A Phase 1/2a, Open-Label, Dose Escalation Trial of GEN3017 With Expansion Cohorts in Relapsed or Refractory CD30+ Classical Hodgkin Lymphoma and CD30+ Non-Hodgkin Lymphoma
Phase: PHASE1
Conditions: Classical Hodgkin Lymphoma, Non-Hodgkin Lymphoma
Sponsor: Genmab

Document Name: GCT3017-01 -   Protocol - 18 Oct 2023 
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CLINICAL TRIAL PROTOCOL 
Protocol Title 
A Phase 1/2a, Open-Label, Dose Escalation Trial of GEN3017 With Expansion Cohorts in 
Relapsed or Refractory CD30+ Classical Hodgkin Lymphoma and CD30+ Non-Hodgkin 
Lymphoma 
Protocol 
Number 
GCT3017-01 
Compound 
GEN3017 
Brief Title 
A first-in-human trial of safety and efficacy of GEN3017 in subjects with Hodgkin 
lymphoma or non-Hodgkin lymphoma 
Trial Phase 
1/2a 
Sponsor 
Name 
Genmab* 
Regulatory 
Agency 
Identifier 
Numbers 
EU CT No. 
2023-503348-15-00 
NCT No. 
NCT06018129 
Protocol 
Approver** 
Name 
, MD, PhD 
Title 
 
Protocol 
Version 
History 
Version 
Approval Date 
Original; v1.0 
02 May 2023 
Amendment 1; v2.0 
28 June 2023 
Amendment 2; v3.0 
18 October 2023 
* Genmab is a global organization that operates through different legal entities in various countries. Therefore, 
the legal entity acting as the sponsor for Genmab trials may vary, such as, but not limited to Genmab Holding 
B.V.; Genmab B.V.; Genmab A/S; or Genmab US, Inc. The term “sponsor” is used throughout the protocol to 
represent these various legal entities; the sponsor is identified on the following sponsor information page. 
** This protocol was approved via electronic signature on the approval page appended to the document. 
CONFIDENTIALITY STATEMENT 
The information in this document contains trade secrets and commercial information that are 
privileged or confidential and may not be disclosed unless such disclosure is required by 
applicable law or regulations. In any event, persons to whom the information is disclosed 
must be informed that the information is privileged or confidential and may not be further 
disclosed by them. These restrictions on disclosure will apply equally to all future 
information supplied that is indicated as privileged or confidential. 
PPD
PPD

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Sponsor Information Page 
Sponsor information for countries in the 
European Economic Area, Switzerland, and the 
United Kingdom 
Genmab A/S 
Carl Jacobsens Vej 30 
2500 Valby 
Denmark 
Sponsor information for all other countries 
Genmab US, Inc. 
777 Scudders Mill Rd 
Plainsboro, New Jersey 08536 
United States of America 
The sponsor contact information page will be provided separately; listing the trial responsible 
medical officer, as well as the CRO(s), laboratory(ies) (names and addresses), and other 
technical/medical services used. 

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Investigator Agreement 
I have read this protocol and agree that it contains all necessary details for carrying out this 
trial. I will conduct the trial as outlined herein and will complete the trial within the time 
designated. 
I agree to comply with the International Council for Harmonisation (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP), the principles in the Declaration of Helsinki, the 
Japanese Ministerial Ordinance on GCP, and applicable national or regional 
regulations/guidelines. 
I will provide copies of the protocol and all pertinent information to all individuals 
responsible to me who assist in the conduct of this trial. I will discuss this material with them 
to ensure that they are fully informed regarding the trial treatment, the conduct of the trial, 
and the obligations of confidentiality. 
Principal (Site) Investigator: 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
Telephone Number: 
 
Signature: 
 
Date: 
 
 
 
 
(DD-Mmm-YYYY) 
NOTE: The Coordinating Investigator section below is applicable only to the 
country-specific coordinating investigators within the European Union, where applicable. 
Coordinating Investigator (where required): 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
Signature: 
 
Date: 
 
 
 
 
(DD-Mmm-YYYY) 
Note: If the address or telephone number of the investigator changes during the course of the trial, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required. 

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Table of Contents 
 
SPONSOR INFORMATION PAGE ................................................................................2 
INVESTIGATOR AGREEMENT ...................................................................................3 
TABLE OF CONTENTS ..................................................................................................4 
LIST OF TABLES .............................................................................................................7 
LIST OF FIGURES ...........................................................................................................7 
LIST OF ABBREVIATIONS AND DEFINITIONS ......................................................8 
1 
PROTOCOL SUMMARY .......................................................................................13 
1.1 
Trial Synopsis .......................................................................................................13 
1.2 
Schema ..................................................................................................................18 
1.3 
Schedule of Activities ...........................................................................................19 
2 
INTRODUCTION ....................................................................................................34 
2.1 
Background ..........................................................................................................34 
2.1.1 
Overview of Diseases......................................................................................34 
2.1.2 
Introduction to GEN3017 ..............................................................................36 
2.2 
Trial Rationale .....................................................................................................38 
2.3 
Benefit-Risk Assessment ......................................................................................39 
2.3.1 
Potential Benefit .............................................................................................39 
2.3.2 
Potential Risks ................................................................................................40 
2.3.3 
Conclusion ......................................................................................................42 
3 
OBJECTIVES AND ENDPOINTS .........................................................................43 
4 
TRIAL DESIGN .......................................................................................................45 
4.1 
Description of Trial Design .................................................................................45 
4.1.1 
Dose Escalation...............................................................................................46 
4.1.2 
Expansion........................................................................................................50 
4.2 
Trial Design Rationale .........................................................................................50 
4.3 
Dose and Schedule Rationale ..............................................................................51 
4.3.1 
IMP Dose and Schedule Rationale ...............................................................51 
4.3.2 
AMP Dose and Schedule Rationale ..............................................................52 
4.4 
Primary Completion Date, Estimated Trial Duration, and End of Trial 
Definition ..............................................................................................................52 
4.4.1 
Primary Completion Date .............................................................................52 
4.4.2 
Estimated Trial Duration ..............................................................................53 
4.4.3 
Estimated Trial Duration for an Individual Subject ..................................53 
4.4.4 
End of Trial ....................................................................................................53 
5 
TRIAL POPULATION ............................................................................................54 
5.1 
Inclusion Criteria .................................................................................................54 
5.1.1 
Inclusion Criteria – Dose Escalation (All Disease Cohorts) .......................54 
5.1.2 
Inclusion Criteria – Expansion .....................................................................57 
5.2 
Exclusion Criteria ................................................................................................60 
5.2.1 
Exclusion Criteria – Dose Escalation ...........................................................60 
5.2.2 
Exclusion Criteria – Expansion ....................................................................62 
5.3 
Screen Failures .....................................................................................................64 
6 
TRIAL TREATMENT .............................................................................................66 
6.1 
Investigational and Auxiliary Medicinal Products ...........................................66 
6.1.1 
GEN3017 Dosing Schedule ............................................................................69 
6.1.2 
Premedication and Post-GEN3017 Monitoring ..........................................69 
6.2 
Product Complaints .............................................................................................70 
6.3 
Preparation/Handling/Storage/Accountability .................................................71 

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6.3.1 
Preparation, Handling, and Storage ............................................................71 
6.3.2 
Drug Accountability and Destruction ..........................................................71 
6.4 
Measures to Minimize Bias: Randomization and Blinding..............................71 
6.4.1 
Treatment Assignment ..................................................................................71 
6.5 
Compliance ...........................................................................................................71 
6.6 
Prior and Concomitant Therapies ......................................................................72 
6.6.1 
Prior Anticancer Therapies ..........................................................................72 
6.6.2 
Prior Therapies ..............................................................................................72 
6.6.3 
Concomitant Therapies .................................................................................72 
6.7 
Dose Modification and Stopping Rules ..............................................................74 
6.7.1 
Dose-Limiting Toxicity (Dose Escalation of GEN3017) .............................74 
6.7.2 
Dose Modification Guidance and Stopping Criteria ..................................76 
6.7.3 
Safety Stopping Guidance for the Trial .......................................................81 
6.8 
Treatment of Overdose ........................................................................................82 
6.9 
Continued Access to Trial Drug After the End of the Trial ............................82 
7 
DISCONTINUATION OF TREATMENT AND DISCONTINUATION 
FROM TRIAL ..........................................................................................................82 
7.1 
Discontinuation of Treatment .............................................................................82 
7.1.1 
End of Treatment ...........................................................................................83 
7.1.2 
Safety Follow-up Visit(s) ...............................................................................83 
7.1.3 
Post-Treatment Follow-up ............................................................................83 
7.1.4 
Survival Status Follow-up .............................................................................83 
7.2 
Discontinuation From the Trial ..........................................................................84 
7.3 
Lost to Follow-up .................................................................................................84 
8 
TRIAL ASSESSMENTS AND PROCEDURES ....................................................85 
8.1 
Demography and Baseline Assessments.............................................................85 
8.1.1 
Demographics .................................................................................................85 
8.1.2 
Diagnosis and Disease Status ........................................................................85 
8.1.3 
Medical History ..............................................................................................85 
8.1.4 
Concomitant Procedures ...............................................................................86 
8.2 
Efficacy Assessments ...........................................................................................86 
8.2.1 
Evaluations .....................................................................................................86 
8.3 
Safety Assessments ...............................................................................................88 
8.3.1 
Physical Examination ....................................................................................88 
8.3.2 
Body Measurements.......................................................................................88 
8.3.3 
Vital Signs .......................................................................................................88 
8.3.4 
Electrocardiograms........................................................................................89 
8.3.5 
Echocardiograms or MUGA Scans ..............................................................89 
8.3.6 
Performance Status ........................................................................................89 
8.3.7 
Clinical Laboratory Assessments .................................................................90 
8.3.8 
Other Safety Assessments..............................................................................92 
8.4 
Adverse Events and Serious Adverse Events ....................................................93 
8.4.1 
Definition of Adverse Events and Serious Adverse Events ........................93 
8.4.2 
Adverse Event Reporting ..............................................................................93 
8.4.3 
Events Requiring Immediate Reporting ......................................................94 
8.4.4 
Regulatory Reporting Requirements for SUSARs .....................................95 
8.4.5 
Disease-Related Events/Outcomes and Other Events/Procedures Not 
Qualifying as Adverse Events or Serious Adverse Events .........................96 
8.4.6 
Follow-up of Adverse Events and Serious Adverse Events ........................96 
8.4.7 
Precautions and Warnings ............................................................................96 

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8.5 
Pharmacokinetics .................................................................................................97 
8.6 
Pharmacodynamics ..............................................................................................97 
8.7 
Biomarkers ...........................................................................................................97 
8.7.1 
Biomarker Assessments in Tumor Samples ................................................97 
8.7.2 
Protein Expression Analyses .........................................................................98 
8.7.3 
RNA Expression Analyses .............................................................................98 
8.7.4 
DNA Analyses .................................................................................................98 
8.7.5 
DNA/RNA Analyses .......................................................................................98 
8.7.6 
Biomarker Assessments in Blood Samples ..................................................99 
8.7.7 
Immunophenotyping Analyses .....................................................................99 
8.7.8 
Cytokine (Soluble Factors) Analyses ............................................................99 
8.7.9 
 ...............................................................99 
8.8 
Immunogenicity....................................................................................................99 
9 
STATISTICAL CONSIDERATIONS ..................................................................101 
9.1 
Statistical Hypotheses ........................................................................................101 
9.2 
Population for Analyses .....................................................................................101 
9.3 
Statistical Analyses.............................................................................................101 
9.3.1 
General Considerations ...............................................................................101 
9.3.2 
Analysis of the Dose Escalation Part ..........................................................102 
9.3.3 
Analysis of the Expansion Part ...................................................................102 
9.3.4 
Safety Analyses .............................................................................................104 
9.3.5 
Other Analyses .............................................................................................105 
9.3.6 
Planned Analyses .........................................................................................105 
9.3.7 
Pharmacokinetic Analyses ..........................................................................105 
9.3.8 
Immunogenicity Analyses ...........................................................................106 
9.4 
Sample Size Determination ...............................................................................106 
10 APPENDICES: SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS ...............................................................107 
10.1 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations .......107 
10.1.1 
Regulatory and Ethical Considerations .....................................................107 
10.1.2 
Investigator Responsibilities .......................................................................107 
10.1.3 
Independent Ethics Committee or Institutional Review Board ..............107 
10.1.4 
Financial Disclosure .....................................................................................108 
10.1.5 
Administrative Procedures .........................................................................108 
10.1.6 
Informed Consent Process ..........................................................................109 
10.1.7 
Data Protection.............................................................................................110 
10.1.8 
Committees Structure ..................................................................................111 
10.1.9 
Dissemination of Clinical Trial Data ..........................................................112 
10.1.10 
Data Quality Assurance, Record Retention, Monitoring, and On-Site 
Audits ............................................................................................................112 
10.1.11 
Source Documents and Case Report Form Completion ..........................114 
10.1.12 
Trial and Site Start and Closure.................................................................115 
10.1.13 
Publication Policy.........................................................................................116 
10.2 
Appendix 2: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, and Reporting ................................................................................118 
10.2.1 
Definitions .....................................................................................................118 
10.2.2 
Procedures for Recording and Reporting..................................................119 
10.2.3 
Evaluation of Adverse Events .....................................................................119 
10.2.4 
Annual Safety Reporting by Sponsor .........................................................120 
10.3 
Appendix 3: Definition of Reproductive Potential and Contraception ........121 
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List of Abbreviations and Definitions 
Abbreviation 
Definition 
Ab 
antibody 
ADA 
anti-drug antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
 
 
ALCL 
anaplastic large cell lymphoma  
 
 
AMP 
auxiliary medicinal product 
anti-HBc 
antibodies to the hepatitis B core antigen 
anti-HBs 
antibodies to the hepatitis B surface antigen 
aPTT 
activated partial thromboplastin time 
ASTCT 
American Society for Transplantation and Cellular Therapy 
AU 
Australia 
AUCinf 
area under the concentration-time curve from time 0 to infinity 
AUClast 
area under the concentration-time curve from time 0 to last quantifiable sample 
BOIN 
Bayesian optimal interval design 
bsAb 
bispecific antibody 
BV 
brentuximab vedotin 
C 
cycle 
CAR-T 
chimeric antigen receptor T cell 
CD 
cluster of differentiation 
CFR 
Code of Federal Regulations 
cHL 
classical Hodgkin lymphoma 
CHOEP 
cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone 
CHOP 
cyclophosphamide, doxorubicin, vincristine, and prednisone 
CLIA 
Clinical Laboratory Improvement Amendment 
Cmax 
maximum concentration 
CNS 
central nervous system 
CONSORT 
Consolidated Standards of Reporting Trials 
COVID-19 
coronavirus disease 2019 
CPI 
checkpoint inhibitor 
CR 
complete response 
CrCl 
creatinine clearance 
CRO 
contract research organization 
CRS 
cytokine release syndrome 
CT 
computed tomography 
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Abbreviation 
Definition 
CTCAE 
Common Terminology Criteria for Adverse Events 
 
 
CTFG 
Clinical Trials Facilitation Group 
CTLS 
clinical tumor lysis syndrome 
Ctrough 
predose trough concentration 
D 
day 
DEC 
Dose Escalation Committee 
DL 
dose level 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
 
 
EBV 
Epstein-Barr virus 
EC50 
concentration at which 50% of the maximum effect is observed 
ECG 
electrocardiogram 
ECHO 
echocardiogram 
ECOG PS 
Eastern Cooperative Oncology Group Performance Status 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EEA 
European Economic Area 
 
 
EoT 
end of treatment 
EPOCH 
etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin 
EU 
European Union 
FAS 
Full Analysis Set 
Fc 
crystallizable fragment 
FDA 
Food and Drug Administration 
FDG 
fluorodeoxyglucose 
FFPE 
formalin-fixed paraffin-embedded 
FIH 
first-in-human 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
G-CSF 
granulocyte colony-stimulating factor 
GDPR 
General Data Protection Regulation 
GLP 
Good Laboratory Practice 
GVHD 
graft-versus-host disease 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
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Abbreviation 
Definition 
HIV 
human immunodeficiency virus 
HSCT 
hematopoietic stem cell transplant 
HTLV-1 
human T-cell leukemia virus type 1 
HTLV-2 
human T-cell leukemia virus type 2 
IB 
investigator’s brochure 
ICANS 
immune effector cell-associated neurotoxicity syndrome 
ICE 
immune effector cell-associated encephalopathy 
ICF 
informed consent form 
ICH 
International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IEC 
independent ethics committee 
Ig 
immunoglobulin  
IgG 
immunoglobulin G 
IL 
interleukin 
IMP 
investigational medicinal product 
INR 
international normalized ratio 
IRB 
institutional review board 
IRC 
independent review committee 
IRT 
interactive response technology 
IV 
intravenous(ly) 
LDH 
lactate dehydrogenase 
LLOQ 
lower limit of quantification 
LVEF 
left ventricular ejection fraction 
mAb 
monoclonal antibody 
MAD 
maximum administered dose 
MMAE 
monomethyl auristatin E 
MOA 
mechanism of action 
MRD 
minimal residual disease 
MRI 
magnetic resonance imaging 
mRNA 
messenger ribonucleic acid 
MTD 
maximum tolerated dose 
MUGA 
multigated acquisition 
NCI 
National Cancer Institute 
NGS 
next-generation sequencing 
NHL 
non-Hodgkin lymphoma 
NK 
natural killer 
 
 
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Abbreviation 
Definition 
ORR 
objective response rate 
OS 
overall survival 
PBMC 
peripheral blood mononuclear cell(s) 
PCR 
polymerase chain reaction 
PD 
pharmacodynamic 
PD-1 
programmed cell death protein 1 
 
 
PET 
positron emission tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PO 
orally 
PR 
partial response 
PRES 
posterior reversible encephalopathy syndrome 
PS 
performance status 
PSA 
prostate-specific antigen 
PT 
prothrombin time 
PTCL 
peripheral T-cell lymphoma 
 
 
 
 
QA 
quality assurance 
QTcF 
corrected QT interval by Fridericia’s formula 
RES 
Response Evaluable Set 
RP2D(s) 
recommended phase 2 dose(s) 
R/R 
relapsed/refractory 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SC 
subcutaneous(ly) 
SOC 
standard of care 
 
 
SUSAR 
suspected unexpected serious adverse reaction 
t1/2 
elimination half-life 
TCL 
T-cell lymphoma 
TEAE 
treatment-emergent adverse event 
TLS 
tumor lysis syndrome 
Tmax 
time to reach Cmax 
TNFR 
tumor necrosis factor receptor 
Trial drug(s) 
specifically refers to IMP(s) 
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Abbreviation 
Definition 
Trial treatment 
any IMP, AMP, or medical device(s) intended to be administered to a trial subject 
according to the trial protocol 
TTR 
time to response 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States prescribing information 
WHO 
World Health Organization 
yo 
years old 

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1.3 
Schedule of Activities 
Table 1-1 
Dose Escalation: Schedule of Activities 
Table 1-2 
Expansion: Schedule of Activities 
Table 1-3 
Dose Escalation: Schedule of Pharmacokinetics and ADA Assessments 
Table 1-4 
Expansion: Schedule of Pharmacokinetics and ADA Assessments 
Table 1-5 
Dose Escalation and Expansion: Schedule for Biomarker Assessments 
Table 1-1 
 
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Table 1-3 
 
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Table 1-4 
 
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Table 1-5 
 
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2 INTRODUCTION 
2.1 
Background 
2.1.1 
Overview of Diseases 
2.1.1.1 
Classical Hodgkin Lymphoma 
Classical Hodgkin lymphoma (cHL) accounts for 10% to 15% of all lymphomas (Brice et al., 
2021). It is characterized by rare malignant Reed-Sternberg (HRS) cells surrounded by extensive 
yet ineffective inflammatory/immune cells, which enable the immune evasion of tumor cells (Liu 
and Shipp, 2017; Weniger and Küppers, 2021). The HRS cells of cHL are known to express high 
cluster of differentiation (CD)30 antigen (Hsu and Hsu, 2000). Most cHL patients are diagnosed 
between ages 15 and 30 years, followed by another peak in adults ≥55 years. In the United States 
(US), an estimated 8,540 new cases of cHL will be diagnosed in 2022 with 920 deaths expected 
(SEER, 2022). 
Although cHL has an 85% to 95% complete remission (CR) rate following frontline 
chemotherapy and radiotherapy, up to 30% of patients will eventually relapse (Chohan and 
Ansell, 2022). Conventional salvage therapies rely upon high-dose chemotherapy followed by 
autologous hematopoietic stem cell transplant (HSCT). Although allogeneic HSCT is potentially 
curative, its application is still limited and post-transplant relapse is common. 
In the past decade, novel agents such as brentuximab vedotin (BV), pembrolizumab, and 
nivolumab have dramatically improved the clinical outcome as from salvage therapies for R/R 
cHL with reduced short- and long-term toxicities. Several clinical trials have assessed the 
utilization of BV-containing chemotherapy regimens in the frontline setting and anti- 
programmed cell death protein 1 (PD-1) inhibitors as combination therapies with either 
chemotherapy or BV in relapsed/refractory (R/R) disease care (ADCETRIS, 2022; Bryan et al., 
2023; KEYTRUDA, 2023; Massaro et al., 2022; OPDIVO, 2023). As anti-PD-1 inhibitors and 
BV are moving up in the cHL treatment paradigm, patients who are relapsed after or refractory 
to these treatments are in dire need of new treatment options.  
Early phase trials of CD30-directed chimeric antigen receptor T cell (CAR-T) cell therapy have 
shown encouraging anti-tumor activity in heavily pretreated cHL patients: 2 parallel phase 1/2 
trials reported an objective response rate (ORR) of 72% with 59% complete response (CR) 
(Ramos et al., 2020). In a third trial (phase 2), among 15 response-evaluable patients, ORR was 
73% with CR 60% (Ahmed et al., 2022). Autologous CD30-directed CAR-T therapy has 
demonstrated a well-tolerated safety profile: only grade 1 cytokine release syndrome (CRS) was 
observed and there was no event of immune effector cell-associated neurotoxicity syndrome 
(ICANS). Some patients have benefited from a second infusion of CD30 CAR-T cells (Ahmed et 
al., 2022). 
Although CD30/CD16A bispecific antibody(bsAB) (AFM13) alone has limited clinical activity 
against cHL, promising efficacy has been observed in R/R cHL treated with the combination of 
AFM13 and allogeneic natural killer (NK) cell infusion. Specifically, among 24 patients treated 
at the recommended phase 2 dose (RP2D), all patients achieved a response (ORR 100%) with 
CR 70.8%. The safety profile was favorable with no cases of CRS or ICANS (Nieto et al., 2022). 

