Conditions: Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 60
Healthy volunteers: no

Brief summary:
This is an open-label, single arm, and registered study of ATG-010 in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

Detailed description:
This is an open-label, single arm, and registered study. About 60 patients with relapsed/refractory DLBCL plan to be enrolled in about 10 study sites of the study. It is planned that at least 50% (\~30 patients) will have the GCB subtype of DLBCL. Enrolled patients will be treated with a fixed dose, 60 mg of ATG-010, orally, twice weekly, each 4 week (28-day) a cycle. Patients should remain on the study treatment of ATG-010, until either PD or occurrence of unacceptable toxicity.

Arms:
arm 1: Enrolled patients will be treated with a fixed dose, 60 mg of ATG-010.

Interventions: intervention 1: ATG-010 60 mg, orally, twice weekly, each 4 week (28-day) a cycle
Intervention descriptions: intervention 1: Enrolled patients will be treated with a fixed dose, 60 mg of ATG-010, orally, twice weekly, each 4 week (28-day) a cycle.

Protocol document:
Prot_SAP_000.pdf: 
ATG-010-DLBCL-001 
Clinical Study Protocol 
 
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PROTOCOL SYNOPSIS 
Title of Study: 
An Open-label and Single Arm Study of ATG-010 in Patients with Relapsed or Refractory 
Diffuse Large B-Cell Lymphoma (DLBCL) 
Indication 
Relapsed or Refractory DLBCL 
Objectives 
Primary Objective: 
To determine the overall response rate (ORR) of ATG-010 evaluated by central radiological 
review in relapsed or refractory DLBCL subjects who have at least 2 but no more than 5 previous 
systemic regimens. 
Secondary Objectives: 
• To determine the ORR evaluated by investigator 
• To determine the duration of response (DOR) evaluated by central radiological review 
• To determine the disease control rate (DCR) evaluated by central radiological review 
• To determine the median overall survival (OS) 
• To determine the median progression-free survival (PFS) 
• To determine the PFS, ORR, DOR, DCR, and OS in subjects with “double hit” DLBCL 
(DH-DLBCL) and non-DH-DLBCL; in subjects with GCB and non-GCB DLBCL; as 
well as with “very good”, “good”, and “poor” Revised International Prognostic Index 
(R-IPI) 
• To assess the safety and tolerability of ATG-010 
Background and Study Rationale 
Study Background 
DLBCL is an aggressive cancer with current immunochemotherapy, 60 to 65% of patients are 
progression-free at 5 years, but the remaining about 1/3 of patients with DLBCL have a poor 
prognosis with disease resistant to available agents. A very clear unmet medical need persists for 
patients with relapsed or refractory DLBCL. 
Study Rationale: 
ATG-010 (Selinexor) is an orally bioavailable selective inhibitor of nuclear export (SINE) 
compound that specifically blocks exportin 1 (XPO1). Preclinical studies showed that ATG-010 
can lead to the nuclear accumulation and re-activate of tumor suppressor proteins and other 
growth modulators, promote rapid onset of apoptosis both in vitro and in vivo of hematological 
and solid tumor cells; meanwhile it has little effect on normal cells. SADAL is an international, 
multicenter, open IIb, ongoing study. As of 15 November 2018, the efficacy data 
(Karyopharm，2018) for SADAL Study were updated and ORR was 29.6% by central 
radiology laboratory based on 115 subjects in modified intent-to-treat (mITT) population, 
including CR 9.6% and PR 20.0%; the median DOR was 9.2 months in all ATG-010 responders 


