Clinical trial NCT04052997
Conditions: Relapsed Hodgkin Lymphoma Refractory Hodgkin Lymphoma
Keywords: Camidanlumab Tesirine; Relapsed or Refractory Hodgkins Lymphoma; Classical Hodgkins Lymphoma; Lymphoma
Sponsor: ADC Therapeutics S.A.
Start date: 2019-09-13; Completion date: 2023-01-19
Enrollment: 117 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL).

Detailed description:
This is a phase 2, multi-center, open-label, single-arm study of efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin lymphoma. This study will enroll approximately 100 participants.

Camidanlumab Tesirine (ADCT-301) is an antibody drug conjugate (ADC), composed of the human monoclonal antibody, HuMax®-TAC, which is directed against human CD25. The antibody is conjugated through a protease cleavable linker to SG3199, a pyrrolobenzodiazepine (PBD) dimer cytotoxin.

For each participant the study will include a screening period (of up to 28 days), a treatment period (cycles of 3 weeks), and a follow-up period (approximately every 12-week visits) for up to 3 years after treatment discontinuation.

Participants may continue treatment for up to 1 year or until disease progression, unacceptable toxicity, or other discontinuation criteria, whichever occurs first.

Additionally, patients benefiting clinically at 1 year may continue treatment after a case by case review with the Sponsor.

Arms: arm 1: Camidanlumab Tesirine is administered as a 30- minute intravenous (IV) infusion on Day 1 of each cycle (every 3 weeks). Camidanlumab Tesirine will be administered at a dose of 45 μg/kg every 3 weeks for 2 cycles, then 30 μg/kg for subsequent cycles.
Interventions: intervention 1: Camidanlumab Tesirine
Intervention descriptions: intervention 1: Intravenous Infusion

Protocol documents:
Prot_000.pdf: 
Protocol Number: ADCT-301-201 
 
Official Title: A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of 
Camidanlumab Tesirine (ADCT-301) in Patients with Relapsed or Refractory Hodgkin Lymphoma 
 
NCT Number: NCT04052997 
 
Document Date: 16 February 2022 






ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 3 of 87 
Declaration of Investigator 
I have read and understood all sections of the protocol entitled: “A Phase 2, Open-Label, 
Single-Arm Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) 
in Patients with Relapsed or Refractory Hodgkin Lymphoma” and the accompanying 
Investigator’s Brochure (IB). 
I agree to supervise all aspects of the protocol and to conduct the clinical investigation in 
accordance with the Protocol Amendment 5, dated 16 February 2022, the current version of 
International 
Council 
for 
Harmonisation 
(ICH) 
harmonised 
tripartite 
guideline 
E6: Good Clinical Practice, and all applicable governmental regulations. I will not make 
changes to the protocol before consulting with ADC Therapeutics or implement protocol 
changes without independent ethics committee approval except to eliminate an immediate risk 
to patients. I agree to administer the study drug only to patients under my personal supervision 
or the supervision of a sub-Investigator. 
I will not supply the study drug to any person not authorized to receive it. Confidentiality will 
be protected. Patient identity will not be disclosed to third parties or appear in any study reports 
or publications. 
I will not disclose information regarding this clinical investigation or publish results of the 
investigation without authorization from ADC Therapeutics SA. 
 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
Date 
 
 
 
 
 
 
 
