Clinical trial NCT04836195
Conditions: B-cell Non Hodgkin Lymphoma Advanced Solid Tumor
Sponsor: Pacylex Pharmaceuticals
Start date: 2021-09-14; Completion date: 2024-10-28
Enrollment: 29 participants; Allocation: RANDOMIZED; Intervention model: SEQUENTIAL

Brief summary:
This is a phase I dose-escalation study of oral PCLX-001, conducted in a multicenter, non-randomized, open-label, non-controlled design. The study is comprised of two parts: Part A (single-agent dose escalation) and Part B (single-agent expansion cohorts).

Detailed description:
This is a phase I dose-escalation study of oral PCLX-001, conducted in a multicenter, non-randomized, open-label, non-controlled design. The study is comprised of two parts: Part A (single-agent dose escalation) and Part B (single-agent expansion cohorts).

For Part A dose-escalation, patients will be enrolled in cohorts of 3 to 6 patients to each dose level. A new dose level cannot open to accrual until toxicity has been determined in the preceding dose level (i.e. all patients have completed their first cycle of therapy and data for all patients in that dose level have been reviewed at a safety cohort review meeting). Six patients will be treated at the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). If required, the MTD cohort may be expanded by an additional 10 patients for further toxicity and response assessment. The MTD cohort expansion may be restricted to B-cell lymphoma or advanced solid tumours to ensure there is proper distribution during dose escalation.

For Part B (single agent expansion cohorts), two expansion cohorts (N=20 each) will be opened to determine the preliminary clinical activity of PCLX-001 at the RP2D:

* Expansion Cohort A: Participants with advanced solid malignancies showing preclinical sensitivity or molecular markers of sensitivity to PCLX-001. This includes breast, nonsmall cell lung (NSCLC), small-cell lung (SCLC), colorectal (CRC), and bladder cancers
* Expansion Cohort B: Participants with relapsed/refractory (R/R) B-cell lymphoma: diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and Burkitt lymphoma. Transformed large B-cell lymphoma will also be included.

Arms: arm 1: Cohort 1: Participants were administered 20mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle. arm 2: Cohort 2: Participants were administered 40mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle. arm 3: Cohort 3: Participants were administered 70mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle. arm 4: Cohort 4: Participants were administered 100mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle. arm 5: Cohort 5: Participants were administered 140mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle. arm 6: Cohort 6: Participants were administered 210mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle. arm 7: Cohort 7: Participants were administered 280mg of PCLX-001 orally as continuous daily dosing on a 28-day cycle.
Interventions: intervention 1: PCLX-001 - 20mg intervention 2: PCLX-001 - 40mg intervention 3: PCLX-001 - 70mg intervention 4: PCLX-001 - 100mg intervention 5: PCLX-001 - 140mg intervention 6: PCLX-001 - 210mg intervention 7: PCLX-001 - 280mg
Intervention descriptions: intervention 1: 20mg daily oral pills intervention 2: 40mg daily oral pills intervention 3: 70mg daily oral pills intervention 4: 100mg daily oral pills intervention 5: 140mg daily oral pills intervention 6: 210mg daily oral pills intervention 7: 280mg daily oral pills

Protocol documents:
Prot_SAP_000.pdf: 
Clinical Protocol 
Version 3.0 dated 5 Jan 2023 
1 
PCLX-001-01 
Phase I Trial of PCLX-001 in Relapsed/Refractory B-cell Non-Hodgkin 
Lymphoma and Advanced Solid Malignancies 
 
 
Protocol Number: 
 
 
PCLX-001-01 
 
Protocol Version and date:  
1.0 Original 
 
 
January 28, 2021 
2.0 Amendment 1 
 
October 23, 2022 
3.0 Amendment 2 
 
January 5, 2023 
 
Test Product:  
 
 
PCLX-001 
 
Sponsor: 
 
 
 
Pacylex Pharmaceutics, Inc. 
4000, 10230 Jasper Avenue 
Edmonton, Alberta, CANADA T5J 4P6 
 
Sponsor’s Medical Advisor: 
John Mackey, MD; CMO, Pacylex Pharmaceuticals, Inc. 
4000, 10230 Jasper Avenue 
Edmonton, Alberta, CANADA T5J 4P6 
Phone: (780) 616-9020 
 
Principal Investigator: 
 
Randeep Sangha, MD, FRCPC 
 
 
 
 
 
Cross Cancer Institute 
 
 
 
 
 
11560 University Avenue 
 
 
 
 
 
Edmonton, Alberta, CANADA T6G 1Z2 
 
 
 
 
 
Phone: (780) 432-8248 | Fax: (780) 432-8888 
 
 
 
 
 
Email: Randeep.Sangha@ahs.ca 
 


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The study will be conducted in compliance with the protocol, ICH-GCP and any applicable 
regulatory requirements.  
Confidential 
The information provided in this document is strictly confidential and is intended solely for the 
guidance of the clinical investigation. Reproduction or disclosure of this document - whether in 
part or in full - to parties not associated with the clinical investigation or its use for any other 
purpose without the prior written consent of the sponsor is not permitted. 
 
 


Clinical Protocol 
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Sponsor’s Agreement to Protocol version 3.0, dated 5 Jan 2023 
 
 
 
 
 
 
 
Name of Authorized Personnel  
(Print) 
 
 
Title of Authorized Personnel  
(Print) 
 
 
Signature of Authorized 
Personnel: 
 
 
______________________________________ 
 
 
 
______________________________________ 
 
 
 
______________________________________ 
 
                    
 
Date of Approval: 
______________________________________ 
 
DD-MMM-YYYY 


Clinical Protocol 
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Protocol Acceptance Form 
By signing below, the Principal Investigator (PI) agrees to adhere to the protocol in the conduct 
of this study.  Any change in the study must be reviewed by a formal protocol amendment 
procedure and the Principal Investigator will submit all changes, amendments and revisions to 
their Research Ethics Board. Any change to the protocol that affects patient selection, safety, or 
changes in the conduct of the trial will require written approval from the REB and Health Canada 
(HC) / the U.S. Food and Drug Administration (FDA) (as applicable) before implementing the 
change. 
The Investigator will provide access to this protocol for personnel at the study center who are 
involved in this clinical study and will ensure that study personnel understand the protocol and 
have knowledge of the investigational medicinal product or intervention.  
The Investigator will keep all study documents in confidence. 
The Investigator(s) also agree(s) to conduct the study in accordance with the Declaration of 
Helsinki and the International Conference on Harmonisation guidelines on Good Clinical Practice 
(ICH GCP). 
The Principal Investigator also thereby agrees that the REB will approve all patient informed 
consent forms (ICF) before the study is initiated.  The investigator will obtain informed consent 
and document this process for all patients enrolled on this study. 
 
 
_______________________  ______________________  _____________________ 
Principal Investigator (Print)  
Signature  
 
Date (dd/mmm/yyyy) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .......................................................................................................... 8 
PROTOCOL SYNOPSIS ............................................................................................................ 12 
1. 
INTRODUCTION ................................................................................................................. 17 
1.1  
Myristoylation and Cancer ............................................................................................ 17 
1.2 
PCLX-001 Overview ..................................................................................................... 17 
1.2.1 PCLX-001 Mechanism of Action and Properties ........................................................ 17 
1.2.2 
Preclinical Studies ................................................................................................. 19 
1.2.3 
PCLX-001 Pharmacokinetics and Pharmacology ................................................. 22 
1.2.4 
PCLX-001 Toxicology and Safety Profile .............................................................. 24 
1.3 
Study Rationale ............................................................................................................ 25 
1.3.1 
Rationale for Patient Selection in Dose Escalation ............................................... 25 
1.3.2 
Rationale for Patient Selection in Dose Expansion ............................................... 25 
2. 
OBJECTIVES ...................................................................................................................... 27 
3. 
STUDY DESIGN .................................................................................................................. 28 
3.1 
Overview of Study Design ............................................................................................ 28 
3.1.1 
Selection of Starting Dose Level and Dosing Considerations ............................... 28 
3.2 
Definition of Dose Limiting Toxicity and Maximum Tolerated Dose.............................. 28 
3.3 
Part A: Dose-Escalation and Determination of MTD .................................................... 29 
3.4 
Part A Dose Escalation Schedule and Treatment Schema .......................................... 30 
3.5 
Design of Part B Expansion Cohorts ............................................................................ 31 
3.6 
Treatment Duration and Discontinuation ...................................................................... 31 
3.7 
End of Treatment Follow-Up ......................................................................................... 32 
4. 
STUDY POPULATION ........................................................................................................ 32 
4.1 
Inclusion Criteria ........................................................................................................... 32 
4.2 
Exclusion Criteria .......................................................................................................... 35 
4.3 
Replacement ................................................................................................................ 37 
5. 
TREATMENTS .................................................................................................................... 37 
5.1 
Identity of Study Treatment .......................................................................................... 37 
5.2 
Dosage and Administration .......................................................................................... 37 
5.3 
Dose Delay and Modifications ...................................................................................... 38 
5.3.1  
Cycle 1 DLT Modifications for Part A Dose-Escalation Cohorts ............................ 38 
5.3.2 
Dose Modifications for HEMATOLOGIC Toxicities ............................................... 38 
5.3.3 
Dose Modifications for NON-HEMATOLOGIC Toxicities ...................................... 38 
5.4 
Prophylaxis and Monitoring of Tumor Lysis Syndrome ................................................ 39 
5.5 
Treatment Compliance ................................................................................................. 40 


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6. 
NON-STUDY THERAPIES .................................................................................................. 40 
6.1 
Concomitant Therapy ................................................................................................... 40 
7. 
STUDY SCHEDULE AND ASSESSMENTS ....................................................................... 41 
7.1 
Study Calendar ............................................................................................................. 41 
7.2 
Visit Description ............................................................................................................ 46 
7.2.1 
Screening .............................................................................................................. 46 
7.2.2 
Treatment Visits .................................................................................................... 46 
7.2.3 
Follow-Up Visit ...................................................................................................... 46 
7.2.4 
End of Treatment Visit ........................................................................................... 46 
7.3 
Determination of Efficacy Outcomes ............................................................................ 46 
7.4 
Pharmacokinetics ......................................................................................................... 47 
7.4.1 
Drug Measurements .............................................................................................. 47 
7.5 
Pharmacodynamics ...................................................................................................... 48 
7.5.1 
Tissue Samples ..................................................................................................... 48 
7.5.2 
Blood Samples ...................................................................................................... 48 
8. 
STASTISTICAL CONSIDERATIONS .................................................................................. 49 
8.1 
Sample Size Determination .......................................................................................... 49 
8.3 
Populations for Analyses .............................................................................................. 49 
8.4 
Statistical Analyses ....................................................................................................... 49 
8.5 
Pharmacokinetic Analyses ........................................................................................... 49 
9. 
ADVERSE EVENT REPORTING ........................................................................................ 50 
9.1 
Definition of an Adverse Event ..................................................................................... 50 
9.2 
Reporting, Recording and Follow-up of Adverse Events .............................................. 50 
9.3 
Serious Adverse Events ............................................................................................... 50 
9.3.1 
SAE Reporting ....................................................................................................... 51 
10. MONITORING, AUDITING, AND INSPECTING .................................................................. 51 
10.1 
Source Data .................................................................................................................. 52 
10.2 
Quality Control and Assurance ..................................................................................... 52 
10.3 
Safety Monitoring Plan ................................................................................................. 52 
10.4 
Deviations ..................................................................................................................... 52 
10.5 
Safety Stopping Rules .................................................................................................. 52 
11. DATA COLLECTION AND DATA MANAGEMENT ............................................................. 53 
11.1 
Data Collection and Case Report Forms ...................................................................... 53 
11.2 
Dose Escalation Safety Cohort Review ........................................................................ 53 
12. ADMINSTRATIVE, ETHICAL, AND REGULATORY STANDARDS .................................... 53 
12.1 
Compliance Statement ................................................................................................. 53 


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12.2 
Ethics ............................................................................................................................ 53 
12.3 
Health Canada .............................................................................................................. 53 
12.4 
Confidentiality and Data Protection .............................................................................. 54 
12.4.1 
Participant Protection ............................................................................................ 54 
12.4.2 
Participant Identification ........................................................................................ 54 
12.4.3 
Confidentiality of Trial Documents and Patient Records ....................................... 54 
12.4.4 
Retention of Patient Records and Study Files ....................................................... 54 
12.5 
Protocol Registration .................................................................................................... 54 
12.6 
Protocol Amendments .................................................................................................. 55 
13. CRITERIA FOR TERMINATION OF TRIAL......................................................................... 55 
13.1 
Futility ........................................................................................................................... 55 
13.2 
Safety ........................................................................................................................... 55 
13.3 
Efficacy ......................................................................................................................... 55 
14. PUBLICATION POLICY ....................................................................................................... 55 
15. REFERENCES .................................................................................................................... 56 
16. LIST OF APPENDICES ....................................................................................................... 57 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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LIST OF ABBREVIATIONS  
Abbreviations 
Definitions 
ADME 
Absorption, distribution, metabolism, and excretion 
AE 
Adverse event 
AML 
Acute myelogenous leukemia 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
ARA 
Acid Reducing Agents 
ASCO 
American Society of Clinical Oncology 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
BCR 
B-cell receptor 
BL 
Burkitt lymphoma 
CK 
Creatine kinase 
CL 
Clearance 
Cmax 
Maximum observed drug concentration 
CRC 
Colorectal cancer 
CT 
Computed tomography 
CTA 
Clinical trial application 
CTCAE 
Common Terminology Criteria for Adverse Events 
DL1 
Dose level 1 
DL-1 
Dose level minus 1 
DLBCL 
Diffuse large B-cell lymphoma 
DLT 
Dose-limiting toxicity 
DMSO 
Dimethyl sulfoxide 
DSMB 
Data Safety Monitoring Board 


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ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
Electronic case report form  
eGFR 
Estimated glomerular filtration rate 
EOT 
End of treatment 
FDA 
Food and Drug Administration 
FL 
Follicular lymphoma 
FLIPI 
Follicular lymphoma International Prognostic Index 
FSH 
Follicle stimulating hormone 
FU 
Follow-up 
GLP 
Good Laboratory Practices 
GMP 
Good Manufacturing Practice 
HBV 
Hepatitis B virus 
HC 
Health Canada 
HCV 
Hepatitis C virus 
HCG 
Human chorionic gonadotropin 
HED 
Human equivalent dose 
hERG 
Human Ether-à-go-go-Related-gene 
HGBL 
High grade B-cell lymphoma 
HIV 
Human immunodeficiency virus 
HNSTD 
Highest non-severely toxic dose 
IC50 
Half-maximal inhibitory concentration 
ICF 
Informed consent form 
ICH-GCP 
International Conference of Harmonization-Good Clinical Practice 
IEC 
Independent Ethics Committee 
IP 
Intraperitoneal 
IPI 
International Prognostic Index 


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IRB 
Institutional Review Board 
IUD 
Intra-uterine device 
IUS 
Intra-uterine hormone-releasing system 
IV 
Intravenous 
LVEF 
Left ventricular ejection fraction 
MCL 
Mantle cell lymphoma 
MIPI 
Mantle Cell Lymphoma International Prognostic Index 
MTD 
Maximum tolerated dose 
MRI 
Magnetic resonance imaging  
MUGA 
Multi-gated acquisition 
NHL 
Non-Hodgkin lymphoma 
NMT 
N-myristoyltransferase 
NOL 
No Objection Letter 
NYHA 
New York Heart Association 
NSCLC 
Non-small cell lung cancer 
OTC 
Over the counter 
PDX 
Patient derived xenograft 
PD 
Pharmacodynamic 
PET 
Positron emission tomography 
P-gp 
P-glycoprotein  
PI 
Principal Investigator 
PK 
Pharmacokinetic 
PPI 
Proton Pump Inhibitor 
PT/INR 
Prothrombin time / International normalized ratio 
PTT 
Partial thromboplastin time 
REB 
Research ethics board 
RECIST 
Response Evaluation Criteria in Solid Tumours 


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RP2D 
Recommended phase II dose 
R/R 
Relapsed/refractory 
SAE 
Serious adverse event 
SC 
Subcutaneous 
SCLC 
Small-cell lung cancer 
SFK 
Src family kinases 
TLS 
Tumour lysis syndrome 
TPD 
Therapeutic Products Directorate 
TSH 
Thyroid stimulating hormone 
Vd 
Volume of distribution 
 
 
 


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PROTOCOL SYNOPSIS 
PROTOCOL TITLE 
Phase I Trial of PCLX-001 in Relapsed/Refractory B-Cell Non-
Hodgkin Lymphoma and Advanced Solid Malignancies 
PROTOCOL NUMBER 
PCLX-001-01 
TEST PRODUCT 
PCLX-001 
PHASE OF DEVELOPMENT 
I 
NUMBER OF 
PARTICIPANTS 
Part A - Dose Escalation: At least 9 and up to 52 participants 
Part B – Dose Expansion: 40 participants 
STUDY DURATION 
24 months 
RATIONALE 
Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for 
membrane targeting and cell signaling. Because cancer cells often have increased NMT expression, 
NMTs are proposed as anti-cancer agents. PCLX-001 is an oral small molecule NMT inhibitor that 
potently and selectively inhibits the growth of a wide spectrum of cultured cancer cells in vitro, with 
particularly pronounced effects in cells derived from hematological cancers including B-cell 
lymphomas. Pre-clinical models also show notable activity of PCLX-001 in vivo and support further 
clinical development.    
OBJECTIVES 
The primary objectives of this study are to: 
• 
Assess safety and tolerability of oral PCLX-001 in patients with B-cell lymphoma and 
advanced solid tumours 
• 
Determine the maximum tolerated dose (MTD) and / or recommended Phase II dose 
(RP2D) of PCLX-001 in patients with B-cell lymphomas and advanced solid tumours 
• 
Evaluate the pharmacokinetics (PK) of PCLX-001 in patients with B-cell lymphomas and 
advanced solid tumours 
The secondary objective of the study is to: 
• 
Evaluate the preliminary single agent anti-tumour activity of PCLX-001 in the patient 
populations studied 
The exploratory objective of this study is to: 
• 
Assess the pharmacodynamic (PD) effects of PCLX-001 in patients with B-cell lymphomas 
and advanced solid tumours 
STUDY DESIGN 
This is a dose-escalation, safety and tolerability study of oral PCLX-001 in patients with B-cell 
lymphoma and advanced solid malignancies. This study will be conducted in a multicenter, non-
randomized, open-label, non-controlled design. There are two parts to study, Part A dose escalation 
and Part B dose expansion.  
Part A dose-escalation will determine the MTD and RP2D. Patient will be accrued in a standard 
3+3 design based on toxicities experienced during the first cycle. For each dose-escalation cohort, 
treatment with the first dose of PCLX-001 will be staggered such that the second participant enrolled 
in the cohort will receive PCLX-001 at least two weeks after the first participant and all subsequent 
participants at least one week after the previous participant.  