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(total 34 subjects; 11 CRs+23 PRs), median DOR in CR subjects was 23 months, and median 
DOR in PR subjects was 7.8 months. The median OS was 9.1 months in all subjects, 29.7 
months for CR/PR subjects, but only 3.2 months for progressive disease/not reached (PD/NR) 
subjects. These results showed the correlation between tumor responses of DLBCL and clinical 
efficacy of treatment, the OS observed in ATG-010 non-responders with PD/NR was also 
consistency with published references. 
Based on the encouraging clinical efficacy and safety data obtained by ATG-010 monotherapy 
in the treatment of subjects with recurrence or refractory DLBCL, FDA granted the rapid 
channel of ATG-010 monotherapy for recurrence or refractory DLBCL on 07 November 2018, 
aiming at accelerating the clinical study and marketing approval of ATG-010. 
According to the efficacy data obtained by SADAL Study in the population of relapse or 
refractory DLBCL subjects in the west, the current study plans to verify the clinical efficacy of 
ATG-010 single drug treatment in subjects with relapse/refractory DLBCL who have received 
no more than 5 systematic treatment regimens in the past. 
Study Design 
This is an open-label, single arm, and registered study. About 60 subjects with relapsed or 
refractory DLBCL plan to be enrolled in about 10 study sites of the study. It is planned that at 
least 50% (~30 subjects) will have the GCB subtype of DLBCL. Enrolled subjects will be 
treated with a fixed dose, 60 mg of ATG-010, orally, twice weekly, each 4-week a cycle. 
Subjects should remain on the study treatment of ATG-010, until either PD or occurrence of 
unacceptable toxicity. 
Confirmed evidence of DLBCL progressive or failed to the last treatment regimen is required 
for study entry, and subjects must have measurable disease at screening per the Lugano criteria 
for response assessment (Cheson, 2014). 
Disease assessment (tumor measurement) will be made by PET-CT and Contrast-enhanced CT 
(Tumor measurement) at screening (within the first 14 days of Cycle 1 Day 1), enhanced CT 
should include the neck, chest, abdomen, pelvic cavity (including the inguinal/femoral region), 
if clinically indicated, as well as other anatomical sites. If CT is contraindicated, MRI scan will 
be performed. PET-CT and contrast-enhanced CT scans will be performed on Cycle 3 Day 1 (± 
1 week) and then every 8±1 weeks (ie, Day 1 of odd numbered cycles) until disease progression 
is confirmed by the central radiological review. The PET-CT is allowed at alternating 
assessment time points (ie, every 16 weeks, or every other scan) if PET-CT cannot be performed 
for every assessment. If CT scan suggests the possibility of obtaining CR, PET-CT should be 
performed for confirmation. Results of PET-CT and contrast-enhanced CT scans performed 
beyond a predetermined time point should be recorded on the eCRF and images of all disease 
assessment scans performed during the study period will be provided to the central radiological 
review. 
Bone marrow aspirates and/or biopsies will be taken within 1 month prior to first dose (baseline) 
to assess bone marrow involvement. The bone marrow biopsy will be repeated whenever 
clinically indicated to confirm CR in only those subjects who had DLBCL with known bone 
marrow involvement prior to dosing. 


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Diagnosis and Main Criteria for Inclusion: 
Inclusion Criteria 
To be included in this study, a patient must meet all the following criteria: 
1. The patient must provide informed consent form (ICF) prior to the first screening 
procedure. 
2. Age ≥18 years. 
3. ECOG performance status of ≤2. 
4. Subjects should have estimated life expectancy of >3 months at study entry. 
5. Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed 
from previously diagnosed indolent lymphoma (e.g., follicular lymphoma). 
6. Subjects must have received at least 2 but no more than 5 previous systemic regimens 
for the treatment of DLBCL, including at least 1 course of anthracycline-based 
chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which 
case other active agents must have been given, such as etoposide, bendamustine, or 
gemcitabine, etc.) and at least 1 course of anti-CD20 immunotherapy (e.g., rituximab), 
unless contraindicated due to severe toxicity. Subjects who were considered ineligible 
for standard multi-agent immunochemotherapy must have received at least 2 and no 
more than 5 prior treatment regimens including at least 1 course of anti-CD20 antibodies 
and must be approved by the Medical Monitor. Prior stem cell transplantation is allowed. 
Induction, consolidation, stem cell collection, preparative regimen, and transplantation ± 
maintenance are considered a single line of therapy. 
7. Documented evidence of DLBCL progressive (PD) or failed (SD) to the last treatment 
regimen. 
8. Subjects must have measurable disease per the Lugano criteria for response assessment 
of lymphoma (Cheson, 2014). 
9. Subjects must not be eligible for high-dose chemotherapy with autologous stem cell 
transplantation rescue, ie, meet any of the following criteria: 
a. Age ≥65years old. 
b. Existed severe organ dysfunction or complications. 
c. Failed to obtain PR or CR through salvage therapy. 
d. Failure of stem cell collection. 
e. Subjects refuse to receive high-dose chemotherapy with autologous stem cell 
transplantation. 
10. Female subjects of child-bearing potential must have a negative serum pregnancy test at 
screening (Female subjects of child-bearing potential is defined as female whose 
menstruation has begun, who are not in the late menopause, and who have not received 
surgical sterile [e.g., hysterectomy, bilateral tubal ligation, bilateral oophorectomy]). 
Post-menopausal period is defined as successive amenorrhea ≥12 months without 
specific reason. Female subjects of child-bearing potential must agree to use reliable 


