with previously 
untreated diffuse large B-cell and follicular lymphoma. Leuk Lymphoma. 2014 
Oct;55(10):2335-40. 
Clinical Study Report 
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De Lartigue J, Polson H, Feldman M, Shokat K, Tooze SA, et al. PIKfyve regulation of 
endosome-linked pathways. Traffic. 2009 Jul;10(7):883-93. 
Erturk SM, Mortelé KJ, Binkert CA, Glickman JN, Oliva MR, Ros PR, Silverman SG. CT 
features of hepatic venoocclusive disease and hepatic graft-versus-host disease in patients after 
hematopoietic stem cell transplantation. AJR Am J Roentgenol. 2006 Jun;186(6):1497-501. 
Flockhart DA. Drug interactions: cytochrome P450 drug interaction table. Indiana University 
School of Medicine. 2007. [Cited 2015 June 12]. Available from: 
http://medicine.iupui.edu/clinpharm/ddis 
Gayle S, Landrette S, Beeharry N, Conrad C, Hernandez M, Beckett P, et al. Identification 
of apilimod as a first-in-class PIKfyve kinase inhibitor for treatment of B-cell non-Hodgkin 
lymphoma. Blood. 2017 Mar 30;129(13):1768-1778. 
Genentech. Rituxan® (rituximab) prescribing information. 2016 Apr. Available at: 
https://www.gene.com/download/pdf/rituxan prescribing.pdf (accessed 2017 Aug 3). 
Genentech. TECENTRIQ® (atezolizumab) prescribing information. 2017 Apr. Available 
at: https://www.gene.com/download/pdf/tecentriq prescribing.pdf (accessed 2017 Aug 3). 
Ghielmini M, Schmitz SF, Cogliatti SB, Pichert G, Hummerjohann J, Waltzer U, et al. 
Prolonged treatment with rituximab in patients with follicular lymphoma significantly 
increases event-free survival and response duration compared with the standard weekly x 4 
schedule. Blood. 2004 Jun 15;103(12):4416-23.  
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, et al. Guidelines for the 
diagnosis and treatment of chronic lymphocytic leukemia: a report from the international 
workshop on chronic lymphocytic leukemia updating the national cancer institute-working group 
1996 guidelines. Blood. 2008 Jun 15;111(12):5446-56. 
Hans CP, Weisenburger DD, Greiner TC, Gascoyne RD, Delabie J, et al. Confirmation of the 
molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a 
tissue microarray. Blood. 2004 Jan 1;103(1):275-82.  
Ikonomov OC, Sbrissa D, Shisheva A. Mammalian cell morphology and endocytic membrane 
homeostasis require enzymatically active phosphoinositide 5-kinase PIKfyve. J Biol Chem. 2001 
Jul 13;276(28):26141-7.  
Ilcus C, Bagacean C, Tempescul A, Popescu C, Parvu A, Cenariu M, Bocsan C, Zdrenghea M. 
Immune checkpoint blockade: the role of PD-1-PD-L axis in lymphoid malignancies. Onco 
Targets Ther. 2017 Apr 28;10:2349-2363. 
Lioté H, Lioté F, Séroussi B, Mayaud C, Cadranel J. Rituximab-induced lung disease: A 
systematic literature review. Eur Respir J. 2010 Mar;35(3):681-7.  
Martelli M, Ferreri AJ, Agostinelli C, Di Rocco A, Pfreundschuh M, et al. Diffuse large B-cell 
lymphoma. Crit Rev Oncol Hematol. 2013 Aug;87(2):146-71. 
Martinelli G, Schmitz SF, Utiger U, Cerny T, Hess U, Bassi S, et al. Long-term follow-up of 
patients with follicular lymphoma receiving single-agent rituximab at two different 
schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480-4.  
Clinical Study Report 
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Matsue K, Kimura S, Takanashi Y, Iwama K, Fujiwara H, Yamakura M, Takeuchi M. 
Reactivation of hepatitis B virus after rituximab-containing treatment in patients with 
CD20-positive B-cell lymphoma. Cancer. 2010 Oct 15;116(20):4769-76. 
MD Anderson Cancer Center (MDACC). Tumor lysis in adult patients. 2013 Apr 30. Available 
at: http://www.mdanderson.org/education-and-research/resources-for-professionals/clinical-
tools-and-resources/practice-algorithms/clin-management-tumor-lysis-web-algorithm.pdf 
(accessed 2016 Jan 24). 
National Cancer Institute [homepage on the Internet]. Maryland: Common terminology criteria 
for adverse events, version 4.0; 2009 [updated 2010 June 14; cited 2015 June 12]. Available 
from: http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE 4.03 2010-06-14 QuickReference 5x7.pdf. 
National Cancer Institute [homepage on the Internet]. Maryland: Surveillance, epidemiology, 
and end results program: SEER stat fact sheets: non-Hodgkin lymphoma [cited 2015 June 12]. 
Available from: http://seer.cancer.gov/statfacts/html/nhl.html. 
Ning YM, Suzman D, Maher VE, Zhang L, Tang S, Ricks T, et al. FDA approval summary: 
atezolizumab for the treatment of patients with progressive advanced urothelial carcinoma 
after platinum-containing chemotherapy. Oncologist. 2017 Jun;22(6):743-749.  
Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, et al. Toxicity and response criteria of 
the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982 Dec;5(6):649-55. 
Ram R, Ben-Bassat I, Shpilberg O, Polliack A, Raanani P. The late adverse events of 
rituximab therapy—rare but there! Leuk Lymphoma. 2009 Jul;50(7):1083-95.  
Raut LS, Chakrabarti PP. Management of relapsed-refractory diffuse large B cell lymphoma. 
South Asian J Cancer. 2014 Jan;3(1):66-70. 
Roberts AW, Davids MS, Pagel JM, Kahl BS, Puvvada SD, et al. Targeting BCL2 with 
venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016 Jan 
28;374(4):311-22. 
Rosenwald A, Wright G, Chan WC, Connors JM, Campo E, et al. The use of molecular profiling 
to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002 
Jun 20;346(25):1937-47. 
Rutherford AC, Traer C, Wassmer T, Pattni K, Bujny MV, et al. The mammalian 
phosphatidylinositol 3-phosphate 5-kinase (PIKfyve) regulates endosome-to-TGN retrograde 
transport. J Cell Sci. 2006 Oct 1;119(Pt 19):3944-57. 
Salmasi G, Li M, Sivabalasundaram V, Tsang R, Kukreti V, Crump M, Kuruvilla J. A 
retrospective study on the incidence of rituximab-related interstitial pneumonitis in 
patients undergoing immunochemotherapy for non-Hodgkin lymphoma. Blood ASH 
Annual Meeting Abstracts 2010 Nov 19;116(21) Abst 3094). 
Subramanian M, Manjunath R, Kilara N, Mohan Rao KN. Rituximab-induced subacute 
interstitial pneumonitis: a case report and review of literature. J Cancer Res Ther. 2010 
Jul-Sep;6(3):344-6. 
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AI Therapeutics 
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Stern A, Green H, Paul M, Vidal L, Leibovici L. Prophylaxis for Pneumocystis pneumonia 
(PCP) in non-HIV immunocompromised patients. Cochrane Database Syst Rev. 2014 Oct 
1;(10):CD005590. PMID: 25269391. 
Wada Y, Cardinale I, Khatcherian A, Chu J et al. Apilimod inhibits the production of IL-12 and 
IL-23 and reduces dendritic cell infiltration in psoriasis. 2012; PloS ONE 7(4): e35069. 
Wada Y, Lu R, Zhou D, Chu J, Przewloka T et al. Selective abrogation of Th1 response by 
STA-5326, a potent IL-12/IL-23 inhibitor. Blood 2007;109:1156-1164. 
Walker HK, Hall WD, Hurst JW, editors. Clinical methods: The history, physical, and laboratory 
examinations. 3rd edition. 1990. Boston; Butterworths. 
Weinstock C, Khozin S, Suzman D, Zhang L, Tang S, Wahby S, et al. U.S. Food and Drug 
Administration approval summary: atezolizumab for metastatic non-small cell lung cancer. 
Clin Cancer Res. 2017 Jun 13. 
Zelenetz AD, Gordon LI, Wierda WG, Abramson JS, Advani RH, Andreadis CB, et al. Non 
Hodgkin’s lymphomas, version 4.2014. J Natl Compr Canc Netw. 2014 Sep;12(9):1282 303.  
Changes made in Amendment 7 (14 Jan 2019) 
In preparing this amendment of the protocol document, the following changes were made. 
Explanations of the changes are provided in italics as “Changes.” Inserted text is indicated by red 
double-underlined font. Deleted text is indicated by red strikeout font. Changes to the synopsis 
also appear in the body of the protocol; thus, changes to the synopsis are not described and only 
changes to the body of the protocol are described. Modifications to the list of abbreviations and 
definitions of terms or minor typographical or syntax corrections are not indicated. 
Title Page 
Change: 
The protocol version and date were updated. 
Protocol Version and Date: 
Version 8.0, 14 Jan 2019 
Version 7.0; 25 Oct 2017 
Investigator’s Agreement 
Change: The date was updated. 
I have read the attached Protocol entitled “A Phase 1 Dose Escalation Study of the Safety and 
Pharmacokinetics of LAM-002A (apilimod dimesylate capsules) Administered Orally in 
Subjects with Relapsed or Refractory B-cell Non-Hodgkin’s Lymphoma” dated 25 Oct 2017 
14 Jan 2019. I agree to abide by all provisions set forth herein. I agree to comply with the 
International Conference on Harmonisation Guidelines on Good Clinical Practice, effective in 
the United States from 09 May 1997, and applicable United States Food and Drug 
Administration regulations set forth in 21 Code of Federal Regulations (CFR) §50, 54, 56, and 
312 and any applicable local regulatory requirements. I agree to ensure that the confidential 
information contained in this document will not be used for any purpose other than the 
evaluation and conduct of the clinical investigation without the prior written consent of 
LAM Therapeutics, 530 Old Whitfield Street, Guilford CT 06437, United States. 
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• To evaluate tumor and/or plasma for gene expression and genetic alterations (with 
saliva and/or B-cell-depleted PBMC collection for germ-line control) and surrogate 
tissue (PBMC/B cells) for gene expression that may predict anti-lymphoma activity. 