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PCLX will be administered as an oral daily dose on a 28-day cycle as per the dose level schedule 
below.  
Dose Level Escalation Schedule (1 cycle = 28 days) 
Dose Level** 
Daily Oral Dose (mg) 
Number of Capsules 
 
 
10 mg 
70 mg 
-1 
10 
1 
0 
1 (starting dose)* 
20 
2 
0 
2 
40 
4 
0 
3 
70 
0 
1 
4 
100 
3 
1 
5 
140 
0 
2 
6 
210 
0 
3 
7 
280*** 
0 
4 
* Trial will start at Dose Level 1 and will de-escalate to Dose Level -1 if DLT is observed. 
** If ≥ 2 out of 6 DLTs are observed in Dose Level -1, 1 or 2 then consideration will be given to 
changing dosing schedule (eg. 28-day schedule with each week comprising 4 days on medication 
and 3 days off medication). 
*** If DLT is not observed at the dose of 280 mg, the dose will be considered the MTD. If required, the 
MTD cohort may be expanded by an additional 10 patients for further toxicity and response 
assessment. 
Part B dose expansion Cohort A will occur once MTD and RP2D has been determined. Part B 
dose expansion Cohort B will occur once dose escalation has achieved a dose that has both 
acceptable safety and achieves drug exposures predicted to have activity in R/R B-cell 
lymphomas. 
Two expansion cohorts of 20 patients will be opened to determine preliminary clinical activity of 
PCLX-001.  
- 
Expansion Cohort A will be patients with advanced breast, NSCLC, SCLC, CRC, and 
bladder cancer.  
- 
Expansion Cohort B will be patients with R/R B-cell lymphomas. These will include 
patients with DLBCL, HGBL, FL, MCL, and BL. 
STUDY POPULATION 
The following eligibility criteria apply to ALL patients (Part A and Part B as specified). 
Select Inclusion Criteria (refer to protocol for full criteria) 
1. Ability to understand and the willingness to sign a written informed consent. A signed informed 
consent must be obtained before any study-specific procedures are performed. 
2. Male or female patients aged ≥ 18 years  
3. Dose Escalation 
a. Participants with histologically-confirmed advanced solid tumor (non-breast cancer) who 
have failed at least one prior therapy and/or are not eligible for therapies expected to 
provide clinical benefit. 
b. Participants with histologically-confirmed metastatic breast cancer with known hormone 
receptor status meeting the therapy requirements as listed below (just prior to criterion #4). 
c. Histologically-confirmed B-cell lymphomas that are expected to express CD20 including 
DLBCL, HGBL, FL (grades 1 to 3b), MCL, and Burkitt lymphoma who have failed at least 
two prior therapies and/or are not eligible for therapies expected to provide clinical benefit 
(including autologous stem cell transplantation). Transformed large B-cell lymphoma 
patients are eligible. FL patients should meet criteria for requiring treatment. These 
histologic subtypes are based on WHO 2016 criteria. 
Dose Expansion 
Cohort A: Participants with histologically-confirmed advanced NSCLC, SCLC, colorectal, 
and bladder cancers who have failed at least one prior therapy and/or are not eligible for 
therapies expected to provide clinical benefit. Participants with histologically-confirmed 


Clinical Protocol 
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metastatic breast cancer with known hormone receptor status meeting the therapy 
requirements as listed below (just prior to criterion #4). 
 
Cohort B: Participants with histologically-confirmed R/R B-cell lymphomas that are 
expected to express CD20 including DLBCL, HGBL, FL (grades 1-3a), FL (grade 3b), MCL, 
and Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for 
therapies expected to provide clinical benefit. Transformed large B-cell lymphoma patients 
are eligible. FL patients should meet criteria for requiring treatment. These histologic 
subtypes are based on WHO 2016 criteria. 
Therapy requirements and stratification factors for histologically-confirmed metastatic 
breast cancer participants in either the dose escalation or dose expansion phases are 
dependent upon hormone receptor status as follows: 
i. 
Estrogen Receptor positive and/ or Progesterone Receptor positive, and HER 2 
negative disease.  
Prior treatment with: 
• 
Two or more lines of endocrine therapy in the adjuvant or metastatic setting 
including the following: Selective Estrogen Receptor Modulators (eg. tamoxifen), 
Aromatase Inhibitors (eg. letrozole, anastrozole, exemestane), Selective Estrogen 
Receptor Downregulators (fulvestrant), and CDK4/6 inhibitors (palbociclib, 
ribociclib, abemaciclib) in combination or monotherapy, and 
• 
at least three lines of cytotoxic chemotherapy given in the adjuvant, neoadjuvant, 
or metastatic setting including an anthracycline, a taxane, and capecitabine. 
ii. 
Estrogen Receptor and Progesterone Receptor and HER2 negative disease. 
• 
Prior treatment with at least three lines of cytotoxic chemotherapy in the adjuvant 
or metastatic setting including the following agents: anthracyclines, taxanes, 
platinum (carboplatin or cisplatinum), and 
• 
if known BRCA1 or BRCA2 mutated disease, prior PARP inhibitor therapy is 
required if available to the patient. 
iii. 
HER2 positive disease with negative Estrogen receptors. 
• 
Prior treatment with three or more lines of HER2-directed therapy in the adjuvant, 
neoadjuvant, or metastatic setting including at least three of the following HER2 
directed agents: trastuzumab, trastuzumab emtansine, trastuzumab deruxtecan, 
pertuzumab, lapatinib, neratinib, tucatinib. 
iv. 
HER2 positive disease with positive Estrogen receptors. 
Prior treatment with: 
• 
three or more lines of HER2-directed therapy in the adjuvant, neoadjuvant, or 
metastatic setting including at least three of the following HER2 directed agents: 
trastuzumab, trastuzumab emtansine, trastuzumab deruxtecan, pertuzumab, 
lapatinib, neratinib, tucatinib, and 
• 
two or more lines of endocrine therapy in the adjuvant or metastatic setting 
including the following: Selective Estrogen Receptor Modulators (eg. tamoxifen), 
Aromatase Inhibitors (eg. letrozole, anastrozole, exemestane), Selective Estrogen 
Receptor Downregulators (fulvestrant), and CDK4/6 inhibitors (palbociclib, 
ribociclib, abemaciclib) in combination or monotherapy, and 
• 
at least three lines of cytotoxic chemotherapy given in the adjuvant, neoadjuvant, 
or metastatic setting including an anthracycline, a taxane, and capecitabine. 
4. Patients must have evaluable or measurable disease (as per Response Evaluation Criteria in 
Solid Tumors, version 1.1 [RECIST 1.1], or the Lugano lymphoma classification.  
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 
6. Life expectancy of at least 12 weeks 
7. Patients must have adequate bone marrow function as assessed by the following laboratory 
tests to be conducted within 7 (±3) days before the first dose of study drug: 
a. Hemoglobin ≥ 85 g/L 
b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
c. Platelet count ≥ 100 x 109/L Platelet count ≥ 100 x 109/L for Dose Escalation and ≥ 75 x 
109/L for Dose Expansion  


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NOTE: For Dose Expansion, patient who do not meet the above hematological criteria, 
because of bone marrow suppression from prior therapies and/or extensive tumour 
involvement in the marrow, may be considered for enrollment in the trial after consultation 
with the Medical Monitor. 
8. Patients must have adequate kidney function, as assessed by both: a) the estimated 
glomerular filtration rate (eGFR) ≥50 mL/min within 7 (±3) days before the first dose of study 
drug (eGFR to be calculated by the Cockcroft-Gault formula), and b) creatinine ≤ 1.5 times the 
ULN. 
9. Patients must have adequate coagulation, as assessed by the following laboratory tests to be 
conducted within 7 (±3) days before the first dose of study drug: 
a. Prothrombin time/International normalized ratio (PT/INR) ≤ 1.5 for patients not on 
anticoagulation 
b. Activated partial thromboplastin time (aPTT) ≤ 1.5 times ULN for patients not on 
anticoagulation 
Note: Patients on anticoagulation with an agent such as heparin (eg. enoxaparin, 
dalteparin, etc.) will be allowed to participate if no prior evidence of underlying abnormality 
in coagulation parameters exists.  
10. Adequate cardiac function per institutional normal measured by echocardiography or 
multigated acquisition (MUGA) scan (LVEF ≥ 50%) 
11. Women of childbearing potential must have a negative serum beta human chorionic 
gonadotropin (β-HCG) pregnancy test obtained within 7 (±3) days before the start of 
administration of study drug. 
12. Women of childbearing potential and fertile men must agree to use adequate contraception 
when sexually active from signing of the informed consent form for the full study until at least 6 
months after the last study drug administration. Patients must agree to utilize 2 reliable and 
acceptable methods of contraception simultaneously.  
 
Select Exclusion Criteria (refer to protocol for full criteria) 
1. Known hypersensitivity to the study drugs or excipients of the preparations or any agent given 
in association with this study 
2. History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class 
> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months 
before study entry), myocardial infarction within the past 6 months before study enrollment 
date, or uncontrolled cardiac arrhythmias 
3. Uncontrolled arterial hypertension despite optimal medical management (per investigator’s 
opinion) 
4. Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C 
5. Patients with known human immunodeficiency virus (HIV) infection 
6. Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 
requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator’s 
discretion provided that the disease is stable and sufficiently controlled under treatment. 
7. Patients with significantly impaired liver function as assessed by the following laboratory tests 
to be conducted within 7 (±3) days before the first dose of study drug: 
• 
Total bilirubin ≥ 1.5 times the upper limit of normal (ULN), and/or 
• 
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 times ULN or ≥ 
5 times ULN for patients with malignant liver involvement. 
8. Infections of CTCAE Grade 2 not responding to therapy or active clinically serious infections of 
CTCAE Grade > 2 
9. Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from 
definitive therapy, has a stable imaging study within 4 weeks prior to the first dose of study 
drug and is clinically stable with respect to the tumor at the time of study entry. Patients with 
asymptomatic brain metastases must not be on steroid therapy. Patients with neurological 
symptoms should undergo a CT / MRI scan of the brain to exclude new or progressive brain 
metastases. 
10. Current or past history of central nervous system (CNS) lymphoma 
11. Uncontrolled seizure disorder requiring therapy (e.g. strong CYP3A4 inducers such as 
carbamazepine and phenytoin) 


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12. History of organ allograft transplantation or autologous stem cell transplantation ≤ 3 months 
prior to the first dose of study drug. Patients who received prior CAR-T or other T-cell 
targeting treatment (approved or investigational) ≤ 4 weeks prior to study drug administration 
13. Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE 
Grade > 2 within 4 weeks before the first dose of study drug 
14. Serious, non-healing wound, ulcer, or bone fracture 
15. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being 
evaluated in this study, with the exception of the following previous or concurrent cancer 
types: 
• 
Curative treatment for localized cancer completed without signs of recurrence and 
treatment-related toxicity and low risk of recurrence as assessed by the investigator, 
• 
In-situ prostate cancer, Gleason Score <7, prostate-specific antigen <10 ng/mL (very low 
risk and low risk, according to therapy guidelines, e.g. the National Comprehensive Cancer 
Network guideline; active surveillance / observation is a recommended option). 
16. Any clinical condition that is considered unstable or might jeopardize the safety of the patient 
and his / her compliance in the study 
17. Inability to swallow oral medications 
18. Any malabsorption condition 
19. Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after 
last study drug administration.  
20. Treatment with anticancer chemotherapy or immunotherapy during the study or within 3 
weeks before the first dose of study drug. For small-molecule drugs, a period of at least 3 half-
lives before the first dose of study drug is acceptable. Mitomycin C or nitrosoureas should not 
be given within 6 weeks before the first dose of study drug. 
21. Treatment with systemic steroids (prednisone dose ≥10 mg/day or equivalent dose). 
22. Acute toxic effects (CTCAE Grade ≥2) of previous anticancer chemotherapy or 
immunotherapy that have not yet stabilized or if significant post-treatment toxicities have been 
observed. (Note however that toxic effects of previous anticancer therapy considered as 
chronic, such as chemotherapy-induced neuropathy, fatigue, alopecia, or anorexia of CTCAE 
Grade <2, for which further resolution is not expected, do not prevent participation in this 
study.) 
23. Radiotherapy to target lesions in the 21 days before starting the first dose of study drug. 
Palliative radiotherapy is allowed to non-target lesions at any time before starting the first dose 
of study drug. 
24. Major surgery or significant trauma within 4 weeks before the first dose of study drug 
25. Previous assignment to treatment during this study 
26. Concomitant participation in another clinical study with investigational medicinal product(s) 
27. Substance abuse, medical, psychological, or social conditions that may interfere with the 
patient’s participation in the study or evaluation of the study results 
28. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent 
person (e.g. employee or student of the investigational site) 
29. Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of 
study drug. Strong CYP3A4 inhibitors and inducers are prohibited during the study and until 
the active FU visit. 
30. Use of Proton Pump Inhibitors (PPIs) must be discontinued at least 48 hours prior to initiation 
of study drug.  
Note: If a potential participant is on a PPI and requires some form of Acid Reducing Agent(s) 
(ARAs), the investigator should consider alternatives for the duration of the trial, including 
Famotidine, or oral antacid drugs such as calcium carbonate.  
31. Clinically relevant findings in the ECG such as a second- or third-degree atrioventricular block, 
prolongation of the QRS complex > 120 ms (except for bundle branch block pattern), or 
prolongation of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise 
between the investigator and the sponsor’s medically responsible person. 
 
 
 


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1. 
INTRODUCTION 
1.1  
Myristoylation and Cancer  
Myristoylation, the N-terminal modification of proteins with the fatty acid myristate, is critical for 
membrane targeting and cell signaling (Beauchamp et. al, 2020). Up to 600 proteoforms in 
humans are myristoylated and the proper membrane targeting and functions of these proteins 
require myristoylation. Src-family kinases (SFK), Abl, Gɑ subunits, Arf GTPases, caspase 
truncated (ct-) Bid, and ct-PAK2 are examples of myristoylated proteins that critically regulate cell 
growth and apoptosis.  
In humans, protein myristoylation is mediated by two ubiquitously expressed N-myristoyl-
transferases (NMT), NMT1 and NMT2. Aberrant myristoylation has been identified in human 
cancer cells including non-Hodgkin lymphoma (NHL) and solid tumours.  Increased NMT 
expression and activity is needed for the localization and function of over-expressed myristoylated 
oncogenes, such as c-Src which must be localized to the plasma membrane in order to 
phosphorylate downstream targets. Hence, inhibition of myristoylation represents a novel 
anticancer treatment strategy.  
1.2 
PCLX-001 Overview 
NMTs are essential for the viability of parasites, and small molecule inhibitors such as DDD85646 
were developed in the Dundee Drug Development program as a Trypanosoma brucei NMT 
inhibitor to treat African sleeping sickness. However, these compounds were not pursued further 
because of a lack of brain penetration required for effective management of advanced African 
trypanosomiasis.   
PCLX-001 is an orally bioavailable derivative of the NMT inhibitor DDD85646, and is more 
selective and potent towards human NMTs.  Preclinical data show that PCLX-001 inhibits the 
viability and growth of hematological cancer cells and other solid cancers. It has been selected 
from other analogs for the treatment of human cancer because of its high affinity for human NMTs, 
high bioavailability, and drug like pharmacokinetic properties. 
1.2.1 PCLX-001 Mechanism of Action and Properties 
Mechanism of Action: 
PCLX-001 inhibits both NMT1 and NMT2 with an IC50 of 5nM and 8nM, respectively (Table 1). It 
completely abrogates myristoylation in cultured human cells within 15 minutes. Given that cancer 
cells are selectively killed at concentrations lower than required to kill and inhibit the proliferation 
of normal cells, PCLX-001 offers a therapeutic window to support development of PCLX-001. 
In cultured human lymphoma cells, PCLX-001 inhibits B-cell receptor signaling and also induces 
apoptosis. Figure 1 demonstrates a model depicting the proposed mechanism of action in B-cell 
lymphoma.  
 
 


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Table 1: PCLX-001 Drug Substance 
Property 
 
Chemical Name 2,6-dichloro-N-(3-isobutyl-1,5-dimethyl-1H-pyrazol-4-yl)-4-(2-
(piperazin-1-yl)pyridin-4-yl)benzenesulfonamide                            
Empirical 
Formula 
C24H30Cl2N6O2S 
Chemical 
Structure 
 
Molecular 
Weight 
537.5 daltons (free base) 
 
 
 


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Figure 1: Model depicting proposed PCLX-001 mechanism of action in B cell lymphoma. a Upon 
BCR activation, first the myristoylated SFK Lyn is recruited to the lipid raft domains of the plasma membrane 
containing the BCR, dephosphorylated Lyn at Y507 leads to its activation and autophosphorylation at Y396. 
This leads to the phosphorylation and activation of BTK at Y551 and Y223. Second, myristoylated HGAL is 
also recruited to the plasma membrane and phosphorylated thereby enhancing BCR signaling by 
stimulating SYK, BTK and the release of Ca++ ions from the endoplasmic reticulum via the inositol-3-
phosphate ion channel receptor (IP3R). Altogether these early signaling events lead to transcription 
activation by c-Myc, P-ERK, NFκB, and CREB. b The NMT inhibitor PCLX-001 prevents the myristoylation 
of Lyn-SFK (as well as other SFKs not shown in this model), HGAL and Arf1 thereby impeding the proper 
membrane targeting and function of these proteins. PCLX-001 treatment impedes calcium homeostasis by 
reducing the BCR mediated Ca++ release from the ER and increasing basal Ca++ levels in cells in addition 
to promote the degradation of both myristoylated (Lyn, HGAL, Arf1) and, surprisingly, non-myristoylated 
proteins (NFκB, P-ERK, c-Myc and CREB), some via the ubiquitin-proteasome pathway thereby further 
abrogating downstream BCR signaling and increasing ER stress leading to apoptosis and cell death. 
1.2.2 Preclinical Studies 
In vitro Efficacy in Cultured Human Cancer Cells   
PCLX-001 was studied using 68 cell lines on the Horizon (St. Louis, MO) platform and 
recapitulated using a 101 cell line Oncolines™ screen. Drug sensitivity varied across lines, but 
was significantly higher in cells of hematologic cancer origin. However, high sensitivity and cell 
kill was also seen in solid tumour lines derived from lung, pancreas, breast, colon, and bladder 
carcinomas as well as melanoma (Figure 2).  