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methods of contraception for 3 months after their last dose of medication.  
11. Male subjects (including those who have undergone vasectomy) must agree to use 
condoms if sexually active with a female of child-bearing potential and must agree that 
they have no plan to make their female partners pregnant during the use of study drug 
and within 3 months after the last dose of medication since they signed ICF. 
Exclusion Criteria 
Subjects meeting any of the following exclusion criteria are not eligible to enroll in this study. 
1. Subjects who are pregnant or lactating. 
2. DLBCL with mucosa-associated lymphoid tissue (MALT) lymphoma, composite 
lymphoma (Hodgkin’s lymphoma + non-Hodgkin's lymphoma[NHL]), or DLBCL 
transformed from diseases other than indolent NHL. 
3. Primary mediastinal (thymic) large B-cell lymphoma. 
4. Known central nervous system lymphoma or meningeal involvement. 
5. Subjects whose most recent systemic anticancer therapy include radiation, 
chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy 
other than glucocorticoids within 4 weeks prior to first dose of study drug. 
6. Subjects who have not recovered to Grade ≤1 clinically significant adverse events, or to 
their baseline, except for the hair loss, from their most recent systemic anti-DLBCL 
therapy. 
7. Subjects with active graft-versus-host disease after allogeneic stem cell transplantation. 
At least 4 months prior to first dose of study drug must have elapsed since completion of 
allogeneic stem cell transplantation. 
8. Major surgery within 2 weeks of first dose of study treatment of ATG-010. 
9. Any life-threatening illness, medical condition, or organ system dysfunction which, in 
the Investigator’s opinion, could compromise the patient’s safety. 
10. Unstable cardiovascular function: 
a. Symptomatic ischemia, or 
b. Uncontrolled clinically significant conduction abnormalities (ie, ventricular 
tachycardia on anti-arrhythmia is excluded; First degree atrioventricular block or 
asymptomatic left anterior fascicular block /right bundle branch block will not be 
excluded), or 
c. Congestive heart failure of New York Heart Association Class ≥3, or 
d. Myocardial infarction within 3 months. 
11. Uncontrolled (ie, clinically unstable) infection requiring parenteral antibiotics, antivirals, 
or antifungals within 1 week prior to first dose; however, prophylactic use of these 
agents is acceptable even if parenteral. 
12. Active hepatitis B virus (HBV) or hepatitis C virus (HCV)infection. 
a. Serological positive for hepatitis B surface antigen (HBsAg) or hepatitis B core 
antibody (HBcAb). Subjects who are HBcAb positive but HBsAg negative can be 


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enrolled if HBV-DNA cannot be detected. The upper limit of normal HBV-DNA 
testing is based on the test value of each site. 
b. HCV antibody positive. But subjects with positive HCV antibodies can be enrolled 
if HCV-RNA cannot be detected.  
13. Known human immunodeficiency virus (HIV) infection. 
14. Subjects unable to swallow tablets, subjects with malabsorption syndrome, or any other 
gastrointestinal disease or gastrointestinal dysfunction that could interfere with 
absorption of study treatment of ATG-010. 
15. Any of the following laboratory abnormalities (without corrective treatment) 
a. Absolute neutrophil count <1000 cells/mm3 or platelet count<75,000/mm3 during 
screening and on C1D1. Platelet infusions within 1 week prior to the first study 
treatment and/or use of granulocyte-stimulating factors and platelet growth factors 2 
weeks prior to the first study treatment 
b. A circulating lymphocyte count of >50,000/µL 
c. Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except 
subjects with Gilbert’s syndrome: total bilirubin of > 3×ULN) and alanine 
aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 ×ULN. In 
subjects with known liver involvement of their DLBCL, AST and ALT >5×ULN  
d. Severe renal dysfunction: estimated creatinine clearance of <30 mL/min, measured 
in 24-hour urine or calculated using the formula of Cockroft and Gault (can refer to 
Appendix 5) 
e. Hematopoietic dysfunction: hemoglobin <10.0 g/dL within 14 days of and including 
C1D1 and/or subjects receiving red blood cell transfusion within 14 days of and 
including C1D1. 
16. Subjects with a body surface area <1.4 m2 (can refer to Appendix 6). 
17. Psychiatric illness or substance use that would prevent the patient from giving informed 
consent or being compliant with the study procedures. 
Duration of Study: 
The enrollment period for the study is expected to be 6 months, the end of study will be 
defined as 12 months after the last patient enrolled in the study, has withdrawn consent, has 
died, or has been lost to follow-up, (whichever occurs first). In addition, Sponsor may at any 
time decide to discontinue the study for reasons including but not limited to security. 
Upon completion of this study, Sponsor will provide continuous treatment (as determined by 
the investigator) to the subjects who still have clinical benefits. The study drug may be 
provided through additional extension studies or in other forms at the discretion of the 
Sponsor. 
Test Product, Dose and Mode of Administration: 
The dosage regimen of ATG-010 specified as follow: Subjects will be administered as a fixed 
oral ATG-010 of 60 mg twice weekly (e.g., Monday and Wednesday or Tuesday and 
Thursday, etc.) on Weeks 1-4 of each 4-week cycle (total of 8 doses per cycle). 
Subjects who achieved partial response (obtained the expected best efficacy judged by 


