Conditions: Relapsed/Refractory Aggressive B-Cell Malignancies
Keywords: Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Mantle Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin ROR1 CAR-T cell therapy Autologous CAR-T cell therapy Adoptive cellular therapy Cellular immunotherapy
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 9
Healthy volunteers: no

Brief summary:
This is a Phase 1/2 study to investigate the safety and efficacy of the CAR-T therapy, ONCT-808, in patients with relapsed/refractory (R/R) aggressive B cell malignancies.

Detailed description:
Study ONCT-808-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and tolerability, pharmacokinetics, and anti-tumor activity of ONCT-808 in subjects with aggressive B cell lymphoma (BCL), including large B-cell lymphoma (LBCL) and mantle cell lymphoma (MCL). The study will be separated into two distinct phases designated as Phase 1 and Phase 2.

After the safety and tolerability of ONCT-808 have been assessed to select the recommended Phase 2 dose (RP2D) in Phase 1, Phase 2 will commence to further validate the dose and evaluate the safety and efficacy of ONCT-808. In Phase 2, subjects with LBCL or MCL will be enrolled into 2 separate dose expansion cohorts.

Arms:
arm 1: Patients will receive a conditioning regimen of cyclophosphamide and fludarabine intravenously (IV) followed by ONCT-808 IV infusion escalated sequentially with a target dose consistent with the dose required by cohort being enrolled to determine Phase 2 dose (RP2d) regimen(s). Participants may receive bridging therapy that is appropriate to the subject's disease and treatment history if clinically indicated to maintain disease stability. arm 2: Patients with LBCL or MCL will receive ONCT-808 for each RP2D regimen determined in Phase 1.

Interventions: intervention 1: ONCT-808 intervention 2: Bridging Therapy
Intervention descriptions: intervention 1: A single infusion of ONCT-808 autologous CAR-T cell infusion will be administered intravenously

Phase 1: Dose Escalation with bridging therapy as needed

Phase 2: Patients with LBCL or MCL will be enrolled into two separate dose expansion cohorts. intervention 2: Bridging therapy can be oral chemotherapy or IV radiotherapy/chemotherapy per institution's guidelines

Protocol document:
Prot_SAP_002.pdf: 
 
PHASE 1/2 MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND 
EFFICACY OF ONCT-808 IN ADULT SUBJECTS WITH RELAPSED OR 
REFRACTORY AGGRESSIVE B-CELL MALIGNANCIES 
 
Investigational Product:  
ONCT-808 (ROR1 Chimeric Antigen Receptor [CAR]-positive 
viable T cells) 
Protocol Number:  
ONCT-808-101 
IND Number:  
28759 
Sponsor Name and Address:  
Oncternal Therapeutics, Inc 
12230 El Camino Real, Suite 230 
San Diego, CA 92130 
Sponsor Signatory: 
Salim Yazji, MD 
 
Chief Medical Officer 
 
Oncternal Therapeutics, Inc. 
Emergency Contact: 
Yisrael Katz, MD 
 
Medical Monitor 
 
+1 858-299-5633  
 
clinical@oncternal.com 
Protocol Version, Date: 
Version 3, 16 JAN 2024 
 
 
FOR QUALIFIED PHYSICIANS AND THEIR INSTITUTIONAL REVIEW 
BOARDS/ETHICS COMMITTEES ONLY 
Confidentiality Statement 
The information contained in this document, as well as results of and the information provided regarding the Study described 
in the enclosed protocol (collectively, the “Confidential Information”), including, without limitation, unpublished data and 
Study design elements and parameters, is proprietary and confidential information of Oncternal Therapeutics, Inc. 
(the “Sponsor”). The Confidential Information cannot be used for any purpose other than the conduct of the clinical 
investigation without the prior written consent of Oncternal Therapeutics Inc. This document must not be disclosed to anyone 
other than the site research staff and members of the institutional review board/independent ethics committee, a scientific 
review board or an equivalent, except to the extent and only to the extent, necessary to obtain informed consent from those 
persons to whom the investigational drug may be administered (or their legal representative) in accordance with the enclosed 
protocol. 


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CLINICAL PROTOCOL APPROVAL FORM 
Protocol Number 
ONCT-808-101 
Protocol Title: 
Phase 1/2 Multi-Center Study to Evaluate the Safety and 
Efficacy of ONCT-808 in Adult Subjects with Relapsed or 
Refractory Aggressive B-Cell Malignancies 
Date of Document Approval: 
16 JAN 2024 
Version Number: 
3 
Sponsor Signatory: 
Salim Yazji, MD 
Chief Medical Officer 
Oncternal Therapeutics, Inc. 
Signature: 
 
 
 
 


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INVESTIGATOR’S AGREEMENT 
I have read the attached protocol entitled, “Phase 1/2 Multi-Center Study to Evaluate the Safety 
and Efficacy of ONCT-808 in Adult Subjects with Relapsed or Refractory Aggressive B-Cell 
Malignancies,” and agree to abide by all provisions set forth therein. I agree to personally 
supervise the conduct of this study at my study site and to ensure its conduct is in compliance 
with the protocol, informed consent, Institutional Review Board/Ethics Committee procedures, 
instructions from Oncternal representatives, the principles of the Declaration of Helsinki, 
International Council for Harmonisation Good Clinical Practices Guidelines, and local 
regulations governing the conduct of clinical studies. 
I agree to maintain the confidentiality of all information received or developed in connection 
with this protocol. 
 
 
 
 
________________________________________ 
Printed Name of Investigator 
 
________________________________________ 
Signature of Investigator 
 
________________________________________ 
Date 
 


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TABLE OF CONTENTS 
STATEMENT OF COMPLIANCE ...............................................................................................10 
1. 
PROTOCOL SUMMARY ..........................................................................................11 
1.1. 
Synopsis ......................................................................................................................11 
1.2. 
Study Schema .............................................................................................................15 
1.3. 
Schedules of Assessments ..........................................................................................15 
LIST OF ABBREVIATIONS AND DEFINITIONS ....................................................................18 
2. 
INTRODUCTION ......................................................................................................22 
2.1. 
Study Rationale ...........................................................................................................22 
2.2. 
Background .................................................................................................................22 
2.2.1. 
Large B-Cell Lymphoma ............................................................................................22 
2.2.2. 
Mantle Cell Lymphoma ..............................................................................................23 
2.2.3. 
Receptor Tyrosine Kinase-Like Orphan Receptor 1 ..................................................24 
2.2.4. 
Nonclinical Experience ...............................................................................................26 
2.2.4.1. 
Nonclinical Experience with Zilovertamab ................................................................26 
2.2.4.2. 
Nonclinical Experience with ONCT-808 ...................................................................26 
2.2.5. 
Clinical Experience with ONCT-808 .........................................................................26 
2.2.5.1. 
Clinical Experience with Other ROR1 CAR T Cells .................................................27 
2.2.5.2. 
Clinical Experience with Zilovertamab ......................................................................27 
2.2.5.3. 
Clinical Experience with Zilovertamab Vedotin ........................................................27 
2.3. 
Risk/Benefit Assessment ............................................................................................28 
2.3.1. 
Known or Potential Risks ...........................................................................................28 
2.3.2. 
Known or Potential Benefits .......................................................................................29 
2.3.3. 
Assessment of Potential Risks and Benefits ...............................................................29 
3. 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................31 
3.1. 
Phase 1 ........................................................................................................................31 
3.2. 
Phase 2 ........................................................................................................................31 
4. 
STUDY DESIGN .......................................................................................................33 
4.1. 
Overall Study Design ..................................................................................................33 
4.1.1. 
Phase 1 Dose Escalation .............................................................................................33 
4.1.2. 
Phase 2 Dose Expansion .............................................................................................35 
4.2. 
Scientific Rationale for Study Design ........................................................................35 


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4.2.1. 
Rationale for Study Population ...................................................................................35 
4.2.2. 
Rationale/Justification of Dose ...................................................................................35 
4.2.3. 
Rationale for Lymphodepeleting Chemotherapy ........................................................36 
5. 
STUDY POPULATION .............................................................................................37 
5.1. 
Subject Inclusion Criteria ...........................................................................................37 
5.2. 
Subject Exclusion Criteria ..........................................................................................38 
6. 
STUDY INTERVENTIONS ......................................................................................41 
6.1. 
Informed Consent .......................................................................................................41 
6.2. 
Leukapheresis Period ..................................................................................................41 
6.3. 
Bridging Therapy ........................................................................................................41 
6.4. 
Lymphodepleting Chemotherapy ...............................................................................42 
6.5. 
ONCT-808 ..................................................................................................................43 
6.5.1. 
Description of ONCT-808 ..........................................................................................43 
6.5.2. 
Administration of ONCT-808 .....................................................................................43 
6.5.3. 
Handling and Accountability of ONCT-808 ..............................................................43 
6.5.4. 
Dispensing and Administration of ONCT-808 ...........................................................43 
6.5.5. 
Packaging and Labeling of ONCT-808 ......................................................................44 
6.5.6. 
Shipping, Storage, and Stability of ONCT-808 ..........................................................44 
6.6. 
Immediate and Post-Treatment Assessment Period ...................................................44 
6.7. 
Intermediate Assessment Period .................................................................................44 
6.8. 
Long-Term Follow-up ................................................................................................45 
6.9. 
Concomitant Therapy or Procedures ..........................................................................45 
6.9.1. 
Permitted Therapies ....................................................................................................45 
6.9.2. 
Management of Common Adverse Events .................................................................46 
6.9.2.1. 
Cytokine Release Syndrome .......................................................................................46 
6.9.2.2. 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) ......................46 
6.9.2.3. 
Fever and Neutropenia ................................................................................................46 
6.9.2.4. 
Infection Prophylaxis ..................................................................................................46 
6.9.2.5. 
Blood Product Support ...............................................................................................46 
6.9.2.6. 
Acute Allergic/Infusion Reaction ...............................................................................47 
6.9.2.7. 
Tumor Lysis Syndrome ..............................................................................................47 
6.9.2.8. 
Hypotension and Renal Insufficiency .........................................................................47 


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6.9.3. 
Prohibited Medications ...............................................................................................47 
7. 
STUDY INTERVENTION DISCONTINUATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWL .....................................................................48 
7.1. 
Reasons for Subject Removal from the Study ............................................................48 
7.1.1. 
End of Study Definition ..............................................................................................48 
7.1.2. 
Study Discontinuation ................................................................................................48 
7.1.3. 
Study Stopping Rules .................................................................................................49 
7.1.4. 
Subject Replacement ..................................................................................................49 
8. 
STUDY ASSESSMENTS AND PROCEDURES ......................................................50 
8.1. 
Response Assessment .................................................................................................50 
8.2. 
Other Assessments and Procedures ............................................................................50 
8.2.1. 
Demographic/Medical History ...................................................................................50 
8.2.2. 
Physical Examination .................................................................................................51 
8.2.2.1. 
Vital Signs ..................................................................................................................51 
8.2.2.2. 
Weight and Height ......................................................................................................51 
8.2.3. 
Cardiac Assessments ..................................................................................................51 
8.2.3.1. 
Electrocardiogram .......................................................................................................51 
8.2.3.2. 
ECHO/MUGA ............................................................................................................51 
8.2.4. 
Neurological and ICANS Assessments ......................................................................51 
8.2.5. 
Replication Competent Lentivirus Monitoring ...........................................................52 
8.2.6. 
Hematology .................................................................................................................52 
8.2.7. 
Serum Chemistry ........................................................................................................52 
8.2.8. 
Urinalysis ....................................................................................................................52 
8.2.9. 
Coagulation .................................................................................................................52 
8.2.10. 
Pregnancy Test ............................................................................................................53 
8.2.11. 
Serum Virology ..........................................................................................................53 
8.2.12. 
Cytokines ....................................................................................................................53 
8.2.13. 
Immunogenicity Assessments ....................................................................................53 
8.2.14. 
ONCT-808 Pharmacokinetic Assessments .................................................................53 
8.2.15. 
Immunophenotyping ...................................................................................................53 
8.2.16. 
Biomarker Assessments ..............................................................................................54 
8.2.17. 
Bone Marrow Biopsy and Aspirate ............................................................................54 
8.2.18. 
Archival or Fresh Tumor Biopsy ................................................................................54 


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8.2.19. 
Blood for Inflammatory Markers ................................................................................54 
8.3. 
Adverse Events and Serious Adverse Events .............................................................54 
8.3.1. 
Definition of an Adverse Event ..................................................................................54 
8.3.2. 
Abnormal Laboratory Values .....................................................................................55 
8.3.3. 
Pre-Existing Medical Conditions ................................................................................56 
8.3.3.1. 
Hospitalization or Prolonged Hospitalization .............................................................56 
8.3.3.2. 
Disease Progression, Relapse, or Disease-Related Death ..........................................56 
8.3.4. 
Grading of Adverse Events .........................................................................................56 
8.3.5. 
Relationship to Study Drug ........................................................................................57 
8.3.6. 
Definition of a Serious Adverse Event .......................................................................59 
8.3.7. 
Definition of Dose-Limiting Toxicity ........................................................................59 
8.3.8. 
Adverse Events of Special Interest .............................................................................60 
8.3.9. 
Time Period and Frequency for Collecting AE and SAE Information .......................60 
8.3.10. 
Recording of Adverse Events and Serious Adverse Events .......................................61 
8.3.11. 
Pregnancy and Reporting ............................................................................................61 
8.4. 
Reporting of SAEs, AESIs, and DLTs .......................................................................62 
8.5. 
Follow-up of AEs and SAEs .......................................................................................63 
8.5.1. 
Regulatory Reporting Requirements for SAEs ...........................................................63 
8.5.2. 
Reporting Requirements for Pregnancies ...................................................................63 
9. 
STATISTICS ..............................................................................................................65 
9.1. 
Sample Size Determination ........................................................................................65 
9.2. 
Populations for Analysis .............................................................................................65 
9.3. 
Statistical Analyses .....................................................................................................65 
9.3.1. 
Statistical Hypotheses .................................................................................................65 
9.4. 
Statistical Analysis Methods .......................................................................................66 
9.5. 
Analysis of the Primary Endpoints .............................................................................66 
9.5.1. 
Analysis of the Anti-Tumor Endpoints .......................................................................66 
9.5.2. 
Safety Analyses ..........................................................................................................66 
9.6. 
Pharmacokinetic Analysis ..........................................................................................67 
9.7. 
Baseline Descriptive Statistics ....................................................................................67 
9.8. 
Tabulation of Individual Subject Data ........................................................................67 
10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ..................................................................................................68 


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10.1. 
Regulatory, Ethical, and Oversight Considerations ....................................................68 
10.1.1. 
Institutional Review Board/Ethics Committee Process ..............................................68 
10.1.1.1. 
Written Informed Consent ..........................................................................................68 
10.1.2. 
Study Discontinuation and Closure ............................................................................68 
10.1.3. 
Confidentiality and Privacy ........................................................................................69 
10.1.4. 
Safety Oversight .........................................................................................................70 
10.1.4.1. 
Safety Review Committee ..........................................................................................70 
10.1.5. 
Study Monitoring ........................................................................................................70 
10.1.6. 
Quality Assurance and Quality Control ......................................................................71 
10.1.7. 
Data Handling and Record Keeping ...........................................................................72 
10.1.7.1. 
Data Collection and Management Responsibilities ....................................................72 
10.1.7.2. 
Study Records Retention ............................................................................................72 
10.1.8. 
Protocol Deviations ....................................................................................................72 
10.2. 
Financial Disclosure ...................................................................................................73 
10.3. 
Publication Policy .......................................................................................................73 
11. 
REFERENCES ...........................................................................................................74 
APPENDIX 1. LUGANO CLASSIFICATION ..........................................................................80 
APPENDIX 2. EASTERN COOPERATIVE ONCOLOGY GROUP PERFORMANCE 
STATUS .....................................................................................................................82 
APPENDIX 3. AMERICAN SOCIETY FOR TRANSPLANTATION AND 
CELLULAR THERAPY CONSENSUS GRADING SYSTEM AND 
TOXICITY MANAGEMENT ....................................................................................83 
APPENDIX 4. ASTCT IMMUNE EFFECTOR CELL-ASSOCIATED 
NEUROTOXICITY SYNDROME GRADING .........................................................84 
 
LIST OF TABLES 
Table 1: 
Schedule of Assessment: Screening Through Month 3 ..............................................16 
Table 2: 
Schedule of Assessment: Intermediate Assessment Period and Long-Term 
Follow-Up ...................................................................................................................17 
Table 3: 
CRS and Neurotoxicity with Approved Autologous CD19 CAR T-Cell 
Therapies in Relapsed/Refractory B-Cell Lymphoma ...............................................29 
Table 4: 
Phase 1 Objectives and Endpoints ..............................................................................31 
Table 5: 
Phase 2 Objectives and Endpoints ..............................................................................31 
Table 6: 
Phase 1 Dose Levels ...................................................................................................34 


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Table 7: 
Grading of Adverse Event Severity Using CTCAE, Version 5.0 ...............................57 
Table 8: 
Relationship of Study Treatment to Adverse Event ...................................................58 
Table 9: 
ASTCT Cytokine Release Syndrome Consensus Grading System a ..........................83 
Table 10: ASTCT Immune Effector Cell-Associated Neurotoxicity Syndrome Gradinga .........84 
 
LIST OF FIGURES 
Figure 1: 
Survival of Patients with Mantle Cell Lymphoma Who Progressed After 
Brexucabtagene Autoleucel Therapy (n=6) ................................................................24 
Figure 2: 
ROR1 Cell Surface Levels on MCL Patient Cells ......................................................25 
Figure 3: 
Expression of the ROR1 Protein in DLBCL Lymphoma Tissues ..............................25 
 
 


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STATEMENT OF COMPLIANCE 
The study will be conducted in accordance with International Council for Harmonisation Good 
Clinical Practice (ICH GCP), applicable United States (US) Code of Federal Regulations (CFR), 
and the country-specific Health or Regulatory Authority regulations and guidance. The Principal 
Investigator will assure that no deviation from, or changes to the protocol will take place without 
prior agreement from Oncternal Therapeutics, Inc. (the Sponsor) and documented approval from 
the Institutional Review Board (IRB) or Ethics Committee (EC), except where necessary to 
eliminate an immediate hazard(s) to the study subjects. All personnel involved in the conduct of 
this study have completed Human Subjects Protection and ICH GCP Training. 
The protocol, Informed Consent Form(s) (ICF[s]), recruitment materials, and all subject 
materials will be submitted to the IRB/EC for review and approval. Approval of both the 
protocol and the ICF must be obtained before any subject is enrolled. Any amendment to the 
protocol will require review and approval by the IRB/EC before the changes are implemented to 
the study. All changes to the ICF will be IRB/EC approved; a determination will be made 
regarding whether a new consent needs to be obtained from participants who provided consent, 
using a previously approved ICF. 