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Figure 2: PCLX-001 selectively kills hematological and solid cancer cell lines. Percentage of 
maximum growth inhibition of various cell lines following 96 h treatment with 1.2 μM PCLX-001 as 
determined using a Horizon cell line screen (a, b), or following 72 h treatment with 1 μM of PCLX-001 using 


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a OncolinesTM cell line screen (c, d). Cell lines are arranged according to tumor cell type. Cross-hatched 
zone represents cytotoxic effect. Hematological cancer cell lines are depicted in gray while all other types 
of cancer cell lines are depicted in white. Corresponding violin graphs compare the average PCLX-001-
mediated growth inhibition on hematological cancer cell lines to cancer cell lines of other origins combined 
as calculated from the Horizon (b) and OncolinesTM (d) cell screens (Unpaired t test, two-tailed P < 
0.0001). Quartiles are separated by dotted lines. Error bars represent standard deviation within each group. 
Normalized cell viability curves of immortalized lymphocyte (IM9, VDS), BL (BL2, Ramos, BJAB), and 
DLBCL (DOHH2, WSU-DLCL2, SU-DHL-10) cell lines treated with 0.001–5 μM of PCLX-001 for 96 h as 
determined by CellTiter Blue Viability Assay (e). Corresponding histograms of absolute IC50 (and SD) 
values calculated from a log(inhibitor) vs response (three parameters) equation cell viability curves plotted 
in e (f). ***Indicates a significant difference (P ≤ 0.001) in IC50 between IM9 cells and all other cell lines 
tested (Ordinary oneway Anova, Tukey’s multiple comparisons test, P < 0.0001). Normalized proliferation 
of IM9 (g) and BL2 (h) cells reated with 0–5 μM of PCLX-001 for 96 h as determined by cell count. Values 
are mean ± s.e.m. of three independent experiments 
 
In vivo Efficacy with Cell Line Derived Xenografts (CDX) 
PCLX-001 mitigates tumor progression in vivo in two lymphoma cell line derived subcutaneous 
tumor xenograft models. These models were developed by injecting 1 x 107 DOHH2 (DLBCL: 
diffuse large B-cell lymphoma) or BL2 (BL: Burkitt lymphoma) NMT2-deficient cells 
subcutaneously in the flank of NOD/SCID mice (10 mice per group). PCLX-001 was injected 
subcutaneously once a day into the opposite flank. In mice bearing DOHH2 tumors (125–200 
mm3), PCLX-001 had a significant, tumoricidal effect at 20 mg/kg daily or 50 mg/kg every other 
day (P<0.001). When injected daily at 50 mg/kg, PCLX-001 shrank tumors by 70% from their 
original size (average tumor size at day 7 = 44.0 ± 8.1 mm3). Similarly, in mice bearing BL2 
xenografts, PCLX-001 showed partial total growth inhibition (TGI) at 20 mg/kg reaching 42.5% by 
day 9 (P=0.016) (Figure 3). PCLX-001 given at 50 or 60 mg/kg for 13 consecutive days caused 
100% tumor regression in 9 of 9 and 7 of 7 surviving mice, respectively. Therefore, the optimal 
biological dose appears to be 50 mg/kg in NOD/SCID mice. 
 
Figure 3: PCLX-001 inhibited tumor growth of DOHH2 and Burkitt lymphoma murine xenografts. 
DOHH2 (a) and BL2 cells (b) were injected subcutaneously (sc) into the flanks of 10 NOD/SCID mice per 
group. PCLX-001 was injected sc once daily into the opposite flank at 20-60 mg/kg/day. Survival was 
significantly improved compared to vehicle: * p0.01; *** p< 0.0001 
 
 


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In vivo Efficacy with Patient Derived Xenografts 
Since cell line derived xenografts lack the complexity of human tumours, PCLX-001 was studied 
in a patient derived xenograft model (PDX). This was established from patient “DLBCL3” whose 
cancer 
was 
refractory 
to 
multiple 
lines 
of 
chemotherapy 
[R-CHOP 
(Rituxumab, 
Cyclophosphamide, 
Hydroxydaunorubicin, 
Vincristine, 
Prednisone); 
R-ICE 
(Rituximab, 
Ifosfamide, Carboplatin, Etoposide); DHAP (Dexamethasone, Cytarabine, Cisplatin)] and 
propagated in NODscid mice. The mean initial “DLBCL3” tumor volume was 240 mm3. PCLX-001 
treatment regimens were assessed in groups of 8 mice each. At a 20 mg/kg subcutaneous daily 
dose for 21 days, PCLX-001 caused a TGI of 66% (P<0.001). At 50 mg/kg subcutaneously daily 
for two 9-day periods separated by a 3-day treatment suspension, PCLX-001 caused the tumors 
to regress completely in 6 of 7 surviving mice at day 13; one mouse with no detectable tumor died 
at day 7. In surgically removed control and PCLX-001-treated PDX tumors, there was confirmation 
of concentration-dependent reduction in tumor size. In the only remaining tumor from the 50 
mg/kg treatment, PCLX-001 effectively induced apoptosis and reduced malignant cell 
proliferation. 
1.2.3 PCLX-001 Pharmacokinetics and Pharmacology 
Mouse Pharmacokinetics 
PCLX-001 was dosed as a bolus solution intravenously at 3 mg free base/kg (5% DMSO; 95% 
sterile water) or by gavage orally as a solution at 10 mg free base/kg (5% DMSO; 40% PEG400; 
55% sterile water) to female NMRI mice (n=3/dose route).  Blood samples (10 µL) were taken 
from each mouse at 5 (IV only), 15, 30 minutes, 1, 2, 4, 6 and 8 hours post-dose, mixed with two 
volumes of distilled water and stored frozen until analysis. 
Following intravenous administration at 3 mg free base/kg, PCLX-001 mean blood clearance was 
low at 3mL/min/kg (~3% liver blood flow), mean volume of distribution (Vss) was low at 0.4 L/kg, 
resulting in a moderate mean half-life at 1.6 hours.  Mean AUC0-8 was 1,119,500 ng.min/mL. 
Following oral administration at 10 mg free base/kg, PCLX-001 had a mean Cmax of 11,200ng/mL 
and median tmax at 2 hours. Mean AUC0-8 was 3,400,810 ng.min/mL and mean bioavailability 
recorded at 91%. 
PCLX-001 was not brain penetrant in mouse models (B:B ratio following a 1 mg/kg IV dose is 
0.04 at 5- and 30-minutes post-dose).   
Rat Pharmacokinetics 
PCLX-001 was dosed as a bolus solution intravenously at 1 mg free base/kg (5% DMSO; 95% 
saline) or by gavage orally as a solution at 3 mg free base/kg (5% DMSO; 95% sterile water) to 
male Sprague Dawley rat (n=2 IV; n=3 PO).  Blood samples (10 µL) were taken from each rat at 
5 (IV only), 15, 30 minutes, 1, 2, 4, 6 and 8 hours post-dose, mixed with two volumes of distilled 
water and stored frozen until analysis. 
Following intravenous administration at 1 mg free base/kg, PCLX-001 mean blood clearance was 
low at 15 mL/min/kg (~18% liver blood flow), mean volume of distribution (Vss) was moderate at 
1.3 L/kg, resulting in a moderate mean half-life at 1 hour.  Mean AUC0-8 was 67,230 ng.min/mL.  
Blood clearance was well aligned to hepatic extraction (EH) at 16%, determined from a separate 
male Sprague Dawley rat hepatic portal vein study following oral dosing at 3 mg free base/kg. 
Following oral administration at 3 mg free base/kg, PCLX-001 had a mean Cmax of 170ng/mL and 
median tmax at 4 hours. Mean AUC0-8 was 52,868 ng.min/mL and mean bioavailability 26%. 
 
 


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Dog Pharmacokinetics 
PCLX-001 was dosed as a bolus solution intravenously at 1 mg free base/kg (in saline) or by 
gavage orally as a solution at 10 mg free base/kg (in saline) to male beagle dog (n=3/dose route).  
Blood samples (10 µL) were taken from each dog at 5, 15, 30 minutes, 1, 2, 4, 6, 8 and 24 hours 
post-dose, mixed with two volumes of distilled water and stored frozen until analysis. 
Following intravenous administration at 1 mg free base/kg, PCLX-001 mean blood clearance was 
moderate at 22 mL/min/kg (~58% liver blood flow), mean volume of distribution (Vss) was 
moderate at 4.3 L/kg, resulting in a moderate mean half-life at 2.3 hours.  Mean AUC0-24 was 
42,140 ng.min/mL. 
Following oral administration at 10mg free base/kg, PCLX-001 had a mean Cmax of 1229ng/mL 
and median tmax at 1.7 hours. Mean AUC0-24 is 560,220 ng.h/mL and mean bioavailability was 
133%. 
Pharmacokinetics Interpretation 
The low volume of distribution observed in mouse (less than body water) appeared to be a mouse 
specific phenomenon.  Improved efficacy may be seen in higher volume species through better 
distribution to the target such that there is no net change in potential therapeutic index. 
In vitro ADME Profile 
PCLX-001 (0.5 µM) has low intrinsic clearance (Clint) in mouse, rat and human when incubated 
with liver microsomes, with Clint  of <0.5, 1.0 and 0.7 mL/min/g respectively (using 52.5 mg 
microsomal protein/g liver).  Cli in mouse and rat is consistent with the low in vivo ClB observed. 
Blood:plasma ratio was 0.59, 0.56, 0.69 and 0.50 in mouse, rat, dog and human respectively.  
PCLX-001 has high (>99%) plasma protein binding in mice, rat, dog, and human plasma after 4 
hour incubation at 5 µM.  
The cytochrome P450 enzymes (CYP) are a super family of hemethiolate enzymes responsible 
for the metabolic clearance of a wide variety of drugs. To characterize the metabolic clearance of 
PCLX-001, the relative contribution of CYP450 enzymes to the overall elimination process and 
the identification of the enzymes responsible for oxidative reactions were studied using native 
recombinant human CYP enzymes. These studies showed that PCLX-001 directly inhibited 
CYP3A4 (IC50 of 12.1 μM), CYP1A2 (40.6 μM), CYP2B (63.02 μM), CYP2C9 (52.3 μM), and 
CYP2C19 (60.7 μM). There was no inhibition of CYP2D6, CYP2E1, CYP2A6, or CYP2C8 (all with 
IC50 > 100μM). 
PCLX-001 is a substrate for P-glycoprotein, as demonstrated by efflux studies in CaCo2 cells. It 
is not a substrate for or OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, MATE1, MATE2K or 
BRCP. Overall, PCLX-001 shows a low probability for drug-drug interaction. 
PCLX-001 was not mutagenic in the Ames test. 
In vitro hERG Testing 
A non-GLP study was done by a group developing a proprietary system for human ether-á-go-
go-related (hERG) analysis (https://www.achlys-inc.com/Cardiomyocytes). The negative controls 
were acetylsalicylic acid and chloramphenicol and the positive control (determined IC50 of 0.9 µM) 
was Thioridazine Hydrochloride. PCLX-001 had a determined IC50 of 9.9 µM. This concentration 
was well above that expected to be achieved in a human phase I trial and suggests that PCLX-
001 is likely not to be cardiotoxic. 
 
 


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KINOMEscan 
PCLX-001 is a small molecule inhibitor that theoretically could also have the ability to inhibit 
kinases, and cause unexpected off-target effects. PCLX-001 was screened in vitro at 
concentrations of 0.5, 10, and 100 µM (269, 5380, and 53,800 ng/mL) for its ability to inhibit the 
activity 468 human kinases.  PCLX-001 at concentrations up to 10 µM (5380 ng/mL) did not inhibit 
any kinase. PCLX-001 at 100 µM (53,800 ng/mL), a concentration ~4000 x greater than the EC50 
of PCLX-001 for BL2 cells, produced meaningful inhibition of only three kinases:  MRCKA, 
PIP5K2B, and SRPK1.  Based on these results, PCLX-001 is unlikely to produce adverse effects 
in patients due to off-target kinase inhibition and appears to be NMT-specific.  
1.2.4 PCLX-001 Toxicology and Safety Profile  
Non-GLP Toxicity and Safety Profile: 
Tissue of control and PCLX-001 treated (with doses up to 50 mg/kg subcutaneous daily injection) 
NOD/SCID mice were studied after formalin fixation and paraffin-embedding, followed by 
immunohistochemical staining. There was no morphologic evidence of toxicity of PCLX-001 on 
small intestine, kidney, liver, or bone marrow.  Blood counts and standard biochemical testing of 
blood from treated and untreated mice revealed no evidence of marrow, renal, or hepatic toxicity. 
PCLX-001 is >90% orally bioavailable in mice and dogs and 26% in rats, has a half-life from oral 
dosing of 10 mg/kg of 5.7 hours in mice and 3.9 hours in dogs, and is well-tolerated by mice, rats, 
and dogs with a maximum tolerated dose in 14-day repeat dose toxicity studies of >75 mg/kg in 
rats and 4 mg/kg in dogs. Based on a body surface area scaling of the 50 mg/kg dose that resulted 
in complete tumor remission in most mouse xenografts of hematologic malignancies (BL, DLBCL, 
AML), the effective human dose is projected to be ~4 mg/kg daily (250 mg for a 70 kg individual).  
GLP Non-Clinical Safety Testing: 
PCLX-001 was evaluated for safety in 4-week oral toxicity studies with 2-week recovery periods 
in rats at 50, 125, and 300 mg/kg/day and dogs at 2, 4, 8, and 12 mg/kg/day, performed to GLP 
standards (Weickert et al, 2020). The highest non-severely toxic dose levels (HNSTDs) were 125 
mg/kg/day for male rats, 300 mg/kg/day for female rats, and 4 mg/kg/day for dogs of both sexes. 
At higher dose levels, dose-limiting toxicity occurred within the first few days, was similar in both 
species, and was attributed to GI mucosal damage and decreased hematopoiesis, with secondary 
complications such as dehydration and inflammation.  
In dogs, systemic exposure to PCLX-001 increased more-than-proportionally with dose level after 
the first dose and did not change with repeated daily dosing. After the last dose at the HNSTD, 
Cmax averaged 651 ng/mL and 24-hour AUC averaged 3,760 h*ng/mL. In rats, systemic exposure 
to PCLX-001 after the first dose increased approximately proportionally with dose level and was 
much greater in males than females at all dose levels. With repeated daily dosing, exposure 
decreased dramatically in male rats but less so in female rats. As a result, exposure to PCLX-001 
was similar in rats of both sexes after the last dose. After the last dose at the HNSTD in males 
and females, Cmax was 1650 and 8510 ng/mL, respectively, and 24-hour AUC averaged 6470 and 
7590 h*ng/mL, respectively. When expressed on the basis of body surface area, the HNSTDs in 
male rats, female rats, and dogs were 750, 1800, and 80 mg/m2, respectively.  
As recommended in the ICH S9 Guidance, the starting human dose level of 20 mg/m2 would be 
appropriate since this approximates 1/6th of the HNSTD in dogs 
In rat and dog GLP studies, there were no coagulation toxicities noted with PCLX-001. Similarly, 
no significant cardiac findings were elicited in dogs. ECGs at baseline were similar to those after 
4 weeks of dosing or at the end of the recovery period.  
 
 


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1.3 
Study Rationale  
1.3.1 Rationale for Patient Selection in Dose Escalation  
Patients selected for study have relapsed/refractory B-cell lymphomas and advanced solid tumors 
who have failed or are not eligible for therapies expected to provide clinical benefit. This protocol 
will not include patients with leukemia for which an independent phase I study is planned. 
Given the strong in vitro and in vivo single-agent antitumor activity and tolerability of PCLX-001, 
it is hypothesized that in this first-in-human trial, PCLX-001 will be safe, tolerable and 
demonstrates preliminary clinical activity in human patients with specified relapsed/refractory 
(R/R) non-Hodgkin lymphoma (NHL) and advanced solid malignancies.  
Pacylex Pharmaceuticals, Inc. will not study PCLX-001 in a pediatric population in this initial 
phase I study. As this is a novel agent and target, Pacylex Pharmaceuticals, Inc. will consider 
pediatric and adolescent patients once safety has been adequately established in adult patients.  
1.3.2 Rationale for Patient Selection in Dose Expansion 
PCLX-001 has been studied in a number of pre-clinical studies, and these data provide 
justification for the selected patient population. 
Solid tumors: Selected by pre-clinical sensitivity in cell lines 
Three large tumor cell line robotic screens have been performed with PCLX-001, as well as 
several cell line derived murine xenograft studies as well as patient derived murine xenograft 
studies. In aggregate, these data suggest sensitivity in breast, non-small cell lung, small-cell lung, 
colorectal, and bladder cancers (Figure 4). 
 
Figure 4. Breadth of efficacy screen demonstrates that PCLX-001 is active against various other 
cancer cell lines including those derived from solid tumors.  Absolute IC50 values of various cell lines 
treated for 3 days (A, B) or 6 days (C, D) with 0.0005 - 10µM PCLX-001.  Cell lines are arranged according 


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cancer type.  Individual bars represent a single cancer cell line derived from B cell lymphoma and Mantle 
Cell Lymphoma, Acute Myeloid Leukemia (AML), Breast, Small-cell lung carcinoma (SCLC), Non-small-cell 
lung carcinoma (NSCLC). ChemPartner robotic platform determined cell viability using Cell Titer Blue 
viability assay. 
Further evidence of solid tumor activity is provided by murine models of human lung and breast 
cancers (Figure 5). 
 