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investigator) or better response will transition to maintenance dosing until either PD or 
occurrence of unacceptable toxicity.  
The maintenance dose of ATG-010 will be 60 mg orally QW. Subjects whose dose has been 
reduced such that the total weekly dose is <60 mg will continue that tolerated dose. If a 
patient experiences a subsequent increase in disease burden, or per the discretion of the 
Investigator, the dose of ATG-010 can be increased to 60 mg orally twice weekly, after 
discussion with the Medical Monitor. 
If more than one different type of toxicity occurs concurrently, the most severe grade will 
determine the modification. All subjects who have a treatment delay of more than 28 days due 
to drug-related adverse events will withdraw from the study treatment. Each dose 
modification or treatment delay must be documented in the eCRF, including the respective 
reason. 
Concomitant Medications: 
To minimize nausea after oral administration of study drug, all subjects must receive 
5-hydroxytryptamine (5-HT3) antagonists (eg, ondansetron 8 mg or equivalent), unless 
contraindicated, starting before the first dose of ATG-010 and continued twice daily to 3 times 
daily, after which the specific frequency of medication can be determined by the actual 
symptoms of the patient. Olanzapine is also recommended for the first 8 weeks, after which the 
dosage can be gradually reduced according to the situation of patient. Alternative anticathectic 
may be provided if the patient does not tolerate 5-HT3 antagonists. Other anti-nausea and 
anti-anorexia drugs may be administered by the investigator per institutional guidelines 
(National Comprehensive Cancer Network® [NCCN] Antiemetic Clinical Practice Guidelines® 
and NCCN Palliative Care Clinical Practice Guidelines) 
The best supportive care of study permitted includes blood product transfusions, antimicrobials, 
and growth factors including granulocyte colony-stimulating factors (for neutropenia), 
erythropoietins (for anemia), and/or platelet-stimulating factors (for thrombocytopenia). 
Concurrent therapy with any authorized or ongoing investigative anticancer agents is not 
allowed. Subjects are not allowed to participate in any other clinical trials during the study. 
Study Endpoints: 
Primary endpoint 
• 
ORR by central radiological review: PR + CR 
Secondary endpoints 
• 
ORR evaluated by investigator 
• 
DOR (evaluated by central radiological review), defined as the duration of time from 
first occurrence of CR or PR until the first date that disease progression is objectively 
documented 
• 
DCR (evaluated by central radiological review), defined as the proportion of 
subjects who achieve CR, PR, or SD for a minimum of 4 weeks, following the 
first dose of study drug (ie, CR+PR+SD) 
• 
OS, defined as the duration of time from the first dose of study drug until death 
due to any cause 
• 
PFS, defined as the duration of time from the first dose of study drug until 
progression or death due to any cause 