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1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Title 
Phase 1/2 Multi-Center Study to Evaluate the Safety and Efficacy of ONCT-808 in Adult 
Subjects with Relapsed or Refractory Aggressive B-Cell Malignancies  
Indication 
The indication is for the treatment of adult subjects with relapsed or refractory (R/R) B-cell 
malignancies.  
Study Design 
Study ONCT-808-101 is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the 
safety, tolerability, anti-tumor activity, and pharmacokinetics (PK) of ONCT-808 in subjects 
with aggressive B-cell non-Hodgkin malignancies, including large B-cell lymphoma (LBCL) and 
mantle cell lymphoma (MCL). The study will be separated into Phase 1 and Phase 2 portions.  
In Phase 1, all subjects will be assigned to dose levels using a 3+3 dose escalation design. Dose 
escalation or de-escalation will occur based on evaluations by the Safety Review Committee 
(SRC) in consultation with the Investigators. In Phase 1, approximately 3 dose levels will be 
evaluated in a 3+3 design, resulting in an expected sample size of up to 18 subjects for dose 
escalation purposes. After safety has been established and dose escalation may occur at a 
particular dose level, an additional 3 subjects per dose cohort (maximum 9 subjects per dose 
level) may be enrolled to further investigate the safety and PK. The estimated maximum sample 
size in Phase 1 is expected to be 27 subjects. Additional subjects may be enrolled to account for 
dose-limiting toxicity (DLT) unevaluable subjects. Refer to Section 9.2 for the definition of 
evaluability. 
After the safety, PK, pharmacodynamics, and preliminary efficacy of ONCT-808 have been 
assessed by the SRC to select the recommended Phase 2 dose (RP2D) in Phase 1 and the 2 dose 
levels to be studied in Phase 2 (which includes the RP2D), Phase 2 will commence to further 
validate the dose and evaluate the safety and efficacy of ONCT-808.  
The Phase 2 Dose Expansion portion of the study will consist of 2 randomized cohorts. Subjects 
will be assigned randomly to a Phase 2 cohort, stratified by lymphoma subtype (MCL or LBCL) 
and will be assigned 1 of 2 doses of ONCT-808 that will be based on the SRC’s evaluation of 
safety data and any PK, pharmacodynamics, and efficacy data from each dose cohort in Phase 1. 
In Phase 2, up to 18 evaluable subjects will be randomized to 1 of 2 dose-level-specific 
expansion cohorts in a Simon 2-stage design to exclude an objective response rate (ORR; either 
complete response [CR] or partial response [PR]) <10%. The hypothesized response rate under 
treatment is ≥40% and will be evaluated using a one-sided type I error rate of 0.025 with 80% 
power. Each dosing cohort will evaluate the first 7 subjects for efficacy in Stage 1, and a dosing 
cohort will be terminated if <2 subjects respond. A cohort progressing to Stage 2 will treat an 
additional 11 subjects for a total of up to 18 subjects. If at least 5 subjects respond out of the total 
18, there will be demonstration of efficacy of ONCT-808 within that dosing cohort and the 


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corresponding null hypothesis will be rejected. Additional subjects may be enrolled to account 
for unevaluable subjects. The estimated maximum sample size is 24 per cohort. 
All subjects will undergo the following: 
• Screening: Determining eligibility, within 28 days of enrollment. 
• Enrollment/Leukapheresis: Subjects will undergo an unstimulated leukapheresis to 
collect leukocytes for the manufacturing of ONCT-808.  
• Bridging therapy: If indicated in the Investigator’s opinion. Restaging will be 
required. Bridging therapy prior to leukapheresis must be discussed with the Sponsor. 
• Lymphodepletion: Prior to receipt of ONCT-808, subjects will receive 
lymphodepleting chemotherapy. 
• Immediate Post-Treatment Period: ONCT-808 will be infused intravenously (IV) 
followed by 14 days of intensive clinical and laboratory observation. 
• Post-Treatment Assessment Period: Subjects will be evaluated for potential 
toxicities and disease response for a total of 3 months. 
• Intermediate Period: Subjects will be evaluated every 3 months up to Month 12, and 
then every 6 months up to Month 24. 
• Long-Term Follow-Up: Subjects will be monitored for a total of 15 years. 
For study requirements assigned to each study period, please refer to Section 6 for details.  
Study Objectives 
The primary objectives of Phase 1 are to evaluate the safety and tolerability of ONCT-808 and to 
determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of 
ONCT-808. The SRC will evaluate ONCT-808 safety, PK, pharmacodynamics, and preliminary 
efficacy and select the RP2D and the 2 dose levels (which includes the RP2D) to be studied in 
Phase 2.  
The primary objective of Phase 2 is to evaluate the efficacy of ONCT-808, as measured by ORR, 
CR rate, and duration of response (DOR), with tumor response measured according to Lugano 
2014 (Cheson, 2014). Secondary objectives will include assessing the PK of ONCT-808, as well 
as to further characterize the safety and tolerability and evaluate the risk/benefit of ONCT-808 at 
2 dose levels, in alignment with the United States (US) Food and Drug Administration’s (FDA’s) 
Project Optimus. 
Study Eligibility  
Adult subjects with R/R aggressive B-cell malignancies, including LBCL and MCL, able to 
undergo ONCT-808 treatment. Please refer to Section 5 for a complete and detailed list of 
inclusion and exclusion criteria for both phases of the study.  
Treatment  
Investigational Product:  


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• ONCT-808 treatment consists of a single infusion of chimeric antigen receptor 
(CAR)-transduced autologous T cells (CD4+ and CD8+) administered intravenously 
at the appropriate target dose (see Section 4.1). Refer to Section 6.5.2 for treatment 
details.  
Lymphodepleting Chemotherapy Treatment:  
Subjects will receive a lymphodepleting conditioning regimen as outpatients (unless their clinical 
condition requires inpatient administration) consisting of cyclophosphamide and fludarabine to 
induce lymphocyte depletion and create an optimal environment for expansion of ONCT-808. 
Subjects will initiate lymphodepleting chemotherapy with cyclophosphamide 500 mg/m2 and 
fludarabine 30 mg/m2 on 3 days (usually consecutive) beginning 5 to 7 days before the planned 
administration of ONCT-808. A lower dose regimen may be used at the Investigator’s discretion. 
Refer to Section 6.4 for lymphodepleting chemotherapy treatment details.  
Procedures 
At specific timepoints as outlined in the schedules of assessments (Table 1 for Screening through 
Month 3 and  
Table 2 for the Intermediate Assessment Period and Long-Term Follow-Up), subjects will 
undergo assessments/procedures including: informed consent, medical history and disease 
assessment (including and Eastern Cooperative Oncology Group performance status), physical 
examination (including vital signs and weight), cardiac and neurological assessments, blood 
draws for complete blood count, chemistry panels, coagulation tests, markers of inflammation, 
cytokines, exploratory biomarkers lymphocyte subsets, ONCT-808 immunogenicity testing, 
replication competent lentivirus, and ONCT-808 PK assessments. Women of child-bearing 
potential will undergo a urine or serum pregnancy test. Subjects will also undergo a baseline 
electrocardiogram, echocardiogram or multi-gated acquisition cardiac scan, positron emission 
tomography–computed tomography bone marrow aspirate and biopsy (MCL only), and 
leukapheresis. 
Routinely throughout the conduct of the study, subjects will be asked to report concomitant 
medications and adverse events and will have their disease assessed.  
Safety Review Committee 
An SRC that is composed of the Phase 1 study Investigators, cross-functional representatives 
from the Sponsor, and includes at least 1 independent member with clinical and safety expertise 
who is not directly involved with the study will review safety data and make recommendations. 
The SRC will review the safety data from each dose cohort in Phase 1 along with the 
Investigators and will make dosing recommendations prior to proceeding to the next dose level. 
The SRC will also select the 2 doses, which will include the RP2D, to be used in the Phase 2 
expansion based on a combination of safety, PK, pharmacodynamics, and preliminary efficacy 
data. The RP2D may fall at or below the MTD or MAD. Additional details are provided in 
Section 10.1.4.1.  
Statistical Considerations 
The primary endpoints for the Phase 1 part of the study are the incidence, severity of DLTs, as 
well as the safety profile of ONCT-808, including incidence, severity, and relationship of 


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treatment emergent AEs, clinical laboratory assessments, and concomitant medications. Phase 1 
Dose Escalation will proceed to determine the MTD and/or RP2D. No hypothesis testing will be 
performed on Phase 1. 
The primary endpoints for the Phase 2 part of the study are ORR, CR rate, and DOR per 
Lugano 2014 (Cheson, 2014).  
Additional details on the statistical analysis methods planned for this study are provided in 
Section 9.4. 


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1.2. 
Study Schema 
 
CAR, chimeric antigen receptor; CRR, complete response rate; DOR, duration of response; LBCL, large B-cell 
lymphoma; MAD, maximum administered dose; MCL, mantle cell lymphoma; MTD, maximum tolerated dose; 
NHL, non-Hodgkin’s lymphoma; ORR, objective response rate; PK, pharmacokinetic(s) 
1.3. 
Schedules of Assessments 
The Schedules of Assessments for Screening through Month 3 and for the Intermediate 
Assessment Period and Long-Term Follow-Up are provided in Table 1 and Table 2, respectively.


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Table 1: 
Schedule of Assessment: Screening Through Month 3 
Procedure 
 
Screening 
Leukapheresis 
Period 
Lymphodepletion 
Period2 
Immediate Post-
Treatment Period  
Post-Treatment Assessment Period 
(From Day 8) 
Section 
 
5  
6.2  
6.4  
6.5/6.6  
6.7  
Day/Month 
Section 
Within 28 
d of enroll 
 
LC1 
LC2 
LC3 
D1 
D1-14 
± 1 d 
D15 
± 1 d 
D22 
± 2 d 
D29  
± 2 d 
M2 
± 7 d 
M3  
± 7 d 
Informed consent 
6.1  
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history, ECOG & disease 
assessment 
8.2.1  
X 
 
 
 
 
 
 
 
 
 
 
 
ECG & LVEF by ECHO or MUGA 
8.2.3  
X 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy test 
8.2.10  
X 
 
X 
 
 
 
 
 
 
 
 
X 
Blood for HIV, HBV, HCV testing 
8.2.11  
X 
 
 
 
 
 
 
 
 
 
 
 
Blood for inflammatory markers 
8.2.19 
X 
 
 
 
 
 
 
 
 
 
 
 
Urine for urinalysis 
8.2.8  
X 
 
X 
 
 
 
 
 
 
 
 
 
Blood for hematology 
8.2.6  
X 
X 
X 
 
 
X 
D3, 8 & 12 
X 
X 
X 
X 
X 
Blood for chemistry panel 
8.2.7  
X 
 
X 
 
 
X 
QOD 
X 
 
X 
X 
X 
Blood for coagulation tests 
8.2.9  
 
 
X 
 
 
X 
D3 
X 
 
X 
X 
X 
PET-CT & disease assessment 
8.1  
X 
X1 
 
 
 
 
 
 
 
X 
 
X 
Bridging therapy (if indicated) 
6.3  
 
X 
 
 
 
 
 
 
 
 
 
 
Bone marrow biopsy & aspirate 
8.2.17  
 
X3 
 
 
 
 
 
 
 
 
 
 
Archival tissue/fresh tumor biopsy 
8.2.18 
 
X4 
 
 
 
 
 
 
 
 
 
 
Leukapheresis 
6.2  
 
X 
 
 
 
 
 
 
 
 
 
 
Cyclophosphamide/Fludarabine 
6.4  
 
 
X 
X 
X 
 
 
 
 
 
 
 
ONCT-808 infusion IV 
6.5.2  
 
 
 
 
 
X 
 
 
 
 
 
 
Vital signs & physical exam 
8.2.2  
X 
X (+weight) 
X 
 
 
X (+ weight) 
QOD5 
X 
X 
X 
X 
X 
ICANS monitoring 
8.2.4  
X 
 
 
 
 
X 
QOD 
X 
X 
X 
X 
X 
CRS monitoring 
6.9.2.1  
 
 
 
 
 
X 
QOD 
X 
X 
X 
 
 
Serum for cytokines 
8.2.12  
X 
 
 
 
 
X6 
QOD 
X 
X 
X 
X 
X 
Blood for ROR1 CAR-T PK 
8.2.14  
 
 
 
 
 
X6 
D3, 8 & 12 
X 
X 
X 
X 
X 
Blood for immunophenotyping 
8.2.15  
 
 
 
 
 
X6 
 
X 
 
X 
 
X 
Blood/serum for immunogenicity 
8.2.13  
 
 
 
 
 
X6 
 
X 
 
X 
 
X 
Blood for exploratory biomarkers 
8.2.16  
 
 
 
 
 
X6 
 
X 
 
X 
 
X 
Serum for RCL analysis 
8.2.5  
 
X 
 
 
 
 
 
 
 
 
 
X 
AEs/Concomitant medication 
8.3/6.9  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1- Repeat PET-CT only if clinically indicated (e.g., symptomatic deterioration) or if bridging therapy was administered. 
2- LC1 is the first day of the 3 days of lymphodepleting chemotherapy, administered outpatient, starting 5 to 7 days prior to ONCT-808 infusion. 
3- Bone marrow biopsy and aspirate required prior to lymphodepletion and to confirm CR for subjects with MCL only. 
4- Tumor biopsy prior to lymphodepletion only required if archival tissue is not available.  
5- Physical exams and assessments performed in the inpatient setting may be performed by any qualified individual operating within the scope of their license. 
6- Baseline samples to be collected on the day of ONCT-808 administration prior to the infusion. 
 


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Table 2: 
Schedule of Assessment: Intermediate Assessment Period and Long-Term Follow-Up 
1- Until progressive disease or initiation of alternate systemic therapy for their cancer. If the subject is still on study after month 24, disease assessments will continue to be performed 
according to standard of care. 
2- Assessments to be performed up to Month 24, or until progressive disease or initiation of alternate systemic therapy; only AEs attributable to ONCT-808 thereafter. 
3- If no evidence of RCL is observed at the 3-, 6-, and 12-month timepoints, RCL monitoring will not need to be performed for that subject thereafter. 
 
 
 
Intermediate Assessment Period 
LTFU 
Section 
 
6.7 
6.8   
Procedure 
Day 
 
Section 
M6 
± 14 d 
M9 
± 14 d 
M12 
± 14 d 
M18 
± 14 d 
M24 
± 14 d 
Annually for a Total 
of 15 years 
Physical exam2 
8.2.2  
X 
X 
X 
X 
X 
 
PET-CT & disease assessment1 
8.1  
X1 
X1 
X1 
X1 
X1 
X1 
AE/SAEs2 
8.3  
X 
X 
X 
X 
X 
X 
Concomitant medications2 
6.9  
X 
X 
X 
X 
X 
 
Blood for CBC w/differential2 
8.2.6  
X 
X 
X 
X 
X 
 
Blood for ROR1 CAR-T PK2 
8.2.14  
X 
X 
X 
 
X 
 
Blood/Serum for immunogenicity2 
8.2.13  
 
 
X 
 
X 
 
Blood for exploratory biomarkers 
8.2.16  
X 
 
X 
 
 
 
Survival status 
6.8  
 
 
 
 
 
X 
Blood for RCL analysis3 
8.2.5  
X 
 
X 
X3 
X3 
 


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LIST OF ABBREVIATIONS AND DEFINITIONS 
Abbreviation  
Explanation 
ADC 
antibody-drug conjugate 
AE 
adverse event 
AESI 
adverse event of special interest 
ALC 
absolute lymphocyte count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
ASTCT 
American Society for Transplantation and Cellular Therapy 
BCL 
B-cell lymphoma 
βHCG 
beta human chorionic gonadotropin 
BiPAP 
bilevel positive airway pressure 
BTK 
Bruton’s tyrosine kinase 
CAR 
chimeric antigen receptor 
CD 
cluster of differentiation 
CDX 
cell line-derived xenografts 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CLL 
chronic lymphocytic leukemia 
CMV 
cytomegalovirus 
CNS 
central nervous system 
COVID-19 
Coronavirus disease 2019 
CPAP 
continuous positive airway pressure 
CR 
complete response  
CRS 
cytokine release syndrome 
CSF 
cerebrospinal fluid 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLBCL 
diffuse large B-cell lymphoma 
DLT 
dose-limiting toxicity 
DOR 
duration of response 
EC 
Ethics Committee 


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Abbreviation  
Explanation 
ECG 
Electrocardiogram 
ECHO 
echocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
EEG 
electrocardiogram 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
GCP 
Good Clinical Practice 
HBc  
anti-hepatitis B core  
HbsAg 
hepatitis B surface antigen 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplantation 
ICANS 
immune effector cell-associated neurotoxicity syndrome 
ICE 
immune Effector Cell-Associated Encephalopathy 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
ICP 
intracranial pressure 
ICU 
intensive care unit 
IL 
interleukin 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
LBCL 
large B-cell lymphoma 
LC 
lymphodepleting chemotherapy 
LDH 
lactate dehydrogenase 
LTFU 
Long-Term Follow-Up 
LVEF 
left ventricular ejection fraction 
mAb 
monoclonal antibody 


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Abbreviation  
Explanation 
MAD 
maximum administered dose 
MCL 
mantle cell lymphoma 
MMAE 
monomethyl auristatin E 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MUGA 
multi-gated acquisition scan 
NA 
not applicable 
NAT 
nucleic acid test 
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NHL 
non-Hodgkin’s lymphoma 
NOS 
not otherwise specified 
ORR 
objective response rate 
OS 
overall survival 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
PT 
partial thromboplastin time 
QOD 
every other day 
RCL 
replication competent lentivirus 
RP2D 
recommended Phase 2 dose 
R/R 
relapsed or refractory 
ROR1 
receptor tyrosine kinase-like orphan receptor 1 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
scFv 
single chain variable fragment 
SD 
stable disease 
SRC 
Safety Review Committee 
SOP 
Standard Operating Procedures 
TEAE 
treatment-emergent adverse event 


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Abbreviation  
Explanation 
TLS 
tumor lysis syndrome 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States Prescribing Information 
 


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2. 
INTRODUCTION 
2.1. 
Study Rationale 
This is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and 
tolerability, anti-tumor activity, and pharmacokinetics (PK) of ONCT-808 and to determine the 
recommended Phase 2 dose (RP2D) of ONCT-808, an autologous receptor tyrosine kinase-like 
orphan receptor 1 (ROR1) chimeric antigen receptor (CAR) expressing T-cell therapy, in 
subjects with relapsed or refractory (R/R) aggressive B-cell malignancies, including large B-cell 
lymphoma (LBCL) or mantle cell lymphoma (MCL). Patients treated with CAR T-cell therapies 
targeting CD19 have enjoyed dramatic and prolonged clinical responses with substantial but 
acceptable toxicities. A ROR1 targeting CAR T cells is scientifically supported, because ROR1 
expression is associated with a particularly aggressive tumor phenotype and adverse outcomes. 
Patients with LBCL or MCL who have failed CD19 CAR T-cell therapy have a particularly 
dismal prognosis, and their tumors are expected to express ROR1. 
2.2. 
Background 
2.2.1. 
Large B-Cell Lymphoma 
LBCL is the most common subtype of NHL, constituting 25% to 30% of adult NHLs in Western 
countries (Swerdlow, 2008; Flowers, 2010). The age-standardized incidence rate ranges from 
4 to 7 per 100,000 person-years in Western countries, with a median age at diagnosis in the 70s 
(Sant, 2010; Morton, 2006).  
Although many patients with LBCL are cured or achieve long-term remission after rituximab 
and anthracycline-containing first-line immunochemotherapy, and patients who have a relapse 
with chemotherapy-sensitive disease may be treated with high-dose chemotherapy followed by 
autologous stem cell transplantation (Sehn, 2020), patients who have disease that is resistant to 
primary or salvage chemoimmunotherapy or who have had a relapse after transplantation have 
an extremely poor prognosis. In a large, international, retrospective study involving patients with 
non-Hodgkin’s lymphoma (SCHOLAR-1), Investigators found an objective response rate (ORR) 
of 26%, a complete response (CR) rate of 7%, and a median overall survival (OS) of 6.3 months 
with existing therapies among patients who had aggressive B-cell lymphoma (BCL) that was 
resistant to chemotherapy or who had a relapse within 12 months after autologous stem cell 
transplantation (Crump, 2017). 
Recent developments have supported the effectiveness of therapies that utilize T cells in the 
treatment of R/R aggressive B-cell non-Hodgkin lymphomas (NHLs). These therapies generally 
utilize ex vivo genetic engineering of autologous or allogeneic T cells to express CARs that 
target lineage-specific surface proteins such as CD19. CAR T-cell therapy has shown remarkable 
effectiveness for patients with R/R CD19-expressing B lymphoid malignancies (Liu, 2020). 
There are now 3 CD19-targeted CAR T-cell therapies that have been approved by the US Food 
and Drug Administration (FDA) for adult patients with R/R LBCL after 2 or more lines of 
systemic therapy. Axicabtagene ciloleucel (YESCARTA® US Prescribing Information [USPI]), 
tisagenlecleucel (KYMRIAH® USPI) and lisocabtagene maraleucel (BREYANZI® USPI) were 
approved based on observed ORR rates and remissions that are more durable when compared 
with similar patients treated with immunochemotherapy (Crump 2017).  