Figure 5. PCLX-001 inhibits tumor growth in patient derived small cell lung cancer and breast cancer 
xenograft models.  Established tumor in patient derived xenografts grown in immunodeficient mice were 
treated with daily PCLX. Panel A shows oral therapy of a small-cell lung cancer patient derived xenograft, 
showing efficacy superior to that of cisplatin.  Panel B shows the efficacy of subcutaneous PCLX-001 in a 
cell line derived breast cancer model. 
B-cell Lymphomas 
In three large tumor cell line robotic screens, PCLX-001 potently and preferentially inhibited the 
growth of hematological cell lines, including B-cell lymphomas, in comparison to other types of 
cancer cell lines.  Moreover, PCLX-001 selectively killed lymphoma cells while sparing normal 
cells in vitro, as well as in three human lymphoma xenograft models including a patient-derived, 
drug-resistant tumor. The global myristoylation of lymphoma cell proteins, including that of the 
protein tyrosine kinase Src, was found to be especially sensitive to PCLX-001 treatment. This was 
accompanied by the loss of Src localization to the cell membrane and the targeting of Src, as well 
as other SFKs, for degradation by the proteasome. Without functional SFKs (especially Lyn-SFK), 
pro-survival signaling downstream of the B-cell receptor (BCR) was profoundly attenuated in all 
B-cell lymphoma cell lines, resulting in apoptosis.   
Of potential therapeutic relevance, the effects of PCLX-001 on BCR signaling and lymphoma cell 
survival were more potent than those of dasatinib and ibrutinib, two clinically approved drugs. By 
inhibiting critical signaling processes immediately downstream of the BCR, PCLX-001 mediated 
NMT inhibition may provide an effective, selective and novel therapeutic approach for treatment 
of B-cell lymphoma.  
 
 


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NMT1 and NMT2 Expression 
NMT1 number of transcripts is about eight times the number of NMT2 transcripts in all cell lines. 
As well, there is a heterogeneous but significant reduction of NMT2 expression or low levels of 
NMT2 protein in cancer cell lines, and particularly in hematological cancers.  This may account 
for these tumours being more sensitive to PCLX-001. 
NMT2 deficiency has been identified in a high proportion of human tumors interrogated with 
immunohistochemistry using a NMT2 mAb. Normal breast epithelial elements in 10 normal breast 
mammoplasty specimens were universally NMT2 positive (1-2+) on a 0-3 scale (scored as 0 – 
absent; 1+ weak staining; 2+ moderate staining; 3+ strong staining). Primary breast 
adenocarcinoma samples from participants in the BCIRG 001 clinical trial were studied using 1.0 
mm tissue microarrays with triplicate samples for each tumor. NMT2 immunohistochemistry status 
in malignant cells was scored as 0 absent; 1+ weak staining; 2+ moderate staining; 3+ strong 
staining. NMT2 status was generally homogeneous within each core and concordant across 
triplicates. 509 of the 706 breast cancer adenocarcinomas were NMT2 negative. Using identical 
techniques, 157 of 214 (73%) of non-small cell lung carcinomas, and 23 of 23 colon cancers were 
NMT2 deficient by immunohistochemistry. Preliminary data from a series of bladder urothelial 
carcinomas show a significant proportion lack detectible NMT2 protein. 
Altogether, the reduction in NMT2 expression in hematological cancer cell line and the solid 
tumours described may be more prone to growth inhibition. 
Populations for Expansion Cohorts 
Based on the pre-clinical sensitivity in cell lines and molecular markers associated with PCLX-
001 sensitivity, it is hypothesized that an expansion cohort of solid tumors of breast, non-small 
cell lung, small-cell lung, colorectal, and bladder origin would be particularly susceptible. These 
patients will comprise Expansion Cohort A. 
Also, an expansion cohort of relapsed/refractory B-cell lymphomas will be studied. Patients with 
diffuse large B-cell lymphoma (including transformed DLBCL), high grade B-cell lymphoma 
(HGBL), follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma would similarly be 
expected to be sensitive to PCLX-001. These patients will comprise Expansion Cohort B. 
 
2. 
OBJECTIVES  
The primary objectives of this study are to: 
• 
Assess safety and tolerability of oral PCLX-001 in patients with B-cell lymphoma and 
advanced solid tumours 
• 
Determine the maximum tolerated dose (MTD) and / or recommended Phase II dose 
(RP2D) of PCLX-001 in patients with B-cell lymphomas and advanced solid tumours 
• 
Evaluate the pharmacokinetics (PK) of PCLX-001 in patients with B-cell lymphomas and 
advanced solid tumours 
The secondary objective of the study is to: 
• 
Evaluate the preliminary single agent anti-tumour activity of PCLX-001 in the patient 
populations studied 
The exploratory objective of this study is to: 
• 
Assess the pharmacodynamic (PD) effects of PCLX-001 in patients with B-cell lymphomas 
and advanced solid tumours 


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3. 
STUDY DESIGN 
3.1 
Overview of Study Design 
This is a phase I dose-escalation, safety and tolerability study of oral PCLX-001, conducted in a 
multicenter, non-randomized, open-label, non-controlled design. The study is comprised of two 
parts: Part A (single-agent dose escalation) and Part B (single-agent expansion cohorts).  
For Part A dose-escalation, patients will be accrued in cohorts of 3 to 6 patients to each dose 
level. A new dose level cannot open to accrual until toxicity has been determined in the preceding 
dose level (i.e. all patients have completed their first cycle of therapy and data for all patients in 
that dose level have been reviewed at a safety cohort review meeting). Six patients will be treated 
at the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D). If required, 
the MTD cohort may be expanded by an additional 10 patients for further toxicity and response 
assessment. The MTD cohort expansion may be restricted to B-cell lymphoma or advanced solid 
tumours to ensure there is proper distribution during dose escalation.  
For Part B (single agent expansion cohorts), two expansion cohorts (N=20 each) will be opened 
to determine the preliminary clinical activity of PCLX-001. The Part B dose expansion Cohort A 
will occur once MTD and RP2D has been determined. Part B dose expansion Cohort B will occur 
once dose escalation has achieved a dose that has both acceptable safety and achieves drug 
exposures predicted to have activity in R/R B-cell lymphomas. 
Expansion Cohort A: Participants with advanced solid malignancies showing preclinical 
sensitivity or molecular markers of sensitivity to PCLX-001. This includes breast, non-small cell 
lung (NSCLC), small-cell lung (SCLC), colorectal (CRC), and bladder cancers 
Expansion Cohort B: Participants with relapsed/refractory (R/R) B-cell lymphoma: diffuse large 
B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBL), follicular lymphoma (FL), 
mantle cell lymphoma (MCL), and Burkitt lymphoma. Transformed large B-cell lymphoma will 
also be included. 
3.1.1 Selection of Starting Dose Level and Dosing Considerations  
As recommended by the ICH S9 Guidance, the starting dose level is 1/6th the highest non-severely 
toxic dose (HNSTD) from GLP studies in the most sensitive of tested non-rodent species. The 
HNTSD was 4 mg/kg/day for dogs of both sexes and, when expressed as body surface area, this 
calculates to 80 mg/m2. Consequently, the starting dose level in humans would be approximately 
20 mg/m2. To ensure maximal safety in this first-in-human trial, the starting dose level was chosen 
to be 20 mg daily. PCLX-001 will be supplied as 10 mg and 70 mg capsules which provides the 
range of doses required for dose escalation. 
3.2 
Definition of Dose Limiting Toxicity and Maximum Tolerated Dose 
Toxicities are to be graded according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI CTCAE, Version 5.0).  A copy of the CTCAE version 5.0 can be 
downloaded from the CTEP home page (http://ctep.cancer.gov).  
Dose Limiting Toxicity (DLT) for Part A, dose-escalation, is defined as any of the following  AEs 
related to PCLX-001 treatment occurring in Cycle 1: 
Hematologic 
• 
Grade 4 thrombocytopenia (platelet count < 25 x 109/L) 
• 
Grade ≥ 3 thrombocytopenia (platelet count < 50 x 109/L) associated with any major 
bleeding, and/or requirement for transfusion 
• 
Grade 4 neutropenia (ANC  < 0.5 x 109/L) for ≥ 7 daysa 
• 
Febrile neutropenia. (Per NCI CTCAE, ANC < 1.0 x 109/L and fever ≥ 38.3oC or a 


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sustained temperature of > 38oC for more than one hour).  Febrile neutropenia is by 
definition a grade ≥3 toxicity. 
a Detection of CTCAE Grade 4 neutropenia (only in Cycle 1) will trigger twice-weekly white blood 
cell counts to be performed, and will be considered a DLT if drug interruption lasts ≥ 7 days. 
Non-hematologic 
Any non-hematological toxicity of CTCAE Grade ≥ 3 is considered a DLT, excluding the following: 
• 
Grade ≥3 nausea, vomiting and diarrhea which are controlled with anti-emetics and/or 
other supportive care within ≤72hr 
• 
Brief (i.e. lasting ≤ 72 hours) CTCAE Grade 3 fatigue 
• 
Alopecia of any grade 
• 
Isolated, asymptomatic, biochemical laboratory values including electrolyte abnormalities, 
above or below normal reference ranges, which are judged not clinically significant by the 
Investigator 
• 
Miscellaneous 
• 
Any patient meeting Hy’s law of drug-induced hepatic injury (AST or ALT >3 times ULN 
with bilirubin 2 times ULN; absence of initial cholestasis with ALP >2 times ULN; no other 
explanation) is considered a DLT. 
• 
Any toxicity thought to be related to study drug that, at the discretion of the investigator, 
or his/her designated associate(s), is thought to warrant withholding the drug may be 
declared as a DLT. Such toxicities might for example be CTCAE Grade 1 or CTCAE Grade 
2 toxicities that interfere with the activities of daily life, such as long-lasting fatigue, or 
anorexia, making a dose reduction necessary in order to ensure the patient’s compliance.  
• 
Any toxicity thought to be related to study drug which requires interruption of oral PCLX-
001 for longer than 28 consecutive days from the time of scheduled dosing will be declared 
as a DLT. 
In rare instances, an event may fall within the definition of a DLT as defined above but the event 
may be not be considered dose-limiting (i.e. not clinically meaningful/significant).  If this occurs, a 
meeting with investigators and sponsor will take place to thoroughly review the event, supporting 
data and reasons for not considering the event a DLT. This will be clearly documented with 
supporting rationale. Conversely, other events may occur which do not meet the definition of a 
DLT but are sufficient concern to the investigators and sponsor to be considered a DLT.  
Maximum Tolerated Dose (MTD) is defined as the highest dose tested in which fewer than 33% 
of patients experienced DLT attributable to the study drug(s), when at least six patients were 
treated at that dose and are evaluable for toxicity.  The MTD is one dose level below the lowest 
dose tested in which 33% or more patients experienced DLT attributable to the study drugs.  At 
least six patients will be treated at the MTD. 
Dose escalation and determination of the MTD will be based on the occurrence of DLT's in cycle 
1.  Patient safety will be monitored on an ongoing basis during this study.  If cumulative toxicities 
are seen in subsequent treatment cycles, a decision regarding modification or discontinuation of 
the study drug and/or patient enrollment will be made by the investigator in consultation with the 
sponsor.   
3.3 
Part A: Dose-Escalation and Determination of MTD 
The Dose-Escalation phase will follow a standard 3+3 cohort design. Three patients will be treated 
at each dose level.  If 0/3 patients experience DLT, 3 patients will be treated at the next dose 
level.  If DLT attributable to the treatment is experienced in 1/3 patients, three more patients (for 
a total of six patients) will be treated at that dose level.  If no additional DLT is observed at the 
expanded dose level (i.e. 1/6 with DLT), the dose will be escalated.  Escalation will terminate as 
soon as two or more patients experience any DLT attributable to study drugs, at a given dose 


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level.  DLT and determination of MTD will be based on cycle 1 toxicities.  Intra-patient dose 
escalation will not be allowed. Six patients will be treated at the MTD. The MTD cohort may be 
expanded by an additional 10 patients for further toxicity and response assessment. If MTD is not 
reached, the study team will determine the RP2D for further evaluation in Part B, cohort 
expansion.  If ≥ 2 out of 6 DLTs occur for Dose Levels -1, 1, or 2, the dosing schedule may be 
amended to determine the appropriate scheduling regimen. 
No. of Patients 
with DLT at a 
Given Dose Level 
 
Escalation Decision Rule 
0 out of 3 
Enter patient(s) at the next dose level. 
≥ 2 
Dose escalation will be stopped. This dose level will be declared 
the maximally administered dose (highest dose administered). 
Three additional patients will be entered at the next lowest dose 
level if only 3 patients were treated previously at that dose level.  
1 out of 3 
Enter at least 3 more patients at this dose level. 
• 
If 0 of these 3 patients experiences DLT, proceed to 
the next dose level. 
• 
If 1 or more of this group suffer DLT, then dose 
escalation is stopped and this dose is declared the 
maximally administered dose. Three additional 
patients will be entered at the next lowest dose level if 
only 3 patients were treated previously at that dose.  
≤ 1 out of 6 at highest dose level below 
the maximally administered dose 
This will be the MTD. At least 6 patients will be entered at this 
dose. 
3.4 
Part A Dose Escalation Schedule and Treatment Schema 
Oral PCLX-001 will be provided as continuous daily dosing on a 28-day cycle. The starting dose 
of PCLX-001 will be 20 mg daily (Section 3.1.1). Dose escalation will follow a modified Fibonacci 
design such that the magnitude of escalation decreases as the dose level nears the human 
equivalent dose (HED) of the HNSTD in dogs and then escalate at 1.4 times the previous dose 
until MTD or RP2D is reached. 
The dose level schedule is as below (1 cycle = 28 days):  
Dose Level** 
Daily Oral Dose (mg) 
Number of Capsules 
 
 
10 mg 
70 mg 
-1 
10 
1 
0 
1 (starting dose)* 
20 
2 
0 
2 
40 
4 
0 
3 
70 
0 
1 
4 
100 
3 
1 
5 
140 
0 
2 
6 
210 
0 
3 
7 
280*** 
0 
4 
* Trial will start at Dose Level 1 and will de-escalate to Dose Level -1 if DLT is observed. 
** If ≥ 2 out of 6 DLTs are observed in Dose Level -1, 1 or 2 then consideration will be given to changing 
dosing schedule (eg. 28-day schedule with each week comprising 4 days on medication and 3 days off 
medication). 
*** If DLT is not observed at the dose of 280 mg, the dose will be considered the MTD. If required, the 
MTD cohort may be expanded by an additional 10 patients for further toxicity and response assessment. 


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For each dose-escalation cohort, treatment with the first dose of PCLX-001 will be staggered such 
that the second participant enrolled in the cohort will receive PCLX-001 at least two weeks after 
the first participant and all subsequent participants at least one week after the previous participant.  
Each participant will be treated with the dose of PCLX-001 they are assigned to, until the 
occurrence of a DLT or other study stopping point occurs, at which point the dose of PCLX-001 
will be modified as per protocol or study drug administration will be discontinued. 
If DLT occurs at Dose Level 1, a safety meeting will occur to determine the feasibility of continuing 
the study at Dose Level -1. Alternative dose schedules may also be considered if DLTs occur 
during Dose Levels, -1, 1 or 2. 
Participants who experience a DLT or have received at least 21 days of PCLX-001 during cycle 
1 will be evaluable for toxicity. If a participant does not meet these criteria, the participant may be 
replaced (Section 4.3).    
3.5 
Design of Part B Expansion Cohorts 
Once the MTD has been defined, preliminary activity will be further evaluated in the expansion 
part of the study. If clinically indicated, separate cohort(s) may be open for enrollment to evaluate 
a different schedule of PCLX-001 (for example a break within cycles), based on safety, PK and 
preliminary activity data and integrated PK/efficacy and PK/safety modelling from the dose 
escalation. The RP2D will be defined by the sponsor in conjunction with the investigators after 
reviewing the data from all parts and stages of the study, including available PK data and intensity 
of adverse events (AEs), and efficacy parameters, including overall response rate (ORR). The 
RP2D may be the MTD but not necessarily as not only safety data will be taken into account prior 
to its determination.   
Two expansion cohorts will be opened to determine the preliminary clinical activity of PCLX-001. 
Part B dose expansion Cohort A will occur once the MTD and the RP2D are determined by the 
sponsor and investigators after data review.  
Part B dose expansion cohort B will occur once dose escalation has achieved a dose that has 
both acceptable safety and achieves drug exposures predicted to have activity in R/R B-cell 
lymphomas. See Appendix D for the background, rationale, and determinants of the decision to 
open dose expansion cohort B.   
• 
Expansion Cohort A: 20 participants with advanced solid malignancies showing 
preclinical sensitivity or molecular markers of sensitivity to PCLX-001: breast, non-small 
cell lung, small-cell lung, colorectal, and bladder cancers 
• 
Expansion Cohort B: 20 participants with relapsed/refractory (R/R) B-cell lymphoma: 
diffuse large B-cell lymphoma (including transformed disease), high grade B-cell 
lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma.  
3.6 
Treatment Duration and Discontinuation 
In the absence of treatment delays due to adverse events, treatment may continue unless the 
following reasons to discontinue PCLX-001 occur:  
• 
Disease progression 
• 
Intercurrent illness preventing further administration of treatment 
• 
Unacceptable adverse event(s) 
• 
Patient withdrawal from study (patient choice) 
• 
Treating physician choice 
• 
Delay in subsequent cycles of chemotherapy of longer than 28 days due to toxicity 
• 
Failure of patient to adhere to study requirements 


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3.7 
End of Treatment and Follow-Up 
All patients (except for patients who died, withdrew consent and objected to further data collection, 
or were lost to follow-up) will be followed for 30 days (± 4 days) after the last dose of study drug 
or until all treatment related clinically significant adverse events resolve to Grade ≤ 1. Patients will 
have their medical records evaluated every 6 months (+/- 1 month) for a period starting three 
years from enrollment, to determine survival status (alive, deceased, and date of death). 
 