 
Printed Name of Principal Investigator 
 
 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 4 of 87 
Table of Contents 
Title Page .................................................................................................................................. 1 
Protocol Approval – Sponsor Signatory ................................................................................... 2 
Declaration of Investigator ....................................................................................................... 3 
Table of Contents ...................................................................................................................... 4 
List of Tables ............................................................................................................................. 8 
List of Figures ........................................................................................................................... 8 
List of Abbreviations................................................................................................................. 9 
Summary of Changes .............................................................................................................. 12 
List of Prior Protocol Versions ................................................................................................ 13 
Protocol Synopsis.................................................................................................................... 14 
Schedule of Events .................................................................................................................. 21 
1 
Introduction and Background ......................................................................................... 24 
1.1 
Targeting CD25-positive Tumor Cells in Hodgkin Lymphoma .....................................24 
1.2 
Description of Investigational Study Drug .....................................................................24 
1.3 
Safety and Efficacy of Camidanlumab Tesirine in Phase 1 Study, ADCT-301-001 ......25 
2 
Study Rationale .............................................................................................................. 27 
2.1 
Rationale for Study Design ............................................................................................27 
2.2 
Rationale for Dose Selection ..........................................................................................27 
3 
Study Objectives and Endpoints ..................................................................................... 29 
4 
Study Design .................................................................................................................. 31 
4.1 
Overview ........................................................................................................................31 
4.2 
Study Periods ..................................................................................................................31 
4.2.1 
Screening Period .........................................................................................................31 
4.2.2 
Treatment Period .........................................................................................................31 
4.2.3 
End of Treatment ........................................................................................................31 
4.2.4 
Follow-up Period ........................................................................................................32 
4.2.5 
End of Study ...............................................................................................................32 
4.3 
Study Stopping Rules .....................................................................................................32 
5 
Patient Population ........................................................................................................... 33 
5.1 
Inclusion Criteria ............................................................................................................33 
5.2 
Exclusion Criteria ...........................................................................................................34 
5.3 
Screening Failures ..........................................................................................................36 
5.4 
Re-screening Procedures ................................................................................................36 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 5 of 87 
5.5 
Discontinuation ..............................................................................................................36 
5.5.1 
Discontinuation from Study Drug ..............................................................................36 
5.5.2 
Discontinuation from the Study ..................................................................................37 
5.5.3 
Loss to Follow-up .......................................................................................................37 
5.6 
Patient Replacements .....................................................................................................37 
6 
Treatment ........................................................................................................................ 38 
6.1 
Study Drug .....................................................................................................................38 
6.2 
Management of Clinical Supplies ..................................................................................38 
6.2.1 
Packaging and Storage ................................................................................................38 
6.2.2 
Preparation and Administration ..................................................................................38 
6.2.3 
Accountability .............................................................................................................39 
6.3 
Camidanlumab Tesirine Dosing .....................................................................................39 
6.4 
Dose Delays and Modifications .....................................................................................39 
6.4.1 
Guidelines for Dose Modification: General ...............................................................40 
6.4.2 
Guidelines for Dose Modification: Specific Non-hematologic Toxicities .................41 
6.4.3 
Guidelines for Dose Modification: Specific Hematologic Toxicities .........................43 
6.4.4 
Guidelines for Dose Modification: Specific Neurologic Toxicities ...........................43 
6.4.5 
Guidelines for Dose Modification: Specific Skin Toxicities ......................................44 
6.5 
Overdose Management ...................................................................................................47 
6.6 
Treatment Compliance ...................................................................................................47 
6.7 
Premedication and Supportive Care ...............................................................................47 
6.7.1 
Premedication .............................................................................................................47 
6.7.2 
Treatment of Edema and Pleural Effusion ..................................................................47 
6.7.3 
Treatment and Prophylaxis of Infusion-Related Hypersensitivity Reactions .............48 
6.7.4 
Consideration for Skin Toxicity ..................................................................................48 
6.7.5 
Diagnostic, Work-up, and Management of Polyradiculopathy/ Guillain-Barré 
Syndrome ....................................................................................................................49 
6.7.6 
Other Supportive Care ................................................................................................50 
6.8 
Concomitant Medications and Procedures .....................................................................50 
6.8.1 
Permitted During Study ..............................................................................................50 
6.8.2 
Prohibited During Study .............................................................................................50 
7 
Study Assessments and Procedures ................................................................................ 51 
7.1 
Informed Consent ...........................................................................................................51 
7.2 
Demographics and Baseline Characteristics ..................................................................51 
7.3 
Efficacy Assessments .....................................................................................................51 
7.4 
Safety Assessments ........................................................................................................52 
7.4.1 
Physical Examination .................................................................................................52 
7.4.2 
ECOG Performance Status .........................................................................................53 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 6 of 87 
7.4.3 
Height and Weight ......................................................................................................53 
7.4.4 
Vital Signs ...................................................................................................................53 
7.4.5 
Laboratory Tests .........................................................................................................53 
7.4.6 
Pregnancy Test ............................................................................................................55 
7.4.7 
ECG ............................................................................................................................55 
7.5 
Pharmacokinetics, Pharmacodynamics, and Immunogenicity .......................................57 
7.5.1 
Pharmacokinetics ........................................................................................................58 
7.5.2 
Immunogenicity ..........................................................................................................59 
7.5.3 
Biomarkers ..................................................................................................................59 
7.5.3.1 
Blood Samples for Biomarkers ............................................................................. 59 
7.5.3.2 
Tumor Tissue for Biomarkers ............................................................................... 60 
7.6 
Health-Related Quality of Life (HRQoL) Questionnaires .............................................61 
7.6.1 
EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) ..........................................................61 
7.6.2 
Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) .....................61 
8 
Adverse Events ............................................................................................................... 62 
8.1 
Definition of Adverse Events, Serious Adverse Events, and Adverse Events of 
Special Interest ...............................................................................................................62 
8.1.1 
Adverse Events of Special Interest .............................................................................62 
8.2 
Eliciting and Reporting Adverse Events/Adverse Events of Special Interest/Serious 
Adverse Events ...............................................................................................................63 
8.3 
Assessment of Severity ..................................................................................................64 
8.4 
Assessment of Causality .................................................................................................65 
8.5 
Regulatory Reporting .....................................................................................................65 
8.6 
Pregnancy Reporting ......................................................................................................65 
8.7 
Independent Data and Safety Monitoring Board ............................................................66 
9 
Statistical Considerations ............................................................................................... 67 
9.1 
Sample Size Calculation .................................................................................................67 
9.2 
Analysis Populations ......................................................................................................67 
9.3 
Interim Analysis .............................................................................................................67 
9.4 
Final Analysis .................................................................................................................67 
9.5 
Demographics and Baseline Characteristics ..................................................................68 
9.6 
Exposure to Treatments ..................................................................................................68 
9.7 
Efficacy Analyses ...........................................................................................................68 
9.7.1 
Overall Response Rate ................................................................................................68 
9.7.2 
Duration of Response .................................................................................................68 
9.7.3 
Complete Response Rate ............................................................................................69 
9.7.4 
Relapse-free Survival ..................................................................................................69 
9.7.5 
Progression-free Survival ...........................................................................................69 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 7 of 87 
9.7.6 
Overall Survival ..........................................................................................................69 
9.7.7 
Patients Receiving Transplant .....................................................................................69 
9.8 
Safety Analyses ..............................................................................................................69 
9.8.1 
Adverse Events ...........................................................................................................70 
9.8.2 
Clinical Laboratory Results ........................................................................................70 
9.8.3 
Additional Safety Assessments ...................................................................................70 
9.9 
Pharmacokinetic Analyses ..............................................................................................70 
9.10 Immunogenicity Analyses ..............................................................................................71 
9.11 Exploratory Analyses .....................................................................................................72 
10 
Data Management and Quality Assurance ..................................................................... 73 
11 
Ethical, Regulatory, and Study Management Considerations ........................................ 74 
11.1 Regulatory and Ethical Conduct of the Study ................................................................74 
11.2 Independent Ethics Committee or Institutional Review Board ......................................74 
11.3 Patient Information and Consent ....................................................................................74 
11.4 Confidentiality ................................................................................................................75 
11.5 Financial Disclosure and Obligations ............................................................................75 
11.6 Study Conduct ................................................................................................................75 
11.7 Protocol Amendments ....................................................................................................75 
11.8 Monitoring of the Study .................................................................................................76 
11.9 Records Retention ..........................................................................................................76 
11.10 Publications ....................................................................................................................76 
12 
Reference List ................................................................................................................. 77 
13 
Appendices ..................................................................................................................... 80 
13.1 Appendix: Eastern Cooperative Oncology Group Performance Status .........................80 
13.2 Appendix: Clinical Case Definitions: Level 1 of Diagnostic Certainty for Guillain-
Barré Syndrome (GBS) ..................................................................................................81 
13.3 Appendix: Guillain–Barré Syndrome Disability Scale ..................................................82 
13.4 Appendix: Response Assessment of Hodgkin and Non-Hodgkin Lymphoma 
(Lugano Classification) ..................................................................................................83 
13.5 Appendix: Management of Specific Autoimmune Toxicities: Hyperthyroidism, 
Hypothyroidism, and Hepatitis ......................................................................................86 
 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 8 of 87 
List of Tables 
Table 1 
Schedule of Events .............................................................................................. 21 
Table 2 
Study Objectives and Endpoints .......................................................................... 29 
Table 3 
Schedule for Triplicate ECG Collection .............................................................. 56 
Table 4 
Sampling Schedule for PK and ADA .................................................................. 58 
Table 5 
Sampling Schedule for Soluble Biomarkers ........................................................ 60 
Table 6 
Definition of Severity Grades for CTCAE .......................................................... 65 
Table 7 
Number of Responses Needed to Have 95% CI Low Bound of ORR >35% ...... 68 
 