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Despite high response rates and frequent CRs, relapse following CD19 targeted autologous CAR 
T-cell therapy is still observed. Fewer than 50% of patients with high-grade B-cell lymphomas 
(BCL), diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), or LBCL 
transformed from indolent NHL other than follicular lymphoma were relapse-free by 6 months 
after treatment with lisocabtagene maraleucel (Abramson, 2020). Thus, there is unmet need for 
additional therapies for R/R LBCL, including those who have relapsed following CD19 CAR T-
cell therapy. 
2.2.2. 
Mantle Cell Lymphoma 
MCL is another form of B-cell NHL with an aggressive clinical course. MCL consists of 
approximately 7% of the adult NHLs in the US and Europe, with an incidence of approximately 
4 to 8 cases per million persons per year. Incidence is shown to increase with age and appears to 
be increasing overall in the US.  
While there are several therapeutic options available to treat patients with R/R MCL, none of 
these options offer optimal long-term benefit, with most patients relapsing in less than 
20 months. Bruton's tyrosine kinase (BTK) inhibitors have greatly improved outcomes in the 
R/R setting but patients who progress on these agents have a poor prognosis, with an ORR of 
25% to 42% and median OS of 6 to 10 months with salvage therapies (Wang, 2020).  
Brexucabtagene autoleucel (Tecartus PI, 2021), a CD19 CAR T-cell therapy, was approved by 
the FDA in 2020 for treatment of R/R MCL under accelerated approval demonstrating durable 
long-term responses and may confer benefit in patients with high risk characteristics. After ~3 
years of follow-up, the ORR was 91% (CR of 68%; 95% CI, 55.2-78.5); medians for DOR, PFS 
and OS were 28.2 months (95% CI, 13.5 to 47.1), 25.8 months (95% CI, 9.6 to 47.6), and 46.6 
months (95% CI, 24.9 to NE), respectively (Wang, 2022).  
The rationale to include patients with MCL who have relapsed or are refractory to CD19 CAR T-
cell therapy is based on the significant percentage of progressive disease (14 of 56; 25%) in 
patients who initially responded to CD19 CAR T-cell therapy (Jain, 2021). The median response 
duration on CD19 CAR T-cell therapy was 6 months (range 1.2 to 31.2 months). Overall, 
5 patients had died at the time of last follow-up and the median OS from the time of starting 
CD19 CAR T-cell therapy to their last follow-up was 17 months, while the median OS after 
progression on CAR T-cell therapy was only 4.1 months with a 1-year survival of 0% (Figure 1; 
Jain, 2021).  


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Figure 1: 
Survival of Patients with Mantle Cell Lymphoma Who Progressed After 
Brexucabtagene Autoleucel Therapy (n=6) 
 
Source: Jain, 2021 
Therefore, a significant unmet medical need exists for patients with R/R MCL that have disease 
progression after CD19 CAR T-cell treatment.  
The overexpression of ROR1 in many MCL cells combined with the crosstalk observed between 
ROR1 and multiple signaling pathways promoting cancer cell survival, proliferation, and 
metastasis provide a very strong rationale for targeting ROR1 for MCL therapy (Yu, 2018). 
2.2.3. 
Receptor Tyrosine Kinase-Like Orphan Receptor 1 
ROR1 is a type 1 transmembrane protein that shares homology to other receptor tyrosine kinases 
and shows very high evolutionary conservation (Masiakowski, 1992; Forrester, 1999; Yoda, 
2003; Katoh, 2005). It has no known physiological role in the adult but is essential for normal 
embryogenesis (Oishi, 1999; Al-Shawi, 2001; Matsuda, 2001; Lyashenko, 2010). Expression of 
the ROR1 gene is suppressed prior to birth (Masiakowski, 1992; Al-Shawi, 2001; Paganoni, 
2010).  
ROR1 is frequently re-expressed by cancers and its expression is associated with an aggressive 
phenotype, including invasiveness, metastasis, and resistance to therapy in both hematological 
and solid tumors (Li, 2010; Zhang, 2012; Daneshmanesh, 2013; Gentile, 2011; Yamaguchi, 
2012; O'Connell, 2013; Ida, 2016; Janovska, 2016; Karvonen, 2018). Elevated levels of ROR1 
expression in patients’ tumors and cell lines is associated with genes involved in epithelial-
mesenchymal transition (Cui 2013). High levels of ROR1 expression are associated with shorter 
treatment-free survival and OS in patients with both hematological and solid tumors (Cui, 2016; 
Chien, 2016; Zhang, 2014).  
High levels of ROR1 protein expression have been found in multiple cancers, including both 
hematological malignancies such as MCL (Figure 2), chronic lymphocytic leukemia (CLL), 
acute lymphocytic leukemia, and LBCL (Figure 3) (Yu, 2018; Karvonen, 2018; Daneshmanesh, 
2008; Baskar, 2008; Hudecek, 2010; Barna, 2011; Uhrmacher, 2011; Daneshmanesh, 2013; 
Kotašková, 2016), and in solid tumors including but not limited to breast, lung, colon, head and 
neck, prostate and pancreatic cancers (Zhang, 2012; Liu, 2015). 


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Figure 2: 
ROR1 Cell Surface Levels on MCL Patient Cells 
 
ROR1 expression on primary MCL patient samples, including CD19 CAR T-cell resistant MCL patient cells. (a) 
ROR1 expression detected by flow cytometry in primary MCL patient samples (n=26), classified into 4 groups: 
BTKi-naïve (n=4), BTKi-sensitive (n=13), BTKi-resistant (n = 6) and CAR T cell relapsed (n=3). (b) Cell surface 
ROR1 expression of the 4 groups in (a) normalized to controls.  
Source: Jiang, 2021 
ROR1 expression was observed frequently in primary refractory diffuse LBCL (DLBCL; 7/11, 
83%), Richter´s syndrome (9/10, 90%), and transformed follicular lymphoma (9/11, 82%), and 
also in relapsed (8/22, 36%) and non-relapsed DLBCL patients (10/30, 33%) (p < 0.001) 
(Figure 3; Ghaderi, 2020). A negative survival effect of ROR1 expression was observed in R/R 
LBCL patients independent of gender and stage (Ghaderi, 2020). 
Figure 3: 
Expression of the ROR1 Protein in DLBCL Lymphoma Tissues 
 
 
ROR1 expression in aggressive B-cell samples. Numbers in brackets represent the number of ROR1-positive cases 
compared to the total number of cases in each group.  
Source: (Ghaderi, 2020) 
ROR1 expression in LBCL patients correlated with lymph node involvement and clinical stage 
of disease. OS substantially correlated with ROR1 expression. Reduction of ROR1 expression 


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using ROR1-targeted shRNAs in LBCL cell lines in vitro significantly reduced cell proliferation 
and PI3K/AKT signaling and significantly increased apoptosis and caspase-3 activation. In 
xenograft studies using the same shRNA, tumor growth was substantially slower in the 
shRNA-treatment groups (Mao, 2019). 
2.2.4. 
Nonclinical Experience 
2.2.4.1. 
Nonclinical Experience with Zilovertamab 
ONCT-808 expresses a CAR that utilizes the ROR1 binding scFv derived from zilovertamab 
(previously designated UC-961 or cirmtuzumab), which was developed in a bedside to bench 
effort based on the detection of autoantibodies to ROR1 in the sera of patients vaccinated with 
autologous leukemia cells that were capable of inducing apoptosis of CLL cells (Fukuda, 2008). 
Monoclonal antibodies to ROR1 were developed and selected based on the ability to inhibit the 
ROR1 intracellular pathway and decrease the engraftment of ROR1 expressing cell lines 
(Widhopf, 2014), culminating in the development of zilovertamab as a high-affinity humanized 
IgG1 binding to a functionally important epitope of human ROR1 (Choi, 2015). A GLP human 
tissue cross reactivity study showed no binding of zilovertamab to any adult tissues from 
3 individuals at concentrations up to 5 times the optimal concentration for binding to tumor 
tissues (Choi, 2015).  
2.2.4.2. 
Nonclinical Experience with ONCT-808 
In recently completed nonclinical studies, ROR1 CAR-positive viable T cells were shown to 
have selective and significant cytotoxic activity compared with activated T cells against both 
ROR1 positive MEC1 leukemic cells and ROR1 positive MCF-7 breast cancer cells even at low 
effector to target ratios. 
In in vivo efficacy studies using cell line-derived xenografts (CDXs), treatment of mice with 
3×106 ROR1 CAR-positive viable T cells reduced the leukemic burden of luciferase-labeled 
ROR1 positive MEC1 cells to background levels by Day 30, and the animals remained disease 
free without any overt adverse effects (Prussak, 2020).  
In an in vivo CDX model using the ROR1-expressing MCL cell line JeKo-1 performed by 
collaborators at the Karolinska Institutet in Stockholm, Sweden, treatment of mice with 9×106 
ROR1 CAR-positive viable T cells (ONCT-808) eradicated the JeKo-1 tumor cells, and the 
animals remained tumor free to the end of the study. There was a dose response for ONCT-808 
observed, with lesser levels of tumor control at doses of 3×106 or 1×106 CAR-expressing T cells. 
There was no evidence of tumor control in animals who received 12.5×106 viable untransduced 
activated T cells or who received mock treatment.  
In an in vivo CDX model using the ROR1-negative T-cell leukemia cell line Jurkat, there was no 
evidence of tumor control in mice treated with ONCT-808, indicating ONCT-808 killing is 
specific for ROR1-positive tumor cells.  
2.2.5. 
Clinical Experience with ONCT-808 
At the initial dose of 1x106 ONCT-808 CAR T cells per kg in this study, 2 of the 3 subjects 
achieved complete metabolic response and the third subject fluorodeoxyglucose (FDG) positron-
emission tomography-computed tomography (PET-CT). Common adverse events (AEs) in this 


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dosing cohort included decreased blood counts, pneumonia, and Grade 1 to 2 cytokine release 
syndrome (CRS) as of an 04 December 2023 data cutoff. 
The first subject treated at the second dose level of 3x106 CAR T cells per kg experienced a 
Grade 5 (fatal) serious adverse event (SAE) consistent with CRS and immune effector cell-
associated neurotoxicity syndrome (ICANS). No evidence of the subject’s lymphoma was found 
histologically, based on the initial autopsy report. 
2.2.5.1. 
Clinical Experience with Other ROR1 CAR T Cells 
A Phase 1 study (NCT02706392) in 21 patients with ROR1 expressing triple negative breast 
cancer and non-small cell lung cancer was conducted at the University of Washington testing 
autologous CD4+ and CD8+ T cells transfected to express a CAR with a binding domain derived 
from a rabbit monoclonal antibody (mAb) recognizing ROR1 (Hudecek, 2013). In a preliminary 
report, no dose-limiting toxicities, severe neurotoxicity, or severe CRS were observed (Specht, 
2018). CAR T-cell expansion in the peripheral blood without toxicity to normal tissues was 
observed, but there was evidence of early exhaustion of the CAR T cells with limited persistence 
and few infiltrating lymphocytes in a tumor biopsy, and tumor regression was not observed in 
these patients (Srivastava, 2021).  
2.2.5.2. 
Clinical Experience with Zilovertamab 
Based on the selective targeting of ROR1, a review of the clinical safety experience with the 
zilovertamab mAb may be potentially relevant for the initiation of a first-in-human study with 
ONCT-808. Various doses of zilovertamab, ranging from 0.015 to 20 mg/kg, were given alone 
for 4 doses over 2 months in 26 patients with CLL in Study HRPP #140141, ‘UC-961 
(Cirmtuzumab) in Relapsed or Refractory Chronic Lymphocytic Leukemia’ (NCT02222688) and 
the results were published in Cell Stem Cell (Choi, 2018). Zilovertamab was well tolerated up to 
20 mg/kg with no DLT or maximum tolerated dose (MTD) identified. There were no 
characteristic treatment-emergent adverse events (TEAEs) attributed to zilovertamab. Among 
22 evaluable patients, no responses (CR or partial response [PR]) were observed with 7 and 
5 patients having SD and PD, respectively. However, despite the short duration of treatment, 
a dose response trend in absolute lymphocyte count reduction was observed and 1 patient had 
significant reduction of CLL cell infiltration of the bone marrow after therapy. Zilovertamab has 
also been studied alone and in combination with ibrutinib in Study CIRM-0001, ‘A Study of 
Cirmtuzumab and Ibrutinib in Patients With B-Cell Lymphoid Malignancies’ (NCT03088878). 
Zilovertamab was administered as a single agent at dose levels of 2 to 16 mg/kg and 300 mg and 
600 mg fixed doses on Day 1 and Day 14, with observation through Day 28. Zilovertamab was 
well tolerated in both 33 patients with MCL and 52 patients with CLL, with no DLT and no 
MTD determined, and there were no characteristic TEAEs attributed to zilovertamab. Starting on 
Day 28, zilovertamab was administered with daily ibrutinib. No DLTs or Grade 3 AEs occurred 
that were possibly related to zilovertamab alone. Overall, the safety profile of zilovertamab given 
with ibrutinib was consistent with that reported for ibrutinib alone, with no increase in the 
frequency or severity of known ibrutinib-associated AEs, and few if any new AEs. 
2.2.5.3. 
Clinical Experience with Zilovertamab Vedotin 
Clinical results from a Phase 1 study of zilovertamab vedotin (MK-2140), an antibody-drug 
conjugate (ADC) comprising zilovertamab, a proteolytically cleavable linker, and the 


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antimicrotubular cytotoxic agent monomethyl auristatin E (MMAE) may also be relevant. For 
the recommended dosing regimen of 2.5 mg/kg every 3 weeks, the ORR was 60% (1 PR, 2 CR) 
and 47% (4 PR, 3 CR) in heavily pretreated patients with DLBCL (n=5) and MCL (n=15), 
respectively (Wang, 2022). Importantly, observed toxicities were typical of MMAE-containing 
ADCs (myelosuppression and neurotoxicity), with no apparent off-tumor, on-target ROR1 
mediated organ toxicities. 
2.3. 
Risk/Benefit Assessment 
2.3.1. 
Known or Potential Risks 
CAR T-cell therapy is associated with known toxicities, which can be serious or even fatal. CRS, 
one of the most frequently observed toxicities, can range in severity from low-grade 
constitutional symptoms to a high-grade syndrome associated with life-threatening 
hemodynamic instability and multiorgan dysfunction. ICANS is a clinical and neuropsychiatric 
syndrome that may occur concomitantly with CRS, following resolution of CRS, or in the 
absence of CRS.  
Common AEs in the 3 subjects dosed with 1x106 ONCT-808 CAR T cells per kg in this study 
included decreased blood cell counts, pneumonia, and Grade 1 to 2 CRS as of an 
04 December 2023 data cutoff.  
The first subject treated at the second dose level of 3x106 CAR T cells per kg experienced a 
Grade 5 (fatal) SAE consistent with CRS and ICANS (Section 2.2.5). The SRC recommended 
testing reduced doses of ONCT-808, 0.3x106 CAR T cells per kg and 0.6x106 CAR T cells 
per kg, and this protocol was amended (Section 6.5.2). 
Rates of CRS and ICANS for 3 approved CD19 CAR T cell products in patients with BCL are 
provided in Table 3. Note that rates for CRS and ICANS are lower for lisocabtagene maraleucel, 
which contains the same 4-1BB activating domain as ONCT-808. Intensive monitoring and 
prompt management of toxicities is essential to minimize the morbidity and mortality associated 
with these toxicities. Guidance on the assessment, grading and management of these potential 
risks is described in Appendix 3 and Appendix 4. 


St u d y O N C T- 8 0 8- 1 0 1 
Versi o n 3 
 
2 9 
 
 
O ncter nal T hera pe utics I nc., C o nfi de ntial  
 
T a ble  3:  
C R S a n d Ne ur ot o xicit y wit h A p pr o ve d A ut ol o g o us C D 1 9 C A R T-Cell 
T her a pies  i n Rel a pse d/ Refr act or y B-Cell L y m p h o m a  
 
Tis a ge nlecle ucel a 
N = 1 0 6  
A xic a bt a ge ne  Cil ole ucel b  
N = 1 0 8  
Lis oc a bt a ge ne M ar ale ucel c 
N = 4 1 8  
 
All  
Gr a de 3  
All  
Gr a de 3  
All  
Gr a de 3 +  
C R S  
7 4 %  
2 3 %  
9 4 %  
1 3 %  
4 6 %  
3. 1 %  
Ne ur ol o gic 
T o xicities, 
i ncl u di n g I C A Ns 
5 8 %  
1 8 %  
5 7 %  
2 9 %  
3 3 %  
1 0 %  
C A R, c hi meric a nti ge n rece pt or; C R S, c yt o ki ne release s y n dr o me; D L B C L, diff use lar ge B -cell l y m p h o ma; U S PI, 
U nite d States Prescri bi n g I nf or mati o n.  
a K y mria h PI, 2 0 2 2 ; C R S gra di n g per Pe n n Gra di n g S yste m. 
b Yescarta PI, 2 0 2 2  
c Bre ya nzi PI, 2 0 2 2  
T here are c o nflicti n g data i n t he literat ure c o ncer ni n g e x pressi o n of R O R 1 o n h u ma n tiss ues, a n d 
t h us t he ris k of t o xicit y t o n or mal tiss ues fr o m a R O R 1 tar geti n g T-cell t hera p y . S o me st u dies 
re p ort R O R 1 e x pressi o n i n e pit helial tiss ues, i ncl u di n g parat h yr oi d, pa ncreatic islet cells, a n d t he 
gastr oi ntesti nal tract (H u dece k, 2 0 1 0 , Bala kris h na n, 2 0 1 7 ), w hile ot her st u dies s u g gest t hat t he 
R O R 1 pr otei n is mi ni mall y e x presse d o n n or mal a d ult tiss ues (F u k u da, 2 0 0 8 ; H u dece k, 2 0 1 0 ; 
Z ha n g, 2 0 1 2 ; Li u, 2 0 1 5 ; Bas kar, 2 0 0 8 ; Da ve, 2 0 1 2 ), wit h t he e xce pti o n of rare B-l y m p h oc yte 
prec urs ors k n o w n as he mat o g o nes ( Br o o me, 2 0 1 1 ). Res ults of a n o ncli nical pr o gra m 
i n vesti gati n g R O R 1 C A R T cells t hat utilize d a bi n di n g d o mai n fr o m a m A b  cr oss-reacti ve wit h 
h u ma n a n d m uri ne R O R 1 b ut ot her wise u n k n o w n s pecificit y f or R O R 1 were re p orte d ( R ott ma n, 
2 0 1 7 ). T he R O R 1 C A R T cells were s h o w n t o acc u m ulate i n t he l u n g a n d ca use p ul m o nar y 
t o xicit y i n a m o use m o del. T he rele va nce of t hese res ults t o t he p ote ntial safet y of T cells 
e x pressi n g a C A R wit h t he sc F v of zil o verta ma b, w hic h e x hi bits hi g h s pecificit y f or h u ma n 
R O R 1, d oes n ot cr oss- react wit h m uri ne R O R 1, a n d d oes n ot bi n d t o h u ma n l u n g tiss ue, is 
u n k n o w n. 
2. 3. 2.  
K n o w n or P ote nti al Be nefits  
At t he i nitial d ose of 1 x 1 0 6 O N C T - 8 0 8 C A R T cells per k g i n t his st u d y, 2 of t he 3 s u bjects 
ac hie ve d c o m plete meta b olic res p o nse a n d t he t hir d s u bject ac hie ve d a P R b y F D G P E T -C T . 
T he first s u bject treate d at t he sec o n d d ose le vel of 3 x 1 06 C A R T cells per k g e x pire d 8 da ys 
after d osi n g, b ut n o e vi de nce of t he s u bject’s l y m p h o ma was f o u n d hist ol o gicall y, base d o n t he 
i nitial a ut o ps y re p ort (see Secti o n 2. 2. 5 ).  
2. 3. 3.  
Assess me nt of P ote nti al Ris ks a n d Be nefits  
As s u m marize d a b o ve, ad mi nistrati o n of O N C T - 8 0 8 at t he i nitial d ose of 1 x 1 0 6 O N C T -8 0 8 C A R 
T cells per k g  was ass ociate d wit h t olera ble si de effects i ncl u di n g C R S , a n d t here were earl y 
si g ns of a nti-t u m or acti vit y. T here was o ne fatal reacti o n  at d ose le vel 3 x 1 06 C A R T cells per k g, 
a n d n o e vi de nce of l y m p h o ma at a ut o ps y. 
T he S R C  re vie we d t he cli nical data a n d rec o m me n de d re d uci n g t he d ose of O N C T- 8 0 8 t o 
0. 3 x 1 0 6 C A R T cells per k g  f or t he ne xt d osi n g c o h ort. T he U nite d States ( U S ) F o o d a n d Dr u g 


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Administration (FDA) also considered this change to be reasonable. The amended dose levels of 
ONCT-808 are provided in Table 6. 
The use of CD19 CAR T-cell therapy in R/R B-cell malignancies is well established for 
providing high response rates and durable responses, although with known toxicities. ONCT-808 
has shown promise in nonclinical efficacy models. The potential risks of common 
CAR-expressing T-cell therapies such as CRS and ICANS are well known, and safety 
management protocols have been established. The benefit of evaluating the ROR1 targeting 
therapy ONCT-808 is unknown, but there is a reasonable chance of observing anti-tumor 
activity. This study will evaluate and characterize the safety of administering ONCT-808 to 
subjects with advanced LBCL or MCL, and if warranted will explore its efficacy in the same 
patient populations. 