• To evaluate plasma for changes in analytes or tumor for protein expression that may 
predict anti-lymphoma activity 
Section 5.6 Exploratory Endpoints 
Change: 
The exploratory endpoints were updated to reflect changes to the substrates and 
parameters being analyzed. 
• Extent of PIKfyve inhibition as determined by plasma inhibitory assays 
• Changes in gene expression in PBMCs 
• Changes in plasma cytokines (including IL-12 and IL-23) 
• Correlation between genetic alterations as determined by next generation sequencing 
and/or gene expression in tumor tissue, plasma (circulating tumor DNA), or 
PBMCs/B cells and anti-lymphoma activity following treatment with LAM-002A  
• Correlation between changes in plasma bioanalytes or tumor protein expression and 
anti-lymphoma activity following treatment with LAM-002A as determined by 
proteomic tools 
Section 6.1.2 Expansion Stage 
Change: 
The protocol was modified to permit evaluation of single-agent LAM-002A or the 
LAM-002A/rituximab combination in additional patients with FL. Use of either 
intravenously administered rituximab or subcutaneously administered rituximab 
hyaluronidase human was permitted. 
Once the MTD and/or recommended phase 2 dose (RP2D) and schedule is determined, the study 
will enter the expansion stage, in which cohorts of subjects will be accrued in order to obtain 
additional information on safety, tolerability, preliminary anti-tumor activity, PK, and 
pharmacodynamic data at the RP2D and schedule when LAM-002A is administered alone or in 
combination with rituximab/rituximab hyaluronidase or atezolizumab. Expansion-stage cohorts 
will comprise groups of subjects with specific types of previously treated, relapsed, progressive, 
and measurable NHL who will receive LAM-002A monotherapy or LAM-002A-containing 
combination therapy as shown in Table 2. For both monotherapy and combination cohorts, the 
starting dose of LAM-002A will be 125 mg BID administered continuously.  
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Table 2: 
Expansion Stage Disease Types and Therapies 
Cohort 
Number 
NHL Type 
Investigational  
Drug 
Combination  
Drug 
Evaluable  
Subjects, n 
1 
FL 
LAM-002A 
-- 
6Up to ~20 
2 
MZL 
LAM-002A 
-- 
6 
3 
DLBCL-GCB 
LAM-002A 
-- 
6 
4 
DLBCL-ABC 
LAM-002A 
-- 
6 
5 
FL or MZL 
LAM-002A 
Rituximab or rituximab 
hyaluronidase human 
6Up to ~20 
with FL 
6 
DLBCL-GCB or DLBCL-ABC 
LAM-002A 
Rituximab or rituximab 
hyaluronidase human 
6 
7 
FL or MZL 
LAM-002A 
Atezolizumab 
6 
8 
DLBCL-GCB or DLBCL-ABC 
LAM-002A 
Atezolizumab 
6 
Abbreviations: ABC: activated B-cell (subtype); DLBCL: diffuse large B-cell lymphoma; FL: follicular 
lymphoma; GCB: germinal center B-cell (subtype); MZL: marginal zone lymphoma; NHL: non-Hodgkin 
lymphoma 
Section 6.2 Number of Subjects 
Change: 
Information regarding the total potential accrual to the study was updated consistent 
with modifications to the protocol to evaluate single-agent LAM-002A or the 
LAM-002A/rituximab combination in additional patients with FL.  
As many as 145 110 subjects will be enrolled, assuming that: 
• In the dose-escalation stage of the study, the total number of subjects will depend upon 
the numbers of subjects accrued to each dose level and the number of dose levels 
evaluated. If 6 subjects are enrolled at all open starting dose levels (Dose Levels 5, 6, 7, 
and 8) and 6 additional subjects are enrolled at the MTD or RD, as many as 30 subjects 
could be enrolled. To allow for the possibility that some subjects may not be fully 
evaluable for DLT or that an intermediate dose level might be evaluated, up to 
~45 subjects may be enrolled.  
• In the expansion stage of the study, if all 8 potential expansion cohorts of 6 evaluable 
subjects are accrued, as many as ~7648 subjects could be enrolled. To allow for the 
possibility that some subjects may not be fully evaluable for efficacy or to establish 
bounds on efficacy estimates with greater confidence, up to ~65 100 subjects may be 
enrolled.  
Section 6.8.2.2 In-Clinic LAM-002A Administrations 
Change: 
To 3rd paragraph only: Use of either intravenously administered rituximab or 
subcutaneously administered rituximab hyaluronidase human was permitted. 
When given as a component of combination therapy with rituximab, LAM-002A will be started 
on Cycle 1 Day 1 with a BID schedule. LAM-002A will be administered after administration of 
premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of the initial 
rituximab infusion.  On Cycle 1 Day 8, the morning dose of LAM-002A will be administered 
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after premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the rituximab 
infusion/injection. 
Section 6.8.3 Rituximab or Rituximab/Hyaluronidase Human 
Change: 
Use of either intravenously administered rituximab or subcutaneously administered 
rituximab hyaluronidase human was permitted. Relevant changes were made to 
provide necessary dosing and administration information.  
6.8.3.1  
Premedications 
In accordance with rituximab/rituximab hyaluronidase human prescribing information 
(Genentech 2016, Genentech 2018), subjects should be premedicated with an antipyretic and an 
antihistamine to reduce the incidence and severity of infusion/injection reactions. A 
recommended regimen is diphenhydramine, 25 mg orally, and acetaminophen (paracetamol), 
650 mg orally, both given ~30 minutes prior to each rituximab administration. Intravenous 
corticosteroids may also be administered as a premedication. Local practices and guidelines may 
be followed. 
6.8.3.2  
Rituximab Administration 
Based on past experience with this regimen (Ghielmini 2004, Martinelli 2010), rituximab will be 
administered intravenously or rituximab/hyaluronidase human will be administered 
subcutaneously in the clinic for a total of 8 infusions treatments: 
Intravenous rituximab (Rituxan®) 
• Four induction infusions of 375 mg/m2 will be administered weekly on Cycle 1 Day 1, 
Cycle 1 Day 8, Cycle 1 Day 15, and Cycle 1 Day 22.  
• Four subsequent maintenance infusions of 375 mg/m2 will be administered every 8 weeks 
on Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.  
Subcutaneous rituximab (rituximab/hyaluronidase human; Rituxan Hycela®) 
• An initial dose of 375 mg/mg2 will be administered intravenously on Cycle 1 Day1.  
• Three subcutaneous injections of 1,400 mg/23,400 Units (1,400 mg rituximab and 23,400 
Units hyaluronidase human) will be administered weekly on Cycle 1 Day 8, 
Cycle 1 Day 15, and Cycle 1 Day 22.  
• Four subsequent maintenance subcutaneous injections of 1,400 mg/23,400 Units (1,400 
mg rituximab and 23,400 Units hyaluronidase human) will be administered every 
8 weeks on Cycle 4 Day 1, Cycle 6 Day 1, Cycle 8 Day 1, and Cycle 10 Day 1.  
The dose for each infusion will be 375 mg/m2 of body surface area. The dose calculation of body 
surface area for infused rituximab will be based on the subject’s height and actual body weight 
prior to therapy. Once established based on the pretreatment body weight, the total dose of 
rituximab for the subject should not be altered during therapy based on fluctuations in body 
weight unless required by institutional policy. 
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At Cycle 1 Day 1, ~30 minutes after administration of the required antipyretic and antihistamine 
premedications and ~15 to 30 minutes after administration of the first dose of LAM-002A, the 
first infusion of rituximab will be administered via an infusion pump. For the initial infusion, the 
recommended infusion rate is 50 mg/hour. In the absence of infusion toxicity, the infusion rate 
can be increased in 50-mg/hour increments every 30 minutes, to a maximum of 400 mg/hour. 
For subsequent rituximab infusions, the required antipyretic and antihistamine premedications 
will be given and the rituximab will be infused via an infusion pump. For these infusions, the 
infusion can be initiated at 100 mg/hour. In the absence of infusion toxicity, the infusion rate can 
be increased in 100-mg/hour increments every 30 minutes, to a maximum of 400 mg/hour. 
Alternatively, for subjects who tolerate the first infusion with Grade ≤3 infusion toxicity, 
subsequent infusions can be administered over a planned infusion time of 90 minutes, with ~20% 
of the total dose administered in the first 30 minutes and the remaining 80% of the total protein 
dose administered in the subsequent 60 minutes (Dakhil 2014, Genentech 2016).  
For subsequent rituximab/hyaluronidase human injections, the required antipyretic and 
antihistamine premedications will be given and the rituximab/hyaluronidase human will be 
injected into the subcutaneous tissue of the abdomen over ~5 minutes. Areas where the skin is 
red, bruised, tender or hard, or areas where there are moles or scars should be avoided. No data 
are available on performing the injection at other sites of the body. If administration of 
rituximab/hyaluronidase human is interrupted, drug administration can continue at the same site 
or at a different site but restricted to the abdomen. Patients should be observed for ≥15 minutes 
following the completion of injection. During treatment with rituximab/hyaluronidase human, do 
not administer other medications for subcutaneous use at the same sites. 
6.8.3.3  
Management of Rituximab Infusion/Injection Toxicity 