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2.1.2.1 
Summary of Nonclinical Studies 
A nonclinical pharmacology package demonstrating the potency and mechanism of action 
(MOA) of GEN3017 in models representing HL and NHL is available. GEN3017 induced potent 
killing of CD30-expressing tumor cells in vitro using T cells from peripheral blood mononuclear 
cell (PBMC) obtained from healthy donors or HL or NHL patients as effector cells. Activation 
and cytotoxic activity of T cells induced by GEN3017 were dependent on the simultaneous 
binding to both CD3-expressing T cells and CD30-expressing tumor cells. EC50 values for 
GEN3017-induced cytotoxicity toward CD30-expressing HL and NHL cell lines were in the 
picomolar range as determined in a flow cytometry assay. 
The nonclinical safety program for GEN3017 included in vitro assessments as well as in vivo 
toxicology studies in cynomolgus monkeys. In a GLP-compliant tissue cross reactivity study, 
GEN3017 showed expected membrane staining on mononuclear cells in lymphoid and non-
lymphoid tissues in both human and cynomolgus monkey tissue panels. There was also 
membrane staining in epithelial cells in human placenta (specifically extravillus trophoblasts) 
and in epithelial cells in skin (follicular root sheaths of sweat glands), testis (seminiferous 
tubules), and ureter (mucosa) from cynomolgus monkey. A whole blood cytokine release assay, 
using concentrations of GEN3017 up to 
, indicated that GEN3017 was associated 
with cytokine release at the higher concentrations. The hemolytic potential and plasma 
compatibility of GEN3017 was determined at concentrations up to 
 without 
indications of hemolytic potential and with good plasma compatibility. 
Repeated dose safety and toxicity studies were performed in cynomolgus monkey. Of 6 animal 
species commonly evaluated in nonclinical toxicology studies, cynomolgus monkey was the only 
relevant toxicology species with similar binding affinity to human and cynomolgus monkey CD3 
and CD30, and with comparable pharmacological activity in vitro. In the pivotal GLP toxicology 
study, GEN3017 was administered subcutaneously (SC) and intravenously up to 
 
for 5 weeks. In line with the intended immune stimulatory mode of action, GEN3017 
administration was associated with activation of immune cell populations and elevated serum 
levels of proinflammatory cytokines 6 to 12 hours postdosing on Day 1. The cytokine levels 
returned to baseline levels within 72 hours and were of lower magnitude after the second dose on 
Day 8. Changes in clinical chemistry, hematology, and coagulation were transient and mostly 
related to an acute phase response. Histologic assessments were also consistent with the expected 
MOA, where administration of GEN3017 was associated with an increased incidence of 
mononuclear or lymphocytic infiltration and increased cellularity, usually of germinal centers, in 
lymphoid tissues at all doses. There were no adverse findings in urinalysis, ophthalmoscopy, or 
macroscopic assessment of organ tissue. Safety pharmacology evaluations (electrocardiograms 
[ECGs]/heart rate, respiratory rates, and neurobehavioral examinations) were performed as part 
of the study, with no GEN3017-related findings in any parameter. Weekly SC administration of 
GEN3017 was well tolerated locally. 
The first-in-human (FIH) dose selection takes into account the MOA of GEN3017 and is based 
on estimation of the dose that led to 
 using in vitro nonclinical data and 
interspecies scaling and modeling (see Section 4.3). 
For additional details regarding nonclinical studies, refer to the GEN3017 investigator’s 
brochure (IB). 
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15 mg/kg, there were only 6 responders out of 72 patients across all DLs including CR in 2 HL 
and 2 ALCL patients and partial response (PR) in 2 HL patients (Ansell et al., 2007).   
Recently, T-cell engager therapies such as CD30-directed CAR-T cell therapy has demonstrated 
encouraging clinical outcome in R/R cHL and CD30+ TCL patients who have exhausted 
standard therapies including chemotherapy, BV, CPIs, or autologous or allogeneic 
transplantation (Ahmed et al., 2022; Caballero Gonzalez et al., 2022; Quach et al., 2022). It is 
hypothesized that GEN3017 may introduce more potent tumor cell killing by utilizing a novel 
MOA of T-cell-mediated cytotoxicity in a similar fashion. 
Anthracycline-based chemotherapy regimens with or without BV have been considered standard 
therapy for cHL and TCL. Cardiovascular disease, secondary cancers, endocrine toxicity, 
neurological sequelae, and fertility issues are the most significant late effects in long-term 
survivors of cHL due to intensified chemotherapy and radiotherapy (Di Molfetta et al., 2022). 
Although therapy with a CPI is very promising in R/R cHL, some patients may develop 
irreversible and life-long immune-related AEs. Use of BV can cause peripheral neuropathy (52-
67% in adults), an off-target toxicity of BV due to the MMAE payload and represents the most 
common extra-hematological and the main clinically significant BV-related toxicity. An 
increased risk of progressive multifocal leukoencephalopathy associated with BV treatment has 
been reported and added as a boxed warning in the package insert (ADCETRIS, 2022). 
GEN3017, on the other hand, is a bsAb and delayed toxicities from chemotherapy, radiotherapy, 
or irreversible AEs are not expected.  
2.3.2 
Potential Risks 
GEN3017 has not been administered to human subjects; therefore, no clinical data are available. 
Based on nonclinical studies conducted to date (Section 2.1.2.1) and literature review of clinical 
data from CD30-targeting therapies including antibody-drug conjugate, CD30 bsAbs, and CD30-
directed CAR-T cell therapies, the main risks identified for GEN3017 are CRS and, potentially, 
ICANS. 
CRS and neurologic toxicities are 2 major toxicities observed in T-cell engager therapies such as 
CAR-T cell therapy and CD3-bispecific antibodies (Dickinson et al., 2022; Hutchings et al., 
2021; Kamdar et al., 2022). CRS results in a defined constellation of symptoms including but not 
limited to chills, fever, hypoxia, and hypotension. Clinical findings from ICANS strongly 
indicated existence of overactivated peripheral immune response followed by endothelial 
activation-induced blood-brain barrier dysfunction, which triggers subsequent central nervous 
system (CNS) inflammation and neurotoxicity (Gu et al., 2022). It usually occurs concurrently 
with or after CRS onset and may temporarily affect cognitive function, speech, and level of 
consciousness (Lee et al., 2019). Clinical experience with CD30-directed CAR-T cell therapies 
in cHL showed the following:  
1. CRS was reported in R/R cHL patients with low incidence and severity:  
a) In the pilot segment of phase 2 CHARIOT trial (Ahmed et al., 2022), there was 1 subject 
with CRS (grade 1) out of 15 enrolled subjects (6.7%); 
b) In the phase 1/2 CD30.CAR EBVSTs trial (Quach et al., 2022), there were 4 subjects with 
CRS (grade 1) out of 14 subjects (28.6%);  

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2.3.3 
Conclusion 
Collectively, nonclinical data of GEN3017 and clinical data from other CD30-targeting 
compounds warrant clinical development of GEN3017 in both cHL and CD30+ TCL. GEN3017 
has the potential to address the high unmet medical need in these patient populations. With 
safety precautions and a close monitoring plan in place, the described risks are outweighed by 
the potential benefit subjects might receive from GEN3017. 
For more comprehensive information related to the nonclinical studies, potential safety aspects, 
and the known and expected benefits/risks for GEN3017, refer to the IB. 

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If subjects in a given DL experience a ≥ grade 2 AE (except for AEs unequivocally due to the 
underlying disease or an extraneous cause) during the DLT period, the next maximum dose 
increment will be limited to 100%, 
 
 in the next DL. 
If subjects in a given DL experience 2 or more ≥ grade 2 AEs (except for AEs unequivocally due 
to the underlying disease or an extraneous cause) during the DLT period, the next maximum 
dose increment will be limited to 50%, 
 
 in the next DL. 
If subjects in a given DL experience 1 or more DLT during the DLT period, the next maximum 
dose increment will be limited to 50%, 
 
 in the next DL (Table 4-2). 
All other AEs will be evaluated in their totality by the DEC and Safety Committee (see 
Section 10.1.8 for additional information on the DEC and Safety Committee). 
4.1.1.2 
Dose Escalation Strategy 
An mBOIN will be utilized to propose optimal recommendations at the end of each observed 
DL.  
The MTD is defined as the highest DL with the observed DLT rate lower than the target toxicity 
level. 
  
The corresponding decision table for optimal recommendations of a DL after completion of the 
DLT period is presented in Table 4-2. 
Table 4-2 
mBOIN Guidance Table 
 
Total Number of 
DLT-Evaluable Subjects 
3 
4 
5 
6 
7 
8 
9 
Guidance Based 
on Total Number 
of DLTs 
Escalate if # DLT ≤ 
0 
0 
0 
1 
1 
1 
1 
Remain if # DLT ≤ 
1 
1 
1 
NA 
2 
2 
2 
Deescalate if # DLT ≥ 
2 
2 
2 
2 
3 
3 
3 
 
Terminate a dose level if # DLT ≥ 
3 
3 
3 
4 
4 
4 
5 
DLT=dose-limiting toxicity; mBOIN=modified Bayesian optimal interval design; NA=not applicable 
The DEC can at any time propose a lower DL than the mBOIN algorithm recommends as a 
precaution (see Section 4.1.1.7). The Safety Committee will endorse the proposed DL before 
subjects can be enrolled into it. 
4.1.1.3 
Modifications to BOIN 
The BOIN algorithm has been modified to include a DL termination criterion (Table 4-2). For 
DLs with 3 DLT-evaluable subjects, the escalation decision will be consistent with the ‘3+3’ 
design (ie, escalate if no DLT, remain on same DL if 1 DLT, de-escalate if 2 DLTs, and 
terminate DL if 3 DLTs).  
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more than 1 primary endpoint with different completion dates, this term refers to the date on 
which data collection is completed for all of the primary endpoints. 
Primary completion is anticipated to occur at the same time as the end of trial. 
4.4.2 
Estimated Trial Duration 
The maximum trial duration is 5 years after the last enrolled subject’s first treatment in the trial. 
4.4.3 
Estimated Trial Duration for an Individual Subject 
The estimated trial duration for an individual subject is approximately 2 years, consisting of a 
21-day screening period, an estimated 1-year treatment period (the duration of treatment may 
vary for each subject), a 60-day safety follow-up period, post-treatment follow-up for subjects 
who discontinue GEN3017 prior to disease progression, and a survival follow-up period (the 
duration of follow-up may vary for each subject). 
A subject is considered to have completed the trial if the subject has completed all periods of the 
trial including the last visit shown in the Schedule of Activities (Section 1.3). 
4.4.4 
End of Trial 
The end of trial is defined as the date of the last visit of the last subject in the trial globally.  

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5 TRIAL POPULATION 
After obtaining a written informed consent from participating subjects or their guardians, a 
unique subject identifier will be assigned to each subject and the subject can proceed with 
screening procedures. Subjects who meet all of the eligibility criteria may be enrolled. 
The inclusion and exclusion criteria for enrolling subjects in this trial are described below in 
Sections 5.1 and 5.2, respectively. The eligibility information will be submitted to the sponsor’s 
MM for review. If the sponsor agrees that the eligibility criteria have been met, the investigator 
will receive confirmation that the subject may be enrolled into the trial. If the sponsor considers 
that the eligibility criteria have not been met, then the sponsor will contact the investigator to 
discuss the subject. If there is a question about these criteria, the investigator must consult with 
the sponsor and resolve any issues before enrolling a subject in the trial. 
NOTE: After eligibility approval from the sponsor during screening, investigators are 
responsible for ensuring subjects to continue meeting eligibility criteria prior to the first dose of 
GEN3017. Should the subject no longer meet eligibility criteria, investigators are required to 
inform the sponsor’s MM promptly. 
5.1 
Inclusion Criteria 
5.1.1 
Inclusion Criteria – Dose Escalation (All Disease Cohorts) 
Each potential subject must fulfill all of the following inclusion criteria to be enrolled in the dose 
escalation part. 
1. Must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the 
trial is taking place).  
1US and 1AU: R/R cHL Cohort: Subjects with R/R cHL must be at least 16 years of age (US 
and Australia only); assent is required of children capable of understanding the nature of the 
trial as described in the informed consent form (ICF) (Section 10.18.3 and 10.18.4, 
respectively). 
2. Must sign an ICF by the subject or their legally acceptable representative (not applicable in 
EU/EEA) prior to any screening procedures indicating that the purpose of the trial and the 
procedures required for the trial are understood and indicating that the subject is willing to 
participate in the trial. Where required by local or country-specific regulations, each subject 
must sign a separate ICF indicating agreement to provide samples for genomic biomarker 
analysis (DNA and RNA).  
3. Histologically confirmed R/R cHL or R/R TCL according to the 2016 WHO classification 
(Swerdlow et al., 2016). 
4. Subjects must have at least 1 measurable lesion according to the 2014 Lugano criteria 
(Cheson et al., 2014). 
a. An FDG-positron emission tomography (PET) scan demonstrating positive lesion 
compatible with computed tomography (CT)- or magnetic resonance imaging (MRI)-
defined anatomical tumor sites 

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5.1.2 
Inclusion Criteria – Expansion  
Each potential subject must fulfill all of the following inclusion criteria to be enrolled in the 
expansion part. 
1. Must be at least 18 years of age (or the legal age of consent in the jurisdiction in which the 
trial is taking place). 
1US and 1AU: For subjects in the R/R CD30+ cHL cohort in the US and Australia only, age 
≥12 and <18 years; assent is required of children capable of understanding the nature of the 
trial as described in the ICF (Section 10.18.3 and 10.18.4, respectively). 
2. Must sign an ICF by the subject or their legally acceptable representative (not applicable in 
EU/EEA) prior to any screening procedures indicating that the purpose of the trial and the 
procedures required for the trial are understood and indicating that the subject is willing to 
participate in the trial. Where required by local or country specific regulations, each subject 
must sign a separate ICF indicating agreement to provide samples for genomic biomarker 
analysis (DNA and RNA). 
3. Histologically confirmed R/R cHL or R/R TCL according to the 2016 WHO classification 
(Swerdlow et al., 2016). 
4. Subjects must have at least 1 measurable lesion according to the 2014 Lugano criteria 
(Cheson et al., 2014). 
a. An FDG-PET scan demonstrating positive lesion compatible with CT- or MRI-defined 
anatomical tumor sites 
AND 
b. A CT scan (or MRI) with involvement of ≥1 measurable nodal lesion (long axis >1.5 cm 
and short axis >1.0 cm) and/or ≥1 measurable extranodal lesion (long axis >1.0 cm) 
5. ECOG performance status score 0, 1, or 2 for subjects with age of 18 and above.  
5US1 and 5AU1: For subjects ≥16 and <18 years old (US and Australia only), Karnofsky 
score of >60% per Karnofsky performance scale (Section 10.18.3 and 10.18.4, respectively). 
5US2 and 5AU2:For subjects ≥12 and <16 years of age) (US and Australia only), Lansky 
score of 
 per Lansky play-performance scale (Section 10.18.3 and 10.18.4, 
respectively). 
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signed ICF, rescreened subjects are required to sign a new ICF before rescreening procedures 
can be initiated. 

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Labeling 
Trial drug labels will contain information to meet the applicable regulatory 
requirements. For further details see the IMP Manual 
CD=cluster of differentiation; cHL=classical Hodgkin lymphoma; CRS=cytokine release syndrome; D=day; 
DL=dose level; EU=European Union; ICANS= immune effector cell-associated neurotoxicity syndrome; 
IMP=investigational medicinal product; 
; R/R=relapsed/refractory; 
. 
a. 
Refer to the IMP Manual for further details. 
b. Refer to Section 10.18.1 for EU authorization status.  
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Table 6-2 
Auxiliary Medicinal Product(s) 
AMP Name 
Dexamethasone or 
methylprednisolone (or 
equivalent) 
Paracetamol/ 
acetaminophen (or 
equivalent) 
Diphenhydramine (or 
equivalent) 
Tocilizumab 
Siltuximaba 
Anakinraa 
Use 
CRS Premedication; CRS/ICANS 
management 
CRS Premedication 
CRS Premedication 
CRS 
CRS 
CRS/ICANS 
Dosage/ 
frequency 
Premedication: dexamethasone 20 
mg, or methylprednisolone 100 
mg, or equivalent 30 minutes to 2 
hours prior to administration of 
GEN3017. 
 
CRS/ICANS management: 
dexamethasone 10-20 mg every 6 
hours, or methylprednisolone 
1000 mg/day 
650 to 1000 mg, or 
equivalent 30 minutes 
to 2 hours prior to 
administration of 
GEN3017 
50 mg, or equivalent 30 
minutes to 2 hours prior to 
administration of GEN3017 
8 mg/kg over 1 hour. 
Repeat after at least 8 
hours as needed. 
Maximum of 2 doses 
in a 24-hour period. 
11 mg/kg 
100 mg to 200 
mg once a day 
Route of Administration 
IV 
PO 
IV or PO 
IV 
IV 
SC 
Dosing Instructions 
See Section 6.1.2 and Table 6-3; 
See Section 10.13 and Section 
10.14 
See Section 6.1.2 and 
Table 6-3 
See Section 6.1.2 and Table 
6-3 
See Section 10.13 
and Section 10.14 
See Section 10.13 
and Section 10.14 
See Section 
10.13 and 
Section 10.14 
Packaging 
N/A 
N/A 
N/A 
Vials  
N/A 
N/A 
Labeling 
AMP labels will contain information to meet the applicable regulatory requirements. 
a. 
Refer to Section 10.18.1 for EU authorization status. Refer to Section 10.18.2 for country-specific information.  

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to the AE and SAE reporting process and timelines (refer to Section 8.4). A sample of the 
suspected product should be maintained for further investigation if requested by the sponsor. 
6.3 
Preparation/Handling/Storage/Accountability 
6.3.1 
Preparation, Handling, and Storage 
Guidance for the preparation, handling, and storage of trial drug(s) is described in the IMP 
Manual. 
6.3.2 
Drug Accountability and Destruction 
The investigator or designee must maintain an accurate record of received, returned, and/or 
destroyed IMP and administration of trial treatment to trial subjects in a drug accountability 
log/record. Drug accountability will be verified by the site monitor on a continuous basis and at 
the completion of the trial. 
When drug accountability has been verified by the site monitor, all expired/unused trial IMP (eg, 
vials, capsules, prefilled syringes) can be destroyed or returned to the sponsor in accordance with 
the guidance in the IMP Manual. 
Final drug accountability will be assessed at the end of the trial (or at site closure, if applicable) 
in accordance with local regulations and guidelines. 
6.4 
Measures to Minimize Bias: Randomization and Blinding 
6.4.1 
Treatment Assignment  
This is an open-label trial; therefore, blinding of treatment will not be performed. Randomization 
will not be used in the dose escalation part of this trial. 
During dose escalation, once a specific DL is open for enrollment, subjects will be assigned to 
that DL using an interactive response technology (IRT) system. Site personnel must contact the 
contract research organization (CRO) and the sponsor when a potential subject has been 
identified. If there is an open slot for enrollment, the site will be given approval to start the 
consenting and screening process. If there is no open slot, investigators should decide on the 
appropriate treatment for the subject should the subject require immediate anticancer treatment; 
otherwise, the subject may be placed on the waiting list, and the site will be alerted once an 
opening has become available. 
During expansion, subjects will be allocated to individual disease cohorts (see Section 5.1.2) 
using an IRT system. 
6.5 
Compliance 
The trial drug(s) will be administered in the controlled environment of a clinical research center, 
and the direct observation of trial drug(s) administration by trial staff will ensure compliance 
with trial requirements. The date and time of each trial treatment drug will be documented. 
Treatment start and stop dates, including dates for trial drug(s) delays will also be documented. 

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6.6 
Prior and Concomitant Therapies 
The sponsor’s medical officer (or delegate) should be contacted if there are any questions 
regarding prior or concomitant medication or therapies. 
6.6.1 
Prior Anticancer Therapies 
Prior anticancer therapies received from the time of initial diagnosis and until signing of 
informed consent for the treatment of study disease (including chemotherapy, radiotherapy, 
antibody-drug conjugates, immune CPIs, antibodies, transplantation, surgery, any investigational 
anticancer drugs etc) must be documented. 
The best response, reason for discontinuation, dates of administration, and date of progression 
should be reported for prior anticancer therapies. 
Refer to Section 5.2 for details regarding prohibited prior anticancer therapies or washout 
periods for prior anticancer therapies. 
6.6.2 
Prior Therapies 
Any medication, (including over-the-counter or prescription medicines, vitamins, and/or herbal 
supplements), vaccine, or blood transfusions received within 28 days before administration of 
the first dose of trial drug must be documented. Any SARS-COV-2 vaccines and seasonal flu 
vaccinations received within 3 months prior to the first dose of GEN3017 must be documented. 
Refer to Section 5.2 for details regarding prohibited prior therapies or washout periods for prior 
therapies. 
6.6.3 
Concomitant Therapies 
Subjects must be told to notify the trial site about any new medications (including over-the-
counter or prescription medicines, vitamins, and vaccines) they take after the start of GEN3017. 
All medications (other than GEN3017) and significant nondrug therapies (including physical 
therapy, herbal/natural medications, and blood transfusions) administered during the trial (ie, 
beginning with administration of the first dose of GEN3017 until 30 days after the last dose of 
GEN3017) must be documented. 
Investigators may prescribe concomitant medications or treatments deemed necessary to provide 
adequate supportive care except for those medications identified as “prohibited” 
(Section 6.6.3.2). 
Concomitant therapies should also be documented beyond 30 days after the last dose of 
GEN3017 only in conjunction with worsening AEs or new SAEs related to GEN3017. 
6.6.3.1 
Permitted Concomitant Therapies 
The following concomitant medication and therapies are permitted during the trial: 
1. SARS-CoV-2 vaccine is generally permitted, including mRNA-based, protein-based, or 
nonreplicating viral vector-based vaccines. Consider choosing an appropriate type of SARS-
CoV-2 vaccine and consult with an infectious disease expert if desired. SARS-CoV-2 
vaccine should not be administered during the screening period and DLT observation period. 