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3. 
STUDY OBJECTIVES AND ENDPOINTS 
3.1. 
Phase 1 
Table 4: 
Phase 1 Objectives and Endpoints 
Primary Objectives 
Primary Endpoints 
• To evaluate the safety and tolerability of 
ONCT-808. 
• To determine the MTD or MAD of 
ONCT-808. 
• Incidence, severity, and relationship of 
DLTs.  
• Safety profile, including incidence, 
severity, and relationship of TEAEs, 
clinical laboratory assessments, and 
concomitant medications. 
• To select a RP2D of ONCT-808, and 2 
dose levels (which includes the RP2D) to 
be tested in Phase 2. 
• Evaluation of safety, PK, 
pharmacodynamics, and preliminary anti-
tumor activity by the SRC. 
Secondary Objectives 
Secondary Endpoints 
• To evaluate the anti-tumor activity of 
ONCT-808. 
• ORR, CR rate, and DOR according to 
Lugano 2014 (Cheson, 2014). 
• To evaluate the PK of ONCT-808. 
• Engraftment, expansion, persistence, and 
immunophenotype of ROR1 
CAR-positive T cells. 
Exploratory Objectives 
Exploratory Endpoints 
• Explore the relationship between CAR 
T cell exposure and responses. 
• ONCT-808 PK, anti-tumor activity. 
• Explore the relationship between tumor 
ROR1 expression and anti-tumor activity. 
• ROR1 expression, anti-tumor activity. 
• Explore the relationship between CAR 
T cell final product characteristics and 
CAR T cell PK profiles. 
• ONCT-808 release and characterizations 
results, ONCT-808 PK. 
CAR, chimeric antigen receptor; CR, complete response; DLT, dose-limiting toxicity; DOR, duration of response; 
MAD, maximum administered dose; MTD, maximum tolerated dose; PK, pharmacokinetic; ORR, objective 
response rate; RP2D, recommended Phase 2 dose; ROR1, receptor tyrosine kinase-like orphan receptor 1; 
SRS, Safety Review Committee; TEAE, treatment-emergent adverse event 
3.2. 
Phase 2 
Table 5: 
Phase 2 Objectives and Endpoints 
Primary Objectives 
Primary Endpoints 
• To evaluate the efficacy of ONCT-808. 
• ORR, CR rate, and DOR according to 
Lugano 2014 (Cheson, 2014). 


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Secondary Objectives 
Secondary Endpoints 
• To further characterize the safety and 
tolerability of ONCT-808. 
• Safety profile, including incidence, 
severity, and relationship of TEAEs, 
clinical laboratory assessments, and 
concomitant medications. 
• To evaluate the risk/benefit of ONCT-808 
at 2 dose levels. 
• Safety and efficacy profiles.  
• To evaluate the PK of ONCT-808. 
• Engraftment, expansion, persistence, and 
immunophenotype of ROR1 
CAR-positive T cells. 
Exploratory Objectives 
Exploratory Endpoints 
• Explore the relationship between CAR 
T cell exposure and responses. 
• ONCT-808 PK, anti-tumor activity.  
• Explore the relationship between tumor 
ROR1 expression and anti-tumor activity. 
• ROR1 expression, anti-tumor activity. 
• Explore the relationship between CAR T 
cell final product characteristics and CAR 
T cell PK profiles. 
• ONCT-808 release and characterizations 
results, ONCT-808 PK. 
CAR, chimeric antigen receptor; CR, complete response; DOR, duration of response; PK, pharmacokinetic; ORR, 
objective response rate; ROR1, receptor tyrosine kinase-like orphan receptor 1; TEAE, treatment-emergent adverse 
event 


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4. 
STUDY DESIGN 
4.1. 
Overall Study Design 
This is a Phase 1/2, single-arm, open-label, multi-center study to evaluate the safety and 
tolerability, anti-tumor activity, and PK of ONCT-808 in subjects with aggressive B-cell 
malignancies, including LBCL and MCL. The study will be separated into 2 portions designated 
as Phase 1 (dose escalation) and Phase 2 (dose expansion). The estimated maximum sample size 
in Phase 1 is expected to be 27 subjects. In Phase 2, up to 18 evaluable subjects will be enrolled 
in each indication-specific expansion cohort (an estimated 36 subjects total).  
Additional subjects may be enrolled to replace unevaluable subjects, or during dose escalation 
once a dose level has been cleared. After the safety and tolerability of ONCT-808 have been 
assessed to select the RP2D in Phase 1, Phase 2 will commence to further validate the dose and 
evaluate the safety and efficacy of ONCT-808.  
All subjects will undergo the following: 
• Screening: Determining eligibility, within 28 days of enrollment. 
• Enrollment/Leukapheresis: Subjects will undergo an unstimulated leukapheresis to 
collect leukocytes for the manufacturing of ONCT-808.  
• Bridging therapy: If indicated in the Investigator’s opinion. Restaging will be 
required. Bridging therapy prior to leukapheresis must be discussed with the Sponsor. 
• Lymphodepletion: Prior to receipt of ONCT-808, subjects will receive 
lymphodepleting chemotherapy. 
• Immediate Post-Treatment Period: ONCT-808 will be infused intravenously (IV), 
followed by 14 days of intensive clinical and laboratory observation. 
• Post-Treatment Assessment Period: Subjects will be evaluated for potential 
toxicities and disease response for a total of 3 months. 
• Intermediate Period: Subjects will be evaluated every 3 months up to Month 12, and 
then every 6 months to Month 24. 
• Long-Term Follow-Up: Subjects will be monitored for a total of 15 years. 
4.1.1. 
Phase 1 Dose Escalation 
The Phase 1 part of the study will enroll subjects with aggressive B-cell NHLs, including LBCL 
and MCL. In Phase 1, all subjects will be assigned to dose levels using a 3+3 dose-escalation 
design, using the dose levels shown below (Table 6), with doses calculated based on actual body 
weight. 


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Table 6: 
Phase 1 Dose Levels 
Dose Level 
Target Dose 
Viable CAR T Cells/kg 
Minimum Dose 
Viable CAR T Cells 
Maximum Dose 
Viable CAR T Cells 
-1 
0.15×106 
7.5×106 
15×106 
1 
0.3×106 
15×106 
30×106 
2 
0.6×106 
30×106 
60×106 
3 
1×106 
50×106 
100×106 
CAR, chimeric antigen receptor 
Dose escalation or de-escalation will occur based on evaluations by the SRC in consultation with 
the Investigators, using the following 3+3 dose-escalation rules. Dose-limiting toxicity is defined 
in Section 8.3.7. The DLT assessment period will be from ONCT-808 administration on Day 1 
through Day 29 and be based on DLT evaluable subjects (Section 9.2).  
• Subjects will be enrolled in cohorts of 3 subjects per dose level with a minimum 
interval of 28 days between ONCT-808 dosing for the first 3 subjects in each dose 
cohort. 
• The minimum interval between ONCT-808 dosing for the last subject in 1 cohort and 
the first subject in a higher dose cohort will be 28 days. 
• If no DLT is reported in the initial cohort of 3 subjects, dose escalation can proceed to 
the next higher dose level.  
• If 1 of the first 3 subjects experiences a DLT, the cohort will be expanded to 6 
subjects, with a minimum of 28 days between ONCT-808 dosing.  
• If 1 of 6 subjects experiences a DLT, dose escalation may proceed to the next higher 
dose level. 
• If 2 or more subjects in a dose cohort experience a DLT, further enrollment in that 
dose cohort will stop, and dose escalation will stop.  
• The dose will be de-escalated to Dose Level -1 if the first 2 subjects treated in Dose 
Level 1 experience a DLT, or if ≥2 of 6 subjects treated at Dose Level 1 experience a 
DLT. 
• The MTD is the highest dose level in a cohort with no DLT in 3 subjects, or at most 
1 DLT in 6 subjects. 
• Based on initial safety results of this study (see Section 2.2.5), SRC 
recommendations, and consultation with the US FDA, the original dose levels -1, 1, 
2, and 3 were amended to 0.15×106, 0.3×106, 0.6×106, and 1×106 viable CAR T 
cells/kg respectively, and the 3×106 and 10×106 viable CAR T cells/kg dose levels 
were removed. If no MTD is observed up to Dose Level 3, higher dose levels may be 
evaluated by the SRC if manufacturing yields suggest it is feasible to produce 
sufficient CAR-expressing T cells. In the absence of establishing the MTD, the 
highest dose level tested will be considered the maximum administered dose (MAD). 


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During Phase 1, the SRC and Investigators will meet to review the safety data from each dose 
cohort and make dosing recommendations prior to proceeding to the next dose level. The SRC 
may recommend enrolling additional cohorts utilizing doses between, below, or above the doses 
in Table 6. The SRC will select the RP2D used in the Phase 2 expansion based on a combination 
of safety, PK, pharmacodynamics, and preliminary efficacy data. The RP2D may fall at or below 
the MTD or MAD and may be weight-based or a fixed dose (with a 30% reduction for subjects 
weighing less than 50 kg).  
If there is initial evidence of anti-tumor response among subjects treated at more than 1 dose 
level at or below the MTD or MAD, the SRC may advise that more than 1 dose level be further 
expanded in Phase 2. 
Once a dose level is cleared according to the above per 3+3 dose-escalation rules (i.e., 0/3 DLT 
or 1/6 DLT), additional subjects who are not DLT evaluable may be enrolled into that dose level, 
with at least 1 day between dosing each additional subject, to a maximum of 9 subjects per dose 
level to further evaluate safety. Dose level stopping rules will not apply to these subjects, but the 
SRC and Investigators will consider their safety experience in making dosing and study conduct 
decisions.  
4.1.2. 
Phase 2 Dose Expansion 
The Phase 2 Dose Expansion portion of the study will consist of 2 randomized cohorts. Subjects 
will be assigned randomly, stratified by lymphoma subtype (MCL or LBCL), to a Phase 2 cohort 
and will be assigned 1 of 2 dose levels of ONCT-808 that will be based on the SRC’s evaluation 
of safety data and any PK, pharmacodynamics, and efficacy data from each dose cohort in 
Phase 1. A planned 18 efficacy-evaluable subjects (Section 9.2) per dose level will be treated at 
each of the 2 dose levels selected, which will include subjects treated with the RP2D identified 
during the Phase 1 Dose Escalation part of the study. Phase 2 subjects will not be required to 
have received prior approved CD19 CAR-T therapy. 
Each cohort in Phase 2 will enroll 7 to 18 efficacy-evaluable subjects, following a Simon 2-stage 
design (see Section 9.5). Unevaluable subjects may be replaced. 
4.2. 
Scientific Rationale for Study Design 
4.2.1. 
Rationale for Study Population 
Aggressive NHL, the focus of this study, is generally considered to include AIDS-associated 
lymphoma, Burkitt lymphoma, primary central nervous system (CNS) lymphoma, LBCL, MCL, 
peripheral T-cell lymphoma and T-cell lymphoblastic lymphoma (LLS 2022). The T-cell 
lymphomas and Burkitt lymphoma do not commonly express ROR1, and NHL likely to involve 
the CNS will not be included for safety reasons, so subjects with LBCL and MCL will be 
enrolled and treated in this study. 
4.2.2. 
Rationale/Justification of Dose 
The appropriate number of ROR1 CAR-expressing T cells required will be calculated based on 
the subject’s weight (kg) and the assigned dose in cells per kg, with minimum and maximum 
doses indicated in Section 4.1. The initial dose tested was 1x106 viable ROR1 CAR-expressing T 
cells per kg with a minimum of 50x106 cells and a maximum of 100x106 cells given once by IV 


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infusion. This initial starting dose was acceptable to the US FDA in a pre-IND interaction, is 
lower than the top approved dose of most CD19 CAR-expressing T-cell therapies, and is a 
typical starting dose (Locke 2017; Abramson, 2020).  
Based on initial safety results of this study (see Section 2.2.5), Safety Review Committee (SRC) 
recommendations, and consultation with the US FDA, dose levels -1, 1, 2, and 3 were amended 
to 0.15×106, 0.3×106, 0.6×106, and 1×106 viable CAR T cells/kg, and the 3×106 and 
10×106 viable CAR T cells/kg dose levels were removed. 
4.2.3. 
Rationale for Lymphodepeleting Chemotherapy 
The purpose of lymphodepleting chemotherapy prior to the administration of ONCT-808 is to 
create an immune microenvironment that promotes adoptive transferred T-cell persistence and 
expansion. This is primarily achieved through promoting homeostatic T-cell proliferation and 
can lead to activation of certain immune-cell subsets, providing a potential mechanism of 
improved anti-tumor responses (Bishop, 2022; King, 2004). Lymphodepletion eliminates 
regulatory T cells and other elements of the immune system that compete for homeostatic 
cytokines and increases the availability of cytokines such as interleukin (IL)-7 and IL-15 
(Klebanoff, 2005). Lymphodepletion with cytarabine and fludarabine has been widely 
established with CD19 CAR T-cell therapies and has demonstrated improved CAR T cell 
expansion and persistence, which has led to clinical benefit in patients with R/R NHL 
(Turtle, 2016). The lymphodepletion regimen (cyclophosphamide 500 mg/m2 and fludarabine 
30 mg/m2) used in this study is the same as the lymphodepleting chemotherapy regimen used 
prior to infusion of axicabtagene ciloleucel (Yescarta®) and brexucabtagene autoleucel 
(Tecartus®).  
Given that patients who have failed previous CAR-T therapy may be more extensively pretreated 
and have lower bone marrow reserve than patients studied in previous CD19 CAR T studies, at 
the Investigator’s discretion a less intensive regimen of lymphodepletion may be used if 
indicated (Section 6.4). 


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5. 
STUDY POPULATION 
The Investigator or designee must ensure that only subjects who meet all the following inclusion 
and none of the exclusion criteria at Screening are offered treatment in the study. 
5.1. 
Subject Inclusion Criteria 
1. Subject has histologically confirmed aggressive B-cell NHL, including: 
a. MCL, with diagnosis confirmed by cyclin D1 overexpression or evidence of t(11;14) 
translocation 
b. LBCL, including: 
− DLBCL NOS 
− Primary mediastinal LBCL 
− High-grade BCL 
− DLBCL arising from indolent lymphoma or CLL 
− Follicular lymphoma grade 3B 
− Richter’s syndrome 
2. Subject has availability of archival tissue or material from a needle biopsy for 
immunohistology or is willing to undergo a baseline biopsy if not available. 
3. Subject has R/R disease with no available therapy. Specifically, subject must: 
a. Have received prior systemic therapy that has included an alkylating agent and an 
anti-CD20 mAb, and for LBCL an anthracycline. 
b. Have received and progressed after autologous hematopoietic stem cell transplant 
(HSCT) or is ineligible for or has refused to receive HSCT.  
c. Have received prior approved CD19 CAR T-cell therapy or is ineligible for or has 
refused CD19 CAR T for the Phase 1 portion of this study. 
4. Subject has had a minimum interval between previous systemic therapy and planned 
leukapheresis: 
a. Chemotherapy: at least 14 days or 5 half-lives (whichever is shorter)  
b. Focal radiotherapy: at least 7 days 
c. Therapeutic doses of systemic steroids: at least 14 days 
d. Investigational therapy: at least 14 days or 5 half-lives (whichever is shorter)  
e. Biologic therapy, including antibody-drug conjugates or bi-specific immune-cell 
engaging antibodies: at least 21 days or 5 half-lives (whichever is shorter)  
f. Autologous HSCT: at least 3 months 
g. CD19 targeting CAR-expressing T-cell therapy: at least 6 months. 
5. Subject has at least 1 lesion measurable in 2 diameters (nodal lesion >1.5 cm in longest 
dimension or extranodal lesion >1.0 cm in longest dimension, Cheson, 2014). Lesions 
that have been previously irradiated will be considered measurable only if progression 
has been documented following completion of radiation therapy  
6. Subject has FDG-avid disease (Deauville score of 4-5). 
7. Subject is ≥18 years and ≤75 years of age. 


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8. Subject has an Eastern Cooperative Oncology Group performance status of 0 or 1. 
9. Subject has adequate renal, hepatic, pulmonary, and cardiac function, as determined by 
meeting the following laboratory parameters: 
a. Absolute lymphocyte count ≥100/uL. 
b. Absolute neutrophil count ≥1,000/uL, or ≥500/uL if due to lymphoma (growth factors 
allowed).  
c. Hemoglobin ≥8 g/dL (transfusion allowed). 
d. Creatinine clearance ≥50 mL/min. 
e. Platelet count ≥75,000/uL or ≥50,000/uL if due to lymphoma (transfusion allowed). 
f. Serum alanine aminotransferase and aspartate aminotransferase (ALT/AST) 
≤2.5 upper limit of normal (ULN). 
g. Total bilirubin ≤1.5 mg/dl, except in subjects with Gilbert’s syndrome.  
h. Cardiac ejection fraction ≥50%, by echocardiogram (ECHO) or multi-gated 
acquisition scan (MUGA).  
i. No clinically significant electrocardiogram findings. 
j. No clinically significant pleural effusion. 
k. Baseline oxygen saturation >92% on room air. 
10. Subject has an estimated life expectancy of >12 weeks. 
11. Subject has signed the Informed Consent Form before any study procedure is performed. 
12. For female subjects of childbearing potential, a negative urine or serum pregnancy test 
13. For female subjects of childbearing potential, willingness to use an effective method of 
contraception from the start of the Screening Phase until ≥3 months after the ONCT-808 
infusion. Note: A female subject is considered to be of childbearing potential unless she 
has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically 
documented ovarian failure (with serum estradiol and follicle-stimulating hormone levels 
within the institutional laboratory postmenopausal range); or is menopausal 
(age ≥50 years with amenorrhea for ≥6 months).  
14. For male subjects who can father a child with a female partner of childbearing potential, 
willingness to use an effective method of contraception and refrain from sperm donation 
from the start of lymphodepletion until ≥3 months after the ONCT-808 infusion. 
Note: A male subject is considered able to father a child unless he has had a bilateral 
vasectomy with documented aspermia or a bilateral orchiectomy. 
5.2. 
Subject Exclusion Criteria 
A subject will be excluded from entering the study if any of the following criteria apply: 
1. Subject has had prior treatment with any ROR1-targeting therapy. 
2. Subject is currently receiving or likely to require systemic immunosuppressive therapy 
(e.g., prednisone >5 mg daily or equivalent) for any indication from the start of 
lymphodepleting chemotherapy until Day 28 post ONCT-808 infusion. 
3. Subject has known active CNS involvement by malignancy within 6 months. 