4. 
STUDY POPULATION 
Patients with histologically confirmed solid tumors or B-cell lymphoma resistant or refractory to 
standard therapy or without standard therapy and in which, in the opinion of the investigator, 
experimental treatment with PCLX-001 may be of benefit will be recruited.  
Patients must have baseline evaluations performed prior to the first dose of study drug and meet 
all eligibility criteria. Results of all baseline evaluations, which assure that all inclusion and 
exclusion criteria have been satisfied, must be reviewed by the Principal Investigator or his/her 
designee prior to enrollment of the patient. The patient must be thoroughly informed about the 
aspects of the study, including the study visit schedule and required evaluations and all regulatory 
requirements for informed consent. The written informed consent must be obtained from the 
patient prior to enrollment. 
4.1 
Inclusion Criteria 
Patient must meet all of the following criteria to be eligible for the study.  
The following inclusion criteria apply to ALL (dose-escalation and expansion) patients: 
1. Ability to understand and the willingness to sign a written informed consent. A signed informed 
consent must be obtained before any study-specific procedures are performed. 
2. Male or female patients aged ≥ 18 years  
3. Dose Escalation 
a. Participants with histologically-confirmed advanced solid tumor (non-breast cancer) who 
have failed at least one prior therapy and/or are not eligible for therapies expected to 
provide clinical benefit. 
b. Participants with histologically-confirmed metastatic breast cancer with known hormone 
receptor status meeting the therapy requirements as listed below (just prior to criterion 
#4).  
c. Histologically-confirmed B-cell lymphomas that are expected to express CD20 including 
DLBCL, HGBL, FL (grades 1 to 3b), MCL, and Burkitt lymphoma who have failed at least 
two prior therapies and/or are not eligible for therapies expected to provide clinical 
benefit (including autologous stem cell transplantation). Transformed large B-cell 
lymphoma patients are eligible. FL patients should meet criteria for requiring treatment. 
These histologic subtypes are based on WHO 2016 criteria. 
Dose Expansion 
Cohort A: Participants with histologically-confirmed advanced NSCLC, SCLC, colorectal, 
and bladder cancers who have failed at least one prior therapy and/or are not eligible for 
therapies expected to provide clinical benefit. Participants with histologically-confirmed 
metastatic breast cancer with known hormone receptor status meeting the therapy 
requirements as listed below (just prior to criterion #4). 
Cohort B: Participants with histologically-confirmed R/R B-cell lymphomas that are expected 
to express CD20 including DLBCL, HGBL, FL (grades 1-3a), FL (grade 3b), MCL, and 


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Burkitt lymphoma who have failed at least two prior therapies and/or are not eligible for 
therapies expected to provide clinical benefit. Transformed large B-cell lymphoma patients 
are eligible. FL patients should meet criteria for requiring treatment. 
Therapy requirements and stratification factors for histologically-confirmed metastatic breast 
cancer participants in either the dose escalation or dose expansion phases are dependent 
upon hormone receptor status as follows: 
i. Estrogen Receptor positive and/ or Progesterone Receptor positive, and HER 2 
negative disease.  
Prior treatment with: 
• 
Two or more lines of endocrine therapy in the adjuvant or metastatic setting including 
the following: Selective Estrogen Receptor Modulators (eg. tamoxifen), Aromatase 
Inhibitors (eg. letrozole, anastrozole, exemestane), Selective Estrogen Receptor 
Downregulators (fulvestrant), and CDK4/6 inhibitors (palbociclib, ribociclib, 
abemaciclib) in combination or monotherapy, and 
• 
at least three lines of cytotoxic chemotherapy given in the adjuvant, neoadjuvant, or 
metastatic setting including an anthracycline, a taxane, and capecitabine. 
 
ii. Estrogen Receptor and Progesterone Receptor and HER2 negative disease. 
• 
Prior treatment with at least three lines of cytotoxic chemotherapy in the adjuvant or 
metastatic setting including the following agents: anthracyclines, taxanes, platinum 
(carboplatin or cisplatinum), and 
• 
if known BRCA1 or BRCA2 mutated disease, prior PARP inhibitor therapy is required 
if available to the patient. 
iii. HER2 positive disease with negative Estrogen receptors. 
• 
Prior treatment with three or more lines of HER2-directed therapy in the adjuvant, 
neoadjuvant, or metastatic setting including at least three of the following HER2 
directed agents: trastuzumab, trastuzumab emtansine, trastuzumab deruxtecan, 
pertuzumab, lapatinib, neratinib, tucatinib. 
 
iv. HER2 positive disease with positive Estrogen receptors. 
Prior treatment with: 
• 
three or more lines of HER2-directed therapy in the adjuvant, neoadjuvant, or 
metastatic setting including at least three of the following HER2 directed agents: 
trastuzumab, trastuzumab emtansine, trastuzumab deruxtecan, pertuzumab, 
lapatinib, neratinib, tucatinib, and 
• 
two or more lines of endocrine therapy in the adjuvant or metastatic setting including 
the following: Selective Estrogen Receptor Modulators (eg. tamoxifen), Aromatase 
Inhibitors (eg. letrozole, anastrozole, exemestane), Selective Estrogen Receptor 
Downregulators (fulvestrant), and CDK4/6 inhibitors (palbociclib, ribociclib, 
abemaciclib) in combination or monotherapy, and 
• 
at least three lines of cytotoxic chemotherapy given in the adjuvant, neoadjuvant, or 
metastatic setting including an anthracycline, a taxane, and capecitabine. 
 
4. Patients must have evaluable or measurable disease (as per Response Evaluation Criteria 
in Solid Tumors, version 1.1 [RECIST 1.1], or the Lugano lymphoma classification.  
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 (Appendix A). 
6. Life expectancy of at least 12 weeks 


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7. Patients must have adequate bone marrow function as assessed by the following laboratory 
tests to be conducted within 7 (±3) days before the first dose of study drug: 
a. Hemoglobin ≥ 85 g/L 
b. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L 
c. Platelet count ≥ 100 x 109/L for Dose Escalation and ≥ 75 x 109/L for Dose Expansion  
NOTE: For Dose Expansion, patient who do not meet the above hematological criteria, 
because of bone marrow suppression from prior therapies and/or extensive tumour 
involvement in the marrow, may be considered for enrollment in the trial after consultation 
with the Medical Monitor. 
8. Patients must have adequate kidney function, as assessed by both: a) the estimated 
glomerular filtration rate (eGFR) ≥50 mL/min within 7 (±3) days before the first dose of study 
drug (eGFR to be calculated by the Cockcroft-Gault formula), and b) creatinine ≤ 1.5 times 
the ULN 
9. Patients must have adequate coagulation, as assessed by the following laboratory tests to 
be conducted within 7 (±3) days before the first dose of study drug: 
a. Prothrombin time/International normalized ratio (PT/INR)  ≤ 1.5 for patients not on 
anticoagulation 
b. Activated partial thromboplastin time (aPTT)  ≤ 1.5 times ULN for patients not on 
anticoagulation 
Note: Patients on anticoagulation with an agent such as heparin (eg. enoxaparin, 
dalteparin, etc.) will be allowed to participate if no prior evidence of underlying abnormality 
in coagulation parameters exists.  
10. Adequate cardiac function per institutional normal measured by echocardiography or 
multigated acquisition (MUGA) scan (LVEF ≥ 50%) 
11. Women of childbearing potential must have a negative serum beta human chorionic 
gonadotropin (β-HCG) pregnancy test obtained within 7 (±3) days before the start of 
administration of study drug. 
Note: A woman is of childbearing potential, i.e. fertile, following menarche and until becoming 
postmenopausal unless permanently sterile. Permanent sterilization methods include but are 
not limited to hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A 
postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be 
used to confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy. 
12. Women of childbearing potential and fertile men must agree to use adequate contraception 
when sexually active from signing of the informed consent form for the full study until at least 
6 months after the last study drug administration. Patients must agree to utilize 2 reliable 
and acceptable methods of contraception simultaneously. A man is considered fertile after 
puberty unless permanently sterile by bilateral orchiectomy. Men being treated with PCLX-
001 are advised not to father a child during and up to 6 months after treatment; prior to 
treatment, advice should be sought for conserving sperm due to the chance of irreversible 
infertility as a consequence of treatment with PCLX-001. Female partners of childbearing 
potential from male study participants have to use adequate contraception / birth control 
between signing of the informed consent and 6 months after the last administration of the 
study drug if the male study participant is not sterilized. 


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The investigator or a designated associate is requested to advise the patient how to achieve 
highly effective birth control. Highly effective (failure rate of less than 1% per year) 
contraception methods, when used consistently and correctly, include: 
• 
Combined (estrogen and progestin containing: oral, intravaginal transdermal and 
progestin-only (oral, injectable, implantable) hormonal contraception associated with 
inhibition of ovulation.  
• 
Intra-uterine device (IUD) or intrauterine hormone-releasing system (IUS). 
• 
Bilateral tubal occlusion or vasectomized partner (provided that partner is the sole sexual 
partner and has received medical assessment of the surgical success). 
• 
Sexual abstinence (reliability to be evaluated in relation to the duration of the clinical trial 
and the preferred and usual lifestyle of the patient). 
Male patients with a female partner of reproductive potential must use a condom and ensure 
that an additional form of contraception is also used during treatment and until 6 months after 
last study drug administration. Patients must agree to utilize reliable and acceptable methods 
of contraception simultaneously. 
4.2 
Exclusion Criteria 
The following exclusion criteria apply to ALL (Dose-escalation and expansion) patients: 
1. Known hypersensitivity to the study drugs or excipients of the preparations or any agent given 
in association with this study 
2. History of cardiac disease: congestive heart failure New York Heart Association (NYHA) class 
> II, unstable angina (angina symptoms at rest), new-onset angina (within the past 6 months 
before study entry), myocardial infarction within the past 6 months before study enrollment 
date, or uncontrolled cardiac arrhythmias 
3. Uncontrolled arterial hypertension despite optimal medical management (per investigator’s 
opinion) 
4. Moderate or severe hepatic impairment, i.e. Child-Pugh class B or C 
5. Patients with known human immunodeficiency virus (HIV) infection 
6. Patients who have an active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection 
requiring treatment. Patients with chronic HBV or HCV infection are eligible at the investigator’s 
discretion provided that the disease is stable and sufficiently controlled under treatment. 
7. Patients with significantly impaired liver function as assessed by the following laboratory tests 
to be conducted within 7 (±3) days before the first dose of study drug: 
• Total bilirubin ≥ 1.5 times the upper limit of normal (ULN), and/or 
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 times ULN or ≥ 
5 times ULN for patients with malignant liver involvement. 
8. Infections of CTCAE Grade 2 not responding to therapy or active clinically serious infections 
of CTCAE Grade > 2 
9. Symptomatic metastatic brain or meningeal tumors unless the patient is > 3 months from 
definitive therapy, has a stable imaging study within 4 weeks prior to the first dose of study 
drug and is clinically stable with respect to the tumor at the time of study entry. Patients with 
asymptomatic brain metastases must not be on steroid therapy. Patients with neurological 
symptoms should undergo a CT / MRI scan of the brain to exclude new or progressive brain 
metastases. 
10. Current or past history of central nervous system (CNS) lymphoma 


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11. Uncontrolled seizure disorder requiring therapy (e.g. strong CYP3A4 inducers such as 
carbamazepine and phenytoin) 
12. History of organ allograft transplantation or autologous stem cell transplantation ≤ 3 months 
prior to the first dose of study drug. Patients who received prior CAR-T or other T-cell targeting 
treatment (approved or investigational) ≤ 4 weeks prior to study drug administration 
13. Evidence or history of bleeding disorder, i.e. any hemorrhage / bleeding event of CTCAE 
Grade > 2 within 4 weeks before the first dose of study drug 
14. Serious, non-healing wound, ulcer, or bone fracture 
15. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being 
evaluated in this study, with the exception of the following previous or concurrent cancer types: 
• Curative treatment for localized cancer completed without signs of recurrence and 
treatment-related toxicity and low risk of recurrence as assessed by the investigator, 
• In-situ prostate cancer, Gleason Score <7, prostate-specific antigen <10 ng/mL (very low 
risk and low risk, according to therapy guidelines, e.g. the National Comprehensive Cancer 
Network guideline; active surveillance / observation is a recommended option). 
16. Any clinical condition that is considered unstable or might jeopardize the safety of the patient 
and his / her compliance in the study 
17. Inability to swallow oral medications 
18. Any malabsorption condition 
19. Breastfeeding. Female patients must not breastfeed during treatment and until 4 months after 
last study drug administration.  
20. Treatment with anticancer chemotherapy or immunotherapy during the study or within 3 
weeks before the first dose of study drug. For small-molecule drugs, a period of at least 3 half-
lives before the first dose of study drug is acceptable. Mitomycin C or nitrosoureas should not 
be given within 6 weeks before the first dose of study drug. 
21. Treatment with systemic steroids (prednisone dose ≥10 mg/day or equivalent dose). 
22. Acute toxic effects (CTCAE Grade ≥2) of previous anticancer chemotherapy or 
immunotherapy that have not yet stabilized or if significant post-treatment toxicities have been 
observed. (Note however that toxic effects of previous anticancer therapy considered as 
chronic, such as chemotherapy-induced neuropathy, fatigue, alopecia, or anorexia of CTCAE 
Grade <2, for which further resolution is not expected, do not prevent participation in this study.) 
23. Radiotherapy to target lesions in the 21 days before starting the first dose of study drug. 
Palliative radiotherapy is allowed to non-target lesions at any time before starting the first dose 
of study drug. 
24. Major surgery or significant trauma within 4 weeks before the first dose of study drug 
25. Previous assignment to treatment during this study 
26. Concomitant participation in another clinical study with investigational medicinal product(s) 
27. Substance abuse, medical, psychological, or social conditions that may interfere with the 
patient’s participation in the study or evaluation of the study results 
28. Close affiliation with the investigational site; e.g. a close relative of the investigator, dependent 
person (e.g. employee or student of the investigational site) 
29. Use of strong CYP3A4 inhibitors and inducers from 14 days prior to first administration of 
study drug. Strong CYP3A4 inhibitors and inducers are prohibited during the study and until 
the active FU visit. 
30. Use of Proton Pump Inhibitors (PPIs) must be discontinued at least 48 hours prior to initiation 
of study drug.  


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Note: If a potential participant is on a PPI and requires some form of Acid Reducing 
Agent(s) (ARAs), the investigator should consider alternatives for the duration of the trial, 
including Famotidine, or oral antacid drugs such as calcium carbonate.  
31. Clinically relevant findings in the ECG such as a second- or third-degree atrioventricular block, 
prolongation of the QRS complex > 120 ms (except for bundle branch block pattern), or 
prolongation of the of the QTc interval (Fridericia) over 450 ms unless agreed otherwise 
between the investigator and the sponsor’s medically responsible person. 
4.3 
Replacement 
Patients who discontinue due to a DLT in Cycle 1 will not be replaced. 
Patients who discontinue during Cycle 1 due to any reason other than a DLT and patients who 
were non-compliant in Cycle 1 will be replaced for the purpose of Cycle 1 DLT determinations, 
but may continue on the study at the discretion of the investigator. Non-compliance is determined 
by the investigator and can include failure to take medications or failure to have study-related 
activities performed. 
Patients who took less than 21-days of the required dose of study drug during Cycle 1 will be 
replaced for the purpose of Cycle 1 DLT determinations, but may continue on the study at the 
discretion of the investigator.  
Patients with insufficient PK data may have to be replaced. The decision to replace a patient due 
to insufficient PK data will be taken on a case-by-case basis after consultation between the 
investigator and the sponsor. 
Patients who discontinue after Cycle 1 will not be replaced. 
If the dropout rate in any expansion cohort is ≥ 20%, additional patients may be enrolled to ensure 
that at least 20 patients per indication will be evaluable for the response assessment. 
5. 
TREATMENTS 
5.1 
Identity of Study Treatment 
All study drugs will be labeled consistent with the requirements of local law and legislation. Label 
text will be approved consistent with the sponsor’s agreed procedures, and a copy of the labels 
will be made available to the study site upon request. 
For all study drugs, a system of numbering in accordance with all requirements of Good 
Manufacturing Practice (GMP) will be used, ensuring that each dose of study drug can be traced 
back to the respective bulk batch of the ingredients. Lists linking all numbering levels will be 
maintained by the sponsor’s clinical supplies quality assurance group. 
A complete record of batch numbers and expiry dates of all study treatment as well as the labels 
will be maintained in the sponsor’s study file. 
5.2 
Dosage and Administration 
PCLX-001 will be provided as an oral daily dose on a 28-day cycle. Doses should be taken around 
the same time each day, within a ±3 hour window. PCLX-001 capsule(s) are to be taken by mouth 
and swallowed with approximately 250 ml of water, at least ninety minutes after eating solid food. 
After PCLX-001 is taken, the patient should wait 2 hours before eating solid food. Missed doses 
for any reason (i.e. outside of the allowable dosing window) will not be administered at a later 
time. In Part A, dose-escalation levels are provided in Section 3.3. PCLX-001 capsules are 
available in doses of 10 mg and 70 mg and the number of capsules will be calculated to ensure 
proper daily dosing is provided.   


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5.3 
Dose Delay and Modifications  
Dose adjustments are to be made according to the organ system showing the greatest degree of 
toxicity. Toxicity will be graded using the National Cancer Institute Common Terminology Criteria 
for Adverse Events (NCI CTCAE, Version 5.0).  
5.3.1  Cycle 1 DLT Modifications for Part A Dose-Escalation Cohorts 
If a patient experiences a treatment related hematological or non-hematological DLT (as defined 
in Section 3.2) during Cycle 1, the next dose of PCLX-001 will be delayed for up to 28 days for 
Part A. If the toxicity fails to resolve to CTCAE Grade ≤2 within 28 days, the patient should be 
withdrawn from study treatment but followed for safety until resolution.  
If the toxicity resolves to CTCAE Grade ≤2, re-treatment with PCLX-001 can be considered. Re-
treatment of this patient should be at 1 dose level below the initial dose. Detailed dose 
modifications are described in Table 5-1. Patients experiencing any drug-related, clinically 
significant, non-hematological CTCAE Grade 4 toxicity will be withdrawn from study treatment but 
followed for safety until resolution. There will be no intrapatient dose escalation and no more than 
two dose reductions will be allowed. 
Table 5–1: Dose Modifications of PCLX-001  
Existing Dose (mg) 
Modified Dose (mg) 
280 
210 
210 
140 
140 
100 
100 
70 
70 
40 
40 
20 
20 
10 
10 
Discontinue study drug 
5.3.2 Dose Modifications for HEMATOLOGIC Toxicities 
For cycle 2 and beyond, Day 1 administration of PCLX-001 requires a platelet count of ≥ 75x109/L 
and an absolute neutrophil count (ANC) of ≥ 1.5x109/L. CBC’s drawn within 72 hours of treatment 
day may be used provided they meet parameters. However, if treatment parameters are not met, 
dose interruption will be made on the basis of blood counts taken the day of scheduled treatment.  
If counts are below this threshold, treatment will be delayed for 1 week and reassessed weekly 
until these parameters are met.  
If a patient experiences a hematologic DLT in the preceding cycle OR if treatment is held for > 7 
days due to neutropenia and/or thrombocytopenia, then the subsequent cycle will be administered 
at one lower dosing level. No more than two dose reductions will be allowed. 
Patients should not receive prophylactic G-CSF for cycle 1. Subsequent use will be at the 
discretion of the treating physician and as per the ASCO guidelines on colony stimulating factors. 
5.3.3 Dose Modifications for NON-HEMATOLOGIC Toxicities 
For a Grade ≥ 3 non-hematological toxicity considered to be clinically significant and attributed to 
PCLX-001, treatment will be delayed for up to a maximum of 28 days.  If the toxicity resolves to 
CTCAE Grade ≤ 2, the next dose of PCLX-001 can be considered at 1 lower dose level (Table 5-
2). Grade 4 clinically significant toxicities related to PCLX-001 will result in discontinuation of 
PCLX-001.  