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For other immunizations, physicians should review the subject’s vaccination status and 
subjects should, if possible, be brought up to date with all immunizations in agreement with 
current immunization guidelines prior to initiating treatment. 
2. Hematopoietic growth factors such as erythropoietin, granulocyte colony-stimulating factor 
(G-CSF) (filgrastim, pegfilgrastim), granulocyte/macrophage colony-stimulating factor 
(sargramostim), or thrombopoietin (oprelvekin, eltrombopag) are permitted if clinically 
indicated. In the case of ≥ grade 3 neutropenia, use of growth factors is mandated in dose 
escalation and at the investigator’s discretion in expansion. 
3. Red blood cell and platelet transfusions, if clinically indicated. 
4. Multivitamins, vitamin D, calcium, and supplements for prevention of weight loss. 
5. Prescribed medicinal cannabinoids as palliative therapy. 
6. Medications to prevent or treat CRS and ICANS are permitted. Please refer to Section 6.7.2 
for AE management guidelines and mitigation plans. 
7. It is recommended that high-risk subjects (ie, those with a high tumor burden) should be 
treated prophylactically in accordance with local standards (eg, rehydration, diuretics, 
allopurinol 300 mg daily, and medication to increase urate excretion). All subjects should be 
monitored for symptoms of TLS (see Section 10.15). Management of TLS, including 
dehydration and abnormal laboratory test results such as hyperkalemia, hyperuricemia, and 
hypocalcemia, is highly recommended. 
8. Anti-infection prophylaxis for bacterial, viral, fungal, or pneumocystis infections is allowed 
and should be given per institutional practice. 
9. Intravenous immunoglobulins are allowed to manage hypogammaglobulinemia at the 
investigator’s discretion per institutional practice. Note, immunoglobulins administered at 
doses on the order of 1 g/kg body weight have the potential to alter the clearance of other 
antibodies. Investigators should therefore be aware that the efficacy of antibody-based 
agents, including GEN3017, may be decreased when administering immunoglobulins at 
these doses, eg, for the treatment of immune thrombocytopenia, or other immune, 
inflammatory, or paraneoplastic conditions. 
10. Dexamethasone and other steroids may induce gastritis. Medications to prevent gastritis are 
permitted per institutional guidelines, for example proton pump inhibitors (omeprazole or 
equivalent) or sucralfate, or H2 blockers (ranitidine or equivalent). 
11. Subjects who use oral contraceptives, hormone-replacement therapy, or other maintenance 
therapy should continue their use. 
6.6.3.2 
Prohibited Concomitant Therapy 
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.  
The following concomitant therapies are prohibited from C1D1 until 30 days after last dose of 
GEN3017 unless otherwise specified: 

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All AEs including DLTs will be graded for severity according to the National Cancer Institute 
(NCI)-CTCAE, v5.0 unless otherwise specified. CRS and ICANS will be evaluated according to 
the ASTCT criteria (Lee et al., 2019). Clinical tumor lysis syndrome (CTLS) will be evaluated 
according to the Cairo-Bishop classification ((Coiffier et al., 2008); Section 10.15). 
The occurrence of any of the toxicities outlined in this section will be considered as a DLT 
except those that are clearly due to the underlying disease or extraneous cause: 
• All grade 5 toxicities 
• Hematological toxicities listed below: 
o Grade 4 neutropenia (ie, absolute neutrophil count <0.5×109 cells/L [<500/µL]) lasting 
>7 days not attributable to underlying disease 
o Grade 3 and grade 4 febrile neutropenia (neutrophil count <1.0×109 cells/L with a single 
temperature of >38.3 °C [100.9 °F] or with a sustained temperature of ≥38 °C 
[≥100.4 °F] for more than 1 hour) lasting >2 days 
o Grade 4 thrombocytopenia (platelet count ≤25.0×109 platelets/L [<25,000/µL]) for 
>7 consecutive days not attributable to underlying disease, or ≥ grade 3 
thrombocytopenia (<50.0×109 platelets/L) of any duration with clinically significant 
bleeding or ≥ grade 3 thrombocytopenia requiring a platelet transfusion 
o Grade 4 anemia 
• Non-hematological toxicities listed below: 
o Grade 4 CRS according to ASTCT criteria (Lee et al., 2019) 
o Grade 3 CRS according to ASTCT criteria (Lee et al., 2019) which has not resolved to 
≤ grade 2 within 48 hours following adequate intervention 
o Grade 4 ICANS according to ASTCT criteria (Lee et al., 2019) 
o Grade 3 ICANS according to ASTCT criteria (Lee et al., 2019) which has not resolved to 
≤ grade 2 within 48 hours following adequate intervention 
o TLS grade 3 that has not resolved within 5 days  
o TLS grade 4 
o Any ≥ grade 3 (severe or life-threatening) non-hematological toxicities, excluding the 
following: 
 Laboratory values out of normal range that do not have any clinical consequence, are 
clinically transient in nature, and that resolve within 7 days (including electrolyte 
abnormalities that respond to medical intervention) 
 Grade 3 aspartate transaminase and/or grade 3 alanine transaminase returning to 
grade 1 or baseline in ≤10 days 

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 Grade 3 nausea that responds to optimal antiemetic treatment in ≤3 days 
 Grade 3 vomiting that responds to optimal antiemetic treatment in ≤3 days 
 Grade 3 diarrhea that responds to optimal antidiarrheal treatment in ≤3 days 
 Grade 3 fatigue/asthenia when fatigue/asthenia was present at baseline or that lasts 
for <14 days after the last dose of GEN3017 
 Grade 3 amylase or lipase that is not associated with symptoms, or clinical 
manifestations, or radiological imaging of pancreatitis 
Note: AEs of specified grades, regardless of relationship to GEN3017, should be considered 
relevant for dose escalation decisions, unless the event can clearly be determined to be unrelated 
to the drug. All of the AEs of specified grades should be classified as DLTs except those that are 
clearly and incontrovertibly due to the underlying disease or extraneous causes. 
Frequent laboratory monitoring of complete blood count, including differential, should be 
initiated to document start and resolution of hematological AEs. All GEN3017-related AEs will 
be monitored and included in the evaluation of the toxicity profile of GEN3017 unless the event 
is clearly determined to be unrelated to GEN3017. AEs clearly not related to GEN3017 such as 
disease progression, environmental factors, unrelated trauma, etc, should not be considered as a 
toxicity event. 
6.7.2 
Dose Modification Guidance and Stopping Criteria 
Dose modification such as increase or decrease of GEN3017 is not permitted for this trial. Dose 
delay of GEN3017 is permitted for this trial, as described below. 
6.7.2.1 
Dose Escalation Part (GEN3017 Monotherapy) 
• If a subject experiences a DLT, GEN3017 treatment will need to be interrupted and further 
doses withheld while managing the DLT. The investigator is required to notify the sponsor’s 
MM promptly and conduct a full assessment of the event and benefit-risk for the subject. The 
subject may continue treatment with GEN3017, if the toxicity recovers to ≤ grade 2 or 
baseline within 4 weeks from occurrence of the DLT. Continuous treatment with GEN3017 
must be approved by the sponsor’s MM. GEN3017 treatment will be permanently 
discontinued 1) in the event the DLT is not resolved to ≤ grade 2 or baseline within 4 weeks 
or 2) in the event a subject experiences a second episode of a DLT with GEN3017. 
Following a DLT of grade 4 non-hematologic toxicity, GEN3017 treatment should be 
immediately interrupted, and proper management of the AE should be initiated promptly. 
Resumption of GEN3017 may be considered under the following conditions after discussion 
with the MM: 1) grade 4 AE has improved to grade 2 or better; or 2) subject has shown 
clinical benefit from the GEN3017 treatment. 
• If a subject experiences toxicity that would have qualified as a DLT but the event occurs 
after the DLT evaluation period, the subject’s benefit-risk must be thoroughly assessed by 
the investigator. Continuous treatment with GEN3017 must be approved by the sponsor’s 
MM. 

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Adverse Event(s) 
Toxicity Grade or 
Condition (CTCAE v5.0 
Except ASTCT for 
CRS/ICANS and Cairo-
Bishop for TLS/CTLS) 
Adverse Event Management  
CRS (see Section 
10.12 and Section 
10.13. If CRS is 
refractory to 
management, 
consider other causes 
including 
macrophage 
activation syndrome 
and hemophagocytic 
lymphohistiocytosis) 
If grade 2 CRS occurs with 
 or 
beyond, administer CRS prophylaxis with the 
next dose until an GEN3017 dose is given 
without subsequent CRS (of any grade). 
Grade 3 
Withhold GEN3017 until resolution of CRS 
event.  
Ensure CRS symptoms are resolved for at least 
72 hours prior to the next dose of GEN3017. 
If grade 3 CRS occurs 
 or 
beyond, administer CRS prophylaxis with the 
next dose until a GEN3017 dose is given without 
subsequent CRS (of any grade). 
Hospitalize for the next dose of GEN3017. 
Recurrent grade 3 CRS: 
Permanently discontinue GEN3017. 
Manage CRS per current practice guidelines 
(Section 10.13) and provide supportive therapy, 
which may include intensive care. 
Cytokine blockade-
refractorya grade 3 for >72 
hours or grade 4 
Permanently discontinue GEN3017. 
Manage CRS per current practice guidelines 
(Section 10.13) and provide supportive therapy, 
which may include intensive care. 
ICANS (see Section 
10.14) 
Grade 1 and grade 2 
Withhold GEN3017 until resolution of ICANS 
event to ≤ grade 1 for at least 72 hours. 
Provide supportive therapy and manage per 
current practice guidelines. 
Grade 3 
Withhold GEN3017 until resolution of ICANS 
event to ≤ grade 1 for at least 72 hours. 
Provide supportive therapy, which may include 
intensive care, consider neurology evaluation, 
and manage per current practice guidelines. 
Recurrent grade 3 ICANS: Permanently 
discontinue GEN3017.  
Grade 4 
Permanently discontinue GEN3017. 
Provide supportive therapy, which may include 
intensive care, consider neurology evaluation, 
and manage per current practice guidelines. 
Hematological 
(see Section 
6.7.2.1 for details)b 
Platelet count 
decreased/ 
thrombocytopenia 
≥ Grade 3 
Withhold GEN3017 until platelet count is 
≥50 × 109/L. 
Platelet infusions may be administered per 
institutional standards. 
Neutropenia and 
febrile neutropenia 
≥ Grade 3 
Withhold GEN3017 until neutrophil count is 
≥0.5 × 109/L. 
Use of growth factors is mandated. 
Anemia 
≥ Grade 3 
Withhold GEN3017 until hemoglobin is ≥8 g/dL 
(≥80 g/L or ≥4.9 mmol/L). 
Red blood cell infusions should be administered 
per institutional standards. 
CCI
CCI

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○ Subject has recovered, defined as resolution of fever without use of antipyretics and 
improvement in respiratory symptoms (eg, cough, shortness of breath), AND subject has 
obtained 2 negative molecular (eg, PCR) tests or negative antigen tests with results ≥ 24 
hours apart, and it has been 7-10 days after the 2nd negative test. 
• 
Asymptomatic subjects:  
○ Subject has obtained 2 negative molecular (eg, polymerase chain reaction [PCR]) tests or 
negative antigen tests with results ≥ 24 hours apart and it has been 7-10 days after the 2nd 
negative test. 
6.7.2.4 
Tumor Flare or Pseudoprogression 
Pseudoprogression, a phenomenon with an influx of immune responsive cells into a lesion that 
causes clinical and imaging findings during treatment suggestive of progressive disease despite 
evidence of clinical benefit, has been reported in lymphomas treated with immunotherapies such 
as rituximab (Han et al., 2009; Skoura et al., 2016), immunomodulatory drugs (eg, lenalidomide 
(Witzig et al., 2011)), anti-PD-1 inhibitors (Ansell et al., 2015; Lesokhin et al., 2016; Westin et 
al., 2014), and bispecific antibodies (eg, glofitamab (Dickinson et al., 2022)). It is important to 
differentiate pseudoprogression from true tumor progression to avoid the premature 
discontinuation of GEN3017. 
6.7.2.4.1 
Criteria for Continuing GEN3017 Treatment During Suspected 
Pseudoprogression 
During the trial, when the investigator believes that a subject is deriving clinical benefit from 
GEN3017 treatment despite radiographic evidence of progressive disease, investigators are 
encouraged to continue GEN3017 treatment until the next scheduled imaging assessment, 
provided the following criteria are met: 
• There is an absence of symptoms and signs (including worsening of laboratory values) 
indicating progression of disease. 
• There is no decline in ECOG performance status (Section 10.5). 
• There is an absence of tumor progression at critical anatomical sites including the central 
airway, the great vessels, and other organs or tissues where compromised function secondary 
to tumor progression would be expected to result acutely in severe and/or irreversible 
disability or death. 
Subjects continuing GEN3017 therapy, despite apparent radiographic progression, will be 
encouraged to undergo a repeat tumor biopsy to assess whether increases in tumor volume are 
due to immune cell infiltration or neoplastic proliferation, provided that such a biopsy can be 
performed safely on a non-target lesion. 
In subjects categorized as having suspected pseudoprogression, it is mandatory to obtain a repeat 
imaging in the next scheduled imaging assessment (Section 1.3) or earlier if clinically indicated.  

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6.7.2.4.2 
Retreatment After Discontinuing From GEN3017 Treatment Due To 
Suspected Pseudoprogression 
Subjects discontinued from GEN3017 treatment due to suspected pseudoprogression, who later 
achieve PR or CR without receiving any other anticancer therapy after the last dose of 
GEN3017, will be allowed to enter the “post-treatment follow-up” period for efficacy. These 
subjects may be eligible for retreatment if, after discussion with the sponsor’s MM, the MM 
agrees to retreat the subject and the subject meets eligibility criteria. 
6.7.2.5 
Monitoring of Rapid Tumor Progression 
Rapid tumor progression (ie, an acceleration of disease activity with disease progression 
according to the 2014 Lugano classification prior to completion of 3 cycles of GEN3017 
treatment) will be closely monitored. If a subject experiences rapid tumor progression per the 
investigator’s assessment, the investigator should promptly discuss this with the sponsor’s MM 
and the subject should be discontinued from GEN3017 treatment. 
During the conduct of the trial, and after at least 3 subjects have been treated with GEN3017 and 
received at least one dose of GEN3017, if >33% of subjects (regardless of the DL or if during 
phase 1 or phase 2a) experience rapid progression, trial accrual will be halted and a full review 
of these events will be performed by the DEC and Safety Committee for phase 1 and Safety 
Committee for phase 2a, respectively. Patient accrual will not resume until approved by the DEC 
and Safety Committee (phase 1) or Safety Committee (phase 2a). 
6.7.3 
Safety Stopping Guidance for the Trial 
The trial can/will be stopped for unacceptable toxicity as per recommendations from DEC and 
Safety Committee in dose escalation or Safety Committee in expansion and based on a risk-
benefit assessment. Fatal events considered related to GEN3017 should always be assessed by 
the DEC and Safety Committee in dose escalation or Safety Committee in expansion. 
In order to ensure subject safety during dose escalation, if any of the boundaries in Table 6-5 are 
crossed for a DL in 1 of the indications (considered independently), a prompt comprehensive 
review of the safety data will be conducted to determine if the trial should be stopped. In 
particular, for treatment-related grade 5 AEs, if the boundary is crossed the enrollment into any 
dose escalation DL is paused and a subsequent review will occur. 
Table 6-5 
Safety Stopping Guidance in Study GCT3017-01 
Number Dosed at DL 
1 
2 
3 
4 
5 
6 
9 
12 
Grade 3 or greater CRS/ICANSa 
- 
- 
3 
≥3 
≥3 
- 
≥5 
≥5 
Grade 4 or greater CRS/ICANS 
- 
2 
≥2 
≥2 
≥2 
≥2 
≥3 
≥3 
Treatment-related grade 5 AEs 
1 
≥1 
≥1 
≥1 
- 
≥2 
≥2 
≥2 
AE=adverse event; CRS=cytokine release syndrome; DL=dose level; ICANS=immune effector cell-associated 
neurotoxicity syndrome. 
a. Which has not resolved to ≤ grade 2 within 48 hours following adequate intervention. 
The boundaries assume acceptable incidences of: 
• 15% incidence for grade 3 or greater CRS/ICANS 

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• 5% incidence for grade 4 or greater CRS/ICANS 
• 1% incidence for treatment-related grade 5 AEs 
When given an acceptable incidence, the probability for crossing the boundary at any monitoring 
time is approximately 5%.  
6.8 
Treatment of Overdose 
For this trial, an overdose is defined as a subject receiving a dose of GEN3017 in excess of 10% 
of that specified in this protocol. 
Sponsor does not recommend specific treatment for an overdose. 
In case of overdose, medication errors, misuse, and/or abuse of GEN3017, subjects should 
receive supportive care according to local guidelines and potential side effects of GEN3017 
should be treated symptomatically. 
In the event of an overdose, the investigator should: 
• Contact the sponsor’s MM (or delegate) immediately (see Section 8.4.3). 
• Closely monitor the subject for any AE/SAE and laboratory abnormalities 
• Obtain a serum sample for PK analysis if requested by the sponsor’s MM. 
• Document the quantity of the excess dose as well as the duration of the overdose. 
6.9 
Continued Access to Trial Drug After the End of the Trial 
For subjects with a potential treatment benefit, subjects may be eligible for continued treatment 
with Genmab IMP(s) by an extension protocol or as provided for by the local country’s 
regulatory mechanism. However, Genmab reserves the unilateral right, at its sole discretion, to 
determine whether to supply Genmab IMP(s) and by what mechanism, after termination of the 
trial and before the product(s) is/are available commercially. 
7 DISCONTINUATION OF TREATMENT AND DISCONTINUATION 
FROM TRIAL 
7.1 
Discontinuation of Treatment 
Subjects can decline to continue receiving GEN3017 treatment and/or other protocol required 
therapies or procedures at any time during the trial but continue participation in the trial. 
Subjects who have discontinued GEN3017 treatment and/or other protocol-required therapies or 
procedures should not be automatically removed from the trial. Whenever safe and feasible, it is 
imperative that subjects remain on-trial to ensure safety surveillance and/or collection of 
outcome data (ie, continue efficacy evaluations according to the trial protocol). 
The subject may discontinue both GEN3017 treatment and further participation in trial activities; 
however, they may continue to be followed for survival (see Section 7.1.4) and are not 
considered discontinued from the trial (see Section 7.2). 

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Reasons for discontinuation from GEN3017 treatment may include any of the following: 
• Disease progression according to response criteria outlined in Section 10.11 (for treatment 
after disease progression, especially in cases of pseudoprogession, see Section 6.7.2.4) 
• Clinical progression  
• Absence of clinical benefit 
• Unacceptable AE(s) requiring treatment discontinuation 
• Initiation of non-GEN3017 anticancer therapy 
• Subject requests to discontinue trial drug treatment 
• Sponsor or investigator decision  
• Subject noncompliance 
• Pregnancy 
7.1.1 
End of Treatment 
The end of treatment (EoT) visit should be conducted as soon as possible after the last dose of 
GEN3017 and no more than 7 days from the decision to end the GEN3017 treatment. If the 
subject initiates new anticancer treatment right after the last dose of GEN3017, the EoT visit 
should be performed prior to the initiation of the new anticancer treatment. 
7.1.2 
Safety Follow-up Visit(s) 
Subjects discontinuing from treatment for any reason will have a safety follow-up visit 60 days 
(+14 days) after the subject receives the last dose of GEN3017. If the subject initiates new 
anticancer treatment within 60 days of the last dose of GEN3017, the safety follow-up visit 
should be performed prior to the initiation of the new anticancer treatment.  
7.1.3 
Post-Treatment Follow-up 
Upon permanent discontinuation of GEN3017 prior to disease progression, post-treatment 
assessments for efficacy should continue until disease progression or start of new anticancer 
therapy. Assessments will be performed based on the schedules described in Section 8.2. 
Subjects will then enter survival status follow-up (Section 7.1.4). 
7.1.4 
Survival Status Follow-up 
Survival status will be assessed every 12 weeks (±14 days), beginning from the day the subject 
received the last dose of GEN3017 and continuing until the subject dies, withdraws consent for 
survival status follow-up, or the trial ends. Survival status may be requested more frequently 
around the time of a database lock or other trial milestones. Refer to Section 7.3 for guidance 
regarding subjects lost to follow-up. 
Site personnel will attempt to collect the survival status of the subject within legal and ethical 
boundaries for all enrolled subjects. Information about survival status may be given by the 

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subject or a family member. Survival status may be collected through medical records, national 
registries, or publicly available information as allowed per local regulation. If survival status is 
determined as deceased, this will be documented along with a date of death, if available. 
7.2 
Discontinuation From the Trial 
Reasons for discontinuation of a subject from the trial are: 
• Death 
• Lost to follow-up 
• Sponsor decision 
• Subject withdraws consent from trial participation 
• Maximum trial duration met 
If the reason for discontinuation from the trial is withdrawal of consent, then no additional 
assessments are allowed, but the sponsor may retain and continue to use any data collected 
before such a withdrawal of the consent. When a subject withdraws before completing the trial, 
the reason for withdrawal should be documented. 
If a subject withdraws from the trial, he/she may request destruction of any samples taken and 
not tested, and the investigator must notify the sponsor accordingly (see Section 10.4 for further 
details). 
7.3 
Lost to Follow-up 
A subject will be considered as lost to follow-up if the subject repeatedly fails to return for 
scheduled visits and is unable to be reached by the trial site. The following actions must be taken 
if a subject fails to return to the clinic for a required trial visit: 
• The site must attempt to contact the subject and reschedule the missed visit as soon as 
possible, counsel the subject on the importance of maintaining the assigned visit schedule 
and ascertain whether the subject wishes to and/or should continue in the trial. 
• Before a subject is deemed lost to follow-up, the investigator or designee must make every 
effort to regain contact with the subject (where possible, 3 telephone calls, and if necessary, a 
certified letter to the subject’s last known mailing address or local equivalent methods). 
These contact attempts should be documented in the subject’s medical record. 
• Should the subject continue to be unreachable, the subject will be considered to have 
discontinued from the trial. 

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8 TRIAL ASSESSMENTS AND PROCEDURES 
The Schedule of Activities (Section 1.3) summarizes the frequency and timing of all assessments 
applicable to this trial. 
All assessments should be performed prior to GEN3017 administration unless otherwise 
indicated in the Schedule of Activities. Sample collections for PK and biomarker assessments 
should be kept within the allowed visit windows. 
Instructions for the collection, handling, storage, and shipment of samples can be found in the 
Laboratory Manual that will be provided. Collection, handling, storage, and shipment of samples 
must be conducted under the specified, and where applicable, controlled temperature conditions 
as indicated in the Laboratory Manual. 
8.1 
Demography and Baseline Assessments 
8.1.1 
Demographics 
The following demographic details will be collected at screening, where permitted by local 
regulations: 
• Age at time of screening 
• Sex at birth 
• Race 
• Ethnicity 
8.1.2 
Diagnosis and Disease Status 
A subject’s history relating to the underlying disease including primary diagnosis, date of 
diagnosis, as well as disease status at trial entry, Ann Arbor staging, and risk category will be 
recorded. 
To confirm eligibility, the local pathology report including CD30 status (eg, CD30 expression on 
tumor tissue) will be collected and reviewed by the sponsor’s MM. The report should include 
relevant markers associated with the cHL or TCL subtype assessed by flow cytometry, 
immunohistochemistry staining, fluorescent in situ hybridization, or PCR. 
8.1.3 
Medical History 
Any medical condition (signs, symptoms, and diagnosis) occurring prior to first dose of 
GEN3017 should be documented in the source documents as medical history. Medical conditions 
that occur after the ICF is signed and prior to first dose of GEN3017 should only be reported as 
AEs if they were assessed by the investigator to be caused by a protocol mandated procedure (eg, 
CT scan), including washout or discontinuation of prior medications. 
Any medical history/current medical condition that worsens after the first dose of GEN3017 will 
be documented as an AE. See additional reporting details in Section 8.4 and Section 10.2. 