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4. Subject has a history or presence of CNS disorder, such as seizure disorder, 
cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, cerebral edema, 
posterior reversible encephalopathy syndrome, or any autoimmune disease with CNS 
involvement within 6 months of study entry. 
5. Subject has clinically significant (i.e., active) cardiovascular disease: myocardial 
infarction or coronary artery bypass grafting within 12 months prior to the planned 
dosing of ONCT-808, unstable angina, congestive heart failure of New York Heart 
Association Classification Class II or higher (Caraballo, 2019) or serious cardiac 
arrhythmia requiring medication. 
6. If receiving anticoagulation therapy, subject is unable to hold therapy for 3 days prior and 
28 days following ONCT-808 administration. 
7. Subject has evidence of human immunodeficiency virus infection; or active hepatitis B 
virus (HBV), or hepatitis C virus (HCV); see Section 8.2.11. 
8. Subject has a systemic fungal infection requiring medication in the previous 12 months. 
9. Subject has a history of COVID-19 infection with residual lung infiltrate/fibrosis. 
10. Subject has a possible requirement for urgent therapy due to ongoing or impending 
oncologic emergency (e.g., tumor mass effect, tumor lysis syndrome). 
11. Subject has a history of severe, immediate hypersensitivity reaction to any of the agents 
used in this study. 
12. Subject has a history of malignancy other than nonmelanomatous skin cancer or 
carcinoma in situ (e.g., cervix, bladder, breast) that has not been in remission for at least 
2 years. 
13. Subject has had vaccination with a live, attenuated vaccine ≤6 weeks prior to planned 
start of the lymphodepleting chemotherapy regimen. 
14. Subject who is pregnant or breastfeeding. 
15. Subject has any medical condition likely to interfere with assessment of safety or efficacy 
of study treatment. 
16. In the Investigator’s judgment, the subject is unlikely to complete all protocol-required 
study visits or procedures, including follow-up visits, or comply with the study 
requirements for participation. 
17. Subject has a history of autoimmune disease (e.g., Crohn’s disease, rheumatoid arthritis, 
systemic lupus) resulting in end organ injury or requiring systemic 
immunosuppression/systemic disease modifying agents within the last 2 years. 
18. Subject has a history of allogeneic organ transplant. 
19. Subject has a history of allogeneic HSCT. 
20. Subject has concurrent enrollment in another therapeutic investigational study. 
21. Subject has bulky disease (≥ 10 cm for a single lesion or contiguous lesions). 
22. Subject has evidence of leukemic transformation. 


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23. Subject has an active post-CAR T immune-mediated disorder (e.g., Grade ≥2 
pneumonitis, thyroiditis). 
24. Subject was refractory to prior CAR T therapy, with progressive disease in ≤3 months. 
 


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6. 
STUDY INTERVENTIONS 
For the purpose of this study, “study treatment” will refer to lymphodepleting chemotherapy and 
ONCT-808.  
6.1. 
Informed Consent  
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. ICFs will be IRB/EC 
approved and the subject will be asked to read and review the document. The Investigator will 
explain the research study to the subject and answer any questions that may arise and will ensure 
that the subject is given full and adequate oral and written information about the nature, purpose, 
possible risk, and benefit of the study. Subjects will have the opportunity to carefully review the 
written ICFs and ask questions prior to signing. The subjects should have the opportunity to 
discuss the study with their family or surrogates or think about it prior to agreeing to participate. 
The subject will sign the ICF during the Screening Phase prior to any procedures being done 
specifically for the study. Subjects must be informed that participation is voluntary and that they 
may withdraw from the study at any time, without prejudice. A copy of the signed ICF will be 
given to the subjects for their records. The informed consent process will be conducted and 
documented in the source document (including the date), and the ICF signed, before the subject 
undergoes any study-specific procedures. The rights and welfare of the subjects will be protected 
by emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
The subject’s signed and dated ICF must be obtained before conducting any study procedures 
and prior to starting intervention or administering study intervention. 
6.2. 
Leukapheresis Period 
Prior to undergoing leukapheresis, subjects will be weighed. Availability of archival tissue for 
immunohistology will be confirmed, and subjects without archival tissue will undergo a tumor 
biopsy (see Section 8.2.18). Subjects with MCL will have a bone marrow biopsy and aspirate for 
disease assessment (see Section 8.2.17).  
Leukapheresis product will be collected at a qualified apheresis center following the policy and 
standard operating procedures (SOPs) of the specific apheresis center. The leukapheresis unit is 
collected using one of the FDA cleared automated continuous-flow centrifuge type apheresis 
systems and associated sterile disposable apheresis kits. Immediately following collection, the 
leukapheresis bag will be packaged per institutional policy and SOPs and be shipped to the 
manufacturing facility. See the Study Manual for further details.  
6.3. 
Bridging Therapy 
If subjects experience progressive disease or require therapy for symptomatic disease after 
enrollment in the study but prior to their lymphodepleting chemotherapy, the Investigator may 
administer bridging therapy that is appropriate to the subject’s disease and treatment history, in 
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Bridging therapy, if administered, must be completed at least 5 days prior to initiating 
lymphodepleting chemotherapy. Bridging therapy prior to leukapheresis must be discussed with 
the Sponsor.  
Further, subjects who receive bridging therapy must undergo another PET-CT scan for restaging 
and subjects with MCL must have a bone marrow aspirate and biopsy to assess disease status 
after bridging therapy and prior to receiving lymphodepleting chemotherapy and ONCT-808 (see 
Section 8.1).  
Radiotherapy may be applied for symptom relief, but a measurable lesion must remain 
unirradiated, and irradiated lesions may not be utilized for disease response assessments. 
6.4. 
Lymphodepleting Chemotherapy 
Within 2 days of being treated with lymphodepleting chemotherapy, subjects should have: 
• Clinical evaluation to confirm they can safely undergo lymphodepletion and 
ONCT-808 treatment and to evaluate for any signs of infection. Lymphodepleting 
chemotherapy should be delayed until resolution of any confounding condition. 
• Absolute neutrophil count ≥1,000/uL or ≥500/uL if due to lymphoma (growth factors 
allowed).  
• Creatinine clearance ≥50 mL/min. 
• Pregnancy test for female subjects of childbearing potential. 
• Confirmation that ONCT-808 is available for administration. If insufficient 
ONCT-808 product is available for administration for any reason, a repeat 
manufacturing procedure may be carried out using either cryopreserved leukocytes or 
freshly collected leukocytes. 
Subjects will receive a lymphodepleting conditioning regimen as outpatients (unless their clinical 
condition requires inpatient administration) consisting of cyclophosphamide and fludarabine to 
induce lymphocyte depletion and create an optimal environment for expansion of ONCT-808. 
Subjects will initiate lymphodepleting chemotherapy beginning 5 to 7 days (i.e., Day -7 to 
Day -5) before the planned administration of ONCT-808. See the prescribing information for 
fludarabine and cyclophosphamide for information on dose adjustment in renal impairment. 
Mesna (sodium 2-mercaptoethanesulfonate) may be administered at the Investigator’s discretion. 
Treatment should be administered according to institutional guidelines including hydration; the 
recommended regimen is:  
• Cyclophosphamide 500 mg/m2 IV over 60 minutes daily for 3 days (usually 
consecutive) followed each day by: 
• Fludarabine 30 mg/m2 IV over 30 minutes  
For subjects with limited bone marrow reserve or chronically low blood counts, 
a cyclophosphamide dose of 300 mg/m2 may be used at the Investigators discretion. Assessments 
should be performed as shown in the Schedule of Assessments (Section 1.3) where LC1 is the 
first day of lymphodepleting chemotherapy. The 3-day regimen may be started between 5 and 
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No other regimen is allowed for lymphodepletion without consulting the Study Medical Monitor. 
Delay of ONCT-808 administration for more than 7 days following the end of lymphodepleting 
chemotherapy must be discussed with the Study Medical Monitor. 
6.5. 
ONCT-808 
6.5.1. 
Description of ONCT-808 
ONCT-808 is an autologous T-cell drug product genetically modified by ex vivo transduction 
with lentivirus vector to express a CAR containing a ROR1-directed single chain variable 
fragment (scFv) region derived from zilovertamab (previously referred to as cirmtuzumab or 
UC-961) and including 4-1BB and CD3ζ signaling domains. 
Each subject’s leukapheresis product will be processed to enrich for T cells, which are then 
stimulated to expand and transduced with a lentivirus vector to introduce the ROR1 CAR gene. 
The T cells are then expanded, washed, concentrated, formulated, and cryopreserved to generate 
the ONCT-808 investigational product under Good Manufacturing Practice and SOPs. Once the 
product has passed required release tests, it will be transferred or shipped back to the treating 
facility (see Study Manual).  
6.5.2. 
Administration of ONCT-808 
Subjects in both study phases will receive ONCT-808 treatment consisting of a single infusion of 
CAR-transduced autologous T cells administered intravenously at the appropriate target dose, 
calculated based on body weight (see Section 4.1). Subjects should be weighed on the day of 
administration and be pre-medicated with acetaminophen 650 mg PO and diphenhydramine 
25 mg IV (or another H1-antihistamine) 30 to 60 minutes prior to infusion of ONCT-808. 
Management of cell infusion reactions, e.g., reaction to dimethyl sulfoxide, allergic reaction to 
the cells, or febrile non-hemolytic infection reactions, should be managed with antihistamines, 
meperidine, or epinephrine as per institutional standards. Corticosteroids should not be used to 
manage immediate infusion-related toxicity unless life-threatening and approval of Study 
Medical Monitor should be sought first, if possible. 
If insufficient ONCT-808 product is available for administration for any reason, a repeat 
manufacturing procedure may be carried out using either cryopreserved leukocytes or freshly 
collected leukocytes. 
6.5.3. 
Handling and Accountability of ONCT-808 
Further information regarding ONCT-808 handling and accountability can be obtained from the 
Study Manual and ONCT-808 Investigator's Brochure.  
6.5.4. 
Dispensing and Administration of ONCT-808 
A pharmacist or other specifically trained and qualified staff member will dispense bags or 
syringes containing ONCT-808 for infusion (see Study Manual). 


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6.5.5. 
Packaging and Labeling of ONCT-808 
At completion of ONCT-808 manufacturing, the drug product is filled into sterile 
cryopreservation bags and frozen in the vapor phase of liquid nitrogen (≤-130°C).  
Each bag will be labeled with subject-specific information including subject name, date of birth, 
donor number, blood type, the manufacturing site, date of manufacture, storage conditions, and 
volume, and will indicate the product is for autologous use only and investigational use only. 
6.5.6. 
Shipping, Storage, and Stability of ONCT-808 
ONCT-808 is transferred from the manufacturing site or shipped in a validated liquid nitrogen 
dry vapor shipping system by a qualified commercial carrier with real time temperature 
monitoring. 
The ONCT-808 product is stable for up to 3 hours at 2°C to 8°C and at room temperature (20°C 
to 25°C) in the original cryobag after the cryopreserved cells are thawed. The product is stable 
for 2 hours once transferred into a secondary bag or syringe, but not more than 3 hours total from 
the time of thawing. 
6.6. 
Immediate and Post-Treatment Assessment Period 
ONCT-808 will be administered in an outpatient setting (unless institutional policies or the 
subject’s clinical condition requires inpatient administration). Subjects who receive ONCT-808 
will remain in close proximity to the treating center for at least 28 days following ONCT-808 
administration. The initial 7 days of observation may take place either in the outpatient setting or 
inpatient setting, at the treating Investigator’s discretion, with frequent clinical and laboratory 
assessments to be performed for the first 14 days as shown in the Schedule of Assessments 
(Table 1). Management of potential or common toxicities including CRS and ICANS is 
discussed in Section 6.9.2. Hospitalization for treatment related toxicity is at the treating 
Investigator’s discretion and according to institutional guidelines. 
Subjects will continue to be evaluated clinically for potential toxicities including DLTs, CRS, 
and ICANS and to have testing performed weekly up to Day 28 and monthly at Month 2 and 
Month 3, and more frequently as clinically indicated. Initial disease response to treatment will be 
evaluated including PET-CT on Day 28 and at Month 3. 
Additional evaluations include physical exams and vitals, safety labs, AE/concomitant 
medications reporting, and peripheral blood collection for PK; other correlative studies will be 
performed for up to 3 months after ONCT-808 administration as specified in the Schedule of 
Assessments (Table 1). 
6.7. 
Intermediate Assessment Period 
Subjects who receive ONCT-808 will return to be evaluated clinically, to have samples 
collected, and for disease response and survival status including PET-CT at Months 6, 9, 12, 18, 
and 24 as shown in the Schedule of Assessments (Table 1). Additional evaluations including 
physical exams, safety labs, AE/concomitant medications reporting, peripheral blood sample 
collection for PK, replication competent lentivirus (RCL) analysis, and other correlative studies 
will be performed for up to 24 months after ONCT-808 administration as specified in the 
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If the subject experiences disease progression and/or receives other systemic therapy for their 
malignancy prior to the 24-month period, the Intermediate Assessment Period follow-up will 
end, and subjects will proceed into Long-Term Follow-up (Section 6.8). 
6.8. 
Long-Term Follow-up 
Subjects who receive ONCT-808 will enter Long-Term Follow-up (LTFU) and be contacted by 
telephone or other electronic means at least annually from Year 3 to Year 15. Yearly review of 
medical history for RCL-related events should focus on outcomes suggestive of lentiviral 
disease, such as subsequent cancers, neurologic disorders, and hematologic disorders. Subjects 
continuing to respond should be followed for disease response assessment according to standard 
of care. Once a subject experiences disease progression and/or receives other systemic therapy 
for their malignancy, the details of the regimen should be collected, and subsequent disease 
assessments will cease, but the subject will remain in LTFU for survival and possibly RCL 
testing (see Section 8.2.5). Refer to the Schedule of Assessments (Table 2) for assessments 
required in LTFU. Only those AEs that are considered to be attributable to ONCT-808 should be 
collected during LTFU. Blood samples may be collected during LTFU for ONCT-808 PK and/or 
biomarkers. 
6.9. 
Concomitant Therapy or Procedures 
Therapy for concomitant medical conditions or for symptom management may be given if 
clinically indicated at the discretion of the Investigator. Concomitant therapy consists of any 
medication (e.g., prescription drugs, OTC drugs, vaccines, herbal or homeopathic remedies, 
nutritional supplements) used by a subject in addition to protocol-mandated treatment from start 
of leukapheresis until going off study. All such medications should be reported and recorded in 
the electronic Case Report Form (eCRF). For subjects who have disease relapse/progression or 
initiate new anti-cancer therapy, only concomitant medications for SAEs possibly or probably 
related to ONCT-808 per Investigator assessment should be collected. The Investigator’s 
decision to authorize the use of any drug other than study treatments will consider subject safety, 
the medical need, the potential for drug interactions, the possibility for masking symptoms of a 
more significant underlying event, and whether use of the drug will compromise the outcome or 
integrity of the study. 
6.9.1. 
Permitted Therapies 
Subjects may receive the following therapies during the study: 
• Supportive care including but not limited to antibiotics, analgesics, growth factors, 
and transfusions.  
• Palliative radiation: subjects may receive limited palliative radiation therapy at any 
time and with schedules at the discretion of the Investigator provided that the 
schedule does not interfere with protocol-specific assessments. Lesions included in a 
radiotherapy field may not be used for disease assessments, and appropriate 
documentation of radiated lesions must be captured in the eCRF. 


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6.9.2. 
Management of Common Adverse Events 
6.9.2.1. 
Cytokine Release Syndrome 
CRS is a symptom complex attributed with the use of adoptive cell therapies and certain 
monoclonal antibodies that activate lymphocytes and release cytokines. When cytokines are 
released, clinical manifestations include cardiac, gastrointestinal, laboratory (coagulation, renal 
and hepatic), vascular (hypotension), neurological, respiratory, skin, and constitutional (fever, 
rigors, headaches, malaise, fatigue, arthralgia, nausea, and vomiting). Because the signs and 
symptoms of CRS are not unique to CRS and may be caused by concomitant conditions and/or 
underlying disease, other causes of fever, hypotension, and/or hypoxia should be excluded. To 
characterize its severity, CRS should be graded based on the American Society for 
Transplantation and Cellular Therapy (ASTCT) CRS consensus grading system (Appendix 4, 
Table 10; Lee, 2019). In addition to clinical signs and symptoms, if CRS is suspected, cytokines, 
C-reactive protein, and ferritin levels should be assessed locally and a blood sample collected for 
central cytokine analysis as per the Schedule of Assessments (Section 1.3). 
6.9.2.2. 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) 
Neurologic toxicity is an identified safety risk associated with adoptive T-cell based therapies 
(Lee, 2019). Clinical manifestations include encephalopathy, confusion, delirium, somnolence, 
aphasia, and seizures (Kymriah PI, 2022; Yescarta PI, 2022). The pathophysiology for 
neurotoxicity is not fully understood but it is considered to be related to generalized T-cell 
mediated inflammation rather than direct toxicity of CAR T cells on the brain (Tey, 2014). There 
are no obvious predictors of neurotoxicity. To characterize the severity, neurotoxicity should be 
graded using the ASTCT guidelines for grading ICANS (Table 10; Lee, 2019).  
6.9.2.3. 
Fever and Neutropenia 
Evaluation for infection source and cases of fever should be treated per standard institutional 
guidelines. Non-steroidal anti-inflammatory drugs and corticosteroids should be avoided. 
Subjects who have neutropenic fever should receive broad-spectrum antibiotics. Establishing an 
even daily fluid balance in subjects who are not hypotensive and not having active tumor lysis 
syndrome (TLS) is recommended. Use of granulocyte colony stimulating factor is permitted and 
should be administered according to institutional or published guidelines but should be used with 
caution for the first 5 days after ONCT-808 infusion or if CRS is suspected. 
6.9.2.4. 
Infection Prophylaxis 
Subjects should receive prophylaxis for infection with pneumocystis jiroveci, herpes virus, and 
fungal infections per National Comprehensive Cancer Network (NCCN) guidelines (NCCN, 
2022) or standard institutional practice. 
6.9.2.5. 
Blood Product Support 
All blood products should be irradiated and screened for CMV, and subjects should receive 
platelet and red blood cell transfusions as clinically indicated and according to institutional 
guidelines.  


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6.9.2.6. 
Acute Allergic/Infusion Reaction 
Subjects should be closely monitored for occurrence of acute allergic/anaphylactoid infusion 
reactions such as rigors and chills, rash, urticaria, hypotension, dyspnea, and angioedema during 
and after ONCT-808 infusion, with management according to standard of care and institutional 
guidelines. Corticosteroids should be avoided if possible. 
6.9.2.7. 
Tumor Lysis Syndrome 
All subjects with significant tumor burden should be considered for prophylaxis of TLS and 
managed per standard institutional practice. 
6.9.2.8. 
Hypotension and Renal Insufficiency 
Hypotension and renal insufficiency should be managed based on the clinical judgment of the 
Investigator and institutional practice. In general, subjects should be kept well hydrated but 
closely monitored to prevent fluid overload. 
6.9.3. 
Prohibited Medications 
Corticosteroid therapy at doses of >5 mg/day of prednisone or equivalent and other 
immunosuppressive drugs should be avoided for 7 days prior to leukapheresis and 5 days prior to 
ONCT-808 administration. 
Corticosteroids and other immunosuppressive drugs should be avoided for 3 months after 
ONCT-808 administration and their use should be discussed with the Study Medical Monitor.  
No systemic anti-cancer therapies (including chemotherapy, antibody therapy, immunotherapy, 
cellular therapy, or other experimental therapies) for the subject’s cancer are permitted while the 
subject is on this study, other than bridging therapy or limited field radiotherapy.  
No anticoagulation therapy is allowed for 3 days prior to and 28 days after receiving ONCT-808. 
Consult the Study Medical Monitor for an urgent requirement for anticoagulation. 
Subjects are not allowed to participate concurrently in any other therapeutic clinical or imaging 
study. 