 
List of Figures 
Figure 1 
Schematic Representation and Chemical Structure of Camidanlumab Tesirine . 25 
Figure 2 
Preferred Sequence for Triplicate Electrocardiogram (ECG), Vital Signs, and 
Pharmacokinetic (PK) Sample Assessments at End of Infusion (EOI) ............... 57 
Figure 3 
Anti-drug Antibody Tiered Immunogenicity Testing Strategy ............................ 71 
 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 9 of 87 
List of Abbreviations 
Abbreviation 
Definition 
ADA 
anti-drug antibody 
ADC 
antibody-drug conjugate 
AE 
adverse event 
AESI 
adverse event of special interest 
AI 
accumulation index 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time  
ASCO 
American Society of Clinical Oncology 
AST 
aspartate aminotransferase 
AUCinf 
area under the concentration-time curve from time zero to infinity 
AUClast 
area under the concentration-time curve from time zero to the last 
quantifiable concentration 
AUCtau 
area under the concentration-time curve from time zero to the end of the 
dosing interval 
BID 
twice daily 
β-HCG 
human chorionic gonadotropin 
BOR 
best overall response 
BP 
blood pressure 
C1D1 
Cycle 1, Day 1 
CD 
cluster of differentiation 
CFR 
Code of Federal Regulations 
cHL 
classical Hodgkin lymphoma 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum concentration 
CMV 
cytomegalovirus 
CR 
complete response 
CRO 
contract research organization 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
EBV 
Epstein-Barr virus 
ECG 
electrocardiogram(s) 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EOI 
end of infusion 
EOS 
end of study 
EOT 
end of treatment 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 10 of 87 
Abbreviation 
Definition 
EQ-5D-5L 
EuroQoL–5 Dimensions–5 Levels 
FACT-Lym 
Functional Assessment of Cancer Therapy-Lymphoma 
FDA 
Food and Drug Administration 
FFPE 
formalin-fixed paraffin-embedded 
FIH 
first-in-human  
FSH 
follicle stimulating hormone 
FT3 
free triiodothyronine 
FT4 
free thyroxine 
G-CSF 
granulocyte colony-stimulating factor 
GBS 
Guillain-Barré syndrome 
GCP 
Good Clinical Practice 
GGT 
gamma glutamyl transferase 
GVHD 
graft-versus-host disease 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
HL 
Hodgkin lymphoma 
HR 
heart rate 
HRQoL 
health-related quality of life 
HSCT 
hematopoietic stem cell transplant 
HSV1 
herpes simplex virus 1 
HSV2 
herpes simplex virus 2 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
iDSMB 
independent Data and Safety Monitoring Board 
IEC 
independent ethics committee 
IL 
interleukin 
IFNγ 
interferon gamma 
INR 
international normalized ratio 
IRB 
institutional review board 
IV 
intravenous 
IVIg 
intravenous immunoglobulin 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
ORR 
overall response rate 
OS 
overall survival 
PBD 
pyrrolobenzodiazepine 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PET-CT 
positron emission tomography-computed tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PLEX 
plasma exchange 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 11 of 87 
Abbreviation 
Definition 
PR 
partial response 
Q3W 
every 3 weeks 
QoL 
quality of life 
QT 
measure between Q wave and T wave in the electrocardiogram 
QTcB 
Bazett correction of the QT measure 
QTcF 
Fridericia correction of the QT measure 
RBC 
red blood cell 
RFS 
relapse-free survival 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
respiratory syndrome coronavirus 2 
sCD25 
soluble CD25 
SD 
stable disease 
SoC 
standard of care 
SoE 
schedule of events 
SUSAR 
suspected unexpected serious adverse reaction 
TANT 
tumor-associated non-tumor cells 
TEAE 
treatment-emergent adverse event(s) 
TIL 
tumor infiltrating lymphocytes 
TLS 
tumor lysis syndrome 
Thalf 
apparent terminal elimination half-life 
Tmax 
time to maximum concentration 
TNFα 
tumor necrosis factor alpha 
TSH 
thyroid-stimulating hormone 
ULN 
upper limit of normal 
VAS 
visual analog scale 
Vss 
volume of distribution 
VZV 
varicella zoster virus 
WBC 
white blood cell 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 12 of 87 
Summary of Changes 
The primary reason for Protocol Amendment 5 is to extend the contraception period after last 
dose of camidanlumab tesirine, following an urgent safety measure. The contraception period 
is determined based on the compound properties and half-life, and has been updated due to a 
recently revised half-life value of camidanlumab tesirine. 
• In Section 5.1, Inclusion criterion 10: For women of childbearing potential, the period 
of contraception after last dose of camidanlumab tesirine has been extended to at least 
9.5 months. For men with female partners of childbearing potential the period of 
abstinence or use of condom has been extended to at least 6.5 months after last dose of 
camidanlumab tesirine. Section 7.4.6 Pregnancy Test, Section 8.6 Pregnancy 
Reporting, and Schedule of Assessments (Table 1) have been revised accordingly. 
In addition, revisions to the protocol text have also been applied to the synopsis section. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 13 of 87 
List of Prior Protocol Versions 
Document 
Version Date Rationale for Changes  
Amendment 4 
06 Nov 2020 
The primary reasons for this global Protocol Amendment 4 
were to implement the recommendations from the independent 
Data and Safety Monitoring Board (iDSMB), including the 
addition of varicella zoster virus prophylaxis, an update of the 
management guidance in respect to specific autoimmune 
toxicities, and to address the requests from the French and 
Belgian regulatory authorities. 
Amendment 3 
01 Jul 2020 
The primary reason for this global Protocol Amendment 3 was 
to update the stopping rule and to exclude patients that are 
tested positive for influenza and respiratory syndrome 
coronavirus 2 (SARS-CoV-2) before initiating study 
treatment, based on the recommendations by the Food and 
Drug Administration (FDA). 
Amendment 2 
24 Apr 2020 
The primary reason for this global Protocol Amendment 2 was 
to combine the updates required by the Regulatory Authorities 
and Institutional Review Boards (IRB)/Independent Ethics 
Committees (IEC) received to date in one global protocol 
version. In addition, updates in line with study needs had been 
introduced, such as the inclusion of severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2) added to the list of 
pathogens associated to Guillain-Barré syndrome (GBS), 
additional recommendation to capture early signs of 
polyradiculopathy/GBS, and the update of the study stopping 
rule. 
Amendment 1 
24 Jun 2019 
The primary reason for Protocol Amendment 1 was to include 
changes based on recommendations by the US Food and Drug 
Administration. In addition, substantial updates in line with 
study needs had been introduced, e.g., revision of study drug 
instructions or clarifications of male participant contraception 
methods. 
Version 2 
15 Mar 2019 
The primary reasons for Protocol Version 2 (15 March 2019) 
were to include changes based on internal discussion and 