Rituximab can cause severe, including fatal, infusion reactions (Genentech 2016). Patients with 
pre-existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary 
adverse reactions to rituximab, and those with high numbers of circulating malignant cells 
(≥25 x 109/L) may be at particular risk. Severe reactions typically occur during the first infusion 
and are generally less frequent and less severe with subsequent infusions. The time to onset of 
infusion toxicity ranges from 30 to 120 minutes. Rituximab-induced infusion reactions and 
sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary 
infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, 
cardiogenic shock, and/or anaphylactoid events. 
Rituximab infusions/injections should be interrupted or slowed in subjects experiencing Grade 
≥3 rituximab-related infusion reactions. Medical management (eg, oxygen, epinephrine, 
bronchodilators, and/or glucocorticoids) should be instituted, as needed. Upon improvement of 
symptoms, the infusion may be continued at 50% of the previous rate. At the discretion of the 
investigator, rituximab therapy may be permanently discontinued in subjects with Grade 4 
infusion/injection reactions or with reactions requiring substantial intervention. 
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6.8.3.4 
Rituximab/Rituximab Hyaluronidase Human Dose Modifications and Supportive 
Care 
Rituximab-related noninfectious pneumonitis has been described (Subramanian 2010) with an 
incidence of ~4.3% (Salmasi 2010). In patients developing rituximab-associated pneumonitis, 
the mean time from the first rituximab infusion to the onset of respiratory symptoms was 
3 months, with a peak incidence after administration of a mean cumulative dosage of 
1600 mg/m2 (Lioté 2010). 
Severe, including fatal, mucocutaneous reactions can occur in patients receiving rituximab 
during infusion or at later timepoints. Non-infusion related events have included paraneoplastic 
pemphigus, Stevens Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and 
toxic epidermal necrolysis (Genentech 2016). The onset of these reactions has varied from 1 to 
13 weeks following initiation of rituximab exposure. 
Among patients receiving rituximab in combination with chemotherapy, rare instances of life-
threatening bowel obstruction or perforation has been observed (Ram 2009), primarily in patients 
with NHL. In post-marketing reports, the mean time to documented gastrointestinal perforation 
was 6 (range 1–77) days from start of chemoimmunotherapy.  
Fulminate and fatal HBV infection and reactivation can occur during or after treatment with 
rituximab (Genentech 2016). The risk is very low among patients with negative anti-HBc 
serology (Matsue 2010) and/or undetectable HBV DNA as assessed by quantitative PCR. 
Because subjects with such evidence of persistent HBV infection are excluded from this study, 
reactivation is not anticipated. Other serious bacterial, fungal, and new or reactivated viral 
infections have also occurred during and for ~1 year following rituximab-based therapy 
(Gea-Banacloche 2010). Other new or reactivated viral infections in patients receiving rituximab 
have included CMV, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile 
virus, and HCV. Progressive multifocal leukoencephalopathy (PML) due to polyomavirus JC has 
been observed in patients who have received rituximab therapy for hematologic malignancies 
(Carson 2009).  
No dose reductions of rituximab/rituximab hyaluronidase human are recommended. If a subject 
experiences an AE that is suspected to be related to rituximab/rituximab hyaluronidase human 
and is of sufficient severity to warrant modification of therapy, administration of the drug should 
be interrupted or discontinued. Protocol-recommended management of selected adverse events 
and appropriate supportive care is described in Table 5. 
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Table 5: 
Recommended Rituximab or Rituximab/Hyaluronidase Modifications and 
Supportive Care 
Adverse 
Event 
Rituximab Interruption 
and Resumption 
Rituximab 
Permanent 
Discontinuation 
Supportive Care 
Pneumonitis 
Interrupt for Grade 2; 
resume when Grade ≤ 1 
Grade ≥3 
For Grade ≥2, 
corticosteroids, 1-2 mg/kg 
of prednisone equivalents  
Rash 
Interrupt for Grade 3; 
resume when Grade ≤ 1 
Grade 4 
For Grade 2, topical 
corticosteroids. For 
Grade ≥ 3, corticosteroids, 
1-2 mg/kg of prednisone 
equivalents 
Hepatitis 
Grade ≥3 elevations of 
serum AST or ALT (> 5 x 
ULN); resume when 
Grade ≤ 1 
-- 
Evaluate for HBV 
positivity; if HBV 
reactivation, treat with 
appropriate antiviral 
considering any potential 
for drug-drug interaction 
with LAM-002A. 
Bowel 
obstruction 
or 
perforation 
-- 
Any grade 
Provide appropriate 
antibiotic therapy and 
surgical supportive care. 
Infection 
Grade ≥3; resume when 
control of infection 
achieved 
-- 
Treat with appropriate 
systemic antibiotics for 
suspected or confirmed 
infections 
Abbreviations: ALT=alanine aminotransferase, AST=aspirate aminotransferase, ULN=upper limits of 
normal 
Section 6.11 Duration of Subject Participation 
Change: 
Use of either intravenously administered rituximab or subcutaneously administered 
rituximab hyaluronidase human was permitted. 
Subjects may continue receiving LAM-0002A until the occurrence of any events requiring 
treatment discontinuation as defined in Section 6.8.2.5 and Section 6.12. 
Subjects allocated to LAM-0002A/rituximab may continue to receive rituximab or rituximab 
hyaluronidase human until the earliest of a maximum of 8 infusions or the occurrence of any 
events requiring treatment discontinuation as defined in Section 6.8.3.4 and Section 6.12. 
Subjects allocated to LAM-0002A/atezolizumab may continue to receive atezolizumab until the 
earliest of any events requiring treatment discontinuation as defined in Section 6.8.4.4 or 
Section 6.12. 
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Note: If medically appropriate, subjects allocated to combination doublet therapy may 
continue with protocol-specified therapy for the therapeutic agent (LAM-002A, rituximab, 
rituximab hyaluronidase human, or atezolizumab) that continues to be tolerated, even if the 
other agent need to be discontinued due to drug-specific toxicity. 
Section 7.1 Subject Inclusion Criteria 
Change: 
(Inclusion Criterion 11 only): Biopsy procedures were clarified. 
11. For subjects with lymphoma: The subject is willing to undergo a pretreatment core 
needle, excisional, or incisional biopsy of a lymphoma nodal lesion (preferred); or is 
willing to undergo a pretreatment bone marrow aspirate if there is known bone marrow 
involvement (≥ 50% NHL cells).  If a biopsy or bone marrow aspirate is not possible, 
archived tumor tissue that was obtained within 4 months prior to the start of screening 
can be used, provided adequate quantities are available. The subject has archived tumor 
tissue for analysis that was obtained within 4 months prior to the start of screening; is 
willing to undergo a pretreatment core needle, excisional, or incisional biopsy of a 
lymphoma nodal lesion; or is willing to undergo a pretreatment bone marrow aspirate if 
there is known bone marrow involvement (≥ 50% NHL cells).  
Section 7.2 Subject Exclusion Criteria 
Change: 
(Exclusion Criterion 15 only): The severity of hypertension warranting exclusion 
from protocol therapy was clarified. 
15. The subject has uncontrolled significant intercurrent illness including, but not limited to, 
ongoing or active infection, history of congestive heart failure within 6 months, Grade ≥3 
hypertension, unstable angina pectoris within 6 months, stroke within 6 months, 
myocardial infarction within 6 months, or cardiac arrhythmias. (Controlled chronic atrial 
fibrillation will not be excluded). 
Section 8.1.3 Medical History 
Change: 
The text was clarified to indicate that past pathology data should be collected as part 
of each subject’s medical history. 
At Screening, a complete medical history will be obtained from each subject, including relevant 
medical history, current primary cancer diagnosis, pathology reports (including corresponding 
flow cytometry and cytogenetic reports), prior cancer treatments (chemo- and immunotherapies, 
radiation therapy, surgeries), and disease-specific characteristics, such as tumor stage and 
histology.  
Section 8.1.5 Disease Status Assessment for Subjects with NHL 
Change: 
(Paragraphs 3 and 4 only): Biopsy procedures were clarified. 
Fresh tumor tissue (preferred) or archival tumor tissue that was obtained within 4 months prior to 
the start of screening (provided adequate quantities are available) Archival tissue from the most 
recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained 
pretreatment for nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue 
should be acquired via excisional biopsy, incisional biopsy or core needle biopsy (e.g., 
≥ 3 passes using a 16-gauge core needle).  Confirmation of tumor in biopsy with fine needle 
aspirate, touch prep, or FFPE processing is requested when possible.  The tumor lesion selected 
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should not have been previously irradiated and should not be an index lesion that is followed for 
response assessment. Alternatively, cells from a bone marrow aspirate may be obtained in 
subjects with bone marrow involvement due to NHL (≥50% of cells). Tissue will be submitted 