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7. 
STUDY INTERVENTION DISCONTINUATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWL 
7.1. 
Reasons for Subject Removal from the Study 
Reasons for subject discontinuation from the study prior to receiving lymphodepleting 
chemotherapy and ONCT-808 may include any of the following: 
• ONCT-808 product not available. 
• Investigator decision, including for progressive disease. 
• Noncompliance with study procedures. 
• Withdrawal of consent. 
• The development of intercurrent illness or other substantial change in the subject’s 
condition or circumstances that would place the subject at unacceptable risk as 
determined by the Investigator in consultation with the Study Medical Monitor. 
Reasons for subject discontinuation from the study after receiving ONCT-808 may include the 
following: 
• Completion of all protocol-mandated activities. 
• Withdrawal of consent. 
• Loss to follow-up. 
• Study termination by the Sponsor. 
• Death. 
A discontinuation visit should be conducted that includes the activities indicated for the Day 28 
visit. Every effort should be made to obtain a reason for subject discontinuation from the study. 
The primary reason for study discontinuation should be documented in the eCRF. If a subject 
withdraws from the study, study staff may obtain survival information from public records. 
7.1.1. 
End of Study Definition 
The interim clinical study report will be generated when the last subject has completed their 
24 months follow-up visit or has died. LTFU will continue thereafter for a total of 15 years. 
7.1.2. 
Study Discontinuation 
The Sponsor may terminate this study at any time; although, LTFU would continue. 
Investigators will be notified by the Sponsor (or designee) if the study is placed on hold, 
completed, or closed. Conditions that may lead to study termination may include, but are not 
limited to: 
• Discovery of an unexpected, serious, or unacceptable risk to the subjects in the study, 
as recommended by the SRC (see Section 7.1.3 on study stopping rules). 
• Decision on the part of the Sponsor to suspend or discontinue testing, evaluation, or 
development of the product. 


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• Insufficient compliance to protocol requirements. 
The Sponsor also has the right to discontinue the study at a site at any time. Reasons for early 
discontinuation of the study at a specific site may include but are not limited to: 
• Excessively slow recruitment. 
• Poor protocol adherence. 
• Inaccurate or incomplete data recording. 
• Noncompliance with ICH guidelines or GCP. 
7.1.3. 
Study Stopping Rules 
Any of the following will result in a temporary halt to study enrollment and dosing while the 
SRC evaluates results and makes recommendations: 
• 
Any Grade 5 AE (except for AEs related to disease progression or clearly unrelated 
deaths such as a fatal motor vehicle accident). 
• 
Grade 4 (life-threatening) toxicity that is possibly or probably related to ONCT-808 that 
is unmanageable and unexpected. 
• 
New malignancy (distinct from recurrence/progression of previously treated malignancy) 
and possibly related to ONCT-808. 
• 
Subject incidence of > 33% for any of the following, regardless of duration (including all 
subjects from dose escalation and cohort expansion): 
o Grade 3 or higher neurologic events. 
o Grade 4 CRS. 
o Grade 4 vital organ toxicity. 
o Other nonhematologic SAEs. 
o Grade 3 or higher infections (treatment [including lymphodepleting 
chemotherapy]-related). 
Safety data will be reviewed regularly by the SRC. Based on recommendations of the SRC, 
decisions regarding study conduct including changes to enrollment and remedial actions planned 
to protect subject safety will be made. In addition, the FDA will be promptly notified if any 
events trigger a stopping rule and will receive safety reports prepared by the Sponsor with 
planned remedial actions in response to the triggering event. 
7.1.4. 
Subject Replacement 
Subjects who undergo leukapheresis and/or lymphodepleting chemotherapy but who do not 
receive ONCT-808 for any reason will be replaced. Subjects who are not DLT evaluable as 
defined in Section 9.2 will be replaced. 
Subjects in the dose-escalation cohorts who receive ONCT-808 and who are not DLT evaluable 
as defined in Section 9.2, or who withdraw prior to Day 28 for reasons other than a protocol-
defined DLT (e.g., personal decision, clinical disease progression, or symptomatic deterioration) 
will be replaced for the purpose of determining whether dose escalation should occur. Subjects 
who receive ONCT-808 and withdraw prior to Day 28 due to a DLT will not be replaced. 


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Subjects in the expansion cohorts may be replaced if they are not evaluable for efficacy as 
defined in Section 9.2 for the purpose of estimating clinical activity of ONCT-808. 
Additional subjects may be enrolled beyond the planned sample size to provide enough 
evaluable subjects for analysis. 
8. 
STUDY ASSESSMENTS AND PROCEDURES 
8.1. 
Response Assessment 
Subjects will be evaluated for response by the Investigator based on the Lugano Classification 
for Malignant Lymphoma (Cheson, 2014; Appendix 1) at the times indicated in the Schedule of 
Assessments (Section 1.3). Initial disease assessment to confirm subject eligibility can be taken 
from historical data as long as it was taken within 28 days of enrolling. If bridging therapy is 
administered, disease assessment must be repeated prior to the start of lymphodepleting 
chemotherapy.  
PET-CT scans of disease-specific sites should be performed as indicated in the Schedule of 
Assessments (Section 1.3). A separate high-resolution CT scan is not required. 
For subjects with MCL, bone marrow biopsy and aspirate are required at baseline (prior to start 
of lymphodepleting chemotherapy), and is required to confirm a CR.  
8.2. 
Other Assessments and Procedures 
Study assessments and procedures should be performed as indicated in the Schedule of 
Assessments (Section 1.3). 
8.2.1. 
Demographic/Medical History 
Demographic data collected should include date of birth, sex at birth, ethnicity, and race. 
Medical history represents event(s) starting before informed consent and includes clinically 
significant diseases, surgeries, non-lymphoma cancer history (including prior cancer therapies 
and procedures), and reproductive status. Further, use of alcohol or drugs of abuse, and all 
medications (e.g., prescription drugs, OTC drugs, herbal or homeopathic remedies, nutritional 
supplements) used by the subject at the time of initial Screening visit will be collected. 
“Clinically significant” is defined as an event, diagnosis or presence of signs or symptoms, or 
laboratory value that requires either treatment, medical intervention, and/or additional 
monitoring or follow-up. 
Lymphoma cancer history will include cancer diagnosis, original date of diagnosis, stage at 
diagnosis, stage at Screening. 
Prior cancer treatments (e.g., systemic therapies, surgeries, transplants, and radiation therapy) 
should be collected and data should include indication, dates of start and end, specific 
therapy/type, its dose/schedule, route of administration, best response, reason for 
discontinuation, and if appropriate, site of treatment. If cancer surgery has been performed, 
information should be collected including the indication, surgery date, surgery intent, and a 
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For concomitant medications at enrollment, the data collection should include the medication 
being taken, the start dates, dose/frequency, route of administration, and the indication. 
Eastern Cooperative Oncology Group performance status (Appendix 2) will be used to evaluate 
the subject’s level of function. 
8.2.2. 
Physical Examination 
A complete physical examination will be performed at baseline that includes evaluations of skin, 
nasal cavities, eyes, ears, lymph nodes, and respiratory, cardiovascular, gastrointestinal, 
neurological, and musculoskeletal systems. 
A targeted physical exam will be performed at each subsequent visit as indicated or as clinically 
indicated based on symptoms reported. 
8.2.2.1. 
Vital Signs 
Vital signs, including sitting blood pressure, pulse rate, body temperature, and respiratory rate, 
will be performed at each study visit. 
8.2.2.2. 
Weight and Height 
Weight (in kilograms) will be obtained as indicated in the Schedule of Assessments 
(Section 1.3). Height (in centimeters) will be measured only at Screening. Body weight at or near 
the time of leukapheresis will be used to calculate the dose of ONCT-808 unless there has been a 
substantial delay or change in weight, in which case body weight near the time of infusion 
should be used. 
8.2.3. 
Cardiac Assessments 
8.2.3.1. 
Electrocardiogram 
12-lead electrocardiograms (ECGs) should be performed, read, and assessed locally. 12-lead 
ECGs will be obtained with the subject resting in a supine position. 
8.2.3.2. 
ECHO/MUGA 
An ECHO or MUGA scan is required to be completed at Screening to evaluate left ventricular 
ejection fraction (LVEF). Clinically significant cardiac history or symptoms present when the 
subject signed the informed consent should be reported on the appropriate eCRF page.  
Subjects must have an LVEF ≥45% to be included into the study. 
8.2.4. 
Neurological and ICANS Assessments 
Subjects with a history of CNS involvement with their lymphoma should have a thorough 
neurological examination at baseline, and a magnetic resonance imaging (MRI) scan if any 
abnormalities are noted. 
As presented in Section 2.3.1, ICANS is a clinical and neuropsychiatric syndrome that may 
occur concomitantly with CRS, following resolution of CRS, or in the absence of CRS. Intensive 
monitoring and prompt management of toxicities is essential to minimize the morbidity and 
mortality associated with ICANS.  


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Neurotoxicity will be monitored using ASTCT consensus grading for ICANS based on the 
Immune Effector Cell-Associated Encephalopathy (ICE) score (Appendix 4, Lee, 2019). ICANS 
monitoring will occur at the timepoints specified in the Schedule of Assessments (Section 1.3). 
Unscheduled ICE score assessments should be performed if neurotoxicity is suspected or to 
document resolution to baseline status or a new baseline in confirmed cases. 
8.2.5. 
Replication Competent Lentivirus Monitoring 
Blood will be evaluated for RCL monitoring prior to lymphodepleting chemotherapy and again 
at approximately 3, 6, 12, 18, and 24 months. If no evidence of RCL is observed at the 3-, 6-, and 
12-month timepoints for each subject individually, RCL monitoring will not need to be 
performed for that subject thereafter.  
Yearly review of medical history for RCL-related events should focus on outcomes suggestive of 
lentiviral disease, such as subsequent cancers, neurologic disorders, and hematologic disorders 
through Month 24 of this study and will continue in LTFU. A blood sample for RCL testing 
should be obtained if any potential RCL-related event occurs during intermediate or LTFU. 
8.2.6. 
Hematology 
Hematology includes hematocrit, hemoglobin, erythrocyte count, absolute counts of leukocytes 
(neutrophils, lymphocytes, monocytes, eosinophils, basophils), and platelet count and will be 
performed at the local laboratory at specified visits per the Schedule of Assessments 
(Section 1.3), or as clinically indicated. 
8.2.7. 
Serum Chemistry 
Clinical chemistry includes sodium, potassium, chloride, bicarbonate, blood urea nitrogen or 
urea, creatinine, glucose, calcium, phosphorus, magnesium (only at Screening), total protein, 
albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, creatine 
kinase, lactate dehydrogenase, direct bilirubin, total bilirubin, and uric acid will be performed at 
the local laboratory at specified visits per the Schedule of Assessments (Section 1.3), or as 
clinically indicated. 
8.2.8. 
Urinalysis 
Urinalysis includes specific gravity, pH, protein, glucose, ketones, bilirubin, urobilinogen, blood, 
nitrite, leukocyte esterase as assessed by dipstick, and microscopic urinalysis evaluating white 
blood cells, red blood cells, epithelial cells, bacteria, cast, and crystals will be performed at the 
local laboratory at specified visits per the Schedule of Assessments (Section 1.3) or as clinically 
indicated. 
8.2.9. 
Coagulation 
Coagulation tests includes assessment of international normalized ratio, prothrombin time, and 
activated partial thromboplastin time at specified visits will be performed at the local laboratory 
per the Schedule of Assessments (Section 1.3), or as clinically indicated. 


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8.2.10. 
Pregnancy Test 
A serum or urine pregnancy test will be performed in female subjects of childbearing potential at 
specified visits at the local laboratory per the Schedule of Assessments (Section 1.3), or as 
clinically indicated.  
8.2.11. 
Serum Virology 
Virology evaluations are designed to identify subjects with a history of HIV infections, with 
active HBV or active HCV.  
Subjects will be excluded from the study based on the following: 
• A history of HIV or positive HIV serology testing unless HIV nucleic acid test (NAT) 
suggests false positive HIV serology. 
• Positive for HBV NAT. Subjects who are HepBSAg+, HepBCore Ab+ but NAT 
negative on antivirals must be discussed with the Study Medical Monitor. 
• Positive NAT for HCV. 
8.2.12. 
Cytokines 
Blood for assessment of cytokines will be performed according to local institutional protocols to 
monitor for CAR T related complications (e.g. interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), 
interferon-γ, interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-a) at the timepoints 
specified in the Schedule of Assessments (Section 1.3). A serum sample will be prepared and 
shipped for central processing at each timepoint following instructions outlined in the Study 
Manual. 
8.2.13. 
Immunogenicity Assessments 
In the event ONCT-808 may have the potential to induce anti-product antibodies to the CAR 
protein or other components of the CAR T construct, immunogenicity will be assessed to detect 
anti-product antibodies or anti-CAR cellular immune responses. Blood for assessment of subject 
immune response to ONCT-808 will be collected at the timepoints specified in the Schedule of 
Assessments (Section 1.3). Samples will be prepared and shipped for central processing 
following instructions outlined in the Study Manual. 
8.2.14. 
ONCT-808 Pharmacokinetic Assessments 
Blood for assessment of ROR1 CAR-expressing T cells in peripheral blood will be collected at 
the timepoints specified in the Schedule of Assessments (Section 1.3). Samples will be prepared 
and shipped for central processing following instructions outlined in the Study Manual. 
A complete blood count panel to determine absolute lymphocyte count (ALC) must be collected 
on the same day as any PK specimen.  
8.2.15. 
Immunophenotyping 
Blood for assessment of peripheral blood lymphocyte subsets by immunophenotype will be 
collected at the timepoints specified in the Schedule of Assessments (Section 1.3). Samples will 


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be prepared and shipped for central processing following instructions outlined in the Study 
Manual. 
8.2.16. 
Biomarker Assessments 
Blood for exploratory biomarkers that may be predictive of efficacy or safety will be collected 
on the indicated days (Section 1.3). Tests may include genetic analyses, gene expression, 
circulating tumor DNA, or additional cytokines or chemokines as knowledge of CAR T cell 
biology increases during the study. Samples will be prepared and shipped for central processing 
following instructions outlined in the Study Manual. 
8.2.17. 
Bone Marrow Biopsy and Aspirate 
A bone marrow biopsy and aspirate will be obtained and processed in the local laboratory at 
baseline for subjects with MCL, unless results are available from testing within the previous 
28 days. Testing must be repeated prior to the start of lymphodepletion for subjects with MCL 
who have bridging therapy and must be repeated for subjects with MCL to confirm CR. 
A portion of the marrow aspirate should be prepared and shipped for central processing 
following instructions outlined in the Study Manual. 
8.2.18. 
Archival or Fresh Tumor Biopsy 
An archival tumor sample of either a formalin fixed paraffin embedded tumor block, unstained 
slides or material from a needle biopsy will be required for eligibility. If an archival sample is 
not available, subjects must be willing to undergo a fresh tumor biopsy from a safely accessible 
site to be enrolled onto the study. The fresh tumor biopsy procedure, if required, will be collected 
during the leukapheresis period and prior to administration of bridging therapy if it is clinically 
indicated (see the Schedule of Assessments in Section 1.3). 
8.2.19. 
Blood for Inflammatory Markers 
Blood for assessment of inflammation (including procalcitonin, C-reactive protein and ferritin) 
will be collected at baseline. If inflammatory markers or cytokines (see Section 8.2.12) are 
elevated, or if there is other clinical suspicion of infection, an evaluation for occult infection 
should be performed. 
8.3. 
Adverse Events and Serious Adverse Events 
8.3.1. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical study subject temporally 
associated with the use of study treatment (i.e., lymphodepleting chemotherapy, ONCT-808), 
whether or not considered related to the study treatment.  
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use 
of a medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product.  
DLTs are a subset of AEs that may indicate toxicity that limits further dose escalation. DLTs are 
defined in Section 8.3.7.  


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Events Meeting the Definition of Adverse Event 
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the Investigator (i.e., not related to progression of 
underlying disease). Refer to Section 8.3.10 for recording procedures. 
• Exacerbation of a chronic or intermittent pre-existing condition, including either an 
increase in frequency and/or intensity of the condition. Refer to Section 8.3.10 for 
recording procedures.  
• New conditions detected or diagnosed after study treatment administration even 
though they may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment(s) or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.  
Events NOT Meeting the Definition of Adverse Event (Refer to Section 8.3.10 for recording 
procedures.) 
• The disease/disorder being studied or disease progression as a singular event. 
• Any significant abnormal laboratory findings or other abnormal safety assessments 
that are associated with the underlying disease, unless judged by the Investigator to be 
more severe than expected for the subject’s condition. 
• A pre-existing disease or condition or laboratory abnormality present or detected 
before the initial Screening Visit and that does not worsen. 
• Laboratory abnormalities not considered clinically significant and not requiring 
clinical intervention or further investigation. Such abnormalities will be captured as 
part of laboratory monitoring. 
• Medical or surgical procedure (e.g., endoscopy, appendectomy); the condition that 
leads to the procedure is the AE. 
• Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected 
at the start of the study that are not clinically significant. 
8.3.2. 
Abnormal Laboratory Values 
Laboratory abnormalities without clinical significance are not recorded as AEs or SAEs. 
However, laboratory abnormalities (e.g., clinical chemistry, hematology, and urinalysis) that 
require medical or surgical intervention or lead to study treatment interruption, modification, or 
discontinuation must be recorded as an AE, as well as an SAE, if applicable. In addition, 


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laboratory or other abnormal assessments (e.g., ECG, X-rays, vital signs) that are associated with 
signs and/or symptoms must be recorded as an AE or SAE if they meet the definition of an AE 
or SAE as described in this section and Section 8.3.1. If the laboratory abnormality is part of a 
syndrome, record the syndrome or diagnosis (e.g., anemia), not the laboratory result 
(i.e., decreased hemoglobin). 
8.3.3. 
Pre-Existing Medical Conditions 
Pre-existing medical conditions that are present before the start of lymphodepleting 
chemotherapy or following bridging therapy will not be recorded as TEAEs but will be 
documented as part of the subject’s medical history. Pre-existing medical conditions that worsen 
in frequency, severity, duration, or character after initiation of any study treatment will be 
recorded as AEs. When recording such events on the Adverse Event eCRF, it is important to 
convey the concept that the pre-existing medical condition has changed by including applicable 
descriptors, e.g., “more frequent headaches,” “worsening of,” or “exacerbation of.” 
8.3.3.1. 
Hospitalization or Prolonged Hospitalization 
Any AE that results in hospitalization or prolonged hospitalization should be documented and 
reported as an SAE (per the definition of SAE in Section 8.3.6), except as specified below. 
An event that leads to hospitalization under the following circumstances should not be recorded 
as an SAE: 
• An emergency room or observational unit visit without hospital admission unless 
other serious criteria are met 
• Hospitalization for a procedure scheduled or planned before signing of the ICF 
• Admission to the hospital for social or situational reasons (e.g., no place to stay, live 
too far away to come for hospital visits) 
8.3.3.2. 
Disease Progression, Relapse, or Disease-Related Death 
The events of disease progression, relapse, or disease-related death as distinct descriptive terms 
will not be recorded as AEs but will be assessed as part of the efficacy endpoint of the study and 
will be recorded in an eCRF separate from the Adverse Event eCRF. New or worsening clinical 
symptoms and/or laboratory abnormalities attributed to disease progression or relapse will be 
reported as AEs. 
8.3.4. 
Grading of Adverse Events 
The severity of AEs will be graded using the National Cancer Institute Common Terminology 
Criteria for Adverse Events (NCI-CTCAE), Version 5.0 (NCI, 2017). For each AE, the highest 
severity grade attained should be reported. If a CTCAE criterion does not exist, the Investigator 
should use the grade or adjectives: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), 
Grade 4 (life-threatening), or Grade 5 (fatal) to describe the maximum intensity of the AE. For 
purposes of consistency with the CTCAE, these intensity grades are defined in Table 7. 
The severity of CRS will also be graded using the ASTCT Cytokine Release Syndrome 
Consensus Grading System (Appendix 3), and the severity of ICANS will be also graded using 


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the ASTCT Immune Effector Cell-Associated Neurotoxicity Syndrome Grading system 
(Appendix 4). 
Table 7: 
Grading of Adverse Event Severity Using CTCAE, Version 5.0 
Grade 
Adjective 
Description 
Grade 1 
Mild 
Sign or symptom is present, but it is easily tolerated, is not 
expected to have a clinically significant effect on the subject’s 
overall health and well-being, does not interfere with the 
subject’s usual function, and is not likely to require medical 
attention. 
Grade 2 
Moderate 
Sign or symptom causes interference with usual activity or 
affects clinical status and may require medical intervention. 
Grade 3 
Severe 
Sign or symptom is incapacitating or significantly affects 
clinical status and likely requires medical intervention and/or 
close follow-up. 
Grade 4 
Life-threatening 
Sign or symptom results in a potential threat to life. 
Grade 5 
Fatal 
Sign or symptom results in death. 
CTCAE, Common Terminology Criteria for Adverse Events 
The distinction between the seriousness and the severity of an AE should be noted. Severe is a 
measure of intensity; thus, a severe reaction is not necessarily a serious reaction. For example, a 
headache may be severe in intensity, but would not be classified as serious unless it met one of 
the criteria for serious events (as listed in Section 8.3.6). 
Should a pregnancy occur, it must be reported and recorded on the Sponsor’s pregnancy form. 
Pregnancy in itself is not regarded as an AE unless there is a suspicion that a study treatment 
may have interfered with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth or 
congenital abnormality) must be followed up and documented even if the subject was 
discontinued from the study. 
All reports of congenital abnormalities/birth defects in a fetus are SAEs. Spontaneous abortion, 
induced abortion due to complications, stillbirth, and neonatal death criteria should also be 
reported and handled as SAEs. Elective abortions without complications should not be handled 
as SAEs but should be reported as the outcome of the pregnancy in the pregnancy form. 
8.3.5. 
Relationship to Study Drug 
An Investigator who is qualified in medicine must make the determination of relationship to the 
study treatment for each AE (unrelated, possibly related, or probably related). The Investigator 
should decide whether, in his or her medical judgment, there is a reasonable possibility that the 
event may have been caused by the study treatment using the descriptions provided in Table 8. 