emerging data. 
This version is the first version that was used for submission 
purposes, thus to be considered as the actual Original Protocol. 
Original Protocol 
12 Jul 2018 
This version has been distributed to sites but not for 
submission purposes. 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 14 of 87 
Protocol Synopsis 
Protocol Number: 
ADCT-301-201 
Title: 
A Phase 2, Open-label, Single-Arm Study to Evaluate the Efficacy and 
Safety of Camidanlumab Tesirine (ADCT-301) in Patients with Relapsed 
or Refractory Hodgkin Lymphoma 
Sponsor: 
ADC Therapeutics SA 
Study Phase: 
Phase 2 
Indication: 
Classical Hodgkin Lymphoma (cHL, also known as classical 
Hodgkin Disease) 
Rationale: 
Camidanlumab tesirine is an antibody-drug conjugate (ADC) that has been 
designed to target and kill CD25-expressing cells. Given the encouraging 
overall response rate (ORR) and complete response (CR) rate reported with 
camidanlumab tesirine in the Phase 1 study in relapsed and refractory 
Hodgkin lymphoma (HL) patients at dose levels below the maximum 
tolerated dose (MTD) and the acceptable safety profile, camidanlumab 
tesirine presents a positive risk-benefit for further evaluation in this 
population. 
Objectives: 
Primary Objective 
• Evaluate the efficacy of single agent camidanlumab tesirine in 
patients with relapsed or refractory HL 
Secondary Objectives 
• Characterize additional efficacy endpoints of camidanlumab tesirine 
• Characterize the safety profile of camidanlumab tesirine 
• Characterize the pharmacokinetic (PK) profile of camidanlumab 
tesirine 
• Evaluate the immunogenicity of camidanlumab tesirine 
• Evaluate the impact of camidanlumab tesirine treatment on health-
related quality of life (HRQoL) 
Exploratory Objectives 
• Assess the pharmacodynamic effects of camidanlumab tesirine 
• Characterize tumor and tumor-associated non-tumor cells (TANT), as 
well as immunological relevant parameters, in baseline tumor tissue 
• Evaluate genetic alterations characterizing HL and their evolution 
upon camidanlumab tesirine treatment 
• Explore exposure-response relationships affecting safety and efficacy 
of camidanlumab tesirine 
• Explore correlations between clinical activity or safety of 
camidanlumab tesirine and tumor and/or blood biomarkers 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 15 of 87 
Endpoints: 
Primary Endpoints 
• ORR according to the 2014 Lugano classification as determined by 
central review 
Secondary Endpoints 
• Duration of response (DOR) 
• CR rate 
• Relapse-free survival (RFS) 
• Progression-free survival (PFS) 
• Overall survival (OS) 
• Fraction of patients receiving hematopoietic stem cell transplant 
(HSCT)  
• Frequency and severity of adverse events (AEs) and serious adverse 
events (SAEs) 
• Changes from Baseline of safety laboratory values, vital signs, 
Eastern Cooperative Oncology Group (ECOG) performance status, 
and 12-lead electrocardiograms (ECGs) 
• Concentrations and PK parameters of camidanlumab tesirine total 
antibody, pyrrolobenzodiazepine (PBD)-conjugated antibody, and 
unconjugated warhead SG3199 
• Frequency of confirmed positive anti-drug antibody (ADA) 
responses, their associated (ADA) titers and, if applicable, 
neutralizing activity to camidanlumab tesirine after treatment with 
camidanlumab tesirine 
• Change from Baseline in HRQoL as measured by EuroQoL–5 
Dimensions–5 Levels (EQ-5D-5L) and Functional Assessment of 
Cancer Therapy – Lymphoma (FACT-Lym) 
Exploratory Endpoints 
• Changes in levels of immunologically relevant biomarkers in blood 
such as, but not limited to, interleukin-2 (IL-2), IL-10, and soluble 
CD25 (sCD25) 
• Measurement of CD25(+) tumor cells and TANT in baseline tumor 
tissue 
• Measurement of tumor infiltrating lymphocytes (TILs) and other 
immunologically relevant parameters in baseline tumor tissue 
• Detect HL alterations in plasma circulating free DNA (cfDNA) prior, 
during, and after camidanlumab tesirine treatment, including at 
disease progression 
• Monitor residual disease prior to camidanlumab treatment and upon 
disease progression 
• Relation between exposure (camidanlumab tesirine dose, PK metrics) 
and selected efficacy and safety endpoints 
• Relation between tumor and/or blood biomarkers and selected 
efficacy and safety endpoints 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 16 of 87 
Study Design: 
This is a Phase 2, multi-center, open-label, single-arm study. 
Patient Selection:  
Inclusion Criteria: 
1. Written informed consent must be obtained prior to any procedures. 
2. Male or female patients aged 18 years or older. 
For US sites only: Male or female patients aged 16 years or older. 
3. Pathologic diagnosis of cHL. 
4. Patients with relapsed or refractory cHL, who have received at least 
3 prior lines of systemic therapy (or at least 2 prior lines in 
HSCT ineligible patients) including brentuximab vedotin and a 
checkpoint inhibitor approved for cHL (e.g., nivolumab or 
pembrolizumab). 
Note 1: Receipt of HSCT to be included in the number of prior therapies 
needed to meet eligibility. 
Note 2: The reason(s) for HSCT ineligibility must be documented in 
patient medical records/source documents and eCRF. 
5. Measurable disease as defined by the 2014 Lugano Classification. 
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue 
block (or minimum 10 freshly cut unstained slides if block is not 
available). 
Note 1: Any biopsy since initial diagnosis is acceptable, but if several 
samples are available, the most recent sample is preferred. 
Note 2: If a sufficient amount of tissue is not available, a fresh biopsy 
may be taken, provided the procedure is not deemed high-risk and is 
clinically feasible, and provided it is approved locally. 
7. ECOG performance status 0-2. 
8. Adequate organ function as defined by Screening laboratory values 
within the following parameters: 
a. Absolute neutrophil count (ANC) ≥ 1.0 × 103/µL (off growth factors 
at least 72 h). 
b. Platelet count ≥ 75 × 103/µL without transfusion in the past 2 weeks. 
c. Alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), or gamma glutamyl transferase (GGT) ≤ 2.5 × the upper 
limit of normal (ULN) if there is no liver involvement; ALT or 
AST ≤ 5 × ULN if there is liver involvement. 
d. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert’s 
syndrome may have a total bilirubin up to ≤ 3 × ULN with direct 
bilirubin ≤ 1.5 × ULN). 
e. Blood creatinine ≤ 3.0 × ULN or calculated creatinine 
clearance ≥ 30 mL/min by the Cockcroft-Gault equation. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 17 of 87 
Note: A laboratory assessment may be repeated a maximum of two 
times during the Screening Period to confirm eligibility. 
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test 
within 7 days prior to start of study drug for women of childbearing 
potential. 
10. Women of childbearing potential must agree to use a highly effective 
method of contraception from the time of giving informed consent until 
at least 9.5 months after the last dose of camidanlumab tesirine. Men 