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There will be no intrapatient dose escalation and no more than two dose reductions will be 
allowed. 
Table 5–2: Non-hematological Criteria for Dose Delay and Dose Modification 
CTCAE 
Gradea 
Dose delay 
Dose modification 
0 – 2 
Treat on time 
No change 
3 
Delayb until CTCAE Grade ≤2 
Decrease 1 dose levelc 
4 
Discontinue permanently 
Discontinue permanently 
a Excludes alopecia, non-refractory nausea/vomiting, and non-refractory diarrhea. For TLS see Table 5-3 
b If no recovery after 28-day delay, PCLX-001 treatment will be discontinued. 
c Dose will not be re-escalated after reduction for toxicity. If more than 2 dose reductions are required,  treatment 
will be discontinued. 
Gastrointestinal Events 
Diarrhea: No prophylactic treatment for diarrhea is recommended. Anti-diarrheals can be used 
when needed. A further dose of study medication should not be given before treatment related 
diarrhea has recovered to CTCAE Grade ≤ 2. 
Nausea/Vomiting: No prophylactic treatments for nausea or vomiting are recommended, but 
anti-emetic drugs can be used when needed. A further dose of study medication should not be 
given before treatment related nausea/vomiting has recovered to CTCAE Grade ≤2. 
Constipation: Patients can continue laxative as concomitant medication, but start of prophylactic 
treatments before study drug is administered is not recommended. Laxative can be used when 
needed.  
5.4 
Prophylaxis and Monitoring of Tumor Lysis Syndrome 
Patients with high tumor burden and who are considered by the Investigator to be at risk for tumor 
lysis should receive tumor lysis prior prophylaxis prior to the initiation of treatment. Patients should 
be well-hydrated and maintain a fluid intake of approximately 2 L/day. In addition, patients should 
be treated with allopurinol 300 mg oral daily (or a suitable alternative as per institutional standard) 
ideally 24 - 48 hours prior to Cycle 1 Day of PCLX-001 treatment. Patient should continue to 
receive prophylaxis and adequate hydration as deemed appropriate by the Investigator to mitigate 
against tumour lysis syndrome (TLS).   
The inherent risk of tumor lysis syndrome (TLS) is dependent on the malignancy being treated 
and individual participant characteristics. The risk of TLS with PCLX-001 in NHL patients is 
predicted to be highest for those with bulky disease (defined as any lesion > 10 cm on the 
screening CT scan) and elevated pretreatment lactate dehydrogenase levels, particularly in the 
presence of dehydration or compromised renal function. Whereas patients with DLBCL, MCL, 
and Burkitt lymphoma may be at higher risk of TLS compared to FL, any risk assessment based 
on tumor type must be considered along with the effectiveness of therapy. All patients should be 
assessed for the need for prophylaxis for TLS.  
TLS is an emergency which requires immediate treatment. Balanced or isotonic solutions (without 
potassium) should be administered to ideally maintain urine output > 100 mL/h. Alkalinization of 
the urine is not recommended in the treatment of TLS. In the absence of contraindications, 
patients with established TLS should be considered for rasburicase at a dose of 0.2 mg/kg/day or 
institutional standard. Intractable fluid overload, hyperkalemia, or reduced urine output in the 
setting of acute kidney injury should be assessed for the need for renal dialysis.  


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Dose modifications for TLS are summarized in Table 5-3. 
Table 5–3: Tumor Lysis Syndrome Criteria for Dose Delay and Dose Modification 
CTCAE 
Grade 
Dose delay 
Dose modification 
3 or 4 
Delaya until TLS resolved 
Decrease 1 dose levelb or discuss with 
Medical Monitor to reinitiate at target 
dose 
a 
If no recovery after 28-day delay, PCLX-001 treatment will be discontinued. 
b           Dose will not be re-escalated after reduction for toxicity. If more than 2 dose reductions are required, 
treatment will be discontinued. 
5.5 
Treatment Compliance 
PCLX-001 will be dispensed to patients to be taken orally on an ambulatory basis as well as 
during clinic visits. 
During ambulatory treatment, patients will document the intake of PCLX-001 in a compliance 
diary. 
Unused PCLX-001 study drug will be returned by patients. The time and amount of study drug 
intake will be recorded in the compliance diary. Each patient’s compliance will be evaluated by 
the study center. This information will be transferred into the eCRF taking into account each dose 
interruption and / or any changes in dosing. 
To ensure the required number of patients are evaluable Cycle 1 DLT dose-escalation cohorts, 
participants will need to have received at least 21-days of the planned total dose (unless a DLT 
occurs). Patients non-compliant in Cycle 1 will be replaced. 
Any discrepancies between actual and expected amount of returned study medication must be 
discussed with the patient at the time of the visit, and any explanation must be documented in the 
source records. 
 
6. 
NON-STUDY THERAPIES 
6.1 
Concomitant Therapy  
Concomitant therapy includes any prescription medications or over-the-counter preparations 
used by a participant between the 7 days preceding the baseline evaluations and the end of last 
study visit. All concomitant medications (including start / stop dates, total daily dose, and 
indication), including vaccinations, should be reported by the Investigator and recorded on the 
appropriate eCRF.  
Permitted Therapies 
• 
Patients may receive palliative and supportive care for any underlying illness. 
• 
Patients may receive vaccinations for COVID-19. Ideally, vaccinations would not be 
administered during Cycle 1 of study treatment, however, this is not prohibited.  
• 
Corticosteroids use for cytoreduction due to malignancy-related symptom control of B-cell 
lymphoma may be given prior to initiation of study treatment (up to 100 mg/day of prednisone 
or equivalent for no more than 5 days).  
• 
Palliative radiotherapy during the study will be allowed for local pain control if: 


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• 
In the opinion of the investigator, the patient does not have progressive disease. 
• 
Not more than 10% of the patient’s bone marrow is irradiated. 
• 
The radiation field does not encompass a target lesion; the indication for radiation therapy 
to a target lesion is considered progressive disease. 
• 
The safety of oral PCLX-001 administered concomitantly to radiation therapy has not been 
determined. Therefore, oral PCLX-001 treatment should be held on those days where the 
patient receives palliative radiotherapy, and restarted the day after completion of palliative 
radiotherapy.  
• 
Patients may continue receiving bisphosphonates prophylactically or for bone metastases 
while on study treatment. 
• 
Granulocyte colony-stimulating factor and other hematopoietic growth factors may be used 
for the management of acute toxicity, such as febrile neutropenia, when clinically indicated or 
at the investigator’s discretion, except their preventive use in Cycle 1.  
• 
CYP3A4 substrates should be used with caution, as exposure may be higher or lower when 
concomitantly administered with PCLX-001 due to CYP3A4 inhibition or induction, 
respectively.  
• 
P-gp substrates (e.g. aliskiren, ambrisentan, colchicine, dabigatran etexilate, digoxin, 
fexofenadine, maraviroc, posaconazole, ranolazine, saxagliptin, sitagliptin, talinolol, 
tolvaptan) should be used with caution. 
Prohibited Therapies 
• 
Use of PPIs must be discontinued at least 48 hours prior to initiation of study drug.  
Note: If a potential participant is on a PPI and requires some form of acid reducing agent, 
the investigator should consider alternatives for the duration of the trial, including 
Famotidine, or oral antacid drugs such as calcium carbonate. 
• 
Patients may not receive another investigational treatment or other approved antitumor 
therapy (such as chemotherapy) while on this protocol. In addition, treatment with “non-
conventional therapies” (such as herbal supplements) is not permitted. 
• 
The use of strong CYP3A4 inhibitors and inducers is not permitted from 5 days prior to first 
administration of study drug to the active FU visit. 
• 
Patients should not receive PAXLOVID as components are known to inhibit CYP3A. 
• 
Patients may not receive granulocyte colony-stimulating factor and other hematopoietic 
growth factors for primary prevention during Cycle 1.  
 
7. 
STUDY SCHEDULE AND ASSESSMENTS 
7.1 
Study Calendar  
The calendar below lists the assessments and indicates with an “X” the visits when they are 
performed. Baseline evaluations are to be conducted within 28 days (or 7 days as indicated) prior 
to start of protocol therapy. Diagnostic imaging and LVEF assessment must be done 28 days 
prior to the start of therapy.  In the event that the patient’s condition is deteriorating, laboratory 
evaluations should be repeated within 72 hours prior to initiation of the next cycle of therapy.   


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Table 7A: 
Schedule of Evaluations (Study Flow Chart) – SCREENING 
 
Measures / actions 
Screening 
Within 28 
days 
Within 
7 (±3) days 
before the first dose of PCLX-001 
Informed consent 
Signing of informed consent 
X 
 
Archival tumor tissue a 
X 
 
General screening procedures 
X 
 
Check of inclusion / exclusion criteria 
X 
 
Demographics 
X 
 
Complete medical history including documentation of primary diagnosis b 
X 
 
Abbreviated medical history 
 
X 
Baseline characteristics 
 
 
• 
Prior and concomitant medications (prescribed and OTC) 
X 
 
• 
Baseline toxicities 
X 
 
Assessment of toxicities (open questioning for AEs) 
 
X 
Concomitant medications (prescribed and OTC) 
 
X 
Physical examinationj  
X 
 
Vital signs 
 
 
• 
Blood pressure, heart rate, and body temperature 
X 
 
Body weight and body height 
X 
 
ECOG performance status assessment 
X 
 
Cardiovascular safety assessment 
 
 
• 
12-lead ECG (standard, triplicate)  
X 
 
• 
MUGA scan or echocardiogram 
X 
 
 
 
 
 
 
 
 
 
 
 
 


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Table 7A: 
Schedule of Evaluations (Study Flow Chart) – SCREENING (continued) 
 
Measures / actions 
Screening 
Within 28 
days 
Within 
7 (±3) days 
before the first dose of PCLX-001 
Tumor assessment (CT or MRI)i 
X 
 
Blood sample collection for tumor biomarker, if applicable (e.g. CA125, CEA)  
X 
 
PET-CT (optional, NHL patients only) c 
X 
 
Fresh tumor biopsy (optional) d 
 
X 
Blood sample collection for exploratory biomarker analyses 
 
X 
Blood / urine sample collection for laboratory safety assessments 
 
 
• 
Hematology e,  
 
X 
• 
Blood chemistry f,  
 
X 
• 
Calculation of eGFR by Cockcroft-Gault  
 
X 
• 
Coagulation (aPTT, PT/INR)  
 
X 
• 
Thyroid function (TSH and T4 [total or free per local standard]) 
 
X 
• 
Virology (HBsAg, anti-HCV) g 
 
X 
• 
Pregnancy test (serum) h 
 
X 
• 
Urinalysis (dipstick) 
 
X 
a. 
Archival tumor tissue is mandatory for patients enrolled in the dose escalation levels and expansion cohorts. This specimen could have been collected at any time 
from the initial diagnosis to study entry.  
b. 
Documentation of the primary diagnosis using the complete pathology report. Collection of baseline FLIPI, IPI, or MIPI scores for FL, DLBCL, and MCLC, respectively. 
Collection of staging information for patients with B-cell lymphoma.   
c. 
This scan should only be performed for NHL patients and is optional (i.e. not required for patients with other histologies). If a PET-CT is performed at screening, it 
should be repeated once after the sixth cycle if no progressive disease is detected during the course of treatment and / or to confirm complete response or disease 
progression. 
d. 
Collection of screening fresh tumor biopsy will be optional for patients enrolled in whom an archival biopsy is older than 6 months. The tumor biopsy will be obtained 
before the first dose of study drug (during the screening period when all other general screening procedures have been completed and patients are eligible for study 
treatment).  
e. 
Hematology includes CBC + differential (i.e. hemoglobin erythrocytes, leukocytes, platelets, MCV, RDW, hematocrit, neutrophils, lymphocytes, monocytes, 
eosinophils, basophils, immature granulocytes, nucleated RBCs). 
f. 
Blood chemistry includes:  sodium, potassium, chloride, bicarbonate or total CO2 (as per site practice), calcium, phosphate, magnesium, total protein, albumin, 
glucose, serum creatinine, urea, uric acid, total bilirubin, ALT, AST, LDH, alkaline phosphatase, lipase 
g. 
Virology includes: hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HB-sAb), and hepatitis C virus antibody (anti-HCV) 
h. 
Only for women of reproductive potential (including women of reproductive potential whose partners are sterilized). 
i. 
CT of the relevant disease region for solid tumors and CT thorax, abdomen, pelvis ± neck for NHL. Patients with neurological symptoms should undergo a CT or MRI 
brain to rule out brain metastases. The overseeing physician can use their judgement to choose the appropriate scan type to perform. 
j. 
A full physical exam is required at baseline/screening. The exam should review all body systems as follows: general appearance, respiratory, cardiovascular, 
abdomen, skin, head and neck, lymph nodes, thyroid, musculoskeletal, neurological, and if clinically indicated, any other systems (investigator to specify). Thyroid 
exams may be included as part of the head and neck review. If the review of head and neck is normal, the thyroid can also be considered normal.  


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Table 7B: 
Schedule of Evaluations (Study Flow Chart) – TREATMENT AND FOLLOW-UP  
 
Measures / actions 
Treatmentn 
       FU 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
EOT 
visit 
 Safety FU 
visit b 
Long-Term 
FUo 
D1 a 
D2 
D8 
D15 
D22 
D1 
D15 
D1 
 
 
 
Before study drug administration 
 
 
 
 
 
 
 
 
 
 
 
Check of inclusion / exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
 
Abbreviated medical history 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant medications c 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
 
Assessment of toxicities (AEs) d 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG (standard, triplicate)  
X 
 
 
 
 
X 
 
 
X 
X 
 
Blood pressure, heart rate, & body temperature 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical examinationl 
X 
 
X 
X 
X 
X 
 
X 
X 
X 
 
Body weight 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
ECOG performance status assessment 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Blood sample collection for biomarker analysis f 
X 
 
 
 
 
X 
 
X 
X 
Blood / urine sample collection for laboratory 
safety assessments 
 
 
 
 
 
 
 
 
 
• 
Hematologyg 
X 
 
X 
X 
X 
X 
X 
X 
X 
• 
Blood chemistry h 
X 
 
X 
X 
X 
X 
X 
X 
X 
• 
Calculation of eGFR by Cockroft-Gault 
X 
 
 
 
 
X 
 
 
 
• 
Coagulation (aPTT; PT/INR) 
X 
 
 
 
 
X 
 
 
 
• 
Thyroid function (TSH and T4[total or free 
per local standard]) 
X 
 
 
 
 
X 
 
 
X 
• 
Virology (HBV DNA, HCV RNA)m  
X 
 
 
 
 
 
 
 
 
• 
Pregnancy test (serum or urine) j 
X 
 
 
 
 
 
 
 
 
• 
Urinalysis (dipstick) 
X 
 
 
X 
 
X 
 
 
X 
Tumor assessment all tumors (CT or MRI)i 
 
 
 
 
 
End of every 
second cycle 
 
 
PET-CT (optional, NHL patients only)k 
 
 
 
 
 
Once after sixth 
cycle 
 
 
Blood sample collection for tumor marker, 
if applicable (e.g., CA125, CEA, PSA) 
 
 
 
 
 
End of every 
second cycle 
 
 
Survival status 
 
 
 
 
 
 
 
 
Xo 
 
 
 
 


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Table 7B: 
Schedule of Evaluations (Study Flow Chart) – TREATMENT AND FOLLOW-UP (continued) 
 
Measures / actions 
Treatment 
FU 
Cycle 1 
Cycle 2 
Cycle ≥ 3 
EOT 
visit 
Safety FU 
visit b 
D1 a 
D2 
D8 
D15 
D22 
D1 
D15 
D1 
 
 
Study drug administration 
 
 
 
 
 
 
 
 
 
 
Review of patient study medication diary and 
compliance of medication taken at home 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
PCLX-001 administration at study center 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Before & after study drug administration 
 
 
 
 
 
 
 
 
 
 
PK sampling (plasma) for PCLX-001e escalation 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
PK sampling (plasma) for PCLX-001 e expansion 
X 
 
 
X 
 
X 
 
X 
 
 
 
 
 
a. 
Any of the assessments scheduled before drug administration on C1D1 may be missed without protocol deviation if the same assessment has been 
obtained and reviewed within 3 days before the start of treatment (except PK and exploratory biomarker analysis). 
b. 
If a patient discontinues study treatment at any time during the study for any reason (except for patients who died, withdrew consent and objected 
to further data collection, or were lost to FU), an active FU assessment should be performed 30 days (±4 days) after the last dose of the last study 
drug. 
c. 
Prescribed and OTC. 
d. 
Questioning for AEs will be conducted at clinic visits; in addition, spontaneous reports of AEs will be collected throughout the study. 
e. 
PK sampling: For patients in dose escalation, see Table 7C for schedule. For patients in dose expansion, see Table 7D for schedule. 
f. 
To be taken pre-dose of each cycle Day 1 within 60 min before the morning dose and EOT 
g.    Hematology includes CBC + differential (i.e. hemoglobin erythrocytes, leukocytes, platelets, MCV, RDW, hematocrit, neutrophils, lymphocytes, monocytes, 
eosinophils, basophils, immature granulocytes, nucleated RBCs). Detection of CTCAE Grade 4 neutropenia (only Cycle 1) will trigger twice-weekly white blood cell 
counts to be performed, so that DLT determination can be made. 
h. 
Blood chemistry includes:  sodium, potassium, chloride, bicarbonate or total CO2 (as per site practice), calcium, phosphate, magnesium, total protein, 
albumin, glucose, serum creatinine, urea, uric acid, total bilirubin, ALT, AST, LDH, alkaline phosphatase, lipase. 
i. 
Window for tumour assessment is ± 5 days from Day 28 of the even-numbered cycles. CT of the relevant disease region for solid tumors and CT thorax, 
abdomen, pelvis ± neck for NHL.  
j. 
Women of childbearing potential (including women of childbearing potential whose partners are sterilized) must have a negative pregnancy test. 
k. 
This scan should only be performed for NHL patients and is optional (i.e. not required for patients with other histologies). If a PET-CT is performed at 
screening, it should be repeated once after the sixth cycle if no progressive disease is detected during the course of treatment and / or to confirm 
complete response or disease progression. 
l. 
Exam to be symptom-directed. 
m. To be performed if clinically indicated (e.g. positive HBsAg and/or anti-HCV tests as performed during screening). 
n. 
Unless otherwise indicated, the window for visits is ± 2 days. 
o. 
Electronic records will be used to assess patient survival monthly (± 1 week) from the date of the follow-up visit. 
 