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• 
PFS, ORR, DOR, DCR, and OS in subjects with DH-DLBCL and non-DH- DLBCL; 
with GCB and non-GCB DLBCL; and with “very good”, “good”, and “poor” R-IPI 
• 
Safety and tolerability 
Discontinuation Criteria: 
A subject may be discontinued at the discretion of the Investigator for any of the following 
reasons, the investigator should make the decision after timely communication with the 
clinical trial monitor in specific cases. 
• Disease progression, as assessed by the Investigator and confirmed by the central 
radiological review, defined according to the revised Lugano criteria for response 
assessment of lymphoma (Cheson, 2014)  
− For subjects with disease progression on imaging assessment, if disease 
progression is not clearly unequivocal and/or the patient is clearly deriving 
clinical benefit, after discussion with the Sponsor Medical Monitor, the 
Investigator may elect to continue the patient on study and repeat imaging 
within 4 to 8 weeks for confirmation or negation of PD. 
• Disease progression as determined by the Investigator (should be radiographically 
confirmed whenever possible and must be comprehensively documented by the 
Investigator) 
• Unacceptable adverse event(s) or failure to tolerate the study treatment 
• Treatment delay of more than 28 days, except in specific cases approved by the 
Sponsor 
• Any medically appropriate reason or significant protocol violation, in the opinion 
of the Investigator 
The Investigator must remove a patient from study treatment for any of the following 
reasons: 
• Patient decides to discontinue study treatment or withdraws consent 
• Pregnancy 
Subjects may decide to discontinue study treatment for any reason. Subjects who elect to 
discontinue study treatment will be asked to continue study participation so that follow-up 
information on disease progression and survival status may be obtained. 
Statistical Summaries: 
The primary endpoint analyses will be conducted after at least one efficacy evaluation following 
the enrollment of the last patient to the study (including efficacy and safety), and the amended 
analyses on efficacy and safety will be conducted after the End of Study. 
Determination of Sample Size 
This study is a bridging study based on an international multicenter clinical trial SADAL, and 
aims to verify the efficacy and safety of ATG-010 single drug in the treatment of relapsed or 
refractory DLBLC in the Chinese subjects. Consistent requirements of efficacy results and the 
SADAL study are that the point estimate of ORR in the bridging study falls within the 95% CI 
of the SADAL study (ORR of SADAL study: 28.3%; 95% CI: 20.7% - 37.0%). 60 subjects are 


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enrolled in SEARCH. If ORR reaches 28.3%, it can provide more than 90% power to make its 
assumed ORR to be above 20.7% and obtain sufficient safety data in Chinese subjects. 
Efficacy Assessment 
The primary endpoint analyses will be based on ORR data evaluated by central radiological 
review. The mITT population will be used for analyses of efficacy, which is defined as all 
subjects who received at least 1 dose of study drug administration. 
Analysis of ORR will also be conducted in per-protocol population (PP) and this population 
will be used for supportive efficacy analysis. 
The PP population will consist of the following subjects in the mITT population: 
 Compliance of ATG-010 treatment ≥70%; 
 Subjects who have received at least one complete post-baseline tumor evaluation, 
except for the subjects who died before or withdrew from study; 
 Subjects who have no major protocol violations that would compromise the assessment 
of efficacy.  
Data lists of major violations that would compromise the statistical analysis will be determined 
prior to database lock. 
The secondary efficacy endpoints include ORR evaluated by investigator, DOR and DCR 
evaluated by central radiological review, OS, and PFS, etc, which will be analyzed using the 
mITT and the per protocol populations. Time-to-event with censored value (DOR, PFS and OS, 
etc) will be assessed using Kaplan-Meier methods in survival analysis, 95% CIs will be 
provided for ORR and DCR. 
Safety Assessment 
Data from all subjects who have received at least 1 dose of study drug administration will be 
used for safety analysis. Adverse events will be coded using the Medical Dictionary for 
Regulatory Activities (MedDRA). The severity of the adverse event will be graded according to 
the CTCAE, Version 4.03. 
AEs will be displayed in tables and listings using MedDRA system organ class (SOC) and 
preferred term. subjects occurring more than one same adverse event will be counted only once 
when the number of subjects with adverse event was counted. Other safety endpoints including 
hematology and blood chemistry results will also be analyses in Safety Population.  
 