with female partners who are of childbearing potential must agree to 
use condom when sexually active or practice total abstinence from the 
time of giving informed consent until at least 6.5 months after the 
patient receives his last dose of camidanlumab tesirine. 
Exclusion Criteria: 
1. 
Previous treatment with camidanlumab tesirine. 
2. 
Participation in another investigational interventional study. 
Being in follow-up of another investigational study is allowed. 
3. 
Known history of hypersensitivity to or positive serum human ADA 
to a CD25 antibody. 
4. 
Allogenic or autologous HSCT within 60 days prior to start of study 
drug. 
5. 
Active graft-versus-host disease (GVHD), except for non-neurologic 
symptoms as a manifestation of mild (≤ Grade 1) chronic GVHD.  
6. 
Post-HSCT lymphoproliferative disorders. 
7. 
Active second primary malignancy other than non-melanoma skin 
cancers, non-metastatic prostate cancer, in situ cervical cancer, ductal 
or lobular carcinoma in situ of the breast, or other malignancy that 
the Sponsor’s medical monitor and Investigator agree and document 
should not be exclusionary. 
8. 
History of symptomatic autoimmune disease (e.g., rheumatoid 
arthritis, systemic progressive sclerosis [scleroderma], systemic 
lupus erythematosus, Sjögren’s syndrome, autoimmune vasculitis  
[e.g., Wegener’s granulomatosis]) (subjects with vitiligo, type 1 
diabetes mellitus, residual hypothyroidism, hypophysitis due to 
autoimmune condition only requiring hormone replacement may be 
enrolled). 
9. 
History 
of 
neuropathy 
considered 
of 
autoimmune 
origin  
(e.g., polyradiculopathy including Guillain-Barré syndrome and 
myasthenia gravis) or other central nervous system autoimmune 
disease (e.g., poliomyelitis, multiple sclerosis). 
10. 
History of recent infection (within 4 weeks of Cycle 1, Day 1 
[C1D1]) considered to be caused by one of the following pathogens: 
HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, Zika virus, 
Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, 
enterovirus D68, or severe acute respiratory syndrome coronavirus 2 
(SARS-CoV-2). 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 18 of 87 
Note: An influenza test and a pathogen-directed SARS-CoV-2 test 
(such as polymerase chain reaction) are mandatory and must be 
negative before initiating study treatment (tests to be performed 
3 days or less prior to dosing on C1D1; an additional 2 days are 
allowed in the event of logistical issues for receiving the results on 
time). 
11. 
Patients known to be or having been infected with human 
immunodeficiency (HIV) virus, hepatitis B virus (HBV), or 
hepatitis C virus (HCV), and require anti-viral therapy or 
prophylaxis. 
Note: Serology testing is mandatory for patients with unknown 
status. 
12. 
History of Stevens-Johnson syndrome or toxic epidermal necrolysis. 
13. 
Failure to recover ≤ Grade 1 (Common Terminology Criteria for 
Adverse Events version 4.0 [CTCAE v4.0]) from acute 
non-hematologic toxicity (except ≤ Grade 2 neuropathy or alopecia), 
due to previous therapy, prior to screening. 
14. 
HL 
with 
central 
nervous 
system 
involvement, 
including 
leptomeningeal disease. 
15. 
Clinically significant third space fluid accumulation (i.e., ascites 
requiring drainage or pleural effusion that is either requiring drainage 
or associated with shortness of breath). 
16. 
Breastfeeding or pregnant. 
17. 
Significant 
medical 
comorbidities, 
including 
uncontrolled 
hypertension (blood pressure [BP] ≥ 160/100 mmHg repeatedly), 
unstable angina, congestive heart failure (greater than New York 
Heart Association class II), electrocardiographic evidence of acute 
ischemia, coronary angioplasty or myocardial infarction within 
3 months prior to screening, severe uncontrolled atrial or ventricular 
cardiac arrhythmia, poorly controlled diabetes, or severe chronic 
pulmonary disease. 
18. 
Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic 
therapy, within 14 days prior to start of study drug, except shorter if 
approved by the Sponsor. 
19. 
Use of any other experimental medication within 30 days prior to 
start of study drug. 
20. 
Any live vaccine within 4 weeks prior to start of study drug and 
planned live vaccine administration after starting study drug. 
21. 
Congenital long QT syndrome, or a corrected QTc interval of 
≥ 480 ms, at screening (unless secondary to pacemaker or bundle 
branch block). 
22. 
Any other significant medical illness, abnormality, or condition that 
would, in the Investigator’s judgment, make the patient inappropriate 
for study participation or put the patient at risk. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 19 of 87 
Estimated Duration 
of Patient 
Participation and 
Study Duration: 
The duration of the study participation for each patient is defined as the 
time from the date of signed written informed consent to the completion of 
the follow-up period, withdrawal of consent, loss to follow-up, or death, 
whichever occurs first. 
The study will include a Screening Period (of up to 28 days), 
a Treatment Period (cycles of 3 weeks), and a Follow-up Period 
(approximately every 12-week visits) for up to 3 years from End of 
Treatment (EOT). 
Patients may continue treatment until disease progression, unacceptable 
toxicity, or other discontinuation criteria, whichever occurs first. 
The overall end of study occurs at the last visit or last scheduled procedure 
for the last patient, unless the study is terminated earlier by Sponsor. 
Efficacy 
Assessments: 
• Disease assessments: Positron emission tomography-computed 
tomography (PET-CT) 
Note: If disease is not PET-avid at baseline, CT or MRI may be used 
for follow-up disease assessments. The assessment method determined 
to identify sites of disease at Baseline should be used for all subsequent 
assessments. 
Safety Assessments: 
• Physical examination, including neurological examination 
• ECOG performance status 
• Height and weight 
• Vital signs 
• Safety laboratories (hematology, chemistry, coagulation, urinalysis, 
and as applicable, viral detection and/or additional microbiological 
studies) 
• Pregnancy test, if applicable 
• 12 Lead-ECG (triplicate) 
• AEs/SAEs, graded according to CTCAE version 4.0. 
Other Assessments: 
• Blood sampling for PK, ADA, and biomarkers 
• Tumor tissue for biomarkers 
• HRQoL: EQ-5D-5L and FACT-Lym 
Study Drug, Dosage, 
and Mode of 
Administration: 
Camidanlumab tesirine will be administered in 3-week cycles as an 
intravenous (IV) infusion over 30 minutes on Day 1 of each cycle. 
Patients will receive 45 µg/kg for 2 cycles, then 30 µg/kg for subsequent 
cycles. 
Sample Size: 
The sample size of 100 patients will provide a robust population for safety 
evaluation and adequate precision for observed ORR in the expected range. 
For the test of efficacy, this study has >98% power to distinguish between 
an active therapy with a 55% true response rate from a therapy with a 
response rate of 35% or less with a 1-sided alpha of 0.025.  