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8.1.4 
Concomitant Procedures 
Diagnostic or medical treatment procedures that have been performed or are ongoing during the 
trial should be documented (eg, chest X-ray). The associated diagnosis related to the procedure 
should be documented as an AE (eg, pneumonia). The exception to this is when a diagnostic or 
medical treatment procedure is performed as part of routine care for a pre-existing condition that 
has not worsened from baseline and is documented as part of the subject’s medical history. 
8.2 
Efficacy Assessments 
Efficacy assessments will be conducted at the time points specified in the Schedule of Activities 
(Section 1.3). Imaging must be performed at screening, Week 6 ± 7 days, Week 15 ± 7 days, 
Week 24 ± 7 days, Week 33 ± 7 days, Week 48 ± 7 days, and then every 6 months (± 14 days) 
until subject has disease progression, starts new anticancer therapy, withdraws from trial, or dies, 
whichever comes first. Disease assessment and imaging assessment should not be delayed when 
there is a treatment cycle delay, ie, imaging assessment time points are counted from the date of 
the first dose of GEN3017 by calendar days, not by treatment cycles. Disease evaluation and 
response assessment may be conducted more frequently if clinically indicated. Clinical suspicion 
of disease progression at any time requires a physical examination and imaging assessments to 
be performed promptly rather than waiting for the next scheduled imaging assessment. Please 
refer to Schedule of Activities (Section 1.3) for specified time points.  
For time points when FDG-PET assessment (metabolic response) is available, the FDG-PET 
(metabolic response) assessment is preferred over the CT-response in FDG-avid histologies. For 
time points when only CT is available, following a prior FDG-PET assessment, CT assessments 
may be affected by the prior PET-CT assessment (eg, CT-based PR at current time point, with no 
worsening, does not preclude prior FDG-PET CR [metabolic response] and response can stay as 
CR). 
8.2.1 
Evaluations 
Disease assessments by radiological imaging, physical examination, laboratory testing, and other 
procedures should be performed at the site level throughout the trial as shown in the Response 
assessment in the Schedule of Activities tables (Section 1.3) or more frequently if clinically 
indicated. For imaging assessments, the same radiographic modality used at screening for 
disease evaluation should be used throughout the trial for consistent response evaluations.  
8.2.1.1 
Radiographic Assessments 
A combined FDG-PET/CT scan (or MRI/CT and FDG-PET when PET-CT scan not available) 
must be performed within 21 days before Cycle 1 Day 1. Assessments performed as SOC prior 
to the subject signing informed consent may be submitted as the screening assessment if 
assessment is performed within 42 days of Cycle 1 Day 1. FDG administration for PET should 
be limited to 370 MBq. 
As all subjects are anticipated to have FDG-avid tumors at screening, subsequent disease 
assessments will include FDG-PET using the 5-point scale (Barrington et al., 2014) 
(Section 10.10). For subjects with non-avid or variably FDG-avid tumors, CT scan with IV 
contrast of neck, chest, abdomen, pelvis, and additional known lesions will be performed. The 
CT component of the PET-CT may be used in lieu of a standalone MRI/CT, only if the CT 
component is of similar diagnostic quality as a contrast enhanced CT performed without PET. 

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If contrast enhanced PET-CT is not available, a standalone diagnostic MRI/CT and a standard 
FDG-PET should be performed. If independent CT and PET scanners are used, and the subject is 
receiving both scans on the same day, the PET is recommended to be performed prior to the CT 
with IV contrast in order not to compromise PET results. The PET-CT acquisition methodology 
(eg, administration of intravenous contrast) should remain consistent between screening and 
subsequent assessments for any given subject. 
Subjects who are intolerant of IV CT contrast agents may have CT scans performed with oral 
contrast. MRI may be used to evaluate sites of disease that cannot be adequately imaged using 
CT, for subjects who are intolerant of CT contrast agents or based on local imaging practice. In 
cases where MRI is the imaging modality of choice, the MRI must be obtained at screening and 
at all subsequent response evaluations. For all other sites of disease, MRI studies do not replace 
the required neck, chest, abdomen, and pelvic CT scans. An MRI scan or CT scan of the brain 
should be performed if CNS involvement is suspected at screening and during the trial. 
8.2.1.2 
Bone Marrow Assessment  
For subjects with known bone marrow involvement or whose disease is suspected to have bone 
marrow involvement, fresh bone marrow biopsy and/or bone marrow aspirate must be obtained 
at screening (ie, within 3 weeks prior to the first dose of GEN3017) and to confirm CR or 
suspected CR or as clinically indicated. However, archival bone marrow biopsy obtained as 
routine SOC taken within 42 days before the first dose of GEN3017 is acceptable. Bone marrow 
evaluation must include morphological examination and either flow cytometry or 
immunohistochemistry, if warranted, to confirm the presence or absence (complete remission) of 
lymphoma.  
8.2.1.3 
Assessment of Response and Progressive Disease 
In dose escalation, tumor response will be determined by the investigator based on the Lugano 
criteria (Cheson et al., 2014). In expansion, tumor response will be determined by both the 
independent review committee (IRC) and the investigator based on the Lugano criteria (Cheson 
et al., 2014). PET-CT scan images will be obtained according to local site imaging requirements. 
Submission instructions for the IRC review will be provided in a separate manual. 
All response assessments should be conducted throughout the trial until disease progression or 
withdrawal of consent from trial participation. Response assessments will be performed by the 
investigators at the site to make decisions for continuation of treatment. Imaging findings 
suggestive of progressive disease despite evidence of clinical benefit have been described with 
immunomodulatory agents, eg, tumor flare or pseudoprogression (Cheson et al., 2016). 
Currently, the potential for similar effect of GEN3017 is unknown, but should be taken into 
consideration when evaluating imaging during the trial. Accordingly, an increase in the size of 
previously involved lymph nodes, especially at the beginning of GEN3017 treatment, may 
represent pseudoprogression and may not be designated as progressive disease, unless there is 
continued increase in size on subsequent imaging studies or confirmed with biopsies. Hence, in 
order to avoid premature termination, subjects can continue receiving GEN3017 at investigator 
and subject discretion until the response or lack thereof is confirmed on subsequent imaging. 
In expansion, sites will also be required to submit electronic copies of all scans on an ongoing 
basis to a centralized imaging vendor. An independent review of all scans will be conducted 
retrospectively by the IRC. Information regarding prior interventions (eg, radiotherapy), pre-
existing radiographic findings that mimic metastatic disease at baseline or screening, and on-trial 

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interventions should be transmitted to the imaging CRO via the baseline clinical form along with 
the baseline images for review by IRC members. Sites must ensure that the data entered on the 
form are the same as the data entered into the clinical database. 
8.3 
Safety Assessments 
The trial will include the following evaluations of safety and tolerability according to the time 
points provided in the Schedule of Activities (Section 1.3). 
8.3.1 
Physical Examination 
A complete (full) physical examination (according to SOC) should be performed during the 
screening period, on Day 1 of each cycle, at EOT, and at the post-treatment follow-up visit, as 
specified in the Schedule of Activities (Section 1.3). For C1D1, physical examination may be 
performed within 1 day prior to GEN3017 dosing. In addition, a symptom-directed/clinically 
indicated (brief) physical examination is recommended prior to the rest of trial visits prior to 
GEN3017 administration. After the first dose of GEN3017 treatment, new or worsening findings 
since the last assessment should be documented as AEs. 
Complete (full) physical examinations should at a minimum evaluate possible presence of 
palpable lymph nodes, tumor masses, enlargement of liver and spleen, and include inspection 
and description of the treatment injection site. Complete physical examinations will include 
evaluation of additional organ systems as per site SOC. 
8.3.2 
Body Measurements 
Height (without shoes) must be measured at screening and rounded to the nearest centimeter or 
inch. Body weight (without overcoat and shoes) will be measured as indicated in the Schedule of 
Activities (Section 1.3) and rounded to the nearest kilogram. 
For subjects with weight-based dosage, trial drug doses should be adjusted based on the subject’s 
actual weight in kilograms measured within 3 days prior to the beginning (ie, Day 1) of each 
cycle. If the subjects’ weight on dosing days has changed by >10% of the value for that cycle, 
then the dose should be recalculated for the cycle. This weight will be used for calculation of the 
dose and should be documented. 
8.3.3 
Vital Signs 
Vital signs including temperature (°C or °F), respiratory rate, oxygen saturation, blood pressure 
(mm Hg), and heart rate (beats/min) will be measured in a supine or reclined position as 
indicated in the Schedule of Activities (Section 1.3). Vital signs should also be assessed and 
reported at all unscheduled visits, including any visit that occurs as a result of an AE. 
The subjects should be resting and in a horizontal or half laid position for at least 10 minutes 
before vital signs are measured. 
Temperature should be measured as an oral, axillary, rectal, or ear temperature. The temperature 
should be documented as a value corrected according to local standards. 

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8.3.7 
Clinical Laboratory Assessments 
Samples will be collected as indicated in the Schedule of Activities (Section 1.3). The 
investigator must review the laboratory results, document this review, and record any clinically 
relevant changes occurring during the trial. 
Clinically significant abnormal laboratory findings are those which are not associated with the 
underlying disease, unless judged by the investigator to be more severe than expected for the 
subject’s condition. 
Laboratory test results should be assessed for abnormalities (see Section 10.2 for additional 
information on reporting of laboratory abnormalities that are considered AEs). When an 
abnormal laboratory or test result corresponds to a sign/symptom of an already reported AE, it is 
not necessary to separately record the laboratory/test result as an additional event. 
NOTE: A CTCAE grade 3 or 4 laboratory abnormality does not automatically indicate an SAE. 
The tests detailed in Table 8-1 will be performed locally. The laboratory reports must be filed 
with the source documents.  
Local laboratory values for biochemistry, hematology, and coagulation must be obtained at 
screening and repeated within 3 days prior to the first trial drug administration and reviewed by 
the investigator prior to the first trial drug administration to ensure that the subject is still 
eligible. For subsequent doses, these laboratory values must be obtained within 1 day, preferably 
on the day, prior to each trial drug administration and reviewed by the investigator prior to each 
trial drug administration to ensure the subject can be dosed according to the dosing instructions 
defined in the protocol. 
For unscheduled visits, blood sampling should be performed as clinically indicated. In case of 
symptoms considered likely to be part of CRS, additional samples for C-reactive protein, ferritin, 
fibrinogen, triglycerides, aPTT, and INR (PT is optional) obtained at the local laboratory are 
recommended in addition to sending additional samples for cytokine measurement and PK to the 
central laboratory. 

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Table 8-1 
Protocol-Required Safety Local Laboratory Assessments 
Laboratory 
Assessments 
Test Name 
Hematology 
Hematocrit 
Hemoglobin 
Platelet count 
RBC count 
RBC indices: 
• MCH 
• MCHC 
• MCV 
• % reticulocytes 
White blood cell (WBC) count with 
differential: 
a) Neutrophils 
b) Lymphocytes 
c) Monocytes 
d) Eosinophils 
e) Basophils 
Biochemistry 
Albumin 
Calcium 
Gamma-glutamyl 
transferase 
Potassium 
Alkaline 
phosphatase  
Chloride 
Glucose (non-fasting) 
Sodium 
ALT 
C-reactive proteinb 
LDH 
Total and direct 
bilirubin 
Amylase 
Creatinine and 
CrCla  
Lipase 
Total protein 
AST 
Ferritinb  
Magnesium 
Triglyceridesb 
Blood urea nitrogen  
Fibrinogenb 
Inorganic phosphorus 
(phosphate) 
Uric acid 
Tumor lysis 
sample 
Uric acid 
Potassium 
Inorganic phosphorus 
(phosphate) 
Calcium 
Creatinine 
Coagulation 
factorsb 
PT 
INR 
aPTT 
Urinalysis 
Leukocyte 
esterase/leukocytes 
Protein 
Serology/ 
molecular testingc 
HBsAg and HBcAb. If positive serology, PCR for HBV DNA to be performed. 
HCV antibody. If positive serology, PCR for HCV RNA to be performed. 
CMV serology (IgG and IgM) at screening. If positive serology, CMV PCR to be 
performed. 
Epstein-Barr virus PCR. 
HIV testing at screening only if required per local regulations or institutional standards. 
HTLV-1 and HTLV-2 serology. If positive serology, PCR for HTLV-1 and/or HTLV-2 to 
be performed accordingly. 
Pregnancy testsd 
Serum β-hCG 
Urine pregnancy test 
Additional tests 
Beta2-microglobulin 
Immunoglobulins: IgA, IgE, IgG, and IgM 
Tuberculosis test (if clinical suspicion is high) 
ALT=alanine transaminase; aPTT=activated partial thromboplastin time; AST=aspartate transaminase; β-hCG=beta-
human chorionic gonadotropin; BUN=blood urea nitrogen; CMV=cytomegalovirus; CrCl=creatinine clearance; 
CRS=cytokine release syndrome; GFR=glomerular filtration rate; HBcAb=hepatitis B core antibody; 
HBsAg=hepatitis B surface antigen; HBV=hepatitis B virus; HCV=hepatitis C virus; HTLV-1=human T-cell 
leukemia virus type 1; HTLV-2=human T-cell leukemia virus type 2; Ig=immunoglobulin; LDH=lactate 
dehydrogenase; MCH=mean corpuscular hemoglobin; MCHC=mean corpuscular hemoglobin concentration; 
MCV=mean corpuscular volume; PCR=polymerase chain reaction; PT=prothrombin time; RBC=red blood cell; 
T3=total triiodothyronine; T4=free thyroxine; TSH=thyroid-stimulating hormone; WBC=white blood cell. 
a. 
Estimate creatinine clearance using Cockcroft-Gault (Section 10.7). 
b. As indicated in Section 1.3 and if indicated during CRS (PT is optional). 
c. 
Only performed if required by local regulations. 

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d. For female subjects with childbearing potential, a serum pregnancy test is required to be performed during the 
screening period. Additionally, a urine or serum test should be performed within 24 hours of dosing at the start 
of each cycle and at other visits as indicated in Section 1.3. If a urine pregnancy test is positive, a serum 
pregnancy test is required to confirm. An additional pregnancy test is required 4 months after the last dose of 
GEN3017. 
8.3.8 
Other Safety Assessments 
8.3.8.1 
Neurological Evaluation 
Assessment for neurotoxicity with a neurologic assessment must be performed during therapy 
with GEN3017 by trained trial-site staff. An assessment according to ICANS evaluation (Lee et 
al., 2019) should be performed as indicated in Section 1.3. ICANS assessments must be 
performed at least daily during CRS events, and once daily during hospitalization if subject was 
hospitalized. Finally, additional ICANS assessment should always be performed when clinically 
indicated. 
ICANS is a disorder characterized by a pathologic process involving the CNS following any 
immune therapy that results in the activation or engagement of endogenous or infused immune 
effector cells, including T cells. ICANS may occur concurrently with CRS or shortly after CRS 
symptoms subside (but rarely before). Symptoms can be progressive and may include aphasia, 
altered level of consciousness, delirium, dizziness, encephalopathy, headache, impairment of 
cognitive skills, motor weakness, tremor, seizures, and cerebral edema (Lee et al., 2019). 
The grading of ICANS requires assessment of the 10-point immune effector cell-associated 
encephalopathy (ICE) score as well as evaluation of 4 other neurologic domains: level of 
consciousness, seizures, motor symptoms, and signs of raised intracranial pressure/cerebral 
edema, which may occur with or without encephalopathy. See Section 10.14 for additional 
details for grading and management of ICANS. 
Overall ICANS grade is determined by the most severe event of the neurotoxicity domains (ICE 
score, level of consciousness, seizure, motor findings, raised intracranial pressure/cerebral 
edema) not attributable to any other cause. For example: subject with an ICE score of 3 who has 
a generalized seizure is classified as having grade 3 ICANS. 
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. 
A subject with an abnormal ICE score must be assessed to determine if it is due to ICANS or an 
alternate cause. If not due to ICANS, the relevant condition will be reported as an AE. 
Depressed level of consciousness should not be attributable to another cause (eg, sedating 
medication). 
Tremors and myoclonus associated with immune effector cell therapies may be graded according 
to CTCAE, but they do not influence ICANS grading. 
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 CTCAE. 

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Treatable causes of neurologic dysfunction, such as infection or hemorrhage should be ruled out. 
Common manifestations of neurotoxicity (eg, confusion, seizure, aphasia), can also be seen with 
infection, electrolyte imbalances, metabolic acidosis, uremia, concomitant medication use (eg, 
opioids), and other medical conditions. Other causes for such symptoms should be considered. 
8.3.8.2 
Constitutional Symptoms 
Constitutional symptoms (B symptoms) will be evaluated for all subjects as indicated in the 
Schedule of Activities (Section 1.3). Constitutional symptoms include night sweats, weight loss 
>10% over 6 months, extreme fatigue, and/or fever without infection. 
8.4 
Adverse Events and Serious Adverse Events 
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the sponsor, and are mandated by 
regulatory agencies worldwide. The sponsor has established SOPs in conformity with regulatory 
requirements worldwide to ensure appropriate reporting of safety information; all clinical studies 
conducted by the sponsor or its affiliates will be conducted in accordance with those procedures. 
Information in this section should be used in conjunction with the additional details provided in 
Section 10.2. 
8.4.1 
Definition of Adverse Events and Serious Adverse Events 
The definitions of AEs, SAEs, adverse events of special interest (AESIs), as well as attribution 
definitions; severity criteria; special reporting situations; and procedures, are provided in 
Section 10.2. 
8.4.1.1 
Adverse Events of Special Interest 
The protocol-defined AESIs are: 
1. CRS, graded according to ASTCT criteria ((Lee et al., 2019); Section 10.12 and Section 
10.13)  
2. ICANS, graded as ASTCT Criteria ((Lee et al., 2019); Section 10.14) 
3. CTLS graded according to Cairo-Bishop ((Coiffier et al., 2008); Section 10.15) 
Additional AESIs may be defined on the basis of an ongoing review of the safety data. 
8.4.2 
Adverse Event Reporting 
Trial Period 
Reporting Requirements 
Signing of ICF through prior 
to first dose 
AEs, if assessed by the investigator to be caused by a protocol-mandated 
procedure (eg, CT scan), including washout or discontinuation of prior 
medications. 
First dose through safety 
follow-up visit 
All AEs and SAEs (see definitions in Section 10.2), regardless of casualty, will 
be documented. 

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Safety follow-up visit through 
end of trial/after end of trial 
There is no requirement to monitor subjects for SAEs following the protocol-
required reporting period (ie, after the safety follow-up visit) or after end of 
trial. However, if the investigator becomes aware of an event, SAEs should be 
reported if judged by the investigator as related to trial drug(s). 
NOTE: Any secondary primary malignancy(ies) (not a new lesion, recurrence, or transformation to a more 
aggressive histology of the disease under trial)] regardless of relatedness to trial drug(s), should be reported at any 
time during or after the trial if the investigator becomes aware of such an event. 
For details regarding follow-up of AEs and SAEs, see Section 8.4.6. Refer to Section 6.2 for 
guidance regarding product complaints. 
8.4.3 
Events Requiring Immediate Reporting 
8.4.3.1 
Secondary Primary Malignancy 
Secondary primary malignancy(ies) (not a new lesion, recurrence, or transformation to a more 
aggressive histology of the disease under trial), regardless of relatedness to trial drug(s), must be 
reported to the sponsor within 24 hours of knowledge of the event (at any time during or after the 
trial). 
8.4.3.2 
Serious Adverse Events 
All SAEs occurring during the safety reporting period must be reported from the trial site to the 
sponsor no later than 24 hours following: 
• The subject visit at which the AE was reported, noted, or recognized. 
• The principal investigator’s or any investigator personnel’s receipt of the test results. 
• Other information from which the AE was reported, noted, or recognized. 
8.4.3.3 
Overdose/Medication Errors 
An overdose is defined as a subject receiving a dose of GEN3017 in excess of 10% of that 
specified in this protocol. All cases of overdose with GEN3017, whether associated with an AE 
or not, must be reported to the sponsor within 24 hours of knowledge of the event (see additional 
details in Section 6.8).  
Overdose of concomitant medication should only be reported if associated with adverse events 
whether serious or not. 
Medication errors and uses outside what is foreseen in the protocol, including misuse and abuse 
of the product, whether associated with an AE or not, should be reported within 24 hours of 
knowledge of the event. 
8.4.3.4 
Pregnancy 
Pregnancy is not allowed in this trial. However, if any pregnancy occurs during trial 
participation, the pregnancy must be reported. 
All reports of pregnancy in female subjects or partners of male subjects must be reported to the 
sponsor within 24 hours of knowledge of the event. In the case of pregnancy in the partner of a 

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male subject, a separate ICF will be obtained from the female partner for collection of 
information regarding the pregnancy. 
The pregnancy must be followed up to determine outcome (including premature termination) and 
status of mother and child. The child must be followed at least to the age of 1 month. Pregnancy 
complications and elective terminations must be reported as an AE or SAE. Spontaneous 
abortions must be reported as an SAE. Any SAE occurring in association with a pregnancy 
brought to the investigator’s attention after the subject has completed the trial and considered by 
the investigator as possibly related to GEN3017 must be promptly reported to the sponsor or 
designee. 
Pregnant trial subjects must be withdrawn from treatment immediately, whereas male subjects 
may continue in the trial should pregnancy of female partners occur. 
8.4.3.5 
Adverse Events of Special Interest or Other Events of Interest 
AESIs that have been defined in Section 8.4.1.1 must be reported within 24 hours of their 
knowledge of the event if they meet seriousness criteria, or reported within 72 hours if not 
serious. 
8.4.4 
Regulatory Reporting Requirements for SUSARs 
The sponsor has a legal responsibility to notify, as appropriate and according to local regulations, 
both the local regulatory authority and other regulatory agencies about the safety of the product 
under clinical investigation. Prompt notification of SAEs by the investigator to the sponsor is 
essential so that legal obligations and ethical responsibilities towards the safety of subjects are 
met (see Section 8.4.3.2). 
The sponsor will ensure that all relevant information about suspected unexpected serious adverse 
reactions (SUSARs) is documented and reported as soon as possible, but within a maximum of 
15 calendar days (fatal or life-threatening SUSARs within a maximum of 7 calendar days) of 
first knowledge by the sponsor or designee, to the competent regulatory authorities and/or to the 
ethics committee/IRBs according to the applicable local regulatory requirements. Relevant 
follow-up information of fatal or life-threatening SUSARs will be communicated subsequently 
within the required reporting timelines. The sponsor will also communicate relevant information 
on SUSARs with the investigators in predefined periods and according to local regulations. 
The investigator should be aware of local reporting regulations to the IEC/IRB. The CRO will 
either supply the investigator with the reports which should be passed on to the IEC/IRB or 
report directly to the IEC/IRB, depending on local regulations. For SUSARs aggregated in a line 
listing distributed quarterly, or every 6 months, or in periods as warranted by the nature of the 
IMP and the trial, the investigator must review such safety information in a timely manner and 
signoff for the review as instructed by the sponsor, to document the awareness about the latest 
safety updates that may impact on the investigator’s responsibilities for subject care. 