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7.2 
Visit Description  
If not stated otherwise, the examinations listed in the following sections will be performed by, or 
under the supervision of, an investigator or a qualified delegate. 
Unscheduled visits may occur as necessary, when clinically indicated at the investigator’s 
discretion. Relevant and clinically significant laboratory data and AEs obtained at the unscheduled 
visits should be entered into the eCRF and recorded in the source documentation as necessary. 
7.2.1 Screening  
Pre-study examinations will be performed within 28 days before first administration of PCLX-001. 
Because some patients may not satisfy all inclusion and exclusion criteria, more patients than the 
pre-specified number of evaluable patients will be screened. As soon as fulfillment of all criteria 
is confirmed by the investigator, the patient will be allowed to enter the treatment phase of the 
study. 
A signed written informed consent form (ICF) will be obtained before any general screening 
procedure for the study may begin. 
7.2.2 Treatment Visits 
At each visit, laboratory investigations and/or measures and action will be as per the Schedule of 
Evaluations (Tables 7A and 7B). 
7.2.3 Follow-Up Visits 
If a patient discontinues study drug at any time during the study for any reason (except for patients 
who died, withdrew consent and objected to further data collection, or were lost to FU), an active 
FU assessment should be performed 30 days (± 4 days) after the last dose of the last study drug 
(Table 7B). 
Long-term follow up will occur monthly to assess patient survival only. Patients will not be 
contacted for these visits; electronic records will be reviewed to complete the assessments. 
7.2.4 End of Treatment Visit 
If a patient discontinues the study for any reason except death, withdrawal of consent and 
objection to further data collection, loss to FU, or extended treatment interruption, an EOT 
evaluation should be performed as soon as possible after the last dose of the study drug, but 
always within 30 days (± 4 days) after the last dose of study drug. 
The EOT visit should be performed as a clinic visit (except for patients who died, withdrew consent 
and objected to further data collection, or were lost to FU). 
The assessments to be performed at the EOT visit are described in the Schedule of Evaluations 
(Table 7B).  
7.3 
Determination of Efficacy Outcomes  
Tumor response and progression of solid tumors and NHL will be evaluated by the investigator at 
each study center consistent with RECIST 1.1 criteria (see Appendix B), or Lugano Classification 
of Lymphoma response (see Appendix C).  
Tumor markers can play a role in detecting disease and assessing response to therapy in selected 
groups of patients. In monitoring patients for disease progression, tumor marker levels should be 
determined according to clinical practice (e.g., CA125 for ovarian cancer, CEA for colorectal 
cancer, PSA for prostate cancer).  
 
 


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Solid Tumors  
In measurable lesions (i.e. at the primary site, visceral [≥1.0 cm long axis], or nodal [in lymph 
nodes ≥1.5 cm short axis] lesions), the objective response will be assessed by contrast-enhanced 
CT or MRI and documented consistent with RECIST 1.1 criteria (see Appendix B). Tumor 
measurements for efficacy evaluation will be made every 2 cycles, beginning with a baseline scan 
and unless progression is noted, all lesions will be assessed and reported at the end of every 
second cycle, starting at the end of Cycle 2. 
Non-Hodgkin’s Lymphoma 
Efficacy will be assessed based on radiological tumor evaluations, which will include neck, chest, 
abdomen, and pelvis by contrast-enhanced CT / MRI scans. PET-CT can be utilized throughout 
the study if it is considered standard of care at the institution. Scans will be performed as shown 
in Table 7A and Table 7B and will be evaluated locally at the study site. 
PET-CT is optional in this study and should be done based on institutional standards whereas the 
CT portion of the PET-CT should be of diagnostic quality, i.e. appropriate radiation dose and 
contrast enhancement. In case the CT portion of the PET-CT is performed for attenuation 
correction only an additional whole body CT in diagnostic quality is needed. If a PET-CT with a 
PET positive finding was performed at screening an interim PET-CT should be done after the 
sixth cycle. For any imaging follow-up after interim PET-CT it is recommended to confirm any 
changes in previous metabolic overall response that were assessed with CT alone with PET-CT. 
Response assessment will be based on the Lugano Classification (see Appendix C). 
7.4 
Pharmacokinetics 
7.4.1 Drug Measurements  
In patients enrolled in Part A dose escalation, serial blood (plasma) samples will be collected at 
the time points shown in Table 7C to assess PK of PCLX-001. For patients enrolled in Part B 
dose expansion, serial blood (plasma) samples will be collected at the pre-dose time points shown 
in Table 7D.  
Whenever possible, all efforts should be made to adhere to the blood-sampling schedules given 
in Tables 7C and 7D. However, based on practical considerations, the following time ranges are 
provided as guidance: 
Pre-dose samples should be collected within 15 min before the administration of PCLX-001. For 
0.5 hours post dose, the PK sample should be collected within ± 6 minutes. Subsequent PK 
samples should be collected ± 15 minutes of planned time point. Sampling times outside these 
suggested intervals will not be considered as protocol deviations. The date and time of actual 
blood sampling and dose administration will have to be documented in the eCRF because PK 
calculations will be based on the actual sampling times relative to dosing times.  
Cumulated substantial deviations of sampling times and / or consecutive, missing PK samples 
may lead to an insufficient (inadequate) description of the plasma concentration vs. time profiles 
of PCLX-001, and thus affect the quality of the PK evaluation of the respective patient(s). In this 
case, these deviations should be classified as “important” and may lead as declared “validity 
findings” to the exclusion of the respective patient(s) from the PK analysis set. 
Details on sampling procedures, sample storage, and shipment are documented in separate 
sample handling documentation.  
 
 


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Table 7C: Schedule of pharmacokinetic blood sampling time points in Part A Dose Escalation 
Procedures 
Study Treatment Period 
1 Cycle = 28 days 
 
Cycle 1  
Cycle 2 
Cycle 3/ 
Beyond 
 EOT 
Visit 
Visit Identifier 
(Visit Window) 
Day 1 
Day 2 
Day 8 
(±2) 
Day 15 
(±2) 
Day 22 
(±2) 
Day 1  
(± 2) 
Day 15  
(±2) 
Day 1 
(±2) 
  
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pharmacokinetics 
  
  
  
  
 
  
  
  
  
Pre-dose* (-15 min) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
0.5 hour (± 6 min) 
X 
  
  
X 
 
  
  
  
  
1 hours (± 15 min) 
X 
  
  
X 
 
  
  
  
  
2 hours (± 15 min) 
X 
  
  
X 
 
  
  
  
  
4 hours (± 15 min) 
X 
  
  
X 
 
  
  
  
  
8 hours (± 15 min) 
X 
  
  
X 
 
  
  
  
  
*If patient is receiving a dose on that day 
Table 7D: Schedule of pharmacokinetic blood sampling time points in Part B Dose Expansion 
Procedures 
Study Treatment Period 
1 Cycle = 28 days 
 
Cycle 1  
Cycle 2 
Cycle 3/ 
Beyond 
 EOT 
Visit 
Visit Identifier 
(Visit Window) 
Day 1 
Day 2 
Day 8 
(±2) 
Day 15 
(±2) 
Day 22 
(±2) 
Day 1  
(± 2) 
Day 15  
(±2) 
Day 1 
(±2) 
 
  
X 
 
 
X 
X 
 
X 
 
Pharmacokinetics 
 
 
 
 
 
 
 
 
 
Pre-dose* (-15 min) 
X 
 
 
X 
X 
 
X 
 
*If patient is receiving a dose on that day 
7.5 
Pharmacodynamics 
Tissue and blood samples will be collected to understand the pharmacodynamic effect of PCLX-
001. 
7.5.1 Tissue Samples 
Archived tissue samples will be requested from all patients and pre-treatment biopsies will be 
optional for patients enrolled in whom an archival biopsy is older than 6 months.  These will be 
collected for response prediction analyses and exploratory research. Archived tumour blocks will 
be returned to the clinical investigator at the end of the study or, if requested, once sections have 
been obtained for biomarker analysis.  
7.5.2 Blood Samples 
Collection of blood samples for exploratory biomarker research is also a part of this trial. Blood 
samples will be collected from all patients in this study as specified in the Schedule of Evaluations 
(Table 7A and 7B). Specimens will be stored and may be used for research purposes to identify 
biomarkers useful for predicting and monitoring PCLX-001.   


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8. 
STATISTICAL CONSIDERATIONS 
8.1 
Sample Size Determination  
The exact sample size for Part A dose-escalation cannot be pre-determined and depends on the 
number of cohorts needed to reach MTD. Part A will enroll at least 9 patients and up to 52 patients. 
In Part B, there are two expansion cohorts of 20 patients each for a total of 40 patients.   
8.2 
Populations for Analyses  
Table 8-1: Analysis Populations 
Population 
Description 
Efficacy 
All participants who received at least one dose of PCLX-001 
and had at least one on-treatment tumour assessment will be 
included in the efficacy analysis.  
Safety 
All participants who received at least one dose of study 
treatment, whether prematurely withdrawn from the study or 
not, will be included in the safety analysis.  
MTD-determining population 
(Part A only) 
All participants from the safety analysis population who follow 
the protocol-specified dose regimen within the DLT 
observation period and have undergone the scheduled safety 
evaluations, or who discontinued earlier due to a DLT, will be 
included in the MTD-determining analysis. 
Pharmacokinetic 
All participants who have received at least one dose of study 
treatment and who have data from at least one post-dose 
sample will be included in the PK analysis population. 
Participants will be excluded from the PK analysis population if 
they significantly violate the inclusion or exclusion criteria or 
deviate significantly from the protocol or if their data are 
unavailable or incomplete, which may influence the PK 
analysis. Excluded cases will be documented together with the 
reason for exclusion.  
8.4 
Statistical Analyses 
Descriptive statistics will be utilized to present study patient population and toxicity data.   
8.5 
Pharmacokinetic Analyses 
PK parameters of PCLX-001 will be determined via non-compartmental analysis. Individual and 
mean serum PCLX-001 concentration versus time data will be listed by patient and tabulated by 
dose level. Graphical displays of PK data may also be provided.  
Other PK variables will be summarized using descriptive statistics only. These will include: 
• 
Cmax 
• 
Minimum observed serum concentration (Cmin) at the beginning of Cycle 2 and at the 
beginning of every subsequent cycle where PK data are available 
• 
Time to reach maximum serum concentration (tmax) 
• 
AUC 
• 
CL 
• 
Volume of distribution (Vd) 
 


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9. 
ADVERSE EVENT REPORTING  
9.1 
Definition of an Adverse Event 
Any untoward medical occurrence in a patient or clinical investigation subject administered a 
pharmaceutical product and which does not necessarily have a causal relationship with this 
treatment. An adverse event (AE) can therefore be any unfavourable and unintended sign 
(including a clinically significant abnormal laboratory finding), symptom, or disease temporally 
associated with the use of a medicinal (investigational) product, whether or not related to the 
medicinal (investigational) product. 
9.2 
Reporting, Recording and Follow-up of Adverse Events 
This study will use the International Common Terminology Criteria for Adverse Events (CTCAE), 
version 5.0, for adverse event reporting. 
For all AEs, relationship to study drug will be reported on the appropriate AE eCRF page. The PI 
must judge whether the study drug caused or contributed to the AE in which case it is considered 
to be an adverse drug reaction, and report it as either: 
Related (definitely, probably or possibly): there is a reasonable possibility that the study drug 
caused or contributed to the AE; this conclusion may be supported by the following observations, 
though these are not required for the determination of relatedness: 
• 
There is a plausible time sequence between onset of the AE and study drug 
administration; 
• 
There is a plausible biological mechanism through which study drug may have caused 
or contributed to the AE; 
Not related: It is highly unlikely or impossible that the study drug caused or contributed to the AE; 
this conclusion may be supported by the following observations, though these are not required 
for a determination of not related: 
• 
another cause of the AE is evident and most plausible; 
• 
the temporal sequence is inconsistent between the onset of the AE and study drug 
administration; a causal relationship is considered biologically implausible. 
All AEs and SAEs occurring after initiation of study drug, regardless of relationship to 
intervention, will be reported from time of first dose until 30 days after the last dose of study drug 
or until the initiation of another anti-cancer therapy, whichever occurs first. After this period, 
investigators should report any serious adverse events that the investigator believes have at least 
a reasonable possibility of being related to the investigational product.  
The investigator should follow each adverse event until the event has resolved to baseline grade 
or better or is assessed as stable by the investigator or until the patient is lost to follow-up or 
withdraws consent. Every effort should be made to follow all serious adverse events considered 
related to study drug or study-related procedures until a final outcome can be reported. 
During the study period, resolution of adverse events (with dates) should be documented on the 
Adverse Event electronic Case Report Form (eCRF) and in the patient’s medical record to 
facilitate source data verification. If, after follow-up, return to baseline status or stabilization cannot 
be established, an explanation should be recorded on the Adverse Event eCRF. 
9.3 
Serious Adverse Events 
Serious adverse events (SAE) as defined by the Good Clinical Practice Guideline is any untoward 
medical occurrence that at any dose:  
• 
results in death  


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• 
is life-threatening (defined as an event in which the subject was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if 
it were more severe)  
• 
requires inpatient hospitalization or prolongation of existing hospitalization  
• 
results in persistent or significant disability/incapacity  
• 
is a congenital anomaly/birth defect  
• 
is an important medical event (defined as a medical event(s) that may not be immediately 
life-threatening or result in death or hospitalization but, based upon appropriate medical 
and scientific judgment, may jeopardize the subject or may require intervention to prevent 
one of the other outcomes listed in the definition above 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm; blood dyscrasias or convulsions that do not result in hospitalisation; or 
development of drug dependency or drug abuse. 
SAEs due to progressive disease (including death) should not be reported as SAEs unless the 
investigator also deems there is a possible contribution of the study drug or intervention. 
Hospitalization due solely to the progression of underlying malignancy should NOT be reported 
as a serious adverse event. 
9.3.1 SAE Reporting 
All SAEs defined as per ICH guidelines and other adverse events must be recorded on case 
report forms. In addition, all serious adverse events must be reported by using the SAE form and 
must be submitted to Ozmosis Research Inc.  
Serious Adverse Event Reporting Instructions 
All serious adverse events must be reported as follows: 
Within 24 hours: 
Report initial information (on trial specific SAE report form) by fax to: 
Ozmosis Research Inc. 
Phone: 416-634-8300 
Fax:  416-634-8333 
The initial information should always contain:  
- 
Name of Reporter/Investigator,  
- 
Subject Identification,  
- 
Adverse Event Term,  
- 
Study Drug Dose and Start/Stop Dates 
On the next working day: 
Fax completed trial-specific Serious Adverse Event form  
All follow-up SAE reports should be submitted to Ozmosis as soon as possible. 
The PI/Sponsor will be made aware of all Serious Adverse Events within 24 hours.  All SAEs will 
be reported to the local research ethics board (REB) and regulatory authorities, as applicable, in 
accordance with local guidelines. Health Canada, any collaborating centres and any 
pharmacovigilance teams (as applicable) will be notified by the Sponsor in an expedited manner 
of all SAEs which are unexpected and related to the investigational product. 
10. 
MONITORING, AUDITING, AND INSPECTING  
The investigator(s)/institution(s) will permit trial-related monitoring, audits, REB, Safety 
Monitoring, and regulatory inspection(s), providing direct access to paper and/or electronic 
documentation pertaining to the clinical study (e.g. CRFs, source documents such as hospital 


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patient charts and investigator study files). Monitoring of this study will be conducted as per the 
study monitoring plan. 
Audits may be conducted by the study sponsor, the sponsor’s designate, and/or the jurisdiction 
appropriate regulatory agencies (e.g Health Canada, the FDA). All site facilities related to the 
study conduct could be visited during an audit (e.g. pharmacy, laboratory, outpatient department). 
The investigator agrees to co-operate and provide assistance at reasonable times and places 
with respect to any monitoring or auditing activity. 
10.1 
Source Data 
The Investigator will maintain accurate source records from which the case report forms are 
based.  The investigator agrees to allow the monitor direct access to all relevant documents 
10.2 
Quality Control and Assurance  
The sponsor / designee will monitor the site activity to verify that: 
• 
The rights and well-being of human participants are protected. 
• 
The reported trial data are accurate, complete, and verifiable from source documents. 
• 
The 
conduct 
of 
the 
trial 
is 
in 
compliance 
with 
the 
currently 
approved 
protocol/amendment(s), with GCP, and with applicable regulatory requirements(s). 
10.3 
Safety Monitoring Plan 
A safety monitoring plan will be established for this study in conjunction with Pacylex 
Pharmaceuticals, Inc and Ozmosis Research. 
Regular meetings will occur prior to dose escalation to monitor the safety aspects of the trial and 
review safety data. Additional meetings may be scheduled as necessary and if any of the safety 
stopping rules are met.     
10.4 
Deviations  
The investigator is responsible to identify, document, assess and report all protocol deviations in 
accordance with Sponsor’s, REB’s and Health Canada’s / the FDA’s (as applicable) requirements. 
10.5 
Safety Stopping Rules 
Accrual will be on hold and a meeting held with the principal investigator, investigators and safety 
monitoring team if the following occurs: 
• 
If there is a death or unacceptable toxicity (SAE or AE grade ≥3,) attributed as: possibly, 
probably or definitely related to the experimental product. 
• 
If there is a protocol treatment-related Serious Adverse Event (any SAEs deemed by PI 
to be definitely, probably or possibly related to study drug), or any significant safety 
concerns 
• 
If the first 2 patients enrolled experience DLT 
A decision will be made by the PI and safety monitoring team regarding whether the study will be 
re-opened for the next patient in the study or not.  If there is disagreement in the SAE causality 
assessment or whether or not to re-open accrual between the different parties, the final decision 
will rest on the safety monitoring team.  Ozmosis Research will notify all sites and applicable 
parties on the decision and whether accrual has re-opened.  Only when it is deemed safe can the 
next patient start the treatment phase of the study. 
 