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Table 8: 
Relationship of Study Treatment to Adverse Event 
Relationship  
Description 
Definite  
A clinical event in which a relationship to the use of the study treatment 
seems definite because of such factors as consistency with known effects 
of the drug; a clear temporal association with the use of the drug; lack of 
alternative explanations for the event; improvement upon withdrawal of 
the drug (de-challenge); and recurrence upon resumption of the drug 
(rechallenge). 
Probable  
A clinical event in which a relationship to the study treatment seems 
probable because of such factors as consistency with known effects of the 
drug; a reasonable temporal association with the use of the drug; lack of 
alternative explanations for the event; and improvement upon withdrawal 
of the drug (de-challenge). 
Possible  
A clinical event with a reasonable temporal association with 
administration of the study treatment, and that is not likely to be explained 
by concurrent disease or other drugs or chemicals. Information on drug 
withdrawal may be lacking. 
Unlikely  
A clinical event with a temporal relationship to study treatment 
administration that makes a causal relationship improbable and for which 
other factors suggesting an alternative etiology exist. Such factors might 
include a known relationship of the clinical event to a concomitant drug, 
past medical history of a similar event, the subject’s disease state, 
intercurrent illness, or environmental factors. 
Unrelated 
A clinical event in which a relationship to the study treatment seems 
improbable because of factors such as inconsistency with known effects 
of the study drug; lack of a temporal association with study drug 
administration; lack of association of the event with study drug 
withdrawal or rechallenge; and/or presence of alternative explanations for 
the event. Alternative explanations might include a known relationship of 
the clinical event to a concomitant drug, past medical history of a similar 
event, the subject’s disease state, intercurrent illness, or environmental 
factors. 
If no valid reason exists for suggesting a relationship, then the AE should be classified as 
“unrelated.” If there is any valid reason, even if undetermined, for suspecting a possible cause 
and-effect relationship between the study drug and the occurrence of the AE, then the AE should 
be considered “related.” 
If the relationship between the AE/SAE and the study drug is determined to be “possible” or 
“probable” the event will be considered to be related to the study treatment for the purposes of 
expedited regulatory reporting. 


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8.3.6. 
Definition of a Serious Adverse Event 
SAEs are required to be reported by the Investigator to the Sponsor immediately (i.e., no more 
than 24 hours after awareness of the event; refer to Section 8.3.10 for recording procedures). 
If an event is not an AE per the definition above then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death due 
to progression of disease; see Section 8.3.1). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
• Results in death 
• Is life-threatening 
− The term “life-threatening” in the definition of “serious” refers to an event in 
which the subject was at risk of death at the time of the event. It does not refer to 
an event that hypothetically might have caused death if it were more severe. 
• Requires inpatient hospitalization or prolongation of existing hospitalization.  
• Results in a substantial disruption of a person's ability to conduct normal life 
functions, i.e., the AE resulted in a significant, persistent, or permanent change, 
impairment, damage or disruption in the subject’s body function/structure, physical 
activities, and/or quality of life. 
• Is a congenital anomaly/birth defect. 
• Other situations NOS: 
− Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.  
− Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias, or 
convulsions that do not result in inpatient hospitalization, or the development of 
drug dependency or drug abuse. 
The terms “severe” and “serious” are not synonymous. Severity refers to the intensity of an AE 
(e.g., rated as mild, moderate, or severe, or according to NCI-CTCAE; see Section 8.3.4); the 
event itself may be of relatively minor medical significance (such as severe headache without 
any further findings). 
Severity and seriousness need to be independently assessed for each AE recorded on the eCRF. 
8.3.7. 
Definition of Dose-Limiting Toxicity 
Dose-limiting toxicities are defined as any toxicity defined below occurring within the 28 days 
after infusion of CAR T cells:  
• Death (except due to disease progression). 


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• Grade 4 CRS of any duration. 
• Grade 3 CRS that does not improve to Grade 2 or less in 3 days following adequate 
therapy. 
• Grade 3 or higher ICANS of any duration. 
• Grade 3 toxicity involving vital organs (e.g., cardiac, pulmonary), except Grade 3 or 4 
renal or liver function tests, that do not improve to Grade 2 or less within 7 days. 
• Grade 4 hematologic toxicity that does not improve to Grade 2 or less within 28 days. 
• Grade 3 or higher infections, not including febrile neutropenia attributable to 
myelosuppression from lymphodepleting chemotherapy. 
CRS and ICANS will be graded according to the ASTCT system (Lee, 2019); see Appendix 3 
and Appendix 4. 
During the DLT evaluation period (Day 1 through Day 28) of the dose-escalation cohorts, 
TEAEs identified as DLTs are required to be reported by the Investigator to the Sponsor 
immediately (no more than 24 hours after learning of the event), who will notify the SRC. Refer 
to Section 8.3.10 and Section 8.4 for recording and reporting procedures. 
8.3.8. 
Adverse Events of Special Interest 
The adverse events of special interest (AESIs) in this protocol will be: 
• CRS. 
• ICANS. 
• Infusion-related reaction (≥ Grade 3) during or after ONCT-808 administration. 
• TLS. 
• Secondary malignancies. 
• Clinically significant systemic infections. 
• Prolonged cytopenias (≥ Grade 3, ≥ 21 days). 
• Autoimmune disorders. 
AESIs that fulfill criteria of an SAE must be reported by the Investigator to the Sponsor as an 
SAE immediately, within 24 hours after becoming aware of the event (see Section 8.4). 
8.3.9. 
Time Period and Frequency for Collecting AE and SAE Information 
Investigators will seek information on AEs at each subject contact. All AEs will be collected and 
recorded in the subject’s medical record and on the Adverse Event eCRF as follows: 
• From signing of ICF until first dose of any study treatment (i.e., lymphodepleting 
chemotherapy, ONCT-808): Any SAEs or AEs that are due directly to study-related 
procedures/assessments, and AEs leading to subject/study discontinuation.  
• From first dose of any study treatment through Month 24 of the post-treatment 
follow-up period OR until progressive disease OR until subject/study discontinuation 


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or initiation of subsequent anti-cancer therapies, whichever occurs first: All AEs and 
SAEs. 
• After Month 24 of the post-treatment period OR after subject/study discontinuation 
OR after progressive disease, OR after initiation of subsequent anti-cancer therapies: 
only AEs or SAEs attributed to ONCT-808 treatment. 
See Section 8.3.10 for instructions on recording AEs and SAEs, including abnormal laboratory 
values; pre-existing medical conditions; hospitalization; and disease progression, relapse, or 
disease-related death. 
For each AE recorded on the Adverse Event eCRF, the Investigator will make an assessment of 
seriousness (Section 8.3.6), severity (Section 8.3.4), and causality (Section 8.3.5). 
SAEs are required to be reported by the Investigator to the Sponsor immediately (i.e., no more 
than 24 hours becoming aware of the event). See Section 8.4 for reporting instructions. 
Investigators are not obligated to actively seek AE or SAE collection after conclusion of the 
study participation. However, if the Investigator learns of any SAE, including a death, at any 
time after a subject has been discharged from the study and he/she considers the event to be 
reasonably related to the study drug or study participation, the Investigator must promptly notify 
the Sponsor. 
8.3.10. 
Recording of Adverse Events and Serious Adverse Events 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation 
(e.g., hospital progress notes, laboratory reports, and diagnostics reports) related to the event. 
The Investigator is responsible for ensuring all relevant information is recorded on the Adverse 
Event eCRF and SAE eCRF, as applicable. 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. Avoid the use of vague, ambiguous, or 
colloquial expressions. 
To clearly define the timing of AE onset on the day of the first dose of conditioning and the first 
administration of ONCT-808, the time of onset of AEs will be recorded. 
Refer to Section 8.3.1 and Section 8.3.6 for definitions of AEs and SAEs, respectively. 
8.3.11. 
Pregnancy and Reporting 
Each female subject should be instructed to inform the Investigator immediately if she becomes 
pregnant at any time between the start of study Screening until 30 days after the last 
administration of study treatment. 
The Investigator should counsel the subject regarding the possible effects of study drug exposure 
on the fetus and the need to inform the study center, the Study Medical Monitor, and the Sponsor 
(or designee) of the outcome of the pregnancy. 
Neither the pregnancy itself nor an induced elective abortion to terminate the pregnancy without 
medical reasons is considered an AE; such occurrences should be reported on the appropriate 


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pregnancy report forms. However, if the outcome of the pregnancy meets the criteria for 
classification as an SAE (i.e., spontaneous abortion, induced abortion due to complications, 
stillbirth, neonatal death, or congenital anomaly [including that in an aborted fetus]), the 
Investigator should follow the procedures for reporting SAEs (i.e., report the event to the 
Sponsor [or designee]) and follow-up by submission of the appropriate AE electronic Case 
Report Forms (eCRFs; see Section 8.3.10). 
Information regarding any pregnancy in a study subject or the female partner of a male subject 
must be documented on a pregnancy report form and forwarded to the Sponsor (or designee) 
within 24 hours of becoming aware of the pregnancy. Monitoring of the pregnancy in both 
female study subjects and female partners of male study subjects should continue until the 
conclusion of the pregnancy. For female partners of male study subjects, such monitoring applies 
if they became pregnant in the period from the subject’s start of ONCT-808 until 30 days after 
the subject’s last dose of treatment. The outcome of the pregnancy should be reported on the 
pregnancy outcome report form within 5 days of the conclusion of the pregnancy. If the end of 
the pregnancy occurs after the study has been completed, the outcome should be reported to the 
Sponsor (or designee). 
8.4. 
Reporting of SAEs, AESIs, and DLTs 
The Investigator or designee will notify the Sponsor or their designee and the IRB, if necessary, 
immediately and not later than 24 hours after knowledge of the SAE/serious AESI/DLT. The 
Investigator will submit any updated event data to the Sponsor within 24 hours of it being 
available. 
The following is a list of events that the Investigator must report to the Sponsor within 24 hours 
after learning of the event, regardless of relationship to study drug: 
• SAEs, including serious AESIs (defined in Section 8.3.6 and Section 8.3.8). 
• DLTs during the DLT assessment window (defined in Section 8.3.7). 
• Pregnancies (see Section 8.3.11 for details on reporting requirements). 
The investigative site personnel will be responsible for submitting the completed SAE/serious 
AESI/DLT and pregnancy reports to the Sponsor within 24 hours of discovery or notification of 
the events. The study site will be instructed to de identify (i.e., black out with permanent marker) 
associated medical records of confidential information prior to sending to the Sponsor. 
The primary mechanism for reporting an SAE to the Sponsor will be through the electronic data 
capture (EDC) system. The Sponsor safety group will be notified electronically via email. If the 
study site has a temporary interruption in its internet access or computer access, a paper back-up 
SAE form will be completed and submitted to the Sponsor safety group. When the EDC system 
becomes available, the SAE information must be entered within 24 hours. 
Collection of SAEs during the course of the study are described in Section 8.3.10. Any SAE 
ongoing when the subject completes the study or discontinues from the study will be followed by 
the Investigator until the event has resolved, stabilized, or returned to baseline status. 


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8.5. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each subject at 
subsequent visits/contacts. The Investigator must continue to follow the subject until satisfactory 
resolution stabilization, subsequent anti-cancer therapy is initiated, the subject is lost to 
follow-up, or the subject withdraws consent.  
Procedures for follow-up of AEs and SAEs is as follows: 
• The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by the 
Sponsor to elucidate the nature and/or causality of the AE or SAE as fully as possible. 
This may include additional laboratory tests or investigations, histopathological 
examinations, or consultation with other healthcare professionals. 
• If a subject dies during participation in the study or during a recognized follow-up 
period, the Investigator will provide a copy to the Sponsor of any post-mortem 
findings, including but not limited to histopathology. 
• New or updated information will be recorded in the originally completed eCRF. 
• The Investigator will submit any updated SAE data to the Sponsor within 24 hours of 
receipt of the information. 
All pregnancies reported during the study should be followed according to the instructions 
provided in Section 8.5.2. 
8.5.1. 
Regulatory Reporting Requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of an SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of subjects and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local Regulatory Authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the Regulatory Authority, IRBs/ECs, and Investigators. 
Per 21 CFR 312.32, Investigator safety reports must be prepared for suspected unexpected 
serious adverse reactions, except those related to protocol-mandated procedures according to 
local regulatory requirements and Sponsor policy and forwarded to Investigators as necessary. 
An Investigator who receives an Investigator safety report describing an SAE or other specific 
safety information (e.g., summary or listing of SAEs) from the Sponsor will review and then file 
it along with the Investigator’s Brochure and will notify the IRB/EC, if appropriate, according to 
local requirements. 
8.5.2. 
Reporting Requirements for Pregnancies 
There are no relevant clinical data with ONCT-808 in pregnant or lactating women, and animal 
reproductive studies have not been conducted. The effects of ONCT-808 on fertility and the 
developing fetus are unknown. If the subject or partner of a subject participating in the study 
becomes pregnant during the study at any time after start of study treatment, the Investigator 


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should report the pregnancy to the key Sponsor contact, including the Drug Safety Team within 
24 hours of receiving notification.  
The pregnancy itself is not considered an AE, nor is an induced elective abortion to terminate a 
pregnancy without medical reasons. If the outcome of the pregnancy was abnormal 
(e.g., spontaneous abortion), the Investigator should report the abnormal outcome as an AE.  


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9. 
STATISTICS 
9.1. 
Sample Size Determination 
In Phase 1, approximately 3 dose levels will be evaluated in a 3+3 design, resulting in an 
expected sample size of up to 18 subjects for dose escalation purposes. After safety has been 
established and dose escalation may occur at a particular dose level, an additional 3 subjects per 
dose cohort (maximum 9 subjects per dose level) may be enrolled to further investigate the 
safety and PK. The estimated maximum sample size in Phase 1 is expected to be 27 subjects. 
Additional subjects may be enrolled to account for DLT unevaluable subjects (Section 7.1.4). 
In Phase 2, up to 18 evaluable subjects will be randomized to 1 of 2 dose level-specific 
expansion cohorts in a Simon 2-stage design to exclude an ORR <10%. The hypothesized 
response rate under treatment is ≥40% and will be evaluated using a one-sided type I error rate of 
0.025 with 80% power. After evaluating the first 7 subjects for efficacy in Stage 1 in a dosing 
cohort, the dosing cohort will be terminated if <2 subjects respond (either CR or PR). If the 
dosing cohort progresses to Stage 2, an additional 11 subjects will be treated, for a total of up to 
18 evaluable subjects. If at least 5 subjects respond out of the total 18, there will be 
demonstration of efficacy of ONCT-808 at that dose level and the corresponding null hypothesis 
will be rejected. Additional subjects may be enrolled to account for unevaluable subjects. The 
estimated maximum sample size is 24 per disease subtype. 
9.2. 
Populations for Analysis 
The DLT Evaluable Population is defined as all subjects in the Phase 1 Dose Escalation part of 
the study who received ONCT-808 and either completed the 28-day DLT observation period or 
discontinued the study early due to a DLT. Subjects will be grouped by the dose cohort received. 
The Safety Population is defined as all subjects who received any study procedure or treatment 
post-Screening, including leukapheresis, lymphodepletion (as necessary), and ONCT-808. 
Subjects will be grouped by the ONCT-808 dose level assigned. Subjects who did not receive 
ONT-808 will be grouped separately. 
The Efficacy-evaluable Population is defined as all subjects who received ONCT-808 and 
completed at least 1 post-treatment disease assessment and did not discontinue due to clinical 
evidence of disease progression or toxicity prior to obtaining at least 1 post-treatment disease 
assessment. Subjects will be grouped by dose level assigned. 
Additional populations may be defined in the study Statistical Analysis Plan (SAP). 
9.3. 
Statistical Analyses 
9.3.1. 
Statistical Hypotheses 
Phase 1 Dose Escalation will proceed following a 3+3 study design to determine the MTD, 
MAD, and/or RP2D. No hypothesis testing will be performed on Phase 1. 
For each Phase 2 dose level-specific expansion cohort, up to 18 evaluable subjects will be 
enrolled in a Simon 2-stage design. The hypothesized response rate under treatment is ≥40% and 
will be evaluated using a one-sided type I error rate of 0.025 with 80% power to exclude an ORR 