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8.4.5 
Disease-Related Events/Outcomes and Other Events/Procedures Not Qualifying as 
Adverse Events or Serious Adverse Events 
The following should not be reported as an AE or SAE: 
• Events that are clearly consistent with the expected pattern of progression of the underlying 
disease should not be recorded as AEs or SAEs. 
o That is, the terms “Disease Progression,” “Progression of Disease,” or “Malignant 
Disease Progression” and other similar terms should not be used to describe an AE or 
SAE. These data are captured as efficacy assessment data only. 
 In most cases, the expected pattern of progression will be based on the response 
criteria. In rare cases, the determination of clinical progression will be based on 
symptomatic deterioration. However, every effort should be made to document 
progression through use of objective criteria. 
 Clinical symptoms of progression may be reported as AEs or SAEs if the symptom 
cannot be determined as reasonably due to progression of the underlying malignancy 
or does not fit the expected pattern of progression for the disease under study. 
• Hospitalization due solely to progression of the underlying cancer should not be reported as 
an SAE. See Section 10.2.1.2, under the definition of SAE, for additional reasons when 
hospitalizations should not be reported as SAEs. 
• Unrelated Procedures: Diagnostic and therapeutic noninvasive and invasive procedures, such 
as surgery, should not be reported as AEs. However, a medical condition for which an 
unscheduled procedure was performed should be reported if it meets the definition of an AE 
(eg, an acute appendicitis should be reported as the AE and not the appendectomy). 
8.4.6 
Follow-up of Adverse Events and Serious Adverse Events 
All AEs must be followed until they are resolved or until the safety follow-up visit(s) or the start 
of new anticancer treatment, whichever comes first. 
All SAEs and GEN3017-related AESIs qualifying for immediate reporting that are ongoing at 
the safety follow-up visit(s) should continue to be followed on a regular basis until the event has 
been resolved or until the investigator assesses it as chronic and all queries have been resolved. 
8.4.7 
Precautions and Warnings 
Refer to the IB for detailed information for precautions and warnings. Additional safety 
information collected between IB updates will be communicated in the form of investigator 
notifications. This information will be included in the ICF and should be discussed with the 
subject during the trial as needed. 
For approved products used in combination with GEN3017, reference the current prescribing 
information (eg, USPI, SmPC) for additional safety information. 

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8.5 
Pharmacokinetics 
Blood samples will be collected to evaluate the PK of GEN3017 at the time points specified in 
the Schedule of Activities (Section 1.3). The actual date and time of each sample must be 
recorded. 
Samples will be analyzed to determine concentrations of GEN3017 using a validated, specific, 
and sensitive immunoassay method by or under the supervision of the sponsor. 
Samples collected for analyses of GEN3017 serum concentration may additionally be used to 
evaluate safety or efficacy aspects that address concerns arising during or after the trial period. 
Additional samples may be collected during the trial if warranted and agreed upon between 
investigator and sponsor, eg, for safety monitoring. 
Additional information about the collection, handling, and shipment of samples is included in the 
Laboratory Manual. 
8.6 
Pharmacodynamics 
Pharmacodynamic assessments/samples will be performed/collected as per the time points 
specified in the Schedule of Activities (Section 1.3) to identify potential PD markers for 
GEN3017 treatment. 
8.7 
Biomarkers 
Biomarker Sample Collection 
Samples for biomarker analyses will be collected at the time points specified in the Schedule of 
Activities (Section 1.3). Subjects must consent to biomarker sample collection and assessment in 
order to participate in this trial. Biomarker analyses are dependent upon the availability of 
appropriate biomarker assays and clinical response rates. Biomarker analysis may be deferred or 
not performed, if during or at the end of the trial, it becomes clear that the analysis will not have 
sufficient scientific value for biomarker evaluation, or if there are not enough samples or 
responders to allow for adequate biomarker evaluation. In the event the trial is terminated early 
or shows poor clinical efficacy, completion of biomarker assessments is based on justification 
and intended utility of the data. 
Details on the collection, processing, storage, and shipment of biomarker samples will be 
provided in separate documents (eg, Laboratory Manual and lab flowchart). 
8.7.1 
Biomarker Assessments in Tumor Samples 
A fresh biopsy must be collected before administration of trial drug(s) (ie, during the screening 
period) for all subjects with accessible tumors, unless medically unfeasible. Alternatively, an 
archival tumor biopsy, which is the most recently collected tumor biopsy acquired within 
6 months prior to enrollment, may be provided in lieu of a fresh sample. Aspirates are not 
acceptable. An acceptable archival tumor biopsy may consist of formalin-fixed paraffin-
embedded (FFPE) tumor tissue block; freshly cut unstained slides are also acceptable. If fresh or 
archival (from most recent progression and taken within 6 months) tumor biopsies cannot be 
provided, site may submit an older archival tumor biopsy (most recent available, and preferably 

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Serum samples will be screened for ADAs binding to GEN3017 and the titer of confirmed 
positive samples will be reported. Serum concentrations of GEN3017 will be analyzed (see 
Section 8.5) and those data will be used to for interpretation of the ADA data. The ADA samples 
may additionally be used to evaluate safety or efficacy aspects that address concerns arising 
during or after the trial period for further characterization of immunogenicity. 
Neutralization characterization of ADAs may also be performed using appropriate methods. 
Further details are included in the Laboratory Manual. 

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9.3.2 
Analysis of the Dose Escalation Part 
9.3.2.1 
Primary Endpoint Analysis 
The primary endpoints for the dose escalation part of the trial are the incidence and severity of 
AEs and the incidence of DLTs. For analysis of AEs see Section 9.3.4. 
The incidence of DLTs will be presented for the Dose-Determining Set using descriptive 
statistics. 
9.3.2.2 
Secondary Endpoints Analyses 
For the dose escalation part of the trial the following secondary endpoints are presented: 
Pharmacokinetics 
For reporting of PK concentrations and parameters see Section 9.3.7 
PK data may also be used to create a population PK model that will be reported separately.  
Immunogenicity 
Immunogenicity will be presented as described in Section 9.3.8 
Efficacy 
Objective response rate 
The ORR, as assessed by the investigator, will be classified according to Lugano criteria 
(Cheson et al., 2014), and will be summarized as described in Section 9.3.3.1. 
Duration of response 
DOR is defined as the time from the first documentation of response (CR or PR) to the date of 
progressive disease or death, whichever occurs earlier. DOR will be analyzed as described for 
PFS in Section 9.3.3.2.  
Time to response 
Time to response (TTR) is defined as the time from C1D1 to first documentation of objective 
response (CR or PR) in subjects achieving PR or CR. Time to response will be analyzed as 
described for PFS in Section 9.3.3.2.  
9.3.2.3 
Exploratory Endpoint Analyses 
Exploratory endpoints will be presented descriptively. 
9.3.3 
Analysis of the Expansion Part 
9.3.3.1 
Primary Endpoint Analysis 
The primary endpoint for the expansion part of the trial is ORR based on Lugano criteria 
(Cheson et al., 2014) as assessed by IRC. 

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The ORR is defined as the proportion of subjects with a best overall response of CR or PR. All 
other categories, including not-evaluable are considered non-response.  
Best overall response will be summarized in conjunction with the ORR. The estimated ORR and 
the exact 2-sided 95% confidence interval using the Clopper-Pearson method will be presented.  
The FAS will be used. The RES may also be used for sensitivity analysis. 
9.3.3.2 
Secondary Endpoints Analyses 
Efficacy 
All secondary efficacy analysis will be based on the FAS. 
Objective response rate 
ORR as assessed by investigator by Lugano criteria (Cheson et al., 2014) will be summarized as 
described in Section 9.3.3.1. 
Complete response rate 
The number of patients with CR will be summarized. CR as assessed by investigator and IRC by 
Lugano criteria (Cheson et al., 2014) will be presented.  
Duration of response 
DOR will be presented as described for the dose escalation part of the trial (Section 9.3.2.2) as 
assessed by investigator and IRC by Lugano criteria (Cheson et al., 2014). 
Time to response 
TTR will be presented as described for the dose escalation part of the trial (Section 9.3.2.2) as 
assessed by investigator and IRC by Lugano criteria (Cheson et al., 2014). 
Progression-free survival 
PFS is defined as the time from C1D1 to first documented progressive disease or death due to 
any cause, whichever occurs earlier. PFS will be censored similar to table C1 in Appendix C in 
the FDA Guidance for Industry: Clinical Trial Endpoints for the Approval of Non-small Cell 
Lung Cancer Drugs and Biologics (FDA Guidance for Industry, 2015). Further details will be 
provided in the statistical analysis plan. 
PFS will be defined for all subjects and presented graphically as well as summarized using 
survival analysis methods in terms of Kaplan-Meier estimates. 
PFS will be assessed by investigator and IRC by Lugano criteria. 
Overall survival 
OS is defined as the time from C1D1 to the date of death due to any cause. Subjects who 
withdrew consent to the trial or are lost to follow-up will be censored at the latest date the 
subject was known to be alive (on or before the cutoff date). 

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OS is presented as described for PFS.  
Immunogenicity 
Immunogenicity will be presented as described in Section 9.3.8. 
Incidence of AE 
For reporting of AEs see Section 9.3.4.  
Pharmacokinetics 
For reporting of PK concentrations and parameters see Section 9.3.7. 
9.3.3.3 
Exploratory Endpoint Analyses 
Exploratory endpoints will be presented descriptively. 
9.3.4 
Safety Analyses 
Safety analysis will be done for both escalation and expansion part of the trial. The Safety Set 
will be used.  
Adverse Events 
The on-treatment period is defined as the time from C1D1 until the end of safety follow-up. 
TEAEs are events that occur during the on-treatment period or AEs starting before C1D1 and 
worsening during the on-treatment period.  
Adverse events will be graded according to the NCI-CTCAE as described in Section 10.2.3.1.  
All TEAEs and treatment-emergent SAEs will be presented descriptively.  
Analysis of AEs will be summarized using the Safety Set with the exception of deaths, which 
will be presented for the FAS. 
Clinical Laboratory Tests 
Grading of laboratory values will be assigned programmatically according to the NCI-CTCAE 
v5.0. The calculation of NCI-CTCAE grades will be based on the observed laboratory values 
only, clinical assessment will not be considered. CTCAE grade 0 will be assigned for all 
non-missing values not graded 1 or higher.  
Laboratory tests that are graded by NCI-CTCAE are presented in a shift table presenting baseline 
grade versus worst on-treatment grade. 
Laboratory tests that cannot be graded by NCI-CTCAE are presented in a shift table presenting 
baseline low/normal/high classification versus worst on-treatment value.  
The number of subjects with at least 1 grade 3 or higher on-treatment laboratory test will be 
summarized.  

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ICE Score 
ICE score will be presented descriptively. 
Constitutional Symptoms 
Constitutional symptoms will be presented descriptively.  
ECOG 
ECOG will be presented descriptively.  
ECG 
Evaluation of ECG by investigator will be presented as normal/abnormal and not clinically 
significant/abnormal clinically significant. 
ECG measurements (ie, QTc) will be presented by visit and time point. Abnormal values as read 
by central reader will be presented.  
Vital Signs 
Number of patients with at least 1 clinically notable abnormal value will be presented.  
9.3.5 
Other Analyses 
Subgroup analysis for the primary endpoint in the expansion part of the trial may be explored to 
investigate whether the treatment effect is consistent across various subgroups.  
9.3.6 
Planned Analyses 
9.3.6.1 
Interim Analysis 
An interim analysis is not planned for this trial. 
9.3.6.2 
Primary Analysis 
The primary analysis will be conducted when all subjects have discontinued treatment and have 
completed all required follow-up visits. At this time, a final data sweep will be performed to 
determine the survival status of previously discontinued subjects. 
9.3.7 
Pharmacokinetic Analyses 
Dose Escalation Part 
Individual curves of concentrations of GEN3017, including information on actual dose, will be 
presented for all subjects. All available data will be shown in these figures. PK endpoints will be 
calculated based on non-compartment methods and presented separately 
. 
Predose values will be summarized and presented graphically for all trial days where measured. 
Descriptive statistics of PK endpoints will include arithmetic and geometric means, standard 
deviation, coefficient of variation (CV)%, median, minimum, and maximum values. 
Concentration values below the lower limit of quantification (LLOQ) will be handled as LLOQ/2 
CCI

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in summary statistics and reported as is in data listings. Any missing PK endpoint data will not 
be imputed. 
The FAS will be used. 
Expansion Part 
Trough and peak values will be presented with descriptive statistics over time. The FAS will be 
used.  
9.3.8 
Immunogenicity Analyses 
Dose Escalation and Expansion Parts 
The results from the analysis of immunogenicity samples are given as ADA positive, ADA 
negative, or missing. The ADA positive results are then to be confirmed with a given titer value.  
Data will therefore be categorized as one of the following:  
• ADA confirmed 
• ADA not confirmed (ie, negative samples and not-confirmed positive samples) 
• Missing samples 
The number of subjects having at least 1 confirmed ADA during treatment will be presented and 
the largest titer value will be presented for subjects having at least 1 confirmed ADA sample. 
The Safety Set will be used for immunogenicity analyses. 
9.4 
Sample Size Determination 
No formal sample size calculations will be done for the dose escalation part. Sample size is given 
per the mBOIN algorithm as described in Section 4.1. With 10 expected DLs, and an average of 
6 subjects per DL, 60 subjects are expected to be enrolled in each disease cohort. 
No formal sample size calculations will be done for the expansion part. A sample of 20 subjects 
per cohort per DL is deemed enough to provide a preliminary assessment of efficacy and in line 
with recommendations in the FDA’s Guidance on expansion cohorts (FDA Guidance for 
Industry, 2022).  

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10 APPENDICES: SUPPORTING DOCUMENTATION AND 
OPERATIONAL CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, Ethical, and Trial Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
The principles of the Declaration of Helsinki, the consolidated ICH-GCP, and applicable 
regulations and national law(s) (eg, 21 CFR and European regulation 536/2014 for clinical trials, 
article 80-2 of the “Law on Securing Quality, Efficacy and Safety of Products including 
Pharmaceuticals and Medical Devices,” Japanese Ministerial Ordinance on Good Clinical 
Practice for Drugs [J-GCP]) in the country(ies) where the trial takes place shall constitute the 
main reference guidelines for ethical and regulatory conduct. 
ICH GCP E6(R2) is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting trials that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
trial subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the trial data are credible. 
The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, advertisements) 
must be submitted to an IRB/IEC by the investigator and reviewed and approved by the IRB/IEC 
before the trial is initiated. 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the trial design, except for changes necessary to eliminate an immediate hazard 
to trial subjects. 
10.1.2 
Investigator Responsibilities 
The investigator is responsible for ensuring that the trial is performed in accordance with the 
protocol, ICH GCP E6(R2), and applicable regulatory and country-specific requirements. This 
includes supervision of the trial and staff. Delegation of responsibilities should be to only 
qualified staff and should be documented. In case the investigator is unavailable (eg, on 
vacation), the investigator should ensure that a qualified, trained deputy physician is available for 
medical care of the subjects. The investigator shall notify the sponsor immediately of any serious 
breach of ICH GCP E6(R2), the protocol, or any regulation where required. 
10.1.3 
Independent Ethics Committee or Institutional Review Board 
This trial will be undertaken only after the IEC/IRB has given written approval of the final 
protocol, amendments to the protocol (if applicable), the ICF, applicable recruiting materials, 
subject compensation programs, and other applicable documents that are part of the regulatory 
package, and the sponsor has received a copy of this written approval. This approval letter must 
be dated and must clearly identify the IEC/IRB and the documents being approved. 
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data, or trial conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and written approval before 
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The IB and updates to the IB, unexpected SAEs where a causal relationship cannot be ruled out, 
serious breaches, serious noncompliance, annual written summaries of the trial status, and 
deviations to the protocol implemented to eliminate immediate hazards to the subjects must be 
submitted to the IEC/IRB. 
Interim reports on the trial and/or review(s) of trial progress will be submitted by the 
investigator, where applicable, to the IEC/IRB at intervals stipulated in its guidelines. 
At the end of the trial, the investigator (or sponsor where required) will notify the IEC/IRB about 
the trial completion, within the required timelines. 
10.1.4 
Financial Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the trial and for 
1 year after completion of the trial. 
10.1.5 
Administrative Procedures 
10.1.5.1 
Protocol Amendments 
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. Approval must be obtained from the IRB/EC and regulatory authorities (as 
locally required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to subjects or changes that involve logistical or administrative 
aspects only (eg, change in the sponsor’s medical officer or contact information). Documentation 
of amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When 
the change(s) involves only logistic or administrative aspects of the trial, the IRB (and IEC 
where required) only needs to be notified. 
During the course of the trial, in situations where a deviation from the protocol is unavoidable, 
the investigator or other physician in attendance will contact the sponsor (see the separate 
sponsor Contact Information page, which will be provided separately from the protocol). Except 
in emergency situations, this contact should be made before implementing any deviations from 
the protocol. In all cases, contact with the sponsor must be made as soon as possible to discuss 
the situation and agree on an appropriate course of action. The data documented in the electronic 
case report form (eCRF) and source documents will reflect any deviation from the protocol, and 
the source documents will describe this departure and the circumstances requiring it. 
10.1.5.2 
Regulatory Documentation 
This protocol and any amendments must be submitted to the appropriate regulatory authorities in 
each respective country, in accordance with local regulations. A trial may not be initiated until 
all local regulatory requirements are met. 

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10.1.5.3 
Subject Identification, Enrollment, and Screening Logs 
The investigator agrees to complete a subject identification log to permit easy identification of 
each subject during and after the trial. This document will be reviewed by the sponsor trial-site 
contact for completeness. 
The subject identification log will be treated as confidential and will be filed by the investigator 
in the Investigator Site file and will never be transferred to the sponsor or any third parties. To 
ensure subject confidentiality, no copy will be made. All reports and communications relating to 
the trial will identify subjects by their unique subject identifier. 
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the trial. 
10.1.6 
Informed Consent Process 
The ICF(s) and assent form that is/are used must be approved by the reviewing IEC/IRB and be 
in a language that the subject can read and understand. The ICF should be in accordance with 
principles that originated in the Declaration of Helsinki, ICH GCP E6(R2), applicable regulatory 
requirements, and sponsor policy. 
It is the personal responsibility of the investigator or an authorized member of the trial-site 
personnel to explain to potential subjects (or their legally acceptable representative [not 
applicable in EU/EEA]) the aims, methods, reasonably anticipated benefits, and potential 
hazards of the trial, and any discomfort participation in the trial may entail. 
Subjects will be informed that their participation is voluntary and that they may withdraw 
consent to participate at any time without justifying the reason. They will be informed that 
choosing not to participate will not affect the care the subject will receive for the treatment of 
their disease. Subjects will be told that alternative treatments are available if they refuse to take 
part and that such refusal will not prejudice future treatment. Finally, they will be told that the 
investigator will maintain a subject identification register for the purposes of long-term follow up 
if needed and that their records may be accessed by IRB/IEC and Regulatory Authorities, and 
authorized sponsor personnel without violating the confidentiality of the subject, to the extent 
permitted by the applicable law(s) or regulations. 
By signing the ICF the subject (or legally acceptable representative [not applicable in EU/EEA]) 
is authorizing such access, including permission to obtain information about survival status, and 
agrees to allow their trial physician to re-contact the subject for the purpose of obtaining consent 
for additional safety evaluations, if needed, and subsequent disease-related treatments, or to 
obtain information about survival status. 
The subject (or his/her legally acceptable representative [not applicable in EU/EEA]) will be 
given sufficient time to read the ICF and the opportunity to enquire about details of the trial prior 
to deciding whether to participate in the trial. After this explanation and before any trial-specific 
procedure is performed, consent should be appropriately documented by means of either the 
subject's or their legally acceptable representative's (not applicable in EU/EEA) personally dated 
signature. 
Subjects (or his/her legally acceptable representative [not applicable in EU/EEA]) will be 
required to sign a statement of informed consent that meets the requirements of 21 CFR 50, 

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European regulation 536/2014 for clinical studies, local regulations, ICH guidelines, HIPAA, 
and EU GDPR requirements, where applicable, and the IRB/IEC or trial center. The investigator 
or authorized person obtaining the informed consent must also sign and date the ICF. After 
having obtained the consent, a copy of the ICF must be given to the subject. 
If the subject (or legally acceptable representative [not applicable in EU/EEA]) is unable to read 
or write, an impartial witness should be present for the entire informed consent process (which 
includes reading and explaining all written information) and should personally date and sign the 
ICF after the oral consent of the subject (or legally acceptable representative [not applicable in 
EU/EEA]) is obtained. 
The sponsor will, on an ongoing basis, assess whether reconsent of subjects is needed. 
Subjects who are rescreened are required to sign a new ICF. 
10.1.7 
Data Protection 
The investigator will ensure that the confidentiality of all subjects’ data will be preserved. In the 
eCRF or any other documents submitted to the sponsor/sponsor’s representative, the subjects 
will not be identified by their names, but by an identification code, which consists of an assigned 
number in the trial. The confidential subject identification code and the signed ICF will be 
maintained by the investigator in strict confidence. 
In relation to the collection and handling of data, including any personal data, potential risks to 
the subjects have been assessed and adequate technical and organizational measures are 
implemented to ensure a level of security appropriate to the risk. 
The security measures implemented entail among other things that: 
• Access to data has been restricted so that access is only granted to authorized individuals. 
• Data are only stored on IT systems and networks that are protected against virus, malware, 
and unauthorized access. 
• Data are backed-up at regular intervals. In case of a data breach, a clear allocation of roles 
and responsibilities for managing the data breach, including notifying affected subjects and 
authorities, has been established in order to mitigate any adverse impact on the subjects. 
Additional technical security measures implemented include that: 
• All data are encrypted when at rest. 
• Data have been pseudonymized to the effect that only authorized individuals can link data to 
identified individuals. 
• A data breach response plan has been established. 
The collection and processing of personal data from subjects enrolled in this trial will be limited 
to those data that are necessary to fulfill the objectives and purposes of the trial and as 
specifically defined in the protocol. 