 


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11. 
DATA COLLECTION AND DATA MANAGEMENT  
11.1 
Data Collection and Case Report Forms 
An electronic data capture system will be used in this trial.  A case report form will be completed 
for each consented patient. The site maintains a separate source of data. This data will be entered 
by the site into the electronic data capture system. 
The investigator is ultimately responsible for the collection and timely reporting of all applicable 
data entered in CRFs and any other data collection forms (source documents) and ensuring they 
are accurate, original, attributable, complete, legible, contemporaneous, and available when 
required. Changes to entries made in CRF and source documents must be dated, initialed and 
explained (if necessary). Changes should not obscure original entry. 
Data reported on the CRF that are derived from source documents should be consistent with the 
source documents or the discrepancies should be explained. 
The CRF must be signed by the investigator or by authorized delegate to attest the data in the 
CRF is true. 
11.2 
Dose Escalation Safety Cohort Review 
Within 7 working days of each patient completing cycle 1 of Part A dose escalation, the following 
sections of the eCRF and source documentation for laboratory results must be completed and 
submitted to the Clinical Trials Specialist/Manager at Ozmosis Research Inc.: 
• 
Study Treatment Administration 
• 
Adverse Effects 
• 
Hematology and Biochemistry Results 
• 
Bone Marrow Results, if performed (optional) 
• 
Lab normal ranges page, if applicable 
Additional information may also be requested by Ozmosis Research Inc. from the study site.  It is 
imperative that the eCRF pages listed above are received at Ozmosis Research Inc. within 7 
working days after the patient completes cycle 1 and starting cycle 2 day 1 study drug 
administration, as the information will be used to assess safety at the opened dose level and to 
determine the feasibility of proceeding to a new dose level. 
12. 
ADMINSTRATIVE, ETHICAL, AND REGULATORY STANDARDS  
12.1 
Compliance Statement 
This trial will be conducted in compliance with the protocol, ICH-GCP’s and the applicable 
regulatory requirement(s).  
12.2 
Ethics 
This trial will be submitted and approved by the local Research Ethics Board prior to patient 
accrual. 
12.3 
Regulatory Requirements  
The following documents are required: 
For participating Canadian centres:  
• 
All Investigators must complete and sign the Health Canada Qualified Investigator 
Undertaking form. The completed forms must be returned to the sponsor prior to any 
drug shipment. 
• 
All applicable regulatory documents as listed in the Protocol Activation Checklist 
provided by Ozmosis Research Inc. to the sites. 


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• 
Ozmosis Research Inc. will submit via fax or e-mail to Health Canada a completed 
Health Canada Clinical Trial Site Information Form after local activation of each 
participating Canadian centre. 
 
For participating U.S.A. centres: 
• 
All Investigators must complete and sign FDA Form 1572. The completed forms must 
be returned to the sponsor prior to site activation. 
• 
All Investigators must complete and submit a Financial Disclosure Statement. 
• 
All Investigators must also submit to Ozmosis Research Inc. an up-to-date (current to 
within 2 years of the study start) curriculum vitae. 
• 
Laboratory certification / accreditation and normal ranges for local lab(s). 
• 
Consent forms, reviewed by Ozmosis Research Inc. before submission to the local 
Institutional Review Board (IRB). 
• 
A completed site delegation list. 
• 
A copy of the initial full board approval letter from the local IRB. Continuing approval 
(full board) will be obtained at least yearly until follow-up on patients is completed and 
no further data is being obtained for research purpose. 
12.4 
Confidentiality and Data Protection 
12.4.1 Participant Protection 
The responsible investigator will ensure that this study is conducted in compliance with the 
protocol and in agreement with the Declaration of Helsinki. 
The protocol has been written, and the study will be conducted according to the ICH Harmonized 
Tripartite Guideline on Good Clinical Practice. 
The local research ethics board must approve the protocol, Informed Consent Form and any trial 
materials given to participants. 
All potential serious breaches of GCP must be reported to Sponsor or designee immediately. A 
serious breach is a breach of the conditions and principles of GCP in connection with the study 
or the protocol, which is likely to affect, to a significant degree, the safety or physical or mental 
integrity of the participants of the study or the scientific value of the study. 
12.4.2 Participant Identification 
A sequential identification number will be automatically allocated to each patient registered in the 
trial. This number will identify the patient and will be included on all CRFs. 
12.4.3 Confidentiality of Trial Documents and Patient Records 
The investigators must assure that participants’ anonymity will be maintained and that their 
identities are protected from unauthorized parties. On CRFs patients should not be identified by 
their names, but by an identification code. Investigators should keep patients’ written consent 
forms and a patient enrolment log at the site showing codes, names and addresses. 
12.4.4 Retention of Patient Records and Study Files 
The investigator must retain all study records and source documents for the maximum period 
required by applicable regulations and guidelines, or institution procedures, whichever is longer. 
12.5 
Protocol Registration  
The sponsor has committed to the global industry position on disclosure of information about 
clinical trials. The International Committee of Medical Journal Editors (ICMJE) also requires trial 
registration as a condition of the publication of research results generated by a clinical trial.  The 


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information regarding this trial will be made publicly available on the internet at 
www.clinicaltrials.gov. 
12.6 
Protocol Amendments 
Before study initiation, the Sponsor (or designee) must have written and dated approval/favorable 
opinion from the REB/IRB/Independent Ethics Committee (IEC) and Health Canada (HC) (if 
applicable) for the protocol, consent form, subject recruitment materials (e.g., advertisements), 
and any other written information to be provided to participants. The Sponsor should also provide 
the REB/IRB/IEC and HC (if applicable) with a copy of the Investigator Brochure, Product 
Monograph, etc. (as applicable). 
The Sponsor or designee should provide the REB/IRB/IEC and HC (if applicable) with reports, 
updates and other information (e.g., expedited safety reports, amendments, and administrative 
letters) according to regulatory requirements or institution procedures. 
 
13. 
CRITERIA FOR TERMINATION OF TRIAL 
The Sponsor (or designee) has the right to close this study (or, if applicable individual segments 
thereof at any time, which may be due but not limited to the following reasons: 
13.1 
Futility 
If the study conduct (e.g. recruitment rate, drop-out rate, data quality, protocol compliance) does 
not suggest a proper completion of the study within a reasonable time frame the Sponsor may 
consider terminating the trial. This will be done in consultation with the DSMB.  
13.2 
Safety 
If risk-benefit ratio becomes unacceptable owing to, for example,  
• 
Safety findings from this study (e.g. SAEs);  
• 
Results of any interim analysis 
• 
Results of parallel clinical studies 
• 
Results of parallel animal studies (e.g. toxicity, teratogenicity, carcinogenicity or 
reproduction toxicity). 
13.3 
Efficacy 
For any of the above closures, the following applies: 
• 
Closures should occur only after consultation between involved parties. 
• 
All affected institutions (e.g. REB; competent authorities; study centre(s)) must be 
informed as applicable according to local law. 
• 
All study materials (except documentation that has to remain stored at site) must be 
returned to the sponsor. The investigator will retain all other documents until notification 
given by the sponsor for destruction. 
• 
In case of a partial study closure, ongoing participants, including those in post study follow-
up, must be taken care of in an ethical manner 
 
14. 
PUBLICATION POLICY 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Principal Investigator agrees to submit all manuscripts or abstracts to the Sponsor for approval 
prior to submission.  Authors of the manuscript and abstracts will include at least the Principal 


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Investigator (as first author) and co-investigators who have i) included eligible patients in the trial 
(by order of inclusion) or ii) contributed significantly to the design, conduct and data interpretation 
regarding companion basic science studies. 
The data collected during this study are confidential. 
15. 
REFERENCES 
Beauchamp E, et al. Targeting N-myristoylation for therapy of B-cell lymphoma. Nature 
Communications. 11:5248 (2020). 
Weickert Mt et. al. Nonclinical efficacy and toxicity and selection of a safe clinical starting dose 
for an NMT inhibitor in development for hematological malignancies. ASH 2020 Meeting, Blood, 
abstr 141910. 
Steven H., et. al. The 2016 revision of the World Health Organization classification of lymphoid 
neoplasms. Blood. 127:2375-2390 (2016).  
 
 


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16. 
LIST OF APPENDICES 
 
Appendix A. Eastern Cooperative Oncology Group Scale for Performance Status Grade 
Description 
0 
Normal activity. Fully active, able to carry on all pre-disease performance without restriction. 
1 
Symptoms but ambulatory. Restricted in physically strenuous activity, but ambulatory and able 
to carry out work of a light or sedentary nature (eg, light housework, office work). 
2 
In bed <50% of the time. 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 
In bed >50% of the time. Capable of only limited self-care, confined to bed or chair more than 
50% of waking hours. 
4 
100% bedridden. Completely disabled. Cannot carry on any self-care. Totally confined to 
bed or chair. 
5 
Dead 
Source: Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and 
response criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology 
1982;5(6):649-55. 
 
 
 
 


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Appendix B. Response Evaluation Criteria In Solid Tumors (RECIST Version 1.1) 
The following information is extracted/summarized from Eisenhauer, 2009, New Response 
Evaluation Criteria in Solid Tumors: Revised RECIST Guideline (Version 1.1). Please refer to 
the primary reference for further information. 
Definitions 
At screening, tumor lesions/lymph nodes will be categorized as measurable or non-measurable. 
Measurable Disease 
Tumor Lesions. Must be accurately measured in at least one dimension (longest diameter in the 
plane of measurement is to be recorded) with a minimum size of: 
• 
10 mm by CT scan (CT scan slice thickness no greater than 5 mm) 
• 
10 mm caliper measurement by clinical exam (lesions which cannot be accurately 
measured with calipers should be recorded as non-measurable) 
• 
20 mm by chest X-ray 
Malignant Lymph Nodes. To be considered pathologically enlarged and measurable, a lymph 
node must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness 
recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will 
be measured and followed.  
Non-measurable Disease  
All other lesions, including small lesions (longest diameter <10 mm or pathological lymph nodes 
with ≥ 10 to < 15 mm short axis) as well as truly non-measurable lesions. Lesions considered 
truly non-measurable include: leptomeningeal disease, ascites, pleural or pericardial effusion, 
inflammatory breast disease, lymphangitic involvement of skin or lung, abdominal 
masses/abdominal organomegaly identified by physical exam that is not measurable by 
reproducible imaging techniques. 
Choosing Target Lesions 
• 
Select up to 5 lesions (up to 2 per organ). 
• 
Select largest reproducibly measurable lesions. 
• 
If the largest lesion cannot be measured reproducibly, select the next largest lesion 
which can be. 
• 
Add up longest diameters (LD) of non-nodal lesions (axial plane). 
• 
Add short axis diameters of nodes. 
• 
This is the sum of the longest diameters (SLD). 
Nontarget Lesions 
• 
All other sites of disease present at baseline and not classified as target lesions will be 
classified as nontarget lesions, including any measurable lesions that were not chosen 
as target lesions. 
• 
It is possible to record multiple nontarget lesions involving the same organ as a single 
item on the eCRF (eg, “multiple enlarged pelvic lymph nodes”). 
• 
Measurements are not required but these lesions should be noted at baseline and 
should be followed as “present,” “absent,” or “unequivocal progression.” 


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Determining Response 
• 
Assess at baseline and on study with consistent modalities (CT, MRI, PET/CT). 
– Measure target lesions and calculate SLD. 
– Visually assess nontarget lesions. 
– Search for new lesions. 
– Combine these assessments into the overall response. 
Target Lesion Response 
Complete response (CR) 
• 
Disappearance of all extranodal target lesions. 
• 
All pathological lymph nodes must have decreased to <10 mm in short 
axis. 
Partial response (PR) 
• 
At least a 30% decrease in the SLD of target lesions, taking as 
reference the baseline sum diameters. 
Progressive disease (PD) 
• 
SLD increased by at least 20% from the smallest value on study 
(including baseline, if that is the smallest). 
• 
SLD must also demonstrate an absolute increase of at least 5 mm. (2 
lesions increasing from, for example, 2 mm to 3 mm, does not qualify). 
Stable disease (SD) 
• 
Neither sufficient shrinkage to qualify for PR nor sufficient increase to 
qualify for PD. 
Nonevaluable (NE) 
• 
One or more lesions cannot be evaluated because of missing data or 
poor image quality unless a convincing argument can be made that the 
contribution of the individual missing lesion(s) would not change the 
assigned time point response (eg, PD based on other findings). 
Abbreviations: SLD, sum of the longest diameters. 
Nontarget Lesion Response 
Complete response (CR) 
• 
Disappearance of all extranodal nontarget lesions. 
• 
All lymph nodes must be nonpathological in size (<10 mm short axis). 
• 
Normalization of tumor marker level. 
Non-CR/non-PD 
• 
Persistence of 1 or more nontarget lesions(s) and/or maintenance 
of tumor marker level above the normal limits. 
Progressive disease (PD) 
• 
Unequivocal progression of existing nontarget lesions (subjective 
judgment by experienced reader). 
Unable to evaluate (UE) 
• 
One or more lesions cannot be evaluated because of missing data or 
poor image quality unless a convincing argument can be made that the 
contribution of the individual missing lesion(s) would not change the 
assigned time point response (eg, PD based on other findings). 
New Lesions 
• 
Should be unequivocal and not attributable to differences in scanning technique or 
findings which may not be a tumor (does not have to meet criteria to be 
“measurable”). 
• 
If a new lesion is equivocal, continue to next time point. If confirmed then, PD is 
assessed at the date when the lesion was first seen. 
• 
Lesions identified in anatomic locations not scanned at baseline are considered new. 
• 
New lesions on ultrasound should be confirmed on CT or MRI. 
 


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Evaluation of Overall Time Point Response for Patients With Measurable Disease at Baseline 
Abbreviations: CR, complete response; PR, partial response; PD, progressive disease; SD, stable 
disease; NE, nonevaluable. 
Target Lesions 
Nontarget Lesions 
New Lesions 
Overall Response 
CR 
CR 
No 
CR 
CR 
Non-CR/non-PD 
No 
PR 
CR 
NE 
No 
PR 
PR 
Non-PD or NE 
No 
PR 
SD 
Non-PD or NE 
No 
SD 
Not all evaluated 
Non-PD 
No 
NE 
PD 
Any 
Yes or no 
PD 
Any 
PD 
Yes or no 
PD 
Any 
Any 
Yes 
PD 


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Appendix C. The Lugano Classification Criteria for the Evaluation of Non-Hodgkin Lymphoma 
The following information is extracted/summarized from Cheson, 2014, Recommendations for Initial Evaluation, Staging, and Response 
Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification. 
Criteria for Involvement of Site 
Tissue Site  
Clinical 
FDG Avidity 
Test 
Positive Finding 
Lymph nodes 
Palpable 
FDG-avid 
histologies 
PET-CT 
Increase FDG uptake 
 
Nonavid disease 
CT 
Unexplained node enlargement 
Spleen 
Palpable 
FDG-avid 
histologies 
PET-CT 
Diffuse uptake, solitary mass, liliary lesions, 
nodules  
 
Nonavid disease 
CT 
> 13cm in vertical length, mass, nodules 
Liver 
Palpable 
FDG-avid 
histologies 
PET-CT 
Diffuse uptake, mass 
 
Nonavid disease 
CT 
Nodules 
CNS 
Signs, 
symptoms 
 
CT 
Mass lesion(s) 
 
 
MRI 
Leptomeningeal infiltration, mass lesions 
 
 
CSF 
assessment 
Cytology, flow cytometry 
Other (eg, skin, 
lung, GI tract, 
bone, bone 
marrow) 
Site 
dependent 
 
PET-CT*, 
biopsy 
Lymphoma involvement 
CNS = central nervous system; CSF = cerebrospinal fluid; CT = computed tomography; FDG = fluorodeoxyglucose; 
GI = gastrointestinal; MRI = magnetic resonance imaging; PET = positron emission tomography. 
* PET-CT is adequate for determination of bone marrow involvement and can be considered highly suggestive for involvement of other extralymphatic sites. Biopsy 
confirmation of those sites can be considered if necessary. 
 
 
 
 


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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† 
It is recognized that in Waldeyer's ring or extranodal sites 
with high physiologic uptake or with activation within 
spleen or marrow (eg, 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 physiologic 
uptake 
Target nodes/nodal masses must regress to ≤ 1.5 cm in 
LDi 
No extralymphatic sites of disease 
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 
At interim, these findings suggest responding disease 
At end of treatment, these findings indicate residual 
disease 
≥ 50% decrease in SPD of up to 6 target measurable 
nodes and extranodal sites 
When a lesion is too small to measure on CT, assign 5 
mm × 5 mm as the default value 
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 
Not applicable 


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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 
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 (eg, a 15-cm spleen must increase to > 
16 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 


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New lesions 
New FDG-avid foci consistent with lymphoma rather than 
another etiology (eg, 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 
5PS = 5-point scale; CT = computed tomography; FDG = fluorodeoxyglucose; GI = gastrointestinal; 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.  
* A score of 3 in many Subjects 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 undertreatment).  
Measured dominant lesions: Up to six of the largest dominant nodes, nodal masses, and extranodal lesions selected to be clearly measurable in two 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 (eg, liver, spleen, kidneys, and 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 (eg, 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 (eg, 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.