for evaluation of the percentage of tumor cells and analysis of genetic alterations and/or gene 
expression that may predict anti-lymphoma activity and/or pharmacodynamics activity.  
In addition, tumor tissue from the fresh biopsy or most recently availably biopsy or surgery will 
be evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; 
expression of BCL2, BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, 
and for immune infiltration. The baseline biopsy procedure (if required) should ideally be 
performed after the study candidate has undergone the baseline radiology examination and is 
otherwise considered eligible for study participation. 
Section 8.3.1.3 PK and Biomarker Assessments 
Change: 
More detailed information regarding PK and biomarkers was included. 
Pharmacokinetic samples will be collected for determination of apilimod and metabolite 
concentrations in plasma at the time points indicated in Section 12. All subjects must participate 
in PK assessments. Fasting status must be recorded at the time of each PK blood draw. 
Comprehensive information on blood sample acquisition, handling, storage and sample 
shipments can be found in the laboratory manual “Procedures for Processing and Shipping PK 
and Biomarker Samples.” pharmacokinetic laboratory manual.  
Biomarker samples will be obtained at time points indicated in Section 13. Comprehensive 
information on tissue acquisition, handling, storage, and sample shipments can be found in the 
laboratory manual “Procedures for Processing and Shipping PK and Biomarker Samples.” 
Section 8.7 Schedules of Assessments; Table 8 Schedule of Assessments (LAM-002A 
Continuous Monotherapy Administration) 
Changes: (Table 8, Footnotes f and q): Text regarding the timing of laboratory assessments was 
clarified.  Information regarding biopsy procedures was clarified. 
f. All hematology and chemistry laboratory parameters should be assessed at Screening and at C1D1, C1D8, 
C1D15, C≥2D1 (all subsequent cycles) Days 1, 8, and 15 of Cycles 1 and 2, and then at least once prior to the 
start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of 
Cycle 1 is only required in subjects with intermediate or high risk of TLS (per the risk definition in Section 
6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters may be obtained within 72 hours prior to the 
planned day of collection. Abnormal test values should be monitored per protocol guidance. 
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q 
Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 
months prior to the start of screening) must be obtained pretreatment for nucleic acid extraction. For subjects 
undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core 
needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle 
aspirate, touch prep, or FFPE processing is requested when possible.  The tumor lesion selected should not have 
been previously irradiated and should not be an index lesion that is followed for response assessment. 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics 
activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or surgery will be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, 
BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The 
baseline biopsy procedure (if required) should ideally be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participationArchival tissue from 
the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for 
nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via 
excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16 gauge core needle). 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti lymphoma activity and/or pharmacodynamics 
activity. In addition, tumor tissue from the most recently availably biopsy or surgery will be evaluated for known 
prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki 67, CD20, 
and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure 
(if required) should ideally be performed after the study candidate has undergone the baseline radiology 
examination and is otherwise considered eligible for study participation. 
Section 8.7 Schedules of Assessments; Table 9 Schedule of Assessments (LAM-002A 
Intermittent Monotherapy Administration) 
Changes: (Table 9, Footnotes f and q): Text regarding the timing of laboratory assessments was 
clarified.  Information regarding biopsy procedures was clarified. 
f. All hematology and chemistry laboratory parameters should be assessed at Screening and at C1D1, C1D8, 
C1D15, C≥2D1 (all subsequent cycles) Days 1, 8, and 15 of Cycles 1 and 2, and then at least once prior to the 
start of all subsequent cycles and at EOT. Obtaining a chemistry laboratory parameter on Days 2 and Day 3 of 
Cycle 1 is only required in subjects with intermediate or high risk of TLS (per the risk definition in Section 
6.8.1).  Except for Days 1, 2, and 3 of Cycle 1, these parameters may be obtained within 72 hours prior to the 
planned day of collection. Abnormal test values should be monitored per protocol guidance. 
q 
Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 
months prior to the start of screening) must be obtained pretreatment for nucleic acid extraction. For subjects 
undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core 
needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle 
aspirate, touch prep, or FFPE processing is requested when possible.  The tumor lesion selected should not have 
been previously irradiated and should not be an index lesion that is followed for response assessment. 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics 
activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or surgery will be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, 
BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The 
baseline biopsy procedure (if required) should ideally be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participationArchival tissue from 
the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for 
nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via 
excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16 gauge core needle). 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
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to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti lymphoma activity and/or pharmacodynamics 
activity. In addition, tumor tissue from the most recently availably biopsy or surgery will be evaluated for known 
prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki 67, CD20, 
and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure 
(if required) should ideally be performed after the study candidate has undergone the baseline radiology 
examination and is otherwise considered eligible for study participation. 
Section 8.7 Schedules of Assessments; Table 10 Schedule of Assessments 
(LAM-002A/Rituximab Combination Therapy) 
Changes: (Table 10, Rituximab administration text, Footnotes p, u, v, w): Use of either 
intravenously administered rituximab or subcutaneously administered rituximab 
hyaluronidase human was described. Text regarding the timing of laboratory 
assessments was clarified.  
Rituximab infusion/injectionw 
p. Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 
months prior to the start of screening) must be obtained pretreatment for nucleic acid extraction. For subjects 
undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core 
needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle 
aspirate, touch prep, or FFPE processing is requested when possible.  The tumor lesion selected should not have 
been previously irradiated and should not be an index lesion that is followed for response assessment. 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics 
activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or surgery will be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, 
BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The 
baseline biopsy procedure (if required) should ideally be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participation.Archival tissue from 
the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for 
nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via 
excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16 gauge core needle). 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti lymphoma activity and/or pharmacodynamics 
activity. In addition, tumor tissue from the most recently availably biopsy or surgery will be evaluated for known 
prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki 67, CD20, 
and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure 
(if required) should ideally be performed after the study candidate has undergone the baseline radiology 
examination and is otherwise considered eligible for study participation. 
u 
Oral antipyretic, oral or intravenous antihistamine, and intravenous corticosteroid (at investigator discretion) (see 
Section 6.8.3.1) to be administered to the subject ~30 minutes prior to each rituximab infusion/injection (see 
Footnote w). 
v 
LAM-002A to be administered to the subject in clinic (with recording of the date and actual clock time of the 
LAM-002A administration). On C1D1, LAM-002A will be started on a BID schedule after administration of 
premedications (see Section 6.8.3.1) and ~15 to 30 minutes prior to the start of the initial rituximab infusion. On 