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These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place, as detailed above. Sponsor personnel whose responsibilities require access to 
personal data agree to keep the identity of subjects confidential. 
The informed consent obtained from the subject (or their legally acceptable representative [not 
applicable in EU/EEA]) includes explicit consent or description of other legal basis for the 
processing of personal data for the purpose of the trial and for the investigator/institution to 
allow direct access to original medical records (source data/documents) for trial-related 
monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also addresses the 
transfer of the data to other entities and to other countries, as specified in the ICF. 
The subject has the right to request access to their personal data and the right to request 
rectification of any data that are not correct or complete by contacting the investigator. 
Reasonable steps will be taken by the investigator to respond to such a request, taking into 
consideration the nature of the request, the conditions of the trial, the clinical trial agreement 
including any other relevant agreement, and applicable laws and regulations. The investigator 
will inform and work together with the sponsor when handling such requests. 
In case of a potential data breach of the personal data, the investigator will inform the sponsor 
immediately and will contain the breach from spreading, where possible. Investigator and 
sponsor will work together to assess the risk to the individuals concerned, based on the 
circumstances of the case, including which data was involved, what security measures were in 
place (for instance, if the data was encrypted or pseudonymized), and who might have accessed 
the data, etc. 
Based on this assessment, the data breach might be reported to the relevant authorities and/or the 
individuals concerned. Mitigating actions will be taken to avoid this event from reoccurring. 
10.1.8 
Committees Structure 
Dose Escalation Committee 
The DEC will be chaired by the sponsor’s medical officer (or delegate) and membership will 
include investigator(s), a sponsor clinical scientist, a safety physician, a statistician, a clinical 
pharmacologist, and other sponsor staff, as appropriate. The DEC will meet at regular frequency 
throughout the dose escalation part. 
The schedule of DEC meetings will depend on the completion of DLT(s) evaluation period(s) 
(period is defined for each trial). 
All available data, including but not limited to safety, pharmacokinetic, and pharmacodynamic 
data, covering the DLT evaluation period will be reviewed by the DEC. Cumulative data from 
treatment doses after the DLT period may also be monitored. Recommendations on dose 
escalation (or de-escalation) will be made by the DEC to the Safety Committee. 
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The sponsor’s Safety Committee is a cross-functional committee that evaluates the evolving 
safety profile of the product, supports assessment of the product's benefit/risk profile and 
recommends risk management strategies to ensure safety of subjects who participate in Genmab 
sponsored clinical trials or patients treated with marketed Genmab drugs. For FIH dose 
escalation Phase, the Safety Committee will consider the recommendation made by the DEC and 
make the final decision regarding dose escalation (or de-escalation). The Safety Committee can 
also stop further enrollment if treatment-emergent toxicity is determined to result in an 
unfavorable change in subject benefit/risk. Enrollment may be temporarily held, if needed, for 
the Safety Committee to evaluate the emerging data. 
Decisions will be communicated to investigators and decisions with the potential to affect 
subject safety (eg, unfavorable change in benefit/risk assessment) will be promptly 
communicated to investigators and regulatory authorities, as required. 
10.1.9 
Dissemination of Clinical Trial Data 
The protocol information will be registered in a publicly accessible database (eg, 
clinicaltrials.gov, CTIS, and/or other national registries/Health Authority websites). In addition, 
after trial completion (defined as last subject last visit globally) and finalization of the study 
report, the results of this trial will be submitted for disclosure and posted in a publicly accessible 
database of clinical trial results as required by local regulations (eg, clinicaltrials.gov, CTIS). 
10.1.10 
Data Quality Assurance, Record Retention, Monitoring, and On-Site Audits 
10.1.10.1 
Data Quality Management 
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate trial sites, review of protocol procedures with the investigator and 
trial-site personnel before the trial, periodic monitoring visits by the sponsor (or sponsor’s 
delegate), and direct transmission of clinical laboratory data from a central laboratory, ECG data 
from the ECG vendor, and review of radiographic scans and pathology reports (as applicable) 
from the central imaging vendor (expansion only) into the sponsor's data base. Written 
instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for eCRF completion will be provided. The sponsor/CRO will review eCRFs for 
accuracy and completeness during on-site or remote monitoring visits and after transmission to 
the sponsor; any discrepancies will be resolved with the investigator or designee, as appropriate. 
After upload of the data into the trial database, the data will be reviewed for accuracy and 
consistency with the data sources. 
10.1.10.2 
Record Retention 
In compliance with ICH GCP E6(R2), the investigator/institution will maintain all eCRFs and all 
source documents, as well as a source document location list, that support the data collected from 
each subject, as well as all trial documents as specified in ICH GCP Guideline Section 8, 
Essential Documents for the Conduct of a Clinical Trial, and all trial documents as specified by 
the applicable regulatory requirement(s). The investigator/institution will take measures to 
prevent accidental or premature destruction of these documents. 
Essential documents must be retained for 25 years after end of trial. These documents will be 
retained for a longer period if required by the applicable regulatory requirements. It is the 

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responsibility of the sponsor to inform the investigator/institution as to when these documents no 
longer need to be retained. Medical Records (subjects’ hospital record) is retained/archived 
according to applicable local regulation. 
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the trial records, custody must be transferred to a qualified and trained 
person who will accept the responsibility. The sponsor must be notified in writing of the name 
and address of the new custodian. Under no circumstance shall the investigator relocate or 
dispose of any trial documents before having obtained written approval from the sponsor. 
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this trial, the investigator/institution must permit access to such 
reports. 
10.1.10.3 
Monitoring 
The sponsor will use a combination of remote and on-site monitoring to monitor this trial. The 
sponsor or delegate will perform on-site monitoring visits as frequently as necessary. The 
monitor will record dates of the visits in a trial-site visit log that will be kept at the trial site. The 
first post-initiation visit will be made as soon as possible after enrollment (ie, the first subject has 
signed the ICF) has begun. At these visits, the monitor will verify the data entered into the 
eCRFs with the hospital or clinic records (source documents). The nature and location of all 
source documents will be identified to ensure that all sources of original data required to 
complete the eCRF are known to the sponsor and trial-site personnel and are accessible for 
verification by the sponsor trial-site contact. If electronic records are maintained at the trial site, 
the method of verification must be discussed with the trial-site personnel. Where allowed in 
accordance with local regulations, or in the event of a national emergency, and in agreement with 
the investigator, remote source data verification or source data review may be performed. 
The investigator must permit the monitor access to all source data, including electronic medical 
records, and/or documents with the purpose of verifying that the data recorded in the eCRF are 
consistent with the original source data. 
Findings from this review of eCRFs and source documents will be discussed with the trial-site 
personnel. The sponsor expects that, during monitoring visits, the relevant trial-site personnel 
will be available, the source documentation will be accessible, and a suitable environment will 
be provided for review of trial-related documents. The monitor will meet/talk with the 
investigator on a regular basis during the trial to provide feedback on the trial conduct. 
In addition to on-site monitoring visits, remote contact can occur. It is expected that during these 
remote contacts, trial-site personnel will be available to provide an update on the progress of the 
trial at the site. 
10.1.10.4 
On-Site Audits and Inspections 
Representatives of the sponsor's clinical quality assurance department may visit the trial site at 
any time during or after completion of the trial to conduct an audit of the trial in compliance with 
regulatory guidelines and company policy. These audits will require access to all trial records, 
including source documents, for inspection and comparison with the eCRFs. Subject privacy 
must, however, be respected. The principal investigator and trial-site personnel are responsible 

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for being present and available for consultation during routinely scheduled trial-site audit visits 
conducted by the sponsor or its designee(s). 
Similar procedures for inspections may also be conducted by agents of any regulatory body, 
either as part of a national GCP compliance program or to review the results of this trial in 
support of a regulatory submission. The investigator should immediately notify the sponsor if 
they have been contacted by a regulatory agency concerning an upcoming inspection. Regulatory 
inspectors must be allowed direct access to original medical records (source data/documents). 
10.1.11 
Source Documents and Case Report Form Completion 
10.1.11.1 
Source Documentation 
Source documents provide evidence for the existence of the subject and substantiate the integrity 
of the data collected. Source documents are filed at the investigator’s site. At a minimum, the 
type and level of detail of source data available for a subject should be consistent with that 
commonly documented at the trial site as a basis for standard medical care. Specific details 
required as source data for the trial will be reviewed with the investigator before the trial, 
described in the monitoring guidelines (or equivalent), and captured in a source data verification 
log at site. 
For each subject, the investigator must indicate in the hospital/medical source records that the 
subject participates in this trial and the date of obtaining the ICF. The records should document 
data on the condition of the subject at the time the subject is enrolled in the trial, to enable 
verification of eligibility. Signed and dated ICFs will be stored and archived according to local 
requirements.  
In addition, the following information, at the minimum, will also be recorded in the 
hospital/medical source records for each subject: 
• subject’s name and date of birth 
• screening/subject/randomization number 
• trial identification 
• confirmation of eligibility for participation in the trial, including diagnosis 
• medical history 
• date of each visit 
• any assessment performed eg, results of safety and efficacy evaluations 
• concomitant medications 
• occurrence of any AEs/SAEs (including description and duration) 
• status of the subject at the end of trial 
• reason for treatment discontinuation/trial withdrawal, if applicable 

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Any worksheets used to capture data to facilitate completion of the eCRF will become part of the 
subject's source documentation. In some cases, eg, demographic data (race, ethnicity, sex at 
birth), the eCRF may be considered the subject’s source documentation. 
In addition to the source data in medical records, data may be recorded directly electronically 
(eg, ECGs, PROs). Such data are considered source data and are accessible by both the 
investigator and sponsor. 
The author of an entry in the source should be identifiable. 
Information included in the subject’s hospital records may be subject to local regulations. If there 
is a discrepancy between local requirements and the protocol, local regulations should be 
followed. 
10.1.11.2 
Case Report Form Completion 
CRF data will be transcribed into an electronic data capture (EDC) system by trial-site personnel 
from the source documents. Both EDC and other electronically captured trial data will be 
transmitted in a secure manner to the sponsor within agreed upon time frames. 
Data relating to the trial must be documented and reported in English. Trial site personnel must 
complete the CRF as soon as possible after the data are available and preferably within 5 days. 
Source data and the CRFs should be available for review at the next scheduled monitoring visit. 
All eCRF entries, response to queries, corrections, and alterations must be made by the 
investigator or other authorized trial-site personnel. The completed eCRF must be verified and 
approved by the investigator or qualified physician who is a subinvestigator and who is 
delegated this task on the Delegation of Authority Form. 
Corrections to the eCRF after data entry can be done as follows (corrections must be verified and 
approved by the investigator or qualified physician who is a subinvestigator and who is 
delegated this task on the Delegation of Authority Form.): 
• Trial-site personnel can make corrections in the EDC tool at their own initiative or as a 
response to an auto query (generated by the EDC tool). 
• The monitor can generate a query for resolution by the trial-site personnel. 
• The sponsor or designee can generate a query for resolution by the trial-site personnel. 
10.1.12 
Trial and Site Start and Closure 
The trial start date will be the first act of recruitment (ie, the first subject that signs the ICF). 
The sponsor reserves the right to close the trial site or terminate the trial at any time for any 
reason at the sole discretion of the sponsor. Trial sites will be closed upon trial completion. A 
trial site is considered closed when all required documents and trial supplies have been collected 
and a trial-site closure visit has been performed. 
In addition, the investigator may initiate trial-site closure at any time, provided there is 
reasonable cause and sufficient notice is given to the sponsor in advance of the intended 
termination. 

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Reasons for the early closure of a trial site by the sponsor or investigator may include but are not 
limited to: 
• Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's guidance documents/trial plans, ICH GCP E6(R2), and 
applicable regulatory requirements. 
• Inadequate recruitment of subjects by the investigator 
• Discontinuation of further GEN3017 development. 
The sponsor may, based on available data, discontinue further development of GEN3017. 
If the trial is prematurely terminated or suspended, the sponsor shall promptly inform the 
investigators, the IECs/IRBs, the regulatory authorities, and any CRO(s) used in the trial of the 
reason for termination or suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the subject(s) and should ensure appropriate subject therapy 
and/or follow-up. 
10.1.13 
Publication Policy 
All information, including but not limited to information regarding GEN3017 or the sponsor's 
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the sponsor to the investigator and not 
previously published, and any data, including exploratory research data, generated as a result of 
this trial, are considered confidential and remain the sole property of the sponsor. The 
investigator agrees to maintain this information in confidence and use this information only to 
accomplish this trial and will not use it for other purposes without the sponsor's prior written 
consent. CROs involved in the trial are not permitted to publish without the sponsor’s prior 
written approval. 
The investigator understands that the information developed in the trial will be used by the 
sponsor in connection with the continued development of GEN3017, and thus may be shared as 
required to other clinical investigators or regulatory agencies. To permit the information derived 
from the clinical trial to be used, the investigator is obligated to provide the sponsor with all data 
obtained in the trial. 
Trial subject identifiers will not be used in publication of results. Any work created in 
connection with performance of the trial and contained in the data that can benefit from 
copyright protection (except any publication by the investigator as provided for below) shall be 
the property of the sponsor as author and owner of copyright in such work. 
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines (Battisti et al., 2015; ICMJE, 2010; ICMJE, 2019) the sponsor in conjunction 
with any collaborative group(s), shall have the right to publish such primary (multicenter) data 
and information as per the prespecified and approved publication plan. If an investigator wishes 
to publish information from the trial, a copy of the manuscript must be provided to the sponsor 
for review at least 60 days before submission for publication or presentation. Expedited reviews 
will be arranged for abstracts, poster presentations, or other materials. If requested by the 
sponsor in writing, the investigator will withhold such publication for up to an additional 60 days 
to allow for filing of a patent application. In the event that issues arise regarding scientific 

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integrity or regulatory compliance, the sponsor will review these issues with the investigator. 
The sponsor will not mandate modifications to scientific content and does not have the right to 
suppress information. For multicenter trial designs and sub-trial approaches, secondary results 
generally should not be published before the primary endpoints of a trial have been published. 
Similarly, investigators will recognize the integrity of a multicenter trial by not submitting for 
publication data derived from the individual trial site until the combined results from the 
completed trial have been submitted for publication, within 12 months of the availability of the 
final data (tables, listings, graphs), or the sponsor confirms there will be no multicenter trial 
publication. Authorship of publications resulting from this trial will be based on the guidelines 
on authorship, such as those described in the current version of ‘Recommendations for the 
Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals’ (ICMJE 
Recommendations, http://www.icmje.org/recommendations/), which state that the named authors 
must have made a significant contribution to the design of the trial or analysis and interpretation 
of the data, provided critical review of the paper, given final approval of the final version, and 
agreed to be accountable for all aspects of the work. 

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10.2 
Appendix 2: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
and Reporting 
10.2.1 
Definitions 
10.2.1.1 
Definition of Adverse Event 
An AE is any untoward medical occurrence in a patient or clinical trial subject, temporally 
associated with the use of a medicinal product, whether or not considered related to the 
medicinal product. 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 product. 
AEs (including laboratory abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. When a 
clear diagnosis cannot be identified, each sign or symptom should be reported as a separate AE. 
10.2.1.2 
Definition of Serious Adverse Event 
An SAE is defined as an AE that meets 1 of the following criteria: 
• Is fatal or life-threatening 
o 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 which 
hypothetically might have caused death if it were more severe. 
• Results in persistent or significant disability/incapacity 
• Constitutes a congenital anomaly/birth defect 
• Is medically significant, ie, defined as an event that jeopardizes the subject or may require 
medical or surgical intervention to prevent 1 of the outcomes listed above 
• Requires inpatient hospitalization or prolongation of existing hospitalization. 
o Hospitalizations for the following reasons should not be reported as SAEs: 
 Routine treatment or monitoring of the underlying disease, not associated with any 
deterioration in the condition 
 Solely due to progression of the underlying cancer 
 Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
underlying disease and has not worsened since signing the ICF 
 Social reasons and respite care in the absence of any deterioration in the subject’s 
general condition 
 Treatment on an emergency outpatient basis that does not result in hospital admission 
and involves an event not fulfilling any of the definitions of an SAE given above. 

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10.2.1.3 
Definition of Adverse Events of Special Interest 
AESIs are defined as events (serious or nonserious) which are of scientific and medical concern 
specific to the sponsor’s product or program, for which ongoing monitoring and rapid 
communication by the investigator to the sponsor may be appropriate. Such events may require 
further investigation in order to characterize and understand them. Additional AESIs can also be 
defined on the basis of an ongoing review of the safety data. AESIs are discussed further in 
Section 8.4.1.1 and the IB. 
10.2.2 
Procedures for Recording and Reporting 
All AEs, serious or nonserious, must be documented. 
• The diagnosis/cause of an AE should be documented rather than the symptoms of the AE. 
• If no diagnosis is available, then each sign and symptom should be documented as an 
individual AE. 
• All AEs that occur during the AE reporting period must be documented, whether or not the 
event is considered treatment-related. 
• All AEs should be documented and reassessment made at each visit (or more frequently, if 
necessary). 
• Final assessment of AEs must be performed by a medically qualified person. 
Laboratory abnormalities that are considered clinically significant, induce clinical signs or 
symptoms, require concomitant therapy, or require changes in trial drug(s) should be 
documented as an AE. 
• Whenever possible, a diagnosis should be provided (eg, anemia instead of low hemoglobin). 
Laboratory abnormalities that meet the criteria for AEs should be followed until they have 
returned to normal or an adequate explanation for the abnormality is found. 
• NOTE: A CTCAE grade 3 or 4 laboratory abnormality does not automatically indicate an 
SAE. 
10.2.3 
Evaluation of Adverse Events 
10.2.3.1 
Severity 
Toxicities will be graded for severity according to the NCI-CTCAE, v5.0. CRS and ICANS will 
be evaluated according to the ASTCT criteria (Lee et al., 2019). CTLS will be evaluated 
according to the Cairo-Bishop classification (Coiffier et al., 2008). 
10.2.3.2 
Relationship to the Investigational Medicinal Product 
The investigator must assess whether or not the event is related to the trial drug(s). The 
relationship is to be judged using the following terms: 
• Related 

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• Not related 
If the relationship changes over time, the last judgment by the investigator should be reported. 
Relatedness has to be assessed and reported from the first time the event is being reported. 
A suspected adverse reaction is one in which there is a reasonable possibility that the trial 
drug(s) caused the AE, this means there is evidence to suggest a causal relationship between the 
trial drug(s) and the AE (ie, considered related). Refer to the GEN3017 IB. 
10.2.4 
Annual Safety Reporting by Sponsor 
Within the EU, the sponsor will submit independent Annual Safety Reports for all trial drugs in 
this clinical trial. 

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10.3 
Appendix 3: Definition of Reproductive Potential and Contraception 
Female subjects of reproductive potential must agree to use adequate contraception during 
GEN3017 treatment and for 4 months after receiving the last dose of GEN3017. Based on 
preliminary data, recommendation for the period of contraception and prohibition of egg 
donation after the last dose of GEN3017 may be extended. Adequate contraception is defined as 
highly effective methods of contraception (see Table 10-1). Birth control methods are considered 
highly effective if they have a failure rate of less than 1% per year when used consistently and 
correctly. For the definitions of reproductive potential and contraception in Japan, see 
Section 10.18.2. 
In this trial, subjects are considered to have reproductive potential unless they are 
postmenopausal or permanently sterile. 
A postmenopausal state is defined as no menses in subjects >45 years of age for 12 months 
without an alternative medical cause. A high FSH level in the postmenopausal range may be 
used to confirm a postmenopausal state in subjects not using hormonal contraception or 
hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single 
FSH measurement is insufficient. 
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral 
oophorectomy. 
All female subjects must agree not to donate eggs (ova, oocytes) for the purpose of assisted 
reproduction during GEN3017 treatment and for 4 months after receiving the last dose of 
GEN3017. 
Table 10-1 
Highly Effective Methods of Contraception 
• 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationa: 
○ 
Oral 
○ 
Intravaginal 
○ 
Transdermal 
• 
Progestogen-only hormonal contraception associated with inhibition of ovulation: 
○ 
Oral 
○ 
Injectable 
○ 
Implantablea 
• 
Intrauterine devicea 
• 
Intrauterine hormone-releasing systema 
• 
Bilateral tubal occlusiona 
• 
Vasectomized partnera, b 
• 
Sexual abstinencec 
Adapted from “Recommendations related to contraception and pregnancy testing in clinical trials, version 1.1.” 
(CTFG, 2020). 
a. 
Contraception methods that, in the context of this guidance, are considered to have low user dependency. 
b. Vasectomized partner is a highly effective birth control method provided that partner is the sole sexual partner 
of the female subject of reproductive potential (ie, the trial subject) and that the vasectomized partner has 
received medical assessment of the surgical success. 
c. 
In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the trial drug(s). The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 

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10.4 
Appendix 4: Sample Storage and Destruction 
Any sample collected according to the Schedule of Activities (Section 1.3) can be analyzed for 
any of the tests outlined in the protocol and for any tests necessary to minimize risks to trial 
subjects. This includes testing to ensure analytical methods produce reliable and valid data 
throughout the course of the trial. This can also include, but is not limited to, investigation of 
unexpected results, incurred sample reanalysis, and analyses for method transfer and 
comparability.  
All samples and associated results will be coded before being shipped from the site for analysis 
or storage. Samples will be tracked using a unique identifier that is assigned to the samples for 
the trial. Results are stored in a secure database to ensure confidentiality.  
Exploratory biomarker research may also be performed to investigate and better understand R/R 
cHL and R/R TCL, the dose response and/or prediction of response to GEN3017, and 
characterize aspects of the molecule (eg, mechanism of action/target, metabolites). Results from 
this analysis are to be documented and maintained; but are not necessarily reported as part of this 
study. Samples can be retained for up to 5 years. 
Since the evaluations are not expected to benefit the subject directly or to alter the treatment 
course, the results of any exploratory biomarker research are not placed in the subject’s medical 
record and are not to be made available to the subject, members of the family, the personal 
physician, or other third parties, except as specified in the informed consent.  
The subject retains the right to request that the sample material be destroyed by contacting the 
investigator. Following the request from the subject, the investigator is to provide the sponsor 
with the required trial and subject number so that any remaining samples and any other 
components from the cells can be located and destroyed. Samples will be destroyed once all 
protocol-defined procedures are completed. However, information collected from samples before 
the request for destruction will be retained by Genmab.  
The sponsor is the exclusive owner of any data, discoveries, or derivative materials from the 
sample materials and is responsible for the destruction of the sample(s) at the request of the 
subject through the investigator, at the end of the storage period, or as appropriate (eg, the 
scientific rationale for experimentation with a certain sample type no longer justifies keeping the 
sample). If a commercial product is developed from this research project, the sponsor owns the 
commercial product. The subject has no commercial rights to such product and has no 
commercial rights to the data, information, discoveries, or derivative materials gained or 
produced from the sample. See Section 10.1.7 for subject confidentiality. 

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10.5 
Appendix 5: ECOG Performance Status 
Score 
Definition 
0 
Fully active, able to carry out all normal activity without restriction. 
1 
Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light housework, office work. 
2 
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 out any self-care. Totally confined to bed or chair. 
5 
Dead. 
Source: (Oken et al., 1982) 
 

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10.6 
Appendix 6: Karnofsky and Lansky Performance Status 
 
Condition 
Percentage 
Lansky level of performance 
(<16 years) 
Karnofsky level of performance 
(≥16 to <18 years) 
Able to carry on 
normal activity and to 
work; no special care 
needed. 
100 
Fully active; normal 
Normal no complaints; no evidence of 
disease. 
90 
Minor restrictions in physically 
strenuous activities 
Able to carry on normal activity; 
minor signs 
or symptoms of disease. 
80 
Active, but tires more quickly 
Normal activity with effort; some 
signs or symptoms of disease. 
Unable to work; able 
to live at home and 
care for most personal 
needs; varying amount 
of assistance needed. 
70 
Restriction in and less time 
spent in active play 
Cares for self; unable to carry on 
normal activity or to do active work. 
60 
Up and around; minimal active 
play; keeps busy with quieter 
activities 
Requires occasional assistance, but is 
able to care for most of his personal 
needs. 
50 
Gets dressed but lies around 
much of the day; no active play; 
able to participate in all quiet 
play and activities 
Requires considerable assistance and 
frequent medical care. 
Unable to care for 
self; requires 
equivalent of 
institutional or 
hospital care; disease 
may be progressing 
rapidly. 
40 
Mostly in bed; participates in 
quiet activities 
Disabled; requires special care and 
assistance. 
30 
In bed; needs assistance even 
with quiet play 
Severely disabled; hospital admission 
is indicated although death not 
imminent. 
20 
In bed, often sleeping; play 
limited to very passive activities 
Very sick; hospital admission 
necessary; active supportive treatment 
necessary. 
10 
Does not get out of bed; does 
not play 
Moribund; fatal processes progressing 
rapidly. 
0 
Unresponsive; dead 
Dead 
Source: (Karnofsky and Burchenal, 1949; Lansky et al., 1987) 
 
 

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10.7 
Appendix 7: Estimation of Glomerular Filtration Rate Using Cockroft-Gault 
Formula 
Glomerular filtration rate (GFR) may be estimated using the Cockroft-Gault formula 
 
(140 - age)  ×  weight  ×  FS 
 
GFR =  
───────────────────── 
 
Serum Creatinine  ×  72 
Units: GFR [mL/min], age [years], weight [kg], serum creatinine [mg/dl], FS is a correction 
Factor for Sex: in males FS = 1, in females FS = 0.85 
 
 

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10.8 
Appendix 8: Ann Arbor Staging Classification for Hodgkin and Non-Hodgkin 
Lymphoma 
 
Stage I 
Involvement of a single lymph node region (I) or of a single extralymphatic organ or 
site (IE)a 
Stage II 
Involvement of 2 or more lymph node regions or lymphatic structures on the same side of the 
diaphragm alone (II) or with involvement of limited, contiguous extra-lymphatic organ or tissue 
(IIE) 
Stage III 
Involvement of lymph node regions on both sides of the diaphragm (III) which may include the 
spleen (IIIS) or limited, contiguous extra-lymphatic organ or site (IIIE), or both (IIIES) 
Stage IV 
Diffuse or disseminated foci of involvement of one or more extralymphatic organs or tissues, with 
or without associated lymphatic involvement 
a. The designation “E” generally refers to extranodal contiguous extension (ie, proximal or contiguous extranodal disease) that 
can be encompassed within an irradiation field appropriate for nodal disease of the same anatomic extent. A single 
extralymphatic site as the only site of disease should be classified as IE, rather than Stage IV. 
All cases are subclassified to indicate the absence (A) or presence (B) of the systemic (“B”) 
symptoms of significant unexplained fever (> 38°C), night sweats, or unexplained weight loss 
exceeding 10% of body weight during the 6 months prior to diagnosis. 
Clinical stage refers to the extent of disease determined by diagnostic tests following a single 
diagnostic biopsy. If a second biopsy of any kind is obtained, even if negative, the term 
pathologic stage is used. 
 