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 20 of 87 
Statistical 
Considerations: 
Statistical Analysis: 
ORR, CR rate with 95% confidence interval (CI) from all-treated patients 
will be presented. 
DOR, RFS, PFS, and OS will be analyzed in Kaplan-Meier approach. 
Safety analyses will be presented descriptively. 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 21 of 87 
Schedule of Events 
Table 1 
Schedule of Events 
 
Protocol 
Section 
Screening 
Treatment Period 
Follow-up Period 
(up to 3 years from EOT) 
(1 Cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
-28 to –1 
1 
8 
15 
1 
 
 
Informed consent 
7.1 
X 
 
 
 
 
 
 
Eligibility criteria 
5.1 
5.2 
X 
 
 
 
 
 
 
Demography 
7.2 
X 
 
 
 
 
 
 
Medical/Cancer history 
7.2 
X 
 
 
 
 
 
 
Tumor tissue shipment 
7.5.3.2 
X upon 
confirmed 
eligibility  
 
 
 
 
 
 
Disease assessment 
7.3 
X1 
6 weeks and 12 weeks after C1D1, then every 9 wks1 
X1 
Every 12 weeks until 1 year from 
EOT, then every 6 months until 
disease progression2 
Physical examination, 
incl. neurological examination 
7.4.1 
X 
X 
X 
X 
X 
X 
 
ECOG performance status 
7.4.2 
X 
X 
 
 
X 
X 
 
Height 
7.4.3 
X 
 
 
 
 
 
 
Weight 
7.4.3 
X 
X 
X 
X 
X 
X 
 
Vital signs (BP, HR, RR, Temp) 
7.4.4 
X 
X3 
X 
X 
X3 
X 
 
Hematology and Chemistry 
7.4.5 
X 
X 
X 
X 
X 
X 
 
Coagulation and Urinalysis  
7.4.5 
X 
X 
 
 
 
X 
 
Thyroid function tests 
7.4.5 
X 
On C1D1, thereafter on D1 of every other cycle 
X 
 
Influenza and SARS-CoV-2 
7.4.5 
3 days4 or less prior to 
dosing on C1D1 
 
 
 
 
 