C1D8, the morning dose of LAM-002A will be administered after premedications (see Section 6.8.3.1) and ~15 
to 30 minutes prior to the rituximab infusion/injection. 
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w Rituximab, 375 mg/m2, will be administered by intravenous infusion ~30 minutes after premedication weekly on 
C1D1, C1D8, C1D15, and C1D22 and then every 8 weeks on C4D1, C6D1, C8D1, and C10D1 for a total of 8 
infusions. Alternatively, rituximab, 375 mg/m2, will be administered by intravenous infusion ~30 minutes after 
premedication weekly on C1D1 and then rituximab hyaluronidase human, 1,400 mg rituximab and 23,400 Units 
hyaluronidase human per 11.7 mL, will be administered by subcutaneous injection on C1D8, C1D15, and C1D22 
and then every 8 weeks on C4D1, C6D1, C8D1, and C10D1 for a total of 8 treatments. 
Section 8.7 Schedules of Assessments; Table 11 Schedule of Assessments 
(LAM-002A/Atezolizumab Combination Therapy) 
Changes: (Table 11, Footnote q): Information regarding biopsy procedures was clarified.  
q. Fresh tumor tissue (preferred) or archival tissue from the most recent available biopsy or surgery (within 4 
months prior to the start of screening) must be obtained pretreatment for nucleic acid extraction. For subjects 
undergoing a biopsy, adequate tumor tissue should be acquired via excisional biopsy, incisional biopsy or core 
needle biopsy (e.g., ≥ 3 passes using a 16-gauge core needle). Confirmation of tumor in biopsy with fine needle 
aspirate, touch prep, or FFPE processing is requested when possible.  The tumor lesion selected should not have 
been previously irradiated and should not be an index lesion that is followed for response assessment. 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti-lymphoma activity and/or pharmacodynamics 
activity. In addition, the fresh biopsy or tumor tissue from the most recently availably biopsy or surgery will be 
evaluated for known prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, 
BCL6, Ki-67, CD20, and MYC; other mutational status), for PDL1 status, and for immune infiltration. The 
baseline biopsy procedure (if required) should ideally be performed after the study candidate has undergone the 
baseline radiology examination and is otherwise considered eligible for study participation.Archival tissue from 
the most recent available biopsy or surgery or fresh tumor tissue (preferred) must be obtained pretreatment for 
nucleic acid extraction. For subjects undergoing a biopsy, adequate tumor tissue should be acquired via 
excisional biopsy, incisional biopsy or core needle biopsy (e.g., ≥ 3 passes using a 16 gauge core needle). 
Alternatively, cells from a bone marrow aspirate may be obtained in subjects with bone marrow involvement due 
to NHL (≥50% of cells). Tissue will be submitted for evaluation of the percentage of tumor cells and analysis of 
genetic alterations and/or gene expression that may predict anti lymphoma activity and/or pharmacodynamics 
activity. In addition, tumor tissue from the most recently availably biopsy or surgery will be evaluated for known 
prognostic characteristics (e.g., for DLBCL: ABC or GCB subtype; expression of BCL2, BCL6, Ki 67, CD20, 
and MYC; other mutational status), for PDL1 status, and for immune infiltration. The baseline biopsy procedure 
(if required) should ideally be performed after the study candidate has undergone the baseline radiology 
examination and is otherwise considered eligible for study participation. 
Section 9.3 Rituximab/Hyaluronidase Human (For Subcutaneous Administration) 
Changes: Information regarding subcutaneously administered rituximab hyaluronidase human 
was included. 
9.3 
Rituximab/Hyaluronidase Human (For Subcutaneous Administration) 
9.3.1. Description 
Rituximab/hyaluronidase human (Rituxan Hycela®) is a genetically engineered chimeric 
murine/human monoclonal IgG1 kappa antibody directed against the CD20 antigen found on 
pre-B and mature B cells. In this formulation, it is combined with hyaluronidase human, an 
endoglycosidase (Genentech 2018). Rituximab is produced by mammalian Chinese hamster 
ovary cells. The protein has an approximate molecular weight of 145 kD. Hyaluronidase human 
increases permeability of the subcutaneous tissue by temporarily depolymerizing hyaluronan.  
The drug is provided as a colorless to yellowish, clear to opalescent, preservative-free liquid 
solution. Each mL of solution contains rituximab (120 mg), hyaluronidase human (2,000 Units), 
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L-histidine (0.53 mg), L-histidine hydrochloride monohydrate (3.47 mg), L-methionine 
(1.49 mg), polysorbate 80 (0.6 mg), α,α-trehalose dihydrate (79.45 mg), and Water for Injection. 
9.3.2 
Packaging 
For use in patients with FL/DLBCL, rituximab/hyaluronidase human is supplied in single-dose 
vials containing 1,400 mg rituximab and 23,400 Units hyaluronidase human per 11.7 mL of 
solution.  
9.3.3 
Source 
Unless otherwise instructed by the sponsor, the rituximab/hyaluronidase human to be used in this 
study may be obtained from available commercial supplies.  
9.3.4. Storage and Stability 
Rituximab/hyaluronidase human vials are stable at 2°C-8°C (36°F-46°F). Vials should be 
protected from direct sunlight and should not be frozen or shaken. 
Diluted rituximab/hyaluronidase human solutions for injection may be stored at 2°C-8°C 
(36°F-46°F) for 48 hours and are known to be stable for an additional 8 hours at room 
temperatures up to 30°C (86°F) in diffuse light. However, since rituximab solutions do not 
contain a preservative, solutions should be used as soon as possible after withdrawal from the 
vial. 
Rituximab/hyaluronidase is compatible with polypropylene and polycarbonate syringe material 
and stainless-steel transfer and injection needles.  
9.3.5 
Preparation 
Before use, the rituximab/hyaluronidase human vials should be inspected for particulate matter 
or discoloration. Any vial with evidence of particulates or discoloration should not be used. 
Using aseptic technique, the entire 11.7 mL of rituximab/hyaluronidase human should be 
withdrawn from the vial via a hypodermic needle into a syringe and the vial should be discarded. 
9.3.6 
Accountability 
Acquisition, storage, control, and disposal of rituximab/hyaluronidase used in the study should 
be performed according to institutional procedures and policies. 
The investigator and/or the responsible site personnel must maintain accurate records of the 
source, dates of administration, quantities of administration, and lot numbers of the 
rituximab/hyaluronidase dispensed for this study. 
Section 10. Pregnancy 
Changes: Information regarding pharmacovigilance reporting of pregnancies was corrected. 
Pregnancy occurring in a subject is not considered an AE. However, the investigator must 
capture pregnancy information for subject and/or subject’s partner (as applicable) on a pregnancy 
report form within 24 hours of learning of the pregnancy. Then the site 
• Completes the pregnancy form with as much information as possible; however, at a 
minimum the Subject identification number, name of product, and name of reporter is 
required; 
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experience an objective response, then a population ORR of ≥ 35% for that cancer can be 
excluded with > 90% certainty (1-sided exact binomial 90% CI upper bound = 32%). 
Based on the observation of objective responses among study subjects with FL receiving either 
LAM-002A monotherapy or LAM-002A/rituximab, expanded accrual of subjects with relapsed 
FL is planned to evaluate the level of activity with these 2 regimens. Preference will be given to 
enrolling subjects to receive LAM-002A monotherapy before enrolling subjects to receive 
LAM-002A/rituximab.  
Based on historical data with other treatments (Zelenetz 2014), it is known that an ORR of 
< 20% in subjects with relapsed FL receiving LAM-002A monotherapy would be uninteresting 
while achieving a target ORR of ≥ 40% would suggest that further development is warranted. 
Sequential boundaries will be used to continuously monitor that the ORR is ≥ 40% while 
excluding an ORR of < 20% using a 1-sided test with a significance level of 0.05. A significant 
result with this testing would conclude with 95% confidence that the actual ORR is ≥ 20%. 
Accrual of up to ~20 evaluable subjects will be considered with the potential to stop accrual 
early if the boundary is crossed. Thus, accrual can be considered sufficient if the following n/N 
values are observed: 4/5, 4/6, 4/7, 5/8, 5/9, 5/10, 5/11, 6/11, 6/12, 6/13, 6/14, 7/15, 7/16, 7/17, 
8/18, 8/19, 8/20. For all these values, the ORR is ≥ 40% with a lower 1-sided binomial 
confidence bound of ≥ 20%. 
As noted above, the target ORR with LAM-002A alone is ~40%. Adding rituximab or rituximab 
hyaluronidase human to LAM-002A would be expected to enhance the ORR over that associated 
with single-agent LAM-002A. Thus, the combination of LAM-002A/rituximab could warrant 
further development if an ORR of ≥ 60% could be targeted in preference to an ORR of < 40%.  
Accordingly, for combination therapy, sequential boundaries will be used to continuously 
monitor that the ORR is ≥ 60% while excluding an ORR of 39% using a 1-sided test with a 
significance level of 0.05. A significant result with this testing would conclude with 95% 