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Table 1 
Schedule of Assessments and Study Activities 
Visit Window (days) 
Prescreening and Screening 
Visits may be combined at site 
i
i
Cycle 1 
Cycle >2 
End of 
Treatment 
Visit 
Safety 
Follow- 
up 
Call27 
Survival 
Follow- 
up
28 
Pre-Screenin
g for DLBCL 
Subtyping2 
Screening (prior 
to start of study 
treatment) 
≤ 30 days prior 
to enrollment 
≤ 14 
days 
≤ 7 
days 
Day 1 of 
Weeks 
1-4 
Day 
3 
of 
Week 
1 
only24 
Day 
1 
of 
each 
cycle 
Day 
10 of 
each 
cycle24 
Day 
15 of 
each 
cycl
e 
Day 24 
of each 
cycle2
4 
<14 
days 
after last 
dose 
30 days 
after 
last 
dose 
Every 
3 months 
until the End 
of Study 
± 1 day  
+ 1 
day
± 2 days  
±2  days 
+ 1 day 
+ 1 day 
- 
+7 days 
±14 days  
Study Visit # 
Pre-Screen 
Visit 1 
Visit
2 
Visits 
3-6 
Phone Visits ≥7 
Phone 
Visits 
Phone 
Visits 
Phone 
Phone 
ICF for Pre-Screen of 
DLBCL subtyping1 
X 
 
 
 
 
 
 
 
 
 
 
 
Signing ICF1 
X 
 
 
 
 
 
 
 
 
 
 
Tumor biopsy (subjects 
without known DLBCL 
subtype and no archival 
tissue for subtyping)2 
X 
 
 
 
 
 
 
 
 
 
 
 
Tumor biopsy 
(subjects with 
known DLBCL 
subtype but no 
archival tissue for 
subtyping)2 
X 
 
 
 
 
 
 
 
Inclusion and exclusion 
criteria 
 
X 
X 
 
 
 
 
 
 
 
 
 
Demographics 
 
X 
 
 
 
 
 
 
 
 
 
 
Disease risk 
assessment (Revised 
International 
Prognostic Index: 
R- IPI) 
 
X 
 
 
 
 
 
 
 
 
 
 
Medical history3 
 
X 
X 
 
 
 
 
 
 
 
 
 


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Height4 
 
X 
 
 
 
 
 
 
 
 
 
Weight5 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
 
Vital signs6 
 
 
X 
X 
 
X 
 
 
 
X 
 
 
ECOG score 
 
 
X 
X7 
 
X7 
 
 
 
X 
 
 
Physical examination8 
 
 
X 
X 
 
X 
 
X 
 
X 
 
 
Echocardiogram 
or 
MUGA scan9 
 
X 
 
 
 
 
 
 
 
 
 
 
12-lead ECG10 
 
X 
 
 
 
 
 
 
 
X 
 
 
Ophthalmic exam11 
 
X 
X 
 
 
Urinalysis12 
 
 
X 
X7 
 
X7 
 
 
 
X 
 
 
CBC with differential13 
 
 
X 
X7 
 
X7 
 
 
 
X 
 
 
TSH14 
 
 
X 
X7 
 
X7 
 
 
 
X 
 
 
Serum chemistry 
(Complete)15 
 
 
X 
X7 
 
X7 
 
 
 
X 
 
 
Serum chemistry (Limited)16 
 
 
 
X 
 
 
X 
 
 
 
 
 
Coagulation tests17 
 
 
X 
 
 
 
 
 
 
X 
 
 
Pregnancy test18 
 
 
X 
 
 
X 
 
 
 
X 
 
 
HBV/HCV/HIV testing19 
 
 
X 
 
 
X 
 
 
 
 
 
 
Confirmation of 
PD and SD20 
 
X 
 
 
 
 
 
 
 
 
 
PET-CT or enhanced CT 
scan for tumor 
assessment21 
 
X 
 
 
X 
 
 
 
 
 
 
Revised criteria for 
response assessment of 
lymphoma22 
 
 
 
 
X 
 
 
 
 
 
 


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Bone marrow aspirate 
and/or biopsy23 
 
X 
 
 
 
 
 
 
 
 
 
5-HT3 antagonist dosing24 
 
 
 
X 
 
 
 
 
 
 
 
 
ATG-010 dosing25 
 
 
 
X 
 
X 
X 
 
 
 
 
 
Adverse events 
 
X (adverse events beginning at after first dose of study drug, serious adverse events beginning at before first dose 
of study drug) 
 
Concomitant medication 
 
X (beginning at ICF signing) 
 
 
Supportive care 26 
 
X 
X 
 
X 
 
X 
 
 
 
Information 
on 
antineoplastic 
therapy 
after end of ATG-010 
treatment27 
 
 
 
 
 
 
 
 
 