Viral detection, if applicable5 
7.4.5 
X 
On C1D1, thereafter on D1 of every other cycle 
X 
 
Pregnancy test, if applicable 
7.4.6 
X 
On C1D1, thereafter on D1 of every other cycle (max. 
6 wks apart) 
X6 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 22 of 87 
 
Protocol 
Section 
Screening 
Treatment Period 
Follow-up Period 
(up to 3 years from EOT) 
(1 Cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
-28 to –1 
1 
8 
15 
1 
 
 
12-lead ECG 
7.4.7 
Table 3 
X 
X 
(Pre, EOI, 
Post) 
X 
X 
C3 and C4 (Pre, 
EOI), C5 then 
every other cycle 
(Pre) 
X 
 
Premedication 
6.7.1 
 
D-1 to D2 
 
 
D-1 to D2 
 
 
Camidanlumab tesirine 
administration 
6.3 
 
X 
 
 
X 
 
 
PK sample 
7.5.1 
Table 4 
 
X 
(Pre, EOI, 
Post) 
X 
X 
C3 through C6 
(Pre, EOI), then 
every cycle (Pre) 
X 
 
ADA sample  
7.5.2 
Table 4 
 
X (Pre) 
 
X 
C1 only 
C3 (Pre), then 
every other cycle 
(Pre) 
X7 
 
Soluble biomarkers 
7.5.3.1 
Table 5 
 
X 
(Pre, Post) 
X 
X 
C3 (Pre, EOI), then 
every other cycle 
(Pre) 
X 
 
cfDNA samples (gDNA only at 
C1D1 and EOT) 
7.5.3.1 
 
X (Pre) 
 
 
6 and 12 weeks 
postdose 
(with disease 
assessment) 
X 
X at disease progression 
HRQoL8 
7.6 
 
X 
 
 
X 
X 
 
Concomitant medications9 
6.8 
From ICF signature date or D-14, whichever is earlier, until 30 days after last dose of study drug 
Adverse events 
8 
AE/SAEs from ICF signature date until 30 days after last dose of study drug; thereafter, related SAEs only 
1st New anticancer treatment 
4.2.3 
 
 
 
 
 
X 
X 
Survival 
4.2.5 
 
 
 
 
 
X 
X 
Abbreviations: ADA, anti-drug antibody; AE, adverse event; BP, blood pressure; cfDNA: circulating cell-free DNA; ECG, electrocardiogram; ECOG, Eastern 
Cooperative Oncology Group; EOI, end of infusion; EOT, end of treatment; HR, heart rate; gDNA, genomic DNA; HRQoL, health-related quality of life; ICF, 
informed consent form; PK, pharmacokinetics; post, postdose; pre, predose; RR, respiratory rate; SARS-CoV-2: respiratory syndrome coronavirus 2; SAE, serious 
adverse event; Temp, temperature; VZV, varicella zoster virus. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 23 of 87 
1. 
Screening imaging must be performed within 4 weeks prior to C1D1 and the same assessment method should be used throughout the study. Week 6 imaging 
should be performed within 1 week prior to C3D1 and Week 12 imaging should be performed within 1 week prior to C5D1. All other imaging for disease 
assessment for patients on study drug should be performed within ±2 weeks of the scheduled timepoint. Disease assessments should be performed at the 
timepoints specified even if study drug dosing is delayed. If a scan has been performed within 6 weeks of EOT, it does not need to be repeated at EOT. 
2. 
Disease assessments to be performed in patients having discontinued study drug for reasons other than disease progression or initiation of other anti-cancer 
therapy (except for hematopoietic stem cell transplant or CAR-T therapy). 
3. 
Vital signs to be measured predose and at EOI. 
4. 
Additional 2 days are allowed in the event of logistical issues for receiving the results on time.  
5. 
Serology testing for human immunodeficiency virus, hepatitis B virus, or hepatitis C virus is mandatory at screening for patients with unknown status. 
Seropositive patients for or with prior history of these infections at screening will be tested during the study (not needed if seropositivity is only due to 
vaccination).  
6. 
The EOT visit pregnancy test should be performed ≥9.5 months after the last dose of study drug.  
7. 
Patients who test positive for ADAs will be requested to supply additional ADA samples. 
8. 
FACT-Lym not to be administered for patients <18 years old. 
9. 
VZV prophylaxis is recommended for all enrolled patients as indicated in Section 6.7.6. 
 