confidence that the actual ORR is > 39%. Accrual of up to ~20 evaluable subjects will be 
considered with the potential to stop accrual early if the boundary is crossed. Thus, accrual can 
be considered sufficient if the following n/N values are observed: 7/10, 8/11, 8/12, 9/13, 9/14, 
10/15, 10/16, 11/17, 11/18, 12/19, 12/20. For all these values, the ORR is ≥ 60% with a lower 
1-sided binomial confidence bound of ≥ 39%.
Experience indicates the rates of discontinuations from rituximab or atezolizumab therapy are < 
5% (Genentech 2016, Genentech 2017). A rate of AE discontinuations of therapy due to adverse 
events of ≥25% in the 2 combination therapy groups of LAM-002A/rituximab (N = 12) or 
LAM-002A/atezolizumab (N = 12) would suggest a potential adverse interaction among the 
components of the combination therapy. Sequential Pocock-type boundaries will be used to 
continuously monitor the rate of AE discontinuations and to test the null hypothesis, after each 
subject, that the event rate is ≥ 0.25 using a 1-sided significance test of ~ 0.05. AE 
discontinuation rates will be considered excessive if the following n/N values are observed: -/1, 
-/2, 3/3, 3/4, 4/5, 4/6, 5/7, 5/8, 5/9, 6/10, 6/11, 7/12. With this method, the probability of 
detecting an AE discontinuation safety signal ranges from 0.091 to >0.820 for true 
discontinuation rates of 25% to ≥ 60%. If excessive levels of AE discontinuation are observed, 
the sponsor, working in collaboration with the cooperating companies and investigators, will take 
appropriate actions (eg, continuation of the cohort with modifications in design or monitoring 
plan, interruption of cohort accrual, cohort therapy discontinuation). 
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Section 22. 
List of References 
Changes: Information regarding drugs with known risk of QT prolongation or torsades de 
pointes was updated and the relevant reference was revised accordingly. Use of 
either intravenously administered rituximab or subcutaneously administered 
rituximab hyaluronidase human was permitted; accordingly, reference was made to 
rituximab hyaluronidase human prescribing information. 
CredibleMeds. [homepage on the Internet]. Arizona: Combined list of drugs that prolong QC 
and/or cause tosrades de pointes (TDP). [Updated 2014 May 32; Cited 2015 June 12]. Available 
from: Woosley RL, Romero KA. Drugs with known risk of torsades de pointes. 2018 Oct 31. 
Available at: https://www.crediblemeds.org (accessed 2018 Dec 17). 
Genentech. Rituxan Hycela® (rituximab and hyaluronidase human) prescribing information. 
2018 Apr. Avaliable at: https://www.gene.com/download/pdf/rituxan hycela prescribing.pdf 
(acessed 2018 Dec 18). 
Appendix 3. 
Potential Drug Interactions with LAM-002A, Table 16 Drugs Known to 
Prolong the QT Interval and/or Cause Torsades De Pointes (TDP) 
Changes: Information regarding drugs with known risk of QT prolongation or torsades de 
pointes was updated. To avoid formatting problems, the former table was removed 
without displaying it in strikeout font. 
Table 16: 
Drugs Known to Prolong the QT Interval and/or Cause Torsades De Pointes 
(TDP) 
Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Amiodarone 
Cordarone®, Pacerone®, 
Nexterone® 
Antiarrhythmic 
Abnormal heart rhythm 
Anagrelide 
Agrylin®, Xagrid® 
Phosphodiesterase 3 
inhibitor 
Thrombocythemia 
Arsenic trioxide 
Trisenox® 
Anticancer 
Cancer (leukemia) 
Astemizole (removed 
from market) 
Hismanal® 
Antihistamine 
Allergic rhinitis 
Azithromycin 
Zithromax®, Zmax® 
Antibiotic 
Bacterial infection 
Bepridil (removed 
from market) 
Vascor® 
Antianginal 
Angina Pectoris (heart pain) 
Chloroquine 
Aralen® 
Antimalarial 
Malaria 
Chlorpromazine 
Thorazine®, Largactil®, 
Megaphen® 
Antipsychotic / 
Antiemetic 
Schizophrenia, nausea, many 
others 
Cilostazol 
Pletal® 
Phosphodiesterase 3 
inhibitor 
Intermittent claudication 
Ciprofloxacin 
Cipro®, Cipro-XR®, 
Neofloxin® 
Antibiotic 
Bacterial infection 
Cisapride (removed 
from market) 
Propulsid® 
Gastrointestinal 
stimulant 
Increase gastrointestinal 
motility 
Citalopram 
Celexa®, Cipramil® 
Antidepressant, 
selective serotonin 
reuptake inhibitor 
Depression 
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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Clarithromycin 
Biaxin®, Prevpac® 
Antibiotic 
Bacterial infection 
Cocaine 
Cocaine 
Local anesthetic 
Anesthesia (topical) 
Disopyramide 
Norpace® 
Antiarrhythmic 
Abnormal heart rhythm 
Dofetilide 
Tikosyn® 
Antiarrhythmic 
Abnormal heart rhythm 
Domperidone (only 
on non-US market) 
Motilium®, Motillium®, 
Motinorm Costi®, 
Nomit® 
Antinausea 
Nausea, vomiting 
Donepezil 
Aricept® 
Cholinesterase 
inhibitor 
Dementia (Alzheimer's 
Disease) 
Dronedarone 
Multaq® 
Antiarrhythmic 
Abnormal heart rhythm 
Droperidol 
Inapsine®, Droleptan®, 
Dridol®, Xomolix® 
Antipsychotic / 
Antiemetic 
Anesthesia (adjunct), nausea 
Erythromycin 
E.E.S.®, Robimycin®, 
EMycin®, Erymax®, Ery-
Tab®, Eryc Ranbaxy®, 
Erypar®, Eryped®, 
Erythrocin Stearate 
Filmtab®, Erythrocot®, 
E-Base®, Erythroped®, 
Ilosone®, MY-E®, 
Pediamycin®, Zineryt®, 
Abboticin®, Abboticin-
ES®, Erycin®, PCE 
Dispertab®, Stiemycine®, 
Acnasol®, Tiloryth® 
Antibiotic 
Bacterial infection, increase 
gastrointestinal motility 
Escitalopram 
Cipralex®, Lexapro®, 
Nexito®, Anxiset-E® 
(India), Exodus® (Brazil), 
Esto® (Israel), Seroplex®, 
Elicea®, Lexamil®, 
Lexam®, Entact® 
(Greece), Losita® 
(Bangladesh), Reposil® 
(Chile), Animaxen® 
(Colombia), Esitalo® 
(Australia), Lexamil® 
(South Africa) 
Antidepressant, 
selective serotonin 
reuptake inhibitor 
Depression (major), anxiety 
disorders 
Flecainide 
Tambocor®, Almarytm®, 
Apocard®, Ecrinal®, 
Flécaine® 
Antiarrhythmic 
Abnormal heart rhythm 
Fluconazole 
Diflucan®, Trican® 
Antifungal 
Fungal infection 
Gatifloxacin 
(removed from 
market) 
Tequin® 
Antibiotic 
Bacterial infection 
Grepafloxacin 
Raxar® 
Antibiotic 
Bacterial infection 
Halofantrine 
Halfan® 
Antimalarial 
Malaria 
Haloperidol 
Haldol® (US & UK), 
Aloperidin®, 
Bioperidolo®, Brotopon®, 
Antipsychotic 
Schizophrenia, agitation 
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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Dozic®, Duraperidol® 
(Germany), Einalon S®, 
Eukystol®, Halosten®, 
Keselan®, Linton®, 
Peluces®, Serenace®, 
Serenase®, Sigaperidol® 
Ibogaine (only on 
non-US market) 
None 
Psychedelic 
Narcotic addiction, unproven 
Ibutilide 
Corvert® 
Antiarrhythmic 
Abnormal heart rhythm 
Levofloxacin 
Levaquin®, Tavanic® 
Antibiotic 
Bacterial infection 
Levomepromazine 
(methotrimeprazine) 
only on non-US 
market) 
Nosinan®, Nozinan®, 
Levoprome® 
Antipsychotic 
Schizophrenia 
Levosulpiride (only 
on non-US market) 
Lesuride®, Levazeo®. 
Enliva® (with rabeprazole) 
Antipsychotic 
Schizophrenia 
Levomethadyl 
acetate (removed 
from market) 
Orlaam® 
Opioid agonist 
Narcotic dependence 
Mesoridazine 
(removed from 
market) 
Serentil® 
Antipsychotic 
Schizophrenia 
Methadone 
Dolophine®, Symoron®, 
Amidone®, Methadose®, 
Physeptone®, Heptadon® 
Opioid agonist 
Narcotic dependence, pain 
Moxifloxacin 
Avelox®, Avalox®, 
Avelon® 
Antibiotic 
Bacterial infection 
Ondansetron 
Zofran®, Anset®, 
Ondemet®, Zuplenz®, 
Emetron®, Ondavell®, 
Emeset®, Ondisolv®, 
Setronax® 
Antiemetic 
Nausea, vomiting 
Oxaliplatin 
Eloxatin® 
Antineoplastic 
Agent 
Cancer 
Papaverine HCl 
none 
Vasodilator, 
Coronary 
Diagnostic adjunct 
Pentamidine 
Pentam® 
Antifungal 
Fungal infection 
(Pneumocystis pneumonia) 
Pimozide 
Orap® 
Antipsychotic 
Tourette's Disorder 
Probucol (removed 
from market) 
Lorelco® 
Antilipemic 
Hypercholesterolemia 
Procainamide 
Pronestyl®, Procan® 
Antiarrhythmic 
Abnormal heart rhythm 
Propofol 
Diprivan®, Propoven® 
Anesthetic, general 
Anesthesia 
Quinidine 
Quinaglute®, Duraquin®, 
Quinact®, Quinidex®, 
Cin-Quin®, Quinora® 
Antiarrhythmic 
Abnormal heart rhythm 
Roxithromycin (only 
on non-US market) 
Rulide®, Xthrocin®, 
Roxl-150®, Roxo®, 
Surlid®, Rulide®, 
Antibiotic 
Bacterial infection 
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Generic Name 
Brand Names (Partial 
List) 
Drug Class 
Therapeutic Use 
Biaxsig®, Roxar®, 
Roximycinv®, 
Roxomycin®, Rulid®, 
Tirabicin®, Coroxin® 
Sevoflurane 
Ulane®, Sojourn® 
Anesthetic, general 
Anesthesia 
Sotalol 
Betapace®, Sotalex®, 
Sotacor® 
Antiarrhythmic 
Abnormal heart rhythm 
Sparfloxacin 
(removed from 
market) 
Zagam® 
Antibiotic 
Bacterial infection 
Sulpiride (only on 
non-US market) 
Dogmatil®, Dolmatil®, 
Eglonyl®, Espiride®, 
Modal®, Sulpor® 
Antipsychotic, 
atypical 
Schizophrenia 
Sultopride (only on 
non-US market) 
Barnetil®, Barnotil®, 
Topral® 
Antipsychotic, 
atypical 
Schizophrenia 
Terfenadine 
(removed from 
market) 
Seldane® 
Antihistamine 
Allergic rhinitis 
Terlipressin (only on 
non-US market) 
Teripress®, Glypressin®, 
Terlipin®, Remestyp®, 
Tresil®, Teriss®, and 
others 
Vasoconstrictor 
Septic shock 
Terodiline (only on 
non-US market) 
Micturin®, Mictrol® (not 
bethanechol) 
Muscle relaxant 
Bladder spasm 
Thioridazine 
Mellaril®, Novoridazine®, 
Thioril® 
Antipsychotic 
Schizophrenia 
Vandetanib 
Caprelsa® 
Anticancer 
Cancer (thyroid) 
Note: Includes those drugs known to prolong the cardiac QT interval or cause TdP (Woosley 2018). 
Abbreviation: QT: Time of start of Q wave until end of T wave in the heart’s electrical cycle; TdP: 
Torsades de Pointes; UK: United Kingdom; US: United States  
 