X 
5-HT3 = 5-hydroxytryptamine ; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase, BUN = blood urea nitrogen; 
CBC = complete blood count; CR = complete response; CT = computed tomography; DLBCL = diffuse large B-cell lymphoma; ECG = electrocardiogram; ECOG = Eastern 
Cooperative Oncology Group; GCB = germinal center B-cell; HBV = hepatitis B virus; hCG = human chorionic gonadotropin; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; ICF = informed consent form; INR = international normalization ratio; LDH = lactate dehydrogenase; MRI = magnetic resonance imaging; MUGA = 
multiple gated acquisition; PET = positron emission tomography; PR = partial response; PT = prothrombin time; TSH = thyroid stimulating hormone; TT = thrombin time; 
WBC = white blood cell. 
1 
The patient must provide informed consent for pre-screening and master ICF within 30 days of enrollment and prior to the first screening procedure. 
2 
All subjects must submit either a fresh biopsy or archival tissue to the central DLBCL subtyping laboratory for determination (prior to enrollment) or confirmation 
(by end of Cycle 2) of their DLBCL pathological diagnosis and subtype. In subjects with a known DLBCL subtype but without sufficient archival tissue available 
for confirmatory subtyping, biopsy should be performed before the end of Cycle 1. 
3 
Medical History at Screening Visits 1 & 2 including baseline symptoms as well as a detailed history of prior cancer therapies and procedures for DLBCL with start 
and stop dates, best response and disease progression during or after therapy, as well as discontinuations due to intolerability or any other serious illness. An 
evaluation of the risk of tumor lysis syndrome based on a clinical evaluation of comorbidity will also be performed. 
4 
Height (will be only measured once at Screening Visits 1 or 2).  
5 
Body weight will be measured at each clinic visit up to and including Cycle 5; Cycle 6 onwards only during Day 1 visits. 
6 
The vital sign includes blood pressure, pulse, temperature, and respiration rate; will be measured after the patient has been in a supine or sitting position for 5 minutes, 
on Day 1 of each Cycle only. 
7 
On Day 1 of each Cycle only. 
8 
Full physical exam will be conducted on all subjects at screening and at the End of Treatment Visit; symptom-directed physical examination will be conducted 
during the study.  
9 
Echocardiogram or MUGA scan to be performed during Screening Visit 1 to assess baseline cardiac function and risk of cardiac dysfunction (including 
cardiomyopathy), particularly in subjects who have received prior anthracycline therapy. 
10 An ECG will be done at Screening Visit 1, otherwise only if clinically indicated, and at End of Treatment Visit. 
11 Ophthalmic exam will be conducted on the subjects with previous ocular or visual diseases or clinical indications at Screening; during the study, 
ophthalmological exam should be carried out if there are clinical indications, and an ophthalmologist should be consulted if necessary. 