 
 

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10.9 
Appendix 9: Corticosteroid Dose Equivalents 
 
Steroid 
Approximate Equivalent Dose 
Duration 
Dexamethasone 
20 mg 
Long-acting 
Betamethasone 
20 mg 
Long-acting 
Methylprednisolone 
100 mg 
Intermediate-acting 
Triamcinolone 
100 mg 
Intermediate-acting 
Prednisone 
125 mg 
Intermediate-acting 
Prednisolone 
125 mg 
Intermediate-acting 
 
 

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10.10 Appendix 10: PET Positivity Evaluation Using the 5-Point Scale 
Evaluation of FDG-PET positivity should be performed according to the 5-point scale (5-PS) 
adopted from the Deauville criteria described in (Barrington et al., 2014). 
Five-Point Scale (5-PS) 
At each time point where FDG-PET scans are submitted, visualized disease will be qualitatively 
assessed and evaluated according to the 5-PS to determine uptake (with mediastinum and liver 
cutoffs). 
 
Score 
Definition 
1 
No uptake 
2 
Uptake ≤ mediastinum 
3 
Uptake > mediastinum but ≤ liver 
4 
Uptake moderately higher than liver  
5 
Uptake markedly higher than liver and/or new lesions 
X 
New areas of uptake unlikely to be related to lymphoma 
NE 
Not evaluable 
Notes: 
• “X” will represent any area of uptake identified by the radiologist or equivalent as not likely 
to be related to lymphoma. At screening, these areas could be due to prior radiation therapy, 
surgery, or evidence of a benign radiographic abnormality. These will have no impact on the 
response. 
• At the end of treatment assessment time point and at follow up (if applicable), X will 
represent any new areas of FDG-uptake unlikely due to lymphoma. These will have no 
impact on the response. 
Diffusely increased bone marrow, even if greater than liver uptake, is likely not due to 
lymphoma and rather, due to cytokine effect. 
 
 

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10.11 Appendix 11: Lugano Response Criteria for Malignant Lymphoma  
Target and Non-target Lesions 
Target lesions should consist of up to 6 of the largest dominant nodes, nodal masses, or other 
lymphomatous lesions that are measurable in 2 diameters and should preferably be from different 
body regions representative of the subject’s overall disease burden, including mediastinal and 
retroperitoneal disease, where applicable. At baseline, a measurable node must be greater than 15 
mm in longest diameter (LDi). Measurable extranodal disease may be included in the 6 
representative target lesions. At baseline, measurable extranodal lesions should be greater than 
10 mm in LDi. 
All other lesions (including nodal, extranodal, and assessable disease) should be followed as 
non-target lesions (eg, cutaneous, GI, bone, spleen, liver, kidneys, pleural or pericardial 
effusions, ascites, bone, bone marrow). 
Split Lesions and Confluent Lesions 
Lesions may split or may become confluent over time. In the case of split lesions, the individual 
product of the perpendicular diameters (PPDs) of the nodes should be summed together to 
represent the PPD of the split lesion; this PPD is added to the sum of the PPDs of the remaining 
lesions to measure response. If subsequent growth of any or all of these discrete nodes occurs, 
the nadir of each individual node is used to determine progression. In the case of confluent 
lesions, the PPD of the confluent mass should be compared with the sum of the PPDs of the 
individual nodes, with more than 50% increase in PPD of the confluent mass compared with the 
sum of individual nodes necessary to indicate progressive disease. The LDi and smallest 
diameter (SDi) are no longer needed to determine progression. 
 

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10.12 Appendix 12: Grading and Management of Cytokine Release Syndrome 
Harmonized definitions and grading criteria for CRS, per the American Society for 
Transplantation and Cellular Therapy (ASTCT), formerly American Society for Blood and 
Marrow Transplantation, (ASBMT), are presented below. 
Grading of Cytokine Release Syndrome 
CRS 
parameter 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Fevera 
≥38.0°C 
≥38.0°C 
≥38.0°C 
≥38.0°C 
Death due to 
CRS in which 
another cause 
is not the 
principle 
factor leading 
to this 
outcome 
With 
hypotensionb 
None 
Not requiring 
vasopressors 
Requiring 
1 vasopressor with 
or without 
vasopressin 
Requiring 
≥ 2 vasopressors 
(excluding 
vasopressin) 
And/or 
hypoxiab 
None 
Requiring low-
flow 
(≤6 L/minute) 
nasal cannula 
or blow-by 
Requiring high-flow 
(>6 L/minute) nasal 
cannula, facemask, 
nonrebreather mask, 
or venturi mask 
Requiring positive 
pressure ventilationc 
(eg, CPAP, BiPAP, 
intubation and 
mechanical 
ventilation) 
BiPAP=bilevel positive airway pressure; CPAP=continuous positive airway pressure; CRS=cytokine release syndrome; 
CTCAE= Common Terminology Criteria for Adverse Events. 
Note: organ toxicities or constitutional symptoms associated with CRS may be graded according to CTCAE but they do 
not influence CRS grading. 
a. 
Fever is defined as temperature ≥38.0°C not attributable to any other cause, with or without constitutional symptoms 
(eg, myalgia, arthralgia, malaise). In subjects who have CRS receiving antipyretics, anticytokine therapy, and/or 
corticosteroids, fever is no longer required to grade subsequent CRS severity. In this case, CRS grading is driven by 
hypotension and/or hypoxia. 
b. 
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 grade 3 CRS. Both systolic blood pressure and mean arterial pressure are acceptable for 
blood pressure measurement. No specific limits are required, but hypotension should be determined on a case-by-
case basis, accounting for age and the subject’s individual baseline, ie, a blood pressure that is below the normal 
expected for an individual in a given environment. 
c. 
Intubation of a subject without hypoxia for the possible neurologic compromise of a patent airway alone or for a 
procedure is not by definition grade 4 CRS. 
Source: (Lee et al., 2019) 
 
 

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10.13 Appendix 13: CRS Management Guidance Based on the American Society for 
Transplantation and Cellular Therapy (ASTCT)a Guidelines  
CRS 
Gradea 
Supportive Care 
Anticytokine Therapyb 
Glucocorticoids 
Grade 1 
 
Hold GEN3017 until resolution of 
CRS. 
 
In-person evaluation by medical 
professional, ideally at site or 
center with experience managing 
CRS. 
 
Investigate for infection and 
rapidly startup broad-spectrum 
antibiotics. Continuation of 
antibiotic therapy is recommended 
until fever and any existing 
neutropenia resolve. 
 
Supportive care per institutional 
standard of care (antipyretics and 
IV hydration) 
 
Closely monitor neurologic status  
Consider anticytokine therapye 
in certain cases, eg, advanced 
age, high tumor burden, 
circulating tumor cells, fever 
refractory to antipyretics.  
 
Note: In case of concurrent 
ICANS choose alternative to 
tocilizumab (eg, siltuximab, 
anakinra) 
 
Dexamethasone 10-20 mg 
per day (or equivalent) may 
be initiated. 
 
Note: In case of concurrent 
ICANS, initiation of 
corticosteroids are highly 
recommended (see ICANS 
guidelines in Section 
10.12). 
Grade 2 
 
Hold GEN3017 until resolution of 
CRS. 
 
In-person evaluation by medical 
professional, ideally at site or 
center with experience managing 
CRS. 
 
Investigate for infection and 
rapidly startup broad-spectrum 
antibiotics. Continuation of 
antibiotic therapy is recommended 
until fever and any existing 
neutropenia resolve. 
 
Continuous cardiac telemetry and 
pulse oximetry as indicated 
 
IV fluids bolus for hypotension 
with 0.5 to 1.0 L isotonic fluids 
 
Supplemental oxygen as indicated 
Anticytokine therapy 
recommended.e 
 
If CRS is refractory to initial 
cytokine therapy, 
initiate/increase dose of 
corticosteroid therapy and 
consider alternative 
anticytokine therapy. 
 
Note: In case of concurrent 
ICANS choose alternative to 
tocilizumab (eg, siltuximab, 
anakinra) 
 
Consider dexamethasone 
10-20 mg per day (or 
equivalent).  
 
Note: In case of concurrent 
ICANS, initiation of 
corticosteroids is highly 
recommended (see ICANS 
guidelines in Section 
10.12).  
Grade 3 
 
Hold GEN3017 until resolution of 
CRS. 
 
In-person evaluation by medical 
professional, ideally at site or 
center with experience managing 
CRS. 
 
Investigate for infection and 
rapidly startup broad-spectrum 
Anticytokine therapy 
recommended.e 
 
If CRS is refractory to initial 
cytokine therapy, 
initiate/increase dose of 
corticosteroid therapy and 
consider alternative 
anticytokine therapy. 
 
Dexamethasone (eg, 
10-20 mg IV every 6 
hours). If no response, 
initiate methylprednisolone 
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CRS 
Gradea 
Supportive Care 
Anticytokine Therapyb 
Glucocorticoids 
antibiotics. Continuation of 
antibiotic therapy is recommended 
until fever and any existing 
neutropenia resolve. 
 
Management in intensive care 
unit. 
 
Vasopressor support and/or 
supplemental oxygen. 
 
Consider cardiac echocardiogram. 
 
IV fluids as indicated. 
Note: In case of concurrent 
ICANS choose alternative to 
tocilizumab (eg, siltuximab, 
anakinra) 
 
Grade 4  
 
 
Permanently discontinue 
GEN3017. 
 
In-person evaluation by medical 
professional, ideally at site or 
center with experience managing 
CRS. 
 
Investigate for infection and 
rapidly startup broad-spectrum 
antibiotics. Continuation of 
antibiotic therapy is recommended 
until fever and any existing 
neutropenia resolve. 
 
Management in intensive care 
unit. 
 
Mechanical ventilation and/or 
renal replacement therapy may be 
required 
 
Vasopressor support as indicated 
 
IV fluids as indicated. 
 
Consider and assess for 
development of macrophage 
activation syndrome/ 
hemophagocytic 
lymphohistiocytosis 
(MAS/HLH)d, including 
monitoring of fibrinogen and 
triglyceride levels 
Anticytokine therapy 
recommended.e 
 
If CRS is refractory to initial 
cytokine therapy, 
initiate/increase dose of 
corticosteroid therapy and 
consider alternative 
anticytokine therapy. 
 
Note: In case of concurrent 
ICANS choose alternative to 
tocilizumab (eg, siltuximab, 
anakinra) 
 
Dexamethasone (eg, 
10-20 mg IV every 6 
hours). If no response, 
initiate methylprednisolone 
1000 mg/day.  
MAS/HLH If MAS/HLH is combined with 
CRS, permanently discontinue 
GEN3017. 
 
Intensive supportive care is 
essential because of frequent life-
First-line treatment: Includes IL-6R-blockade with 
tocilizumab, unless tocilizumab was already administered 
for the management of CRS. Glucocorticoids are also 
indicated for the initial treatment of MAS/HLH, irrespective 
of the cause (CRS Grade 4 treatment recommendations 
should be followed).  
 

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CRS 
Gradea 
Supportive Care 
Anticytokine Therapyb 
Glucocorticoids 
threatening, severe manifestations 
at presentation. 
 
Appropriate broad-spectrum 
antiviral, antibacterial, antifungal 
prophylaxis, and treatment must 
be initiated. The elimination of 
triggers (particularly infection) is 
crucial to remove the stimuli that 
initiate the abnormal immune 
system activation. 
 
Second-line treatment: Anakinra should be considered in the 
event that severe CRS is not responding to tocilizumab and 
corticosteroids. Anakinra should be given until resolution of 
CRS with a daily dose of 100 mg SC. 
 
In more severe MAS/HLH cases, especially if combined 
with CRS and/or neurotoxicity, anakinra 100-200 mg SC 
twice daily (every 12 hours), or higher doses (up to 8 
mg/kg/day) in severe cases, should be given until resolution 
of CRS and other concurrent T-cell toxicities, like 
neurotoxicity and/or MAS/HLH which could benefit from 
anakinra treatment. 
 
In case of rapidly progressing clinical course with ongoing 
CRS, anakinra should be administered as first-line 
treatment. 
CRS=cytokine release syndrome; ICANS=immune effector cell-associated neurotoxicity syndrome; IV=intravenous(ly); 
MAS/HLH=macrophage activation syndrome/hemophagocytic lymphohistiocytosis; SC=subcutaneous(ly). 
a. Source: (Lee et al., 2019) 
b. Refer to tocilizumab, siltuximab, or anakinra local prescribing information for product details. 
c. High-dose vasopressors in table below. 
d. Anakinra should be considered in the event that severe CRS is not responding to tocilizumab and corticosteroid. 
e. Suggested anticytokine dosing: 
• 
Tocilizumab 8 mg/kg IV over 1 hour (not to exceed 800 mg per dose). Repeat tocilizumab after at least 8 hours as 
needed. Maximum of 2 doses in a 24-hour period.  
• 
Siltuximab 11 mg/kg IV over 1 hour, 1 time only. 
• 
Anakinra 100 mg SC once/day. 
• 
In more severe CRS cases, especially if combined with MAS/HLH and/or neurotoxicity, anakinra 100-200 mg 
twice daily (every 12 hours) SC should be given until resolution of CRS and other concurrent T-cell toxicities, like 
neurotoxicity and/or MAS/HLH which could benefit from anakinra treatment. 
 
 

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High-Dose Vasopressors (all Doses are Required for ≥3 Hours) 
Pressor 
Dose 
Norepinephrine monotherapy 
≥20 µg/min 
Dopamine monotherapy 
≥10 µg/kg/min 
Phenylephrine monotherapy 
≥200 µg/min 
Epinephrine monotherapy 
≥10 µg/min 
If on vasopressin 
Vasopressin 1 norepinephrine equivalent of ≥10 
µg/mina 
If on combination vasopressors (not vasopressin) 
Norepinephrine equivalent of ≥20 µg/mina 
a. Vasopressor equivalent equation: norepinephrine equivalent dose = [norepinephrine (μg/min)] + [dopamine (μg/kg/min) / 
2] + [epinephrine (μg/min)] + [phenylephrine (μg/min) / 10] 
Source: (Lee et al., 2014) 
 
 

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10.14 Appendix 14: ASTCT ICANS Consensus Grading and Management 
Management Guidelines for Immune Effector Cell-Associated Neurotoxicity Syndrome 
(ICANS) Based on ASTCT Guidelines 
Neurologic Toxicities 
Supportive Care 
Anticytokine Therapy 
Corticosteroids 
Grade 1 
• 
ICE scorea 7-9 and/or 
depressed level of 
consciousnessb but 
awakens 
spontaneously 
• 
No seizures, motor 
weakness, or raised 
ICP/cerebral edema 
• 
Confusion: mild 
disorientation 
• 
Encephalopathy: 
mild limiting of 
ADLs 
• 
Dysphasia: not 
impairing ability to 
communicate 
• 
Hold GEN3017 until 
resolution of ICANS. 
• 
Supportive care per 
institutional standard of 
care  
• 
Closely monitor 
neurologic status 
• 
Recommend initiating 
prophylactic non-sedating 
anti-seizure medication 
until resolution of ICANS 
• 
Aspiration precautions 
• 
Recommend brain 
imaging and EEG per 
institutional guidelines 
No concurrent CRS: 
Anticytokine therapy not 
indicated 
 
Concurrent CRS: 
Anticytokine therapy 
indicated:  
Choose alternative to 
tocilizumab (eg, 
siltuximab, anakinra) if 
possible. (Refer to CRS 
Management Guidance 
Based on the American 
Society for Transplantation 
and Cellular Therapy 
(ASTCT) Guidelines table 
in Section 10.13.) 
 
• 
Consider anakinra as a 
daily dose of 100 mg 
SC or 200 mg SC (100 
mg every 12 hours) 
depending on the 
severity of 
neurotoxicity and 
other concurrent 
toxicities. Anakinra 
should be given until 
resolution of 
neurotoxicity and 
other concurrent 
toxicities which could 
benefit from anakinra 
treatment. 
• 
Consider siltuximab, 
11 mg/kg IV over 
1 hour, one time only. 
Dexamethasone, 10 
mg IV every 12 hours 
• 
Grade 2 
• 
ICE scorea 3-6 and/or 
depressed level of 
consciousnessb but 
awakens to voice 
• 
No seizures, motor 
weakness, or raised 
ICP/cerebral edema 
• 
Somnolence-
moderate, limiting 
instrumental ADLs 
• 
Confusion: moderate 
disorientation 
• 
Hold GEN3017 until 
resolution of ICANS. 
• 
Supportive care per 
institutional standard of 
care 
• 
Closely monitor 
neurologic status 
• 
Recommend initiating 
prophylactic non-sedating 
anti-seizure medication 
until resolution of ICANS 
(eg, levetiracetam) 
• 
Aspiration precautions 
No concurrent CRS: 
Anticytokine therapy not 
indicated. 
 
Concurrent CRS: 
Anticytokine therapy 
indicated: 
Choose alternative to 
tocilizumab (eg, 
siltuximab, anakinra) if 
possible. (Refer to CRS 
Management Guidance 
Based on the American 
Society for Transplantation 
and Cellular Therapy 
Dexamethasone at 10-
20 mg IV every 
12 hours 
 

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Neurologic Toxicities 
Supportive Care 
Anticytokine Therapy 
Corticosteroids 
• 
Encephalopathy: 
limiting instrumental 
ADLs 
• 
Dysphasia: moderate 
impairing ability to 
communicate 
spontaneously 
• 
Continuous cardiac 
telemetry and pulse 
oximetry as indicated 
• 
Closely monitor 
neurologic status with 
serial neurologic 
examinations to include 
fundoscopy. Consider 
neurology consult. 
• 
Perform brain imaging 
(eg, MRI), EEG, and 
lumbar puncture (with 
opening pressure) if no 
contraindications  
• 
Prophylactic non-sedating 
anti-seizure medication 
(ASTCT) Guidelines table 
in Section 10.13.) 
 
• 
Consider anakinra at a 
daily dose of 100 mg 
SC or 200 mg SC (100 
mg every 12 hours) 
depending on the 
severity of 
neurotoxicity and 
other concurrent 
toxicities. Anakinra 
should be given until 
resolution of 
neurotoxicity and 
other concurrent 
toxicities which could 
benefit from anakinra 
treatment. 
• 
Consider siltuximab, 
11 mg/kg IV over 
1 hour, one time only. 
• 
Grade 3 
• 
ICE scorea 0-2 
and/or depressed 
level of 
consciousnessb but 
awakens to tactile 
stimulus 
• 
And clinical seizure 
focal or generalized 
that resolves 
rapidly, or 
nonconvulsive 
seizures on EEG 
that resolve with 
intervention 
• 
No motor weakness 
• 
Focal/local edema 
on neuroimaging 
• 
Somnolence-
obtundation or 
stupor 
• 
Confusion: severe 
disorientation 
• 
Encephalopathy: 
limiting self-care 
ADLs 
• 
Dysphasia: severe 
receptive or 
expressive 
characteristics, 
impairing ability to 
read, write, or 
communicate 
intelligibly 
• 
Hold GEN3017 until 
resolution of ICANS. 
• 
Management in 
monitored care or 
intensive care unit. 
• 
Supportive care per 
institutional standard of 
care  
• 
Closely monitor 
neurologic status 
• 
Recommend initiating 
prophylactic non-
sedating anti-seizure 
medication until 
resolution of ICANS (eg, 
levetiracetam) 
• 
Aspiration precautions 
• 
Continuous cardiac 
telemetry and pulse 
oximetry as indicated 
• 
Closely monitor 
neurologic status with 
serial neurologic 
examinations to include 
fundoscopy. Consider 
neurology consult. 
• 
Perform brain imaging 
(eg, MRI), EEG, and 
lumbar puncture (with 
opening pressure) if no 
contraindications 
• 
Prophylactic non-
sedating anti-seizure 
No concurrent CRS: 
Anticytokine therapy not 
indicated. 
 
Concurrent CRS: 
Anticytokine therapy 
indicated: 
 
Choose alternative to 
tocilizumab (eg, 
siltuximab, anakinra) if 
possible. (Refer to CRS 
Management Guidance 
Based on the American 
Society for 
Transplantation and 
Cellular Therapy 
(ASTCT) Guidelines table 
in Section 10.13.) 
 
• 
Consider anakinra at 
a daily dose of 100 
mg SC or 200 mg SC 
(100 mg every 
12 hours) depending 
on the severity of 
neurotoxicity and 
other concurrent 
toxicities. Anakinra 
should be given until 
resolution of 
neurotoxicity and 
other concurrent 
toxicities which could 
Dexamethasone 10-
20 mg IV every 
6 hours. If no 
response, initiate 
methylprednisolone 
1000 mg/day. 