Changes made in Amendment 8 (18 Feb 2020) 
In preparing this amendment of the protocol document, the following changes were made. 
Explanations of the substantive changes are provided in italics as “Changes.” Inserted text is 
indicated by red double-underlined font. Deleted text is indicated by red strikeout font. 
Changes to the synopsis also appear in the body of the protocol; thus, changes to the synopsis are 
not described and only changes to the body of the protocol are described.  
Modifications to the list of abbreviations and definitions of terms or minor typographical or 
syntax corrections are not indicated.  
Title Pages, Headers, Body of Protocol 
Changes to the company name (from LAM Therapeutics, Inc. to AI Therapeutics, Inc.) and 
modifications to the protocol version and date (from Version 8, dated 14 Jan 2019 to Version 9, 
dated 19 February 2020) were made throughout the document without specific notation. 
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AI Therapeutics Signature Page 
Change: 
Information regarding AI Therapeutics signatories to the protocol was updated. 
AI THERAPEUTICS SIGNATURE PAGE 
 
 
 
 
 
Name: 
Candace A Fuchs, PMP Henri Lichenstein, PhD 
 
 
 
Title: 
Head, Clinical Operations/Project Management 
AI Therapeutics, Inc. Chief Executive Officer 
AI Therapeutics, Inc. 
 
Date: 
 
Signature: 
 
 
18 Feb 2020 
 
 
 
 
 
 
Name: 
Langdon L Miller, MD 
 
 
 
Title: 
Clinical Consultant 
AI Therapeutics, Inc. 
 
Date: 
 
Signature: 
 
 
18 Feb 2020 
 
 
 
 
 