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12 Urinalysis will be done at Screening Visit 2, Day 1 of each cycle, and End of Treatment Visit; and will include urine bilirubin, glucose, red blood cells, ketones, 
pH, protein, specific gravity, and urobilinogen. Microscopy will only be performed if clinically indicated. 
13 The CBC with differential at Screening Visit 2, Day 1 of each cycle, and End of Treatment Visit, will include hemoglobin, hematocrit, mean corpuscular volume, 
mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, WBC count, WBC differential, RBC count, lymphocytes, monocytes, neutrophils, 
eosinophils, basophils, platelets. The WBC differential may be automated or manual as per institutional standards. Reticulocytes may be done only when clinically 
indicated. 
14 The level of TSH will be measured at Screening Visit 2, Day 1 of each cycle, and End of Treatment Visit. 
15 Complete serum chemistry at Screening Visit 2, Day 1 of each cycle, and End of Treatment Visit, will include sodium, potassium, chloride, bicarbonate, blood 
urea/BUN, creatinine, glucose, calcium, phosphate, magnesium, ALT, AST, alkaline phosphatase, total bilirubin, LDH, total protein, albumin, amylase, lipase, 
creatine kinase, and uric acid. 
16 Limited chemistry for Cycle 1 (Weeks 2, 3 and 4) and Day 15 of Cycles ≥2 including sodium, potassium, chloride, bicarbonate, blood urea/BUN, creatinine, glucose, 
ALT, AST, alkaline phosphatase, total bilirubin, and LDH (otherwise other clinical indicated). If total bilirubin concentration increases to more than 1.5 times the 
upper limit of normal, total bilirubin will be divided into direct and indirect bilirubin. 
17 Coagulation Tests to be measured at Screening Visit 2 and End of Treatment Visit including PT, INR, and aPTT. Coagulation may also be measured using TT 
(quick test) if measurement of PT/aPTT is not feasible. If there are coagulation related problems, the investigator may decide to retest at any time at his discretion. 
18 Women of child bearing potential must have a negative serum hCG pregnancy test within 3 days prior to first study dose and at End of Treatment Visit. Women of 
child bearing potential will have urine pregnancy test on Day 1 of Cycle 2, then on Day 1 of even numbered cycles thereafter. A positive urine pregnancy test will be 
confirmed by a serum pregnancy test. 
19 Screening for HBV and HCV at Screening Visit 2. HBV-DNA testing (only for HBcAb positive subjects) should be done each cycle (approximately monthly). At 
Screening Visit 2, HIV testing is required if the patient is known to have prior HIV infection. 
20 Confirmed evidence of DLBCL disease progression (PD) or failure (SD) to the last treatment regimen is required for study entry, and subjects must have measurable 
disease at screening per the Lugano criteria for response assessment of lymphoma (Cheson, 2014). 
21 Disease assessment (tumor measurement) will be made by PET-CT and Contrast-enhanced CT (Tumor measurement) at screening (within the first 14 days of Cycle 1 
Day 1), enhanced CT should include the neck, chest, abdomen, pelvic cavity (including the inguinal/femoral region), if clinically indicated, as well as other 
anatomical sites. If CT is contraindicated, MRI scan will be performed. PET-CT and contrast-enhanced CT scans will be performed on Cycle 3 Day 1 (± 1 week) and 
then every 8±1 weeks (ie, Day 1 of odd numbered cycles) until disease progression is confirmed by the central radiological review. The PET-CT is allowed at 
alternating assessment time points (ie, every 16 weeks, or every other scan) if PET-CT cannot be performed for every assessment. If CT scan suggests the possibility 
of obtaining CR, PET-CT should be performed for confirmation. Results of PET-CT and contrast-enhanced CT scans performed beyond a predetermined time point 
should be recorded on the eCRF and images of all disease assessment scans performed during the study period will be provided to the central radiological review. 
22 Disease status will be assessed by the Lugano criteria for response assessment of lymphoma (Cheson, 2014;Appendix 1) on Cycle 3 Day 1 (±1 week) and then 
every 8 weeks ± 1 week  (ie, Day 1 of odd numbered cycles) until disease progression is confirmed by the central radiological review. 
23 Bone marrow aspirates and/or biopsies will be taken within 1 month prior to first dose (baseline) to assess DLBCL involvement in bone marrow. The bone 
marrow biopsy will be repeated whenever clinically indicated to confirm CR in only those subjects who had DLBCL known bone marrow involvement prior to 
dosing. 
24 To minimize nausea, all subjects should receive 5-HT3 antagonists (8 mg or equivalent) unless contraindicated, starting on Cycle 1 Day 1 before the first dose of 
ATG-010 and continued 2 to 3 times daily thereafter, as needed. Olanzapine is also recommended for the first 8 weeks, after which the dosage can be gradually 
reduced according to the situation of patient. 
25 ATG-010 dosing will occur on Days 1 and 3 of Weeks 1-4 of each 4-week cycle. For doses on non-clinic days, the patient will be provided doses to take home. 
26 Phone call to evaluate supportive care medications and adverse events, and to adjust supportive care as appropriate. In Cycle 1, the telephone contact with the patient 
must take place on Day 3 (+ 1 day) following the Cycle 1 Day 1 of ATG-010 dosing. For Cycles ≥2, this phone call will be made on Day 10 (+ 1 day) and 24 (+ 1 
day), corresponding to Day 3 (+ 1 day) of every week in which a clinic visit does not occur. 
27 By phone (or a visit, if possible), assess patient status, follow-up on any adverse events that were not resolved at the End of Treatment Visit, and information on any 
antineoplastic therapies utilized since discontinuation of study treatment. 


ATG-010-DLBCL-001 
Clinical Study Protocol 
 
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28 After treatment discontinuation, a call will be made to the patient (or the patient’s family) every 3 months (± 14 days) from the date their last dose until the End of 
Study to determine the patient’s survival status and information on any antineoplastic therapies utilized since discontinuation of study treatment.