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Neurologic Toxicities 
Supportive Care 
Anticytokine Therapy 
Corticosteroids 
medication 
• 
Levetiracetam/non-
sedating antiepileptics if 
subject has seizures 
 
benefit from anakinra 
treatment. 
• 
Consider siltuximab, 
11 mg/kg IV over 
1 hour, one time only. 
• 
Grade 4 
• 
ICE scorea 0 and 
patient is 
unarousable or 
requires vigorous or 
repetitive tactile 
stimuli to arouse or 
stupor or coma 
• 
Life-threatening 
prolonged seizure 
(>5 min); or 
repetitive clinical or 
electrical seizures 
without return to 
baseline in between 
• 
Deep focal motor 
weaknessc such as 
hemiparesis or 
paraparesis 
• 
Diffuse cerebral 
edema on 
neuroimagingd; 
decerebrate or 
decorticate 
posturing; or cranial 
nerve VI palsy; or 
papilledema; or 
Cushing’s triad 
• 
Life-threatening 
consequences 
• 
Urgent intervention 
indicated 
• 
Requirement for 
mechanical 
ventilation 
• 
Permanently discontinue 
GEN3017. 
• 
Management in 
monitored care or 
intensive care unit. 
• 
Supportive care per 
institutional standard of 
care 
• 
Closely monitor 
neurologic status 
• 
Recommend initiating 
prophylactic non-
sedating anti-seizure 
medication until 
resolution of ICANS (eg, 
levetiracetam) 
• 
Aspiration precautions 
• 
Continuous cardiac 
telemetry and pulse 
oximetry as indicated 
• 
Closely monitor 
neurologic status with 
serial neurologic 
examinations to include 
fundoscopy. Consider 
neurology consult. 
• 
Perform brain imaging 
(eg, MRI), EEG, and 
lumbar puncture (with 
opening pressure) if no 
contraindications 
• 
Prophylactic non-
sedating anti-seizure 
medication 
• 
Levetiracetam/non-
sedating antiepileptics if 
subject has seizures 
• 
Mechanical ventilation 
may be required 
• 
Consider imaging of 
spine for focal motor 
weakness 
• 
Lower intracranial 
pressure (ICP) by 
hyperventilation, 
hyperosmolar therapy 
with mannitol/hypertonic 
saline, and/or 
neurosurgery 
consultation for 
No concurrent CRS: 
Anticytokine therapy not 
indicated. 
 
Concurrent CRS: 
Anticytokine therapy 
indicated: 
 
Choose alternative to 
tocilizumab (eg, 
siltuximab, anakinra) if 
possible. (Refer to CRS 
Management Guidance 
Based on the American 
Society for 
Transplantation and 
Cellular Therapy 
(ASTCT) Guidelines table 
in Section 10.13.) 
 
• 
Consider anakinra at 
a daily dose of 100 
mg SC or 200 mg SC 
(100 mg every 
12 hours) depending 
on the severity of 
neurotoxicity and 
other concurrent 
toxicities. Anakinra 
should be given until 
resolution of 
neurotoxicity and 
other concurrent 
toxicities which could 
benefit from anakinra 
treatment. 
• 
Consider siltuximab, 
11 mg/kg IV over 
1 hour, one time only. 
 
Dexamethasone 10-
20 mg IV every 
6 hours. If no 
response, initiate 
methylprednisolone 
1000 mg/day 

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Neurologic Toxicities 
Supportive Care 
Anticytokine Therapy 
Corticosteroids 
ventriculoperitoneal 
shunt in patients with 
cerebral edema 
• 
Aggressive management 
of ICP with institutional 
standard of care 
Grade 5 (Fatal) 
Death due to ICANS in 
which another cause is 
not the principal factor 
leading to this outcome. 
 
 
 
ADLs=activities of daily living; ASBMT=American Society for Bone Marrow Transplant; ASTCT=American 
Society for Transplantation and Cellular Therapy; CRS=cytokine release syndrome; CTCAE=Common 
Terminology Criteria for Adverse Events; EEG=electroencephalogram; ICANS=immune effector cell-
associated neurotoxicity syndrome; ICE=immune effector cell-associated encephalopathy; ICP=intracranial 
pressure; IV=intravenous; MRI=magnetic resonance imaging; SC=subcutaneous. 
Note: ICANS grade is determined by the most severe domain event not attributable to any other cause. For 
example, a subject with an ICE score of 3 who has a generalized seizure is classified as Grade 3 ICANS. 
a. 
A subject with an ICE score of 0 may be classified as Grade 3 ICANS if awake with global aphasia, but a 
subject with an ICE score of 0 may be classified as Grade 4 ICANS if unarousable. 
b. Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication). 
c. 
Tremors and myoclonus associated with immune effector cell therapies may be graded according to 
CTCAE v5.0, but they do not influence ICANS grading. 
d. 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 CTCAE v5.0. 
Sources: (Lee et al., 2019) 
 
ICANS Assessment and Grading 
Neurotoxicity 
Domain 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE scorea 
7-9 
3-6 
0-2 
0 (patient is unarousable and 
unable to perform ICE) 
Depressed level 
of 
consciousnessb 
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only to 
tactile stimulus 
Patient is unarousable or 
requires vigorous or repetitive 
tactile stimuli to arouse. 
Stupor or coma 
Seizure 
N/A 
N/A 
Any clinical seizure 
focal or generalized 
that resolves rapidly or 
nonconvulsive seizures 
on EEG that resolve 
with intervention 
Life-threatening prolonged 
seizure (>5 min); or repetitive 
clinical or electrical seizures 
without return to baseline in 
between 
Motor findingsc 
N/A 
N/A 
N/A 
Deep focal motor weakness 
such as hemiparesis or 
paraparesis 
Elevated 
ICP/cerebral 
edema 
N/A 
N/A 
Focal/local edema on 
neuroimagingd 
Diffuse cerebral edema on 
neuroimaging; decerebrate or 
decorticate posturing; or 
cranial nerve VI palsy; or 
papilledema; or Cushing's 
triad 
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; eg, a patient with an ICE score of 3 who 
has a generalized seizure is classified as grade 3 ICANS. Grade 5 is considered to be fatal. 

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CTCAE=Common Terminology Criteria for Adverse Events; EEG=electroencephalogram; ICE=immune 
effector cell-associated encephalopathy; ICP=intracranial pressure; N/A=not applicable. 
a. 
A patient with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a 
patient with an ICE score of 0 may be classified as grade 4 ICANS if unarousable. 
b. Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication). 
c. 
Tremors and myoclonus associated with immune effector cell therapies may be graded according to 
CTCAE v 5.0, but they do not influence ICANS grading. 
d. 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 CTCAE v 5.0. 
Source: (Lee et al., 2019) 
 
The Immune Effector Cell-Associated Encephalopathy (ICE) Assessment Tool  
Cognitive Domain 
Task 
Points 
ICE Scoring 
Orientation 
Orientation to year 
1 
10: No impairment 
7-9: Grade 1 ICANS 
3-6: Grade 2 ICANS 
0-2: Grade 3 ICANS 
0 due to subject unarousable and unable to 
perform ICE assessment: Grade 4 ICANS 
Orientation to month 
1 
Orientation to city 
1 
Orientation to hospital 
1 
Naming 
Naming 3 common objects (eg, point 
to clock, pen, button) 
3 
Following 
commands 
Ability to follow simple commands, 
eg, “Show me two fingers” or “Close 
your eyes and stick out your tongue” 
1 
Writing 
Ability to write a standard sentence, 
eg, “Our national bird is the bald 
eagle” 
1 
Attention 
Ability to count backwards from 100 
by 10 
1 
Maximum ICE Score 
10 
ICANS= immune effector cell-associated neurotoxicity syndrome; ICE= immune effector cell-associated encephalopathy. 
Source: (Lee et al., 2019) 
 
 

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10.15 Appendix 15: Tumor Flare Reaction Management Guidance and Grading 
Subjects in this study should be monitored for tumor flare reaction (TFR). TFR is defined as 
a sudden and tender increase in the size of the disease-bearing sites, including the lymph 
nodes, spleen, and/or the liver often accompanied by low-grade fever, diffuse rash, and in 
some cases increase in the peripheral blood lymphocyte counts. TFR will be assessed 
according to the following CTCAE v5 criteria: 
• Grade 1: Mild pain 
• Grade 2: Moderate pain; limiting instrumental activity of daily life (ADL) 
• Grade 3: Severe pain; limiting self-care ADL 
• Grade 4: Life-threatening consequences; urgent intervention indicated 
• Grade 5: Death 
TFR Management Guidelines 
Treatment of TFR is up to the discretion of the investigator depending upon the severity and 
clinical situation. It is suggested that TFR be treated with corticosteroids at the investigator’s 
discretion. NSAIDs (ie, ibuprofen 400 to 600 mg orally every 4 to 6 hours as needed) and/or 
narcotic analgesics for pain management may also be administered as needed. In mild to 
moderate cases, it is suggested that GEN3017 is continued along with symptomatic treatment 
as indicated above. Table 6-4 includes dose modification guidance as it relates to TFR. 

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10.16 Appendix 16: Classification and Management of Laboratory and Clinical Tumor 
Lysis Syndrome 
Subjects who are considered to have an increased risk for tumor lysis syndrome (TLS), eg, 
due to the type of lymphoma, the tumor burden (bulky disease and/or elevated LDH), renal 
impairment and/or elevated uric acid should be considered for hydration and prophylactic 
treatment with a uric acid lowering agent as well as frequent monitoring, according to local 
standards or available guidelines (Coiffier et al., 2008). 
In addition, close monitoring of laboratory parameters to allow for early diagnosis of possible 
TLS is recommended at the investigator’s discretion. For details, refer to Table 1-1 and Table 
1-2 for the minimum sampling time points for tumor lysis. If signs of TLS occur, supportive 
therapy, including rasburicase, may be used as clinically indicated at the investigator’s 
discretion.  
In laboratory TLS, 2 or more metabolic abnormalities (ie, hyperuricemia, hyperkalemia, 
hyperphosphatemia, and hypocalcemia) must be present during the same 24-hour period 
within 3 days before the start of therapy or up to 7 days afterward.  
Clinical tumor lysis syndrome (CTLS) requires the presence of laboratory TLS plus an 
increased creatinine level, seizures, cardiac dysrhythmia, or death. 
Definitions of Laboratory and Clinical Tumor Lysis Syndrome 
Metabolic 
Abnormality 
Criteria for Classification of 
Laboratory TLS 
Criteria for Classification of CTLS 
Hyperuricemia 
Uric acid >8.0 mg/dL 
(475.8 μmol/liter) in adults or 
above the upper limit of the normal 
range for age in children 
Not Applicable 
Hyperphosphatemia 
Phosphorus >4.5 mg/dL 
(1.5 mmol/liter) in adults or 
>6.5 mg/dL (2.1 mmol/liter) in 
children 
Not Applicable 
Hyperkalemia 
Potassium >6.0 mmol/liter or 
6 mg/L 
Cardiac dysrhythmia or sudden death 
probably or definitely caused by hyperkalemia 
Hypocalcemia 
Corrected calcium <7.0 mg/dL 
(1.75 mmol/liter) or ionized 
calcium <4.5 mg/dL (1.12 
mmol/liter)a 
Cardiac dysrhythmia, sudden death, seizure, 
neuromuscular irritability (tetany, 
paresthesias, muscle twitching, carpopedal 
spasm, Trousseau’s sign, Chvostek’s sign, 
laryngospasm, or bronchospasm), 
hypotension, or heart failure probably or 
definitely caused by hypocalcemia 
Acute kidney injuryb 
Not applicable 
Increase in the serum creatinine level of 0.3 
mg/dL (26.5 μmol/liter) (or a single value 
>1.5 times the upper limit of the age-
appropriate normal range if no baseline 
creatinine measurement is available) or the 
presence of oliguria, defined as an average 
urine output of <0.5 ml/kg/hr for 6 hr 
CTLS= clinical tumor lysis syndrome; TLS=tumor lysis syndrome. 
Note: In laboratory tumor lysis syndrome, 2 or more metabolic abnormalities must be present during the same 
24-hour period within 3 days before the start of therapy or up to 7 days afterward. Clinical tumor lysis syndrome 
requires the presence of laboratory tumor lysis syndrome plus an increased creatinine level, seizures, cardiac 
dysrhythmia, or death. 

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a. 
The corrected calcium level in milligrams per deciliter = measured calcium level in milligrams per deciliter 
+ 0.8×(4 – albumin in grams per deciliter). 
b. Acute kidney injury is defined as an increase in the creatinine level of at least 0.3 mg per deciliter (26.5 
μmol per liter) or a period of oliguria lasting 6 hours or more. By definition, if acute kidney injury is 
present, the subject has clinical tumor lysis syndrome. Data about acute kidney injury are from (Levin et al., 
2007) 
Source: (Howard et al., 2011) 
Cairo-Bishop Definition of Clinical Tumor Lysis Syndrome and Grading 
Complication 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Creatininea 
1.5×ULN 
> 1.5–3.0×ULN 
> 3.0-6.0×ULN 
> 6.0×ULN 
Death 
Cardiac 
arrhythmia 
Intervention 
not 
indicated 
Nonurgent 
medical 
intervention 
needed 
Symptomatic 
and 
incompletely 
controlled 
medically or 
controlled with 
device (eg, 
defibrillator) 
Life-threatening 
(eg, arrhythmia 
associated with 
CHF, 
hypotension, 
syncope, shock) 
Seizure 
None 
One brief 
generalized 
seizure; 
seizure(s) well 
controlled by 
anticonvulsants 
or infrequent 
focal motor 
seizures not 
interfering with 
ADL 
Seizure in which 
consciousness is 
altered; poorly 
controlled 
seizure disorder; 
with 
breakthrough 
generalized 
seizures despite 
medical 
intervention  
Seizure of any 
kind which are 
prolonged, 
repetitive or 
difficult to 
control (eg, 
status 
epilepticus, 
intractable 
epilepsy) 
ADL=activities of daily living; CHF=congestive heart failure; ULN=upper limit of normal. 
a. 
If no institutional ULN is specified, ULN is defined as follows: female 105.6 μmol/L, male 114.4 
μmol/L. 
Source: (Coiffier et al., 2008) 
 
 

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Recommendations for Initial Management of Electrolyte Imbalances and Prevention of 
Tumor Lysis Syndrome 
Abnormality 
Management Recommendations 
Hyperkalemia (including rapidly rising potassium) 
Potassium 
≥0.5 mmol/L increase 
from prior value (even 
if potassium within 
normal limits [WNL]) 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 hour STAT. 
If further ≥0.2 mmol/L increase in potassium, but still < upper limit of normal 
(ULN), manage as per potassium ≥ ULN. Otherwise re-check in 1 hour. 
Resume per protocol testing if change in potassium is <0.2 mmol/L, and potassium 
< ULN, and no other evidence of tumor lysis syndrome. 
At the discretion of the investigator, consider re-checking tumor lysis syndrome 
(TLS) laboratory values prior to hospitalization. If stable or decreased, and still 
within normal limits (WNL), hospitalization is at the discretion of the 
investigator. Potassium, phosphorus, uric acid, calcium and creatinine must be re-
checked within 24 hours. 
Potassium > upper 
limit of normal 
Perform STAT electrocardiogram (ECG) and commence telemetry. 
Nephrology (or other acute dialysis service) notification with consideration of 
initiating dialysis. 
Administer Kayexalate 60 g (or Resonium A 60 g). 
Administer furosemide 20 mg intravenously (IV) × 1. 
Administer calcium gluconate 100 – 200 mg/kg IV slowly if there is ECG/telemetry 
evidence of life-threatening arrhythmias. 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 hour STAT. 
If potassium < ULN 1 hour later, repeat potassium, phosphorus, uric acid, calcium 
and creatinine 1, 2 and 4 hours, if no other evidence of tumor lysis syndrome. 
Potassium 
≥6.0 mmol/L 
(6.0 mEq/L) and/or 
symptomatic 
(eg, muscle cramps, 
weakness, 
paresthesias, nausea, 
vomiting, diarrhea) 
Perform STAT ECG and commence telemetry. 
Nephrology (or other acute dialysis service) assessment with consideration of 
initiating dialysis. 
Administer Kayexalate 60 g (or Resonium A 60 g). 
Administer furosemide 20 mg IV × 1. 
Administer insulin 0.1 U/kg IV + D25 2 mL/kg IV. 
Administer sodium bicarbonate 1 – 2 mEq/kg IV push. 
If sodium bicarbonate is used, rasburicase should not be used as this may exacerbate 
calcium phosphate precipitation. 
Administer calcium gluconate 100 – 200 mg/kg IV slowly if there is ECG/telemetry 
evidence of life-threatening arrhythmias. Do not administer in same IV line as 
sodium bicarbonate. 
Re-check potassium, phosphorus, uric acid, calcium and creatinine every hour 
STAT. 
Hyperuricemia 
Uric acid ≥8.0 mg/dL 
(476 µmol/L) 
Consider rasburicase (dose per institutional guidelines). 
If rasburicase is used, sodium bicarbonate should not be used as this may exacerbate 
calcium phosphate precipitation. 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 hour STAT. 
Uric acid ≥10 mg/dL 
(595 µmol/L) OR 
Uric acid ≥8.0 mg/dL 
(476 µmol/L) with 
25% increase and 
creatinine increase 
≥0.3 mg/dL 
(≥0.027 mmol/L) 
from predose level 
Administer rasburicase (dose per institutional guidelines). 
If rasburicase is used, sodium bicarbonate should not be used as this may exacerbate 
calcium phosphate precipitation. 
Notify nephrology (or other acute dialysis service). 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 hour STAT. 
If uric acid <8.0 mg/dL 1 hour later, repeat potassium, phosphorus, uric acid, 
calcium and creatinine 2 and 4 hours later, if no other evidence of tumor lysis. 

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Abnormality 
Management Recommendations 
Hypocalcemia 
Calcium ≤7.0 mg/dL 
(1.75 mmol/L) AND 
Patient symptomatic 
(eg, muscle cramps, 
hypotension, tetany, 
cardiac arrhythmias) 
Administer calcium gluconate 50 – 100 mg/kg IV slowly with ECG monitoring. 
Telemetry. 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 hour STAT. 
If calcium normalized 1 hour later, repeat potassium, phosphorus, uric acid, calcium 
and creatinine 2 and 4 hours later, if no other evidence of tumor lysis. 
Calculate corrected calcium and check ionized calcium if albumin is low. 
Hyperphosphatemia 
Phosphorus 
≥5.0 mg/dL 
(1.615 mmol/L) with 
≥0.5 mg/dL 
(0.16 mmol/L) 
increase 
Administer a phosphate binder (eg, aluminum hydroxide, calcium carbonate, 
sevelamer hydroxide, or lanthanum carbonate). 
Nephrology (or other acute dialysis service) notification (dialysis required for 
phosphorus ≥10 mg/dL). 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 hour STAT. 
If phosphorus <5.0 mg/dL 1 hour later, repeat potassium, phosphorus, uric acid, 
calcium and creatinine 2 and 4 hours later, if no other evidence of tumor lysis 
syndrome. 
Creatinine 
Increase ≥25% from 
baseline 
Start or increase rate of IV fluids. 
Re-check potassium, phosphorus, uric acid, calcium and creatinine in 1 – 2 hours 
STAT. 
ECG=electrocardiogram; IV=intravenous; TLS=tumor lysis syndrome. 

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10.18 Appendix 18: Country-Specific Considerations 
10.18.1 
IMP/AMP EU Authorisation Status 
Drug Name 
IMP or 
AMPa 
EU 
Authorisation 
Status 
AMPs only: if unauthorised, justification 
for use 
GEN3017 
IMP 
Unauthorised 
 
Tocilizumab 
AMP 
Authorised 
To be administered in cases of CRS per 
Section 10.13. 
Siltuximab 
AMP 
Authorised 
To be administered in cases of ICANS as well 
as cases of CRS with concurrent ICANS per 
Section 10.13 and Section 10.14. 
Anakinra 
AMP 
Authorised 
To be administered in cases of ICANS as well 
as cases of CRS with concurrent ICANS per 
Section 10.13 and Section 10.14. 
Diphenhydramine (or 
equivalent) 
AMP 
Authorised 
 
Paracetamol/acetaminophen 
(or equivalent) 
AMP 
Authorised 
 
Dexamethasone or 
methylprednisolone (or 
equivalent) 
AMP 
Authorised 
 
AMP=auxiliary medicinal product; CRS=cytokine release syndrome; ICANS=immune effector cell-associated 
neurotoxicity syndrome; IMP=investigational medicinal product. 
a. 
For unauthorised AMPs, refer to Section 6.3.2 for details regarding drug accountability and destruction. 
10.18.2 
Japan-Specific Requirements 
Section 
Country-Specific Language 
4.3.2.5 Siltuximab 
Siltuximab is not approved in Japan 
4.3.2.6 Anakinra 
Anakinra is not approved in Japan 
Section 10.3 Definition 
of Reproductive 
Potential and 
Contraception  
Definition of Reproductive Potential and Contraception 
In this trial, a female is considered of childbearing potential, UNLESS they are 
postmenopausal or permanently sterile. 
A postmenopausal state is defined as no menses, in subjects >45 years of age, for 
12 months without an alternative medical cause. A high follicle-stimulating hormone 
(FSH) level in the postmenopausal range may be used to confirm a postmenopausal 
state in subjects not using hormonal contraception or hormonal replacement therapy. 
However, in the absence of 12 months of amenorrhea, a single FSH measurement is 
insufficient. 
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and 
bilateral oophorectomy. 
Female subjects of reproductive potential must agree to use adequate contraception 
during GEN3017 treatment and for 4 months after the last dose of GEN3017. 
Adequate contraception is defined as highly effective methods of contraception 
(Table 10-2). Birth control methods are considered highly effective if they have a 
failure rate of less than 1% per year, when used consistently and correctly. 

Document Name: GCT3017-01 -   Protocol - 18 Oct 2023 
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Version: 3.0 
 
 
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Table 10-2 
Highly Effective Methods of Contraception – Trials 
Conducted in Japan 
• 
Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation: 
○ 
Oral 
• 
Intrauterine devicea 
• 
Intrauterine hormone-releasing systema 
• 
Bilateral tubal occlusiona 
• 
Vasectomized partnera,b 
• 
Sexual abstinencec 
Adapted from “Recommendations related to contraception and pregnancy testing in clinical 
trials, version 1.1.” (CTFG, 2020). 
a. 
Contraception methods that in the context of this guidance are considered to have low user 
dependency 
b. 
Vasectomized partner is a highly effective birth control method, provided that partner is the 
sole sexual partner of the female of childbearing potential trial subject, and that the 
vasectomized partner has received medical assessment of the surgical success. 
c. 
In the context of this guidance, sexual abstinence is considered a highly effective method 
only if defined as refraining from heterosexual intercourse during the entire period of risk 
associated with the trial drug(s). The reliability of ‘not engaging in sexual intercourse’ 
needs to be evaluated in relation to the duration of the clinical trial and the preferred and 
usual lifestyle of the subject. 
 
10.18.3 
United States-Specific Requirements 
Section 
Country-Specific Language 
4.1.1 
In the US, subjects 16-17 years old will be eligible to participate in the R/R CD30+ 
cHL dose escalation cohort.  
4.1.2 
In the US, subjects ≥12 and <18 years old will be eligible to participate in the R/R 
CD30+ cHL expansion cohort 
5.1, 1US 
R/R cHL escalation cohort: Subjects with cHL must be at least 16 years of age.  
5.1, 5US 
For subjects ≥16 and <18 years of age (US), Karnofsky score of >60% per Karnofsky 
performance scale. 
5.1, 7 
Subjects ≥ 18 years of age enrolled in the US 
 
  
For subjects ≥16 and <18 years old, 
 
 
5.1.2, 1US 
For subjects in the R/R CD30+ cHL cohort in the US, age ≥12 and <18 years; assent is 
required of children capable of understanding the nature of the trial as described in the 
ICF 
5.1.2, 5US1 
For subjects ≥16 and <18 years old (US), Karnofsky score of >60% per Karnofsky 
performance scale. 
5.1.2, 5US2 
For subjects ≥12 and <16 years of age) (US), Lansky score of 
 per Lansky play-
performance scale. 
5.1.2, 7 
Subjects ≥18 years of age enrolled in the US 
 
  
5.1.2.1, A.2US 
 
CCI
CCI
CCI
CCI
CCI
CCI