 
Section 4.1.4.2 Efficacy 
Change: 
Information regarding LAM-002A efficacy in NHL was updated in the protocol 
introduction. 
In Study LAM-002A-NHL-CLN01, efficacy has been assessed in subjects with NHL. Decreases 
in tumor metabolic activity were noted in 3 subjects with relapsed DLBCL receiving LAM-002A 
monotherapy but these changes did not meet formal criteria for objective response. Nine subjects 
with FL treated with LAM-002A monotherapy, LAM-002A in combination with rituximab, or 
LAM-002A in combination with atezolizumab have had substantial tumor regressions 
compromising 2 complete responses (CRs) and 7 partial responses (PRs). The responses have 
been long-lasting, with durations exceeding 12 months among several subjects with mature data. 
One subject with MZL receiving LAM-002A/rituximab also experienced a durable PR. 
Efficacy data in patients with hematological malignancies are evolving. As of 14 Jan 2019, 
2/5 patients with FL receiving LAM 002A monotherapy had achieved an objective response 
(1 complete response [CR] and 1 partial response [PR]); 2/4 patients with FL receiving 
LAM 002A/rituximab had achieved PRs, and 1/1 patient with FL receiving 
LAM 002A/atezolizumab had achieved a PR. Among subjects with other types of NHL, positron 
emission tomography (PET) demonstrated systemic partial metabolic responses in nodal and 
extranodal lesions in 3 patients with refractory DLBCL (treated at 100 mg BID, 75 mg TID, and 
125 mg BID) (1 of whom also received radiation for bulky axillary adenopathy); concomitant 
computed tomography (CT) demonstrated anatomic shrinkage of many lesions. One additional 
subject with transformed, refractory DLBCL (treated at 125 mg BID) experienced tumor lysis 
syndrome (TLS). One patient with marginal zone lymphoma (MZL) (treated at 125 mg BID) has 
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had a metabolic response by PET together with a 43% decrease in the sum of the products of the 
perpendicular diameters (SPD) of index lesions by CT. Another patient with MZL and a patient 
with chronic lymphocytic leukemia (CLL) (both receiving 100 mg BID) experienced prolonged 
stable disease through 11+ and 14 cycles, respectively. 
Section 6.1. 
Overall Study Design Stage 
Changes: Text was included consistent with addition of an extension stage to the study. 
This is a Phase 1, single-arm, open-label, dose-escalation study of safety and PK of apilimod 
administered to subjects with refractory or relapsed B-cell NHL. This study will be conducted in 
3 stages consists of 2 stages. 
Section 6.1.3 Extension Stage (Stage 3) 
Changes: Text was included to explain the addition of an extension stage to the study. 
The extension stage (Stage 3) can begin once the last study subject has completed at least 
8 cycles of study treatment. At this time, the study sponsor will conclude the dose-escalation and 
expansion stages of the study, will collate and verify all study data through an appropriate data 
cutoff date, and will lock the study database for preparation of a study report. Subjects who are 
still safely benefiting from Stage 1 or Stage 2 study therapy as of the data cutoff date may 
electively continue their current regimen of study therapy in Stage 3, receiving clinical care and 
diagnostic testing consistent with conventional practice standards as deemed appropriate by the 
treating investigator. Therapy in Stage 3 may continue in the absence of protocol-defined reasons 
to discontinue therapy. During Stage 3, collection of clinical data by the sponsor will be limited 
to serious adverse event (SAE) reports. Study drug accountability will be managed per site 
procedures; relevant pharmacy records may be collected by the sponsor to document study drug 
disposition.  
Section 6.2. 
Number of Subjects 
Changes: Text was included consistent with addition of an extension stage to the study. 
As many as 145 subjects will be enrolled, assuming that: 
• In the dose-escalation stage of the study, the total number of subjects will depend upon the 
numbers of subjects accrued to each dose level and the number of dose levels evaluated. If 6 
subjects are enrolled at all open starting dose levels (Dose Levels 5, 6, 7, and 8) and 
6 additional subjects are enrolled at the MTD or RD, as many as 30 subjects could be 
enrolled. To allow for the possibility that some subjects may not be fully evaluable for DLT 
or that an intermediate dose level might be evaluated, up to ~45 subjects may be enrolled.  
• In the expansion stage of the study, if all 8 potential expansion cohorts are accrued, as many 
as ~76 subjects could be enrolled. To allow for the possibility that some subjects may not be 
fully evaluable for efficacy or to establish bounds on efficacy estimates with greater 
confidence, up to ~100 subjects may be enrolled.  
• In the extension stage of the study, the total number of subjects will include ≤4 subjects who 
have participated in the expansion stage of the study and are still receiving  study therapy on 
the data cutoff date that concludes the dose-escalation and expansion stages of the clinical 
trial. 
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Section 6.5.2. Treatment Period  
Changes: Text was removed consistent with addition of an extension stage to the study. 
The subject is treated and monitored for safety (including assessments of AEs, vital signs, ECGs, 
laboratory tests and concomitant medications). Additionally, preliminary anti-tumor activity will 
be assessed and PK and biomarker samples will be collected. In the absence of protocol defined 
reasons to discontinue therapy, subjects may continue to receive study treatment for up to 1 year 
at the discretion of the investigator and beyond 1 year with the agreement of the investigator and 
the sponsor.  
Section 8. Methods of Assessment and Endpoints 
Changes: Text was included consistent with addition of an extension stage to the study. 
All trial data during the dose-escalation stage (Stage 1) and expansion stage (Stage 2) will be 
recorded on the eCRFs. Timing of study procedures for the dose-escalation stage (Stage 1) and 
expansion stage (Stage 2) are listed in schedules of assessments tables – Table 8: Schedule of 
Assessments (LAM-002A Continuous Monotherapy Administration), Table 9: Schedule of 
Assessments (LAM-002A Intermittent Monotherapy Administration), Table 10: 
Schedule of 
Assessments (LAM-002A/Rituximab Combination Therapy), and Table 11: 
Schedule of 
Assessments (LAM-002A/Atezolizumab Combination Therapy) – in Section 8.7.  During the 
extension stage (Stage 3), collection of clinical data by the sponsor will be limited to serious 
adverse event (SAE) reports. Study drug accountability will be managed per site procedures; 
relevant pharmacy records may be collected by the sponsor to document study drug disposition. 
Section 9.1.6. Handling and Disposal 
Changes: In the context of transitioning to the extension stage of the study, site monitoring of 
drug accountability by the contract research organization, Ce3, was discontinued. 
LAM-002A  accountability and inventory records will be inspected by the sponsor/Ce3 prior to 
final disposition. Instructions will be provided by the sponsor/Ce3 for shipment to and 
destruction of unused LAM-002A product by the designated packaging depot, to include 
unopened bulk bottles at the end of the study and expired product. Unused product returned by 
study subjects or opened bulk bottles will be destroyed by each site per site SOPs. LAM-002A  
should only be shipped or destroyed upon written authorization from the sponsor/Ce3. 
Documentation of return of shipment, including a packing list and copy of the tracking label, 
should be retained in the Pharmacy and/or regulatory files.  
Section 10.6. SAE and AESI Reporting 
Changes: In the context of transitioning to the extension stage of the study, pharmacovigilance 
monitoring of SAEs was transitioned from the contract research organization, 
Pharmalex, Inc. to the study sponsor, AI Therapeutics. 
• The investigator is obligated to immediately report to Pharmalex, Inc.AI Therapeutics each 
SAE and each AESI that occurs during this investigation, within 24 hours from knowledge of 
the event, whether or not it is considered study-drug related.  
• All requested supplementary documents (e.g., discharge summary, autopsy report) and 
relevant data (e.g., ECGs, laboratory tests, discharge summaries, post mortem results) must 
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Additional information on the course of the pregnancy should be supplied on follow-up forms as 
it becomes available and at minimum at termination or birth.  
Section 10.7. 14.1.3 Extension Stage (Stage 3) 
Changes: Text was included in the statistical section of the protocol consistent with addition of 
an extension stage to the study. 
The sample size in the extension stage of the study will be no higher than the total number of 
subjects on study therapy on the data cutoff date that concludes the dose-escalation and 
expansion stages of the clinical trial. 
Section 16. Study Monitoring 
Changes: Text was included consistent with the plan to discontinue regular monitoring of study 
sites during the extension stage of the study. 
Before an investigational site can enter a subject into the study, a representative of 
AI Therapeutics will visit the investigational study site to: 
• Determine the adequacy of the facilities 
• Discuss with the investigator and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of AI Therapeutics or its representatives. This 
will be documented in a Clinical Study Agreement between AI Therapeutics and the 
investigator. 
During the study, a monitor from AI Therapeutics or its representative will have regular contacts 
with the investigational site for the following: 
• Provide information and support to the investigator 
• Confirm that facilities remain acceptable 
• Confirm that the investigational team is adhering to the protocol that data are being 
accurately recorded in the eCRFs, and that investigational product accountability checks are 
being performed 
• Perform source data verification. This includes a comparison of the data in the CRFs with the 
subject’s medical records at the hospital or practice, and other records relevant to the study. 
This will require direct access to all original records for each subject (e.g., clinic charts) 
• Record and report any protocol deviations not previously sent to AI Therapeutics 
• Confirm AEs and SAEs have been properly documented on eCRFs, and confirm any SAEs 
have been forwarded to AI Therapeutics and those SAEs that met criteria for reporting have 
been forwarded to the IRB 
The monitor will be available between visits if the investigator or other staff members need 
information or advice. 
Upon conclusion of the Dose-Escalation (Stage 1) and Expansion (Stage 2) stages of the study, 
routine site monitoring by AI Therapeutics or its representatives will be discontinued. 
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