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<10%. After evaluating the first 7 subjects for efficacy in Stage 1, the dosing cohort will be 
terminated if <2 subjects respond (either CR or PR). If at least 2 subjects achieve CR or PR 
2 months following treatment, the cohort will progress to Stage 2 and an additional 11 subjects 
will be treated, for a total of up to 18 evaluable subjects. If at least 5 subjects respond out of the 
total 18, there will be demonstration of efficacy of the novel product within that dose level-
specific cohort and the corresponding null hypothesis will be rejected. 
9.4. 
Statistical Analysis Methods 
Details of the statistical analyses will be fully described in a separate SAP to be finalized prior to 
the planned analyses. 
Subjects will be randomized in a 1:1 allocation to 1 of the 2 dose levels, stratified by lymphoma 
subtype (MCL or LBCL), using block randomization with a block size of 2. 
All collected data will be reported using summary tables and figures, as appropriate. Tabulations 
will be produced for disposition, demographic, baseline, efficacy, safety, and T-cell activation 
parameters. Summaries will be grouped by dose level in Phase 1 and dose level cohort in 
Phase 2. Categorical variables will be summarized by frequency distributions (number and 
percentage of subjects) and continuous variables will be summarized by descriptive statistics 
(mean, standard deviation, median, minimum, and maximum). For time to event variables, 
percentages of subjects experiencing the event will be presented and median time to event will 
be estimated using Kaplan-Meier methodology. As appropriate, 95% confidence intervals (CIs) 
will be presented.  
No type I error adjustments for multiple testing are planned. No hypothesis testing will be 
performed on secondary endpoints. 
9.5. 
Analysis of the Primary Endpoints 
9.5.1. 
Analysis of the Anti-Tumor Endpoints 
The ORR is defined as the proportion of efficacy-evaluable subjects with a response to treatment 
(defined as CR or PR). The number, percentage, and exact 95% confidence interval will be 
presented.  
The CR Rate is defined as the proportion of efficacy-evaluable subjects with a CR to treatment. 
The number, percentage, and exact 95% confidence interval will be presented. 
The DOR is defined as the time (in months) between initial response (CR or PR) and the date of 
first disease progression, relapse, or death for efficacy-evaluable subjects. DOR will be analyzed 
using Kaplan-Meier methods. Further detail on censoring rules will be described in the SAP. 
Additional anti-tumor assessments may be summarized, as described in the SAP. 
9.5.2. 
Safety Analyses 
Safety assessments include AEs, SAEs, clinical laboratory evaluations, vital sign measurements, 
ECGs, concomitant medications, and exposure to study drug. 
A TEAE is defined as an AE that occurs or worsens in the period from the first dose of 
lymphodepleting chemotherapy to the end of the post-treatment follow-up period (or 


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approximately 24 months after the dose of ONCT-808). TEAEs will be summarized using the 
Medical Dictionary for Regulatory Activities Version 13.1 (or higher) System Organ Class and 
Preferred Term.  
The incidence and percentage of subjects experiencing each Preferred Term will be summarized. 
AEs will also be summarized by NCI-CTCAE, Version 5.0 and by severity and relationship to 
study drug. Incidence of DLTs will be reported by Preferred Term and relationship to study drug. 
Any Grade ≥3 AEs, SAEs, and AESIs will be summarized by Preferred Term. 
Laboratory results will be classified according to NCI-CTCAE, Version 5.0. Laboratory results 
not corresponding to an NCI-CTCAE term will not be graded. Incidences of laboratory 
abnormalities will be summarized with descriptive statistics. 
Vital signs and ECGs will be summarized with descriptive statistics. Concomitant medications 
will be listed. Exposure to study drug will be summarized. 
All safety results will be reported in by-subject data listings. 
9.6. 
Pharmacokinetic Analysis 
Engraftment, expansion, persistence, and immunophenotype of ROR1 CAR-positive T cells will 
be summarized using descriptive statistics. Correlation analyses will be performed to assess 
associations between ONT-808 PK parameters and safety, and anti-tumor activity, including 
tumor size and best response. Additional detail will be provided in the SAP. 
9.7. 
Baseline Descriptive Statistics 
Baseline and demographic characteristics will be summarized. Additional details on the 
summary of disease characteristics will be presented in the study SAP. 
9.8. 
Tabulation of Individual Subject Data 
All data collected will be presented in by-subject data listings. 


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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Regulatory, Ethical, and Oversight Considerations 
10.1.1. 
Institutional Review Board/Ethics Committee Process 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with ICH/GCP, applicable regulatory requirements. 
In obtaining and documenting informed consent during the Screening Phase, the Investigator 
must comply with applicable local regulatory requirements (e.g., 45 CFR Part 46, 21 CFR Part 
50, 21 CFR Part 56) and should adhere to ICH GCP. Prior to the beginning of the study, the 
Investigator should have the IRB/EC’s written approval for the protocol and the written ICF(s) 
and any other written information to be provided to the study subjects. 
The Investigator must obtain IRB/EC approval for the investigation. Initial IRB/EC approval, 
and all materials approved by the IRB/EC for this study, including the subject signed ICF and 
recruitment materials, must be maintained by the Investigator and made available for inspection. 
10.1.1.1. Written Informed Consent 
Informed consent is a process that is initiated prior to the individual’s agreeing to participate in 
the study and continues throughout the individual’s study participation. ICFs will be IRB/EC 
approved and the subject will be asked to read and review the document. The Investigator will 
explain the research study to the subject and answer any questions that may arise and will ensure 
that the subject is given full and adequate oral and written information about the nature, purpose, 
possible risk, and benefit of the study. Subjects will have the opportunity to carefully review the 
written ICFs and ask questions prior to signing. The subjects should have the opportunity to 
discuss the study with their family or surrogates or think about it prior to agreeing to participate. 
The subject will sign the ICF during the Screening Phase prior to any procedures being done 
specifically for the study. Subjects must be informed that participation is voluntary and that they 
may withdraw from the study at any time, without prejudice. A copy of the signed ICF will be 
given to the subjects for their records. The informed consent process will be conducted and 
documented in the source document (including the date), and the ICF signed, before the subject 
undergoes any study-specific procedures. The rights and welfare of the subjects will be protected 
by emphasizing to them that the quality of their medical care will not be adversely affected if 
they decline to participate in this study. 
The subject’s signed and dated ICF must be obtained before conducting any study procedures 
and prior to starting intervention or administering study intervention. 
10.1.2. 
Study Discontinuation and Closure 
This study may be temporarily suspended or prematurely terminated if there is sufficient 
reasonable cause. Written notification, documenting the reason for study suspension or 
termination, will be provided by the Sponsor to the Investigator at each investigational site and 
the Regulatory Authority in each country where this study is being conducted. If the study is 
prematurely terminated or suspended, the Investigator will promptly inform study subjects, the 


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IRB/EC, and the Sponsor will provide the reason(s) for the termination or suspension. Study 
subjects will be contacted, as applicable, and be informed of changes to the study visit schedule. 
Circumstances that may warrant termination or suspension include, but are not limited to: 
• Determination of unexpected, significant, or unacceptable risk to subjects. 
• Demonstration of efficacy that would warrant stopping. 
• Insufficient compliance to protocol requirements. 
• Data that are not sufficiently complete and/or evaluable. 
• Determination that the primary endpoint has been met. 
• Determination of futility. 
The study may resume once concerns about safety, protocol compliance, and data quality are 
addressed, and satisfy the Sponsor, IRB/EC and/or Regulatory Authorities (e.g., FDA, European 
Medicines Agency [EMA]). 
10.1.3. 
Confidentiality and Privacy 
Subject confidentiality and privacy are strictly held in trust by the participating Investigators, 
their staff, and the Sponsor and their interventions. This confidentiality is extended to cover 
testing of biological samples and genetic tests in addition to the clinical information relating to 
subjects. Therefore, the study protocol, documentation, data, and all other information generated 
will be held in strict confidence. No information concerning the study, or the data, will be 
released to any unauthorized third party without prior written approval of the Sponsor. 
All research activities will be conducted in as private a setting as possible. 
The study monitor, other authorized representatives of the Sponsor, representatives of the 
IRB/EC, or the regulatory agencies may inspect all documents and records required to be 
maintained by the Investigator, including but not limited to, medical records (office, clinic, or 
hospital) and pharmacy records for the subjects in this study. The clinical study site will permit 
access to such records. 
The study subject’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure 
location for as long a period as dictated by the reviewing IRB/EC, institutional policies, or 
Sponsor requirements. 
Study subject research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored in a secure clinical study database. This will not include the 
subject contact or identifying information. Rather, individual subjects and their research data will 
be identified by a unique study identification number. At the end of the study, the study 
databases will be de-identified and archived at a secure location. 


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10.1.4. 
Safety Oversight 
10.1.4.1. Safety Review Committee 
Safety oversight will be the responsibility of the SRC, which is a multidisciplinary committee 
with the objectives to evaluate safety data, provide input and recommendations on study conduct 
and risk mitigation related to the following concerns: 
• Are there any newly identified or potential risks with study treatment? 
• Has the benefit/risk profile of ONCT-808 changed? 
• Should the study be amended, paused, or stopped? 
• In collaboration with Investigators, should dose escalation proceed to the next dose 
level? 
• What is the appropriate RP2D? 
The SRC is composed of the Phase 1 study Investigators, cross-functional representatives from 
the Sponsor, and includes at least 1 independent member with clinical and safety expertise who 
is not directly involved with the study. The SRC activities for this trial are described in the SRC 
Charter. 
10.1.5. 
Study Monitoring 
Clinical study monitoring is conducted to ensure that the rights and well-being of study subjects 
are protected, that the reported study data are accurate, complete, and verifiable, and that the 
conduct of the study is in compliance with the currently approved protocol/amendment(s), with 
ICH GCP, and with applicable regulatory requirement(s). 
The Sponsor or designee will conduct site visits at the investigation facilities for the purpose of 
monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts, and study 
source documents, and other records related to study conduct. When on-site monitoring is not 
possible (e.g., during a global pandemic), and where regulatory, local, and institution policies 
allow, remote study monitoring may be performed. 
The Investigator(s)/institution(s) will permit study-related monitoring, audits, IRB/EC review, 
and regulatory inspection(s) by providing direct access to source data/documents to the Sponsor 
or their designees. 
Before an investigational site can enter a subject into the study, a study monitor, on behalf of the 
Sponsor, will provide the Investigator and the study team training on the protocol, study drug, 
data collection, study procedures, safety processes, and the clinical monitoring plan. 
During the study, a monitor from the Sponsor or representative will have regular contacts with 
the investigational site, for the following: 
• Provide information and support to the Investigators. 
• Confirm that facilities remain acceptable. 


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• Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that study drug accountability checks are being 
performed. 
• Perform source data verification. This includes a comparison of the data in the eCRFs 
with the subject’s medical records at the hospital or practice, and other records 
relevant to the study. This will require direct access to all original records for each 
subject (e.g., clinic charts). 
• Record and report any protocol deviations not previously sent to the Sponsor or 
designee. 
• Confirm AEs and SAEs have been properly documented in the eCRFs. 
• Confirm all SAEs have been forwarded to the Sponsor and those SAEs that meet 
criteria for reporting have been forwarded to the IRB. 
The monitor will be available between visits if the Investigator(s) or other staff needs 
information or advice. 
10.1.6. 
Quality Assurance and Quality Control 
Each clinical site will perform internal quality management of study conduct, data and biological 
specimen collection, documentation, and completion. An individualized quality management 
plan will be developed to describe a site’s quality management. 
Following written SOPs, the monitors will verify that the clinical study is conducted; and data 
are generated; and biological specimens are collected, documented (recorded), and reported in 
compliance with the protocol, ICH GCP, and applicable regulatory requirements (e.g., Good 
Laboratory Practices, Good Manufacturing Practices). 
The investigational site will provide direct access to all study-related documents, source 
data/documents, and reports for the purpose of monitoring and auditing by the Sponsor or 
designees, and inspection by local and Regulatory Authorities. 
Authorized representatives of the Sponsor, a Regulatory Authority, an EC, or an IRB may visit 
the site to perform audits or inspections, including source data verification. The purpose of a 
Sponsor audit or inspection is to systematically and independently examine all study-related 
activities and documents to determine whether these activities were conducted, and data were 
recorded, analyzed, and accurately reported according to the protocol, GCP guidelines of the 
ICH, and any applicable regulatory requirements. The Investigator should contact the Sponsor 
immediately if contacted by a regulatory agency about an inspection. 
The final study protocol, including the final version of the ICF, must be approved, or given a 
favorable opinion in writing, by an IRB or EC as appropriate. The Investigator must submit 
written approval to the Sponsor before he or she can enroll any patient/subject into the study. 
The Investigator is responsible for informing the IRB or EC of any amendment to the protocol in 
accordance with local requirements. In addition, approval of all advertising used to recruit 
subjects for the study follow the rules of the IRB/EC and other Regulatory Authorities, if 
appropriate. Protocol amendment approval by the IRB/EC is required, and annually, if 
appropriate. 


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The Investigator is also responsible for providing the IRB with reports of any reportable serious 
adverse drug reactions from any other study conducted with the study drug. The Sponsor will 
provide this information to the Investigator. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or EC according to local regulations and guidelines. 
10.1.7. 
Data Handling and Record Keeping 
10.1.7.1. Data Collection and Management Responsibilities 
Data collection is the responsibility of the clinical study staff at the site under the supervision of 
the site Investigator. The Investigator is responsible for ensuring the accuracy, completeness, 
legibility, and timeliness of the data reported. 
All source documents should be completed in a neat, legible manner to ensure accurate 
interpretation of data. 
Data recorded in the eCRF derived from source documents should be consistent with the data 
recorded on the source documents. 
Clinical data (including AEs, concomitant medications, and expected adverse reactions data) and 
clinical laboratory data will be entered into a 21 CFR Part 11-compliant data capture system 
provided by the Sponsor or designee. The data system includes password protection and internal 
quality checks, such as automatic range checks, to identify data that appear inconsistent, 
incomplete, or inaccurate. Clinical data will be entered directly from the source documents. 
10.1.7.2. Study Records Retention 
Study documents should be retained for a minimum of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the study intervention. These documents should be 
retained for a longer period, however, if required by local regulations. No records will be 
destroyed without the written consent of the Sponsor, if applicable. It is the responsibility of the 
Sponsor to inform the Investigator when these documents no longer need to be retained. 
10.1.8. 
Protocol Deviations 
A protocol deviation is any noncompliance with the clinical study protocol ICH GCP. The 
noncompliance may be either on the part of the subject, the Investigator, or the study site staff. 
As a result of deviations, corrective actions are to be developed by the site and implemented 
promptly. 
All deviations must be addressed in study source documents and reported to the Sponsor or 
designee as per agreed communication channels. Protocol deviations must be sent to the 
reviewing IRB/EC per their policies. The site Investigator is responsible for knowing and 
adhering to the reviewing IRB/EC requirements. 


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10.2. 
Financial Disclosure 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate Health Authorities. 
Investigators are responsible for providing information on financial interests during the course of 
the study and for 1 year after completion of the study. 
10.3. 
Publication Policy 
All information concerning ONCT-808, including but not limited to, Sponsor operations, patent 
applications, formulas, manufacturing processes, scientific data, and formulation information, 
supplied to the Investigator by a Sponsor representative and not previously published, is 
considered confidential and remains the sole property of the Sponsor. The Investigator must 
agree to use this information solely for the purposes of carrying out this study and must not use it 
for other purposes without the Sponsor’s advanced written consent. 
The information developed in this study will be used by the Sponsor in connection with the 
continued development of ONCT-808 and thus may be disclosed to other clinical Investigators 
or government regulatory agencies. The Investigator is obligated to provide the Sponsor with all 
data obtained in the study. 


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11. 
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APPENDIX 1. LUGANO CLASSIFICATION 
The Lugano 2014 revised criteria for response assessment in lymphoma (Cheson, 2014) are 
presented below. 
 


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APPENDIX 2. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS 
Grade 
Description 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a 
light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and 
about more than 50% of waking hours 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours 
4 
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 
5 
Dead 


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APPENDIX 3. AMERICAN SOCIETY FOR TRANSPLANTATION AND 
CELLULAR THERAPY CONSENSUS GRADING 
SYSTEM AND TOXICITY MANAGEMENT 
Table 9: 
ASTCT Cytokine Release Syndrome Consensus Grading System a 
CRS 
P
t
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fever b 
Temperature 
≥38˚C 
Temperature ≥38˚C 
Temperature ≥38˚C 
Temperature 
≥38˚C 
With either: 
Hypotension 
None 
Not requiring 
vasopressors 
Requiring 
vasopressors 
with/without 
vasopressin 
Requiring multiple 
vasopressors 
(excluding 
vasopressin) 
And/or c 
Hypoxia 
None 
Requiring low-flow 
nasal cannula d or 
blow-by 
Requiring high-
flow nasal cannula, 
facemask, 
non-rebreather 
mask, or venturi 
mask 
Requiring positive 
pressure 
(e.g., CPAP, 
BiPAP, intubation 
and mechanical 
ventilation) 
ASTCT, American Society for Transplantation and Cellular Therapy; BiPAP, bilevel positive airway pressure; 
CPAP, continuous positive airway pressure; CRS, cytokine release syndrome; NCI-CTCAE, National Cancer 
Institute Common Terminology Criteria for Adverse Events. 
a Organ toxicities associated with CRS may be graded according to NCI-CTCAE v5.0, but they do not influence 
CRS grading. 
b Fever is defined as temperature ≥38°C not attributable to any other cause. Constitutional symptoms of CRS, such 
as myalgia, arthralgia, and malaise, are by themselves nonspecific; however, when coincident with fever in the 
expected timeframe, the etiology of CRS is more likely. In subjects who have CRS then receive antipyretics or anti-
cytokine therapy such as tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity. In 
this case, CRS grading is driven by hypotension and/or hypoxia. 
c CRS grade is determined by the more severe event: hypotension or hypoxia not attributable to any other cause. For 
example, a subject with temperature of 39.5°C, hypotension requiring 1 vasopressor and hypoxia requiring low-flow 
nasal cannula is classified as having Grade 3 CRS. 
d Low-flow nasal cannula is defined as oxygen delivered at ≤6 liters/minute. Low flow also includes blow-by 
oxygen delivery, sometimes used in pediatrics. High-flow nasal cannula is defined as oxygen delivered at 
≥6 liters/minute. 
Source: Lee, 2019. 


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APPENDIX 4. ASTCT IMMUNE EFFECTOR CELL-ASSOCIATED 
NEUROTOXICITY SYNDROME GRADING 
Table 10: 
ASTCT Immune Effector Cell-Associated Neurotoxicity Syndrome Gradinga 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE Score b  
7 to 9  
3 to 6  
0 to 2  
0 (Subject is unarousable 
and unable to perform ICE.) 
Depressed level of 
consciousness c  
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only to tactile 
stimulus 
Subjects is unarousable or 
requires vigorous or 
repetitive tactile stimuli to 
arouse. Stupor or coma. 
Seizure 
NA 
NA 
Any clinical seizure 
Focal/generalized that 
resolves rapidly; or 
nonconvulsive seizures 
on EEG that resolve with 
intervention 
Life-threatening prolonged 
seizure (≥5 minutes); or 
Repetitive clinical or 
electrical seizures without 
return to baseline in 
between. 
Motor Findings d 
NA 
NA 
NA 
Deep focal motor weakness 
such as hemiparesis or 
paraparesis. 
Raised ICP/ 
Cerebral Edema 
NA 
NA 
Focal/local edema on 
neuroimaging e 
Diffuse cerebral edema on 
neuroimaging; Decerebrate 
or Decorticate posturing; or 
Cranial nerve VI palsy; or 
Papilledema; or Cushing's 
triad. 
ASTCT, American Society for Transplantation and Cellular Therapy; ICANS, immune effector cell-associated 
neurotoxicity syndrome; ICE, Immune Effector Cell-Associated Encephalopathy (score); ICP, intracranial 
pressure; EEG, electroencephalogram; NA, not applicable; NCI-CTCAE, National Cancer Institute Common 
Terminology Criteria for Adverse Events. 
a ICANS grade is determined by the most severe event (ICE score, level of consciousness, seizure, motor 
findings, raised ICP/cerebral edema) not attributable to any other cause. For example, a subject with an ICE score 
of 3 who has a generalized seizure is classified as having Grade 3 ICANS. 
b A subject with an ICE score of 0 may be classified as having Grade 3 ICANS if the subject is awake with global 
aphasia. But a subject with an ICE score of 0 may be classified as having Grade 4 ICANS if the subject is 
unarousable. 
c Depressed level of consciousness should be attributable to no other cause (e.g., no sedating medication). 
d Tremors and myoclonus associated with immune effector cell therapies may be graded according to NCI-
CTCAE v5.0 but they do not influence ICANS grading. 
e Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is 
excluded from ICANS grading. It may be graded according to NCI-CTCAE v5.0. 
Source: Lee, 2019.