Visit Scheduling Windows: 
• 
Treatment Period: visit day ± 2 days (excluding C1D1 which is the reference day)  
• 
EOT: as soon as possible after decision to discontinue the study drug, preferably within 30 days after last dose of study drug, and before initiation of any 
new anticancer treatment  
• 
Follow-up Period: visit day ± 14 days 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 24 of 87 
1 Introduction and Background 
1.1 Targeting CD25-positive Tumor Cells in Hodgkin Lymphoma 
Hodgkin lymphoma (HL) is a lymphoid malignancy of B-cell origin, which is classified into 
either nodular lymphocyte predominant Hodgkin lymphoma or classical Hodgkin lymphoma 
(cHL). The latter accounts for 95% of all HLs and is addressed by this protocol (Fields, 2017). 
Thus, for convenience, cHL/HL will be used interchangeably. 
The epidemiology of HL is characterized by bimodal incidence (15-34 years and 55+ years). 
Therapeutic advances have resulted in durable remission rates of 60-80%. However, there is 
an unmet medical need for patients’ refractory or relapsing from current treatments. Since 
many of these patients are of young age, the potential loss of life years is significant 
(Mehta-Shah, 2018; Fields, 2017; Glimelius, 2017). 
Brentuximab vedotin as a single agent and checkpoint inhibitors have been approved for use 
in the relapsed setting, and thus patients coming onto this trial should have received both of 
these therapies. However, once these therapies fail or are not tolerated, treatment options are 
limited (Mehta-Shah, 2018; Mottok, 2018; Fields, 2017; Glimelius, 2017). It is in this setting 
where camidanlumab tesirine, an antibody-drug conjugate that is directed against human 
cluster of differentiation (CD25), will be clinically tested. 
The CD25 is the alpha-chain of the interleukin (IL)-2 receptor and as such expressed on the 
cell surface of a number of normal cells of the immune system as well as malignant cells 
(Flynn, 2017). 
The presence of CD25-positive cells in hematologic malignancies and the relationship between 
increased CD25 expression and poor prognosis raises the possibility of using an anti-CD25 
antibody to deliver a cytotoxin to these cells in patients. Hematologic malignancies expressing 
CD25 include adult T-cell leukemia (Waldmann, 1995), hairy cell leukemia (Shao, 2013), 
anaplastic large cell lymphoma (Strauchen, 1987), cutaneous T-cell lymphoma (Olsen, 2001; 
Prince, 2010), chronic lymphocytic leukemia (Shvidel, 2012), HL (Schnell, 1998), follicular 
lymphoma (Fujiwara, 2013a), diffuse large B-cell lymphoma (Fujiwara, 2013b), acute myeloid 
leukemia (Cerny, 2013), acute lymphocytic leukemia (Geng, 2012), and systemic mastocytosis 
(Lim, 2009). Expression of CD25 is positive (≥ 20% tumor cells) in approximately 58% to 
78% of HL (Strauchen, 1987; LeMaistre, 1998). 
1.2 Description of Investigational Study Drug 
Camidanlumab tesirine (ADCT-301) is an antibody-drug conjugate (ADC), composed of the 
human monoclonal antibody, HuMax®-TAC, which is directed against human CD25. 
The antibody 
is 
conjugated 
through 
a 
protease 
cleavable 
linker 
to 
SG3199, 
a pyrrolobenzodiazepine (PBD) dimer cytotoxin. 
The schematic representation of camidanlumab tesirine is presented in Figure 1. 




ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 26 of 87 
Treatment-emergent adverse events (TEAEs) were reported in 73 (97%) out of 77 cHL patients 
treated with camidanlumab tesirine. Overall, the most common TEAEs (observed in at least in 
15% of patients), regardless of causality, included: fatigue (42%); rash maculopapular (35%); 
pyrexia (29%); gamma glutamyl transferase (GGT) increased (26%); nausea (25%); 
alanine aminotransferase (ALT) increased (24%); aspartate aminotransferase (AST) increased 
and cough (21% each); rash (20%); dyspnea (18%); blood alkaline phosphatase (ALP) 
increased and anemia (17% each); and abdominal pain and constipation (16% each). 
The TEAEs ≥ Grade 3 were reported in 51 (66%) cHL patients, with the most common 
(observed in at least 5% of patients), regardless of causality, including: GGT increased and 
rash maculopapular (17% each); ALT increased (9%); anemia (8%); AST increased and 
Guillain-Barré syndrome (GBS)/radiculopathy (7% each); and lipase increased (5%). 
The TEAEs in 20 (26%) patients led to treatment discontinuation. At the dose level of 45 µg/kg, 
approximately 89% of HL patients tolerated at least 2 cycles of camidanlumab tesirine before 
an AE leading to dose delay/modification occurred. 
Treatment-emergent serious adverse events (SAEs), irrespective of causality, were reported in 
36 (47%) out of 77 HL patients. Of these, 24 patients (31%) experienced a treatment-emergent 
SAE(s) considered at least possibly related to study drug. The following drug-related 
treatment-emergent SAEs were observed in multiple patients: pyrexia (6), GBS/radiculopathy 
(5), dyspnea (4), pleural effusion (4), acute kidney injury (2), blood creatine phosphokinase 
increased (2), cough (2), febrile neutropenia (2), nausea (2), edema peripheral (2), stomatitis 
(2), and vomiting (2). 
Out of 37 evaluable patients with cHL at the dose of 45 µg/kg Q3W, 18 (49%) achieved 
complete response (CR) and 14 (38%) achieved partial response (PR), for an overall response 
rate (ORR) of 87%, as per Investigator evaluation. Albeit with lower observed response rates, 
30 µg/kg Q3W is an active dose (ORR 50%, 9/18 patients), with both CR (28%) and PR (22%) 
observations. The lowest dose in which antitumor activity has been observed was 13 µg/kg 
Q3W. 
Taking into account all patients treated with camidanlumab tesirine (as of the date of this 
protocol amendment), GBS, dyspnea, pleural effusion, rash, and maculopapular rash have been 
classified as expected serious adverse drug reactions. All events of GBS, even though expected, 
will continue to be subject to expedited reporting. 
As of the date of this protocol amendment, a total of 8 patients with treatment-emergent 
GBS/polyradiculopathy events were reported across the entire camidanlumab tesirine 
development program including 4 studies, 2 of which reported such cases: 5 cHL patients in 
the Phase 1 study (described above) and 3 cHL patients in this ongoing Phase 2 study.  
Neurologic and immune-related adverse events (AEs) including polyradiculopathy and GBS 
have been classified as important identified risks. Increased liver enzymes, skin toxicity 
(epidermal degeneration), and nephropathy have been classified as important potential risks.  
Additional details may be found in the current camidanlumab tesirine (ADCT-301) 
Investigator’s Brochure (IB). 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 27 of 87 
2 Study Rationale 
Camidanlumab tesirine is an ADC that has been designed to target and kill CD25-expressing 
cells. Given the encouraging ORR and complete response (CR) rate reported with 
camidanlumab tesirine in the Phase 1 study in relapsed and refractory HL at dose levels below 
the MTD and the acceptable safety profile (Section 1.3), camidanlumab tesirine presents a 
positive risk-benefit for further evaluation in this population. 
2.1 Rationale for Study Design 
This is a Phase 2, open-label, single-arm study and will enroll approximately 100 patients. 
A single-arm design is commonly used to evaluate efficacy as a primary objective and the 
benefit-risk ratio of an oncology product with considerable anti-tumor activity within a 
well-defined patient population with high unmet medical need. Overall response rate is 
considered an appropriate endpoint in this setting.  
Additionally, because of the considerable ORR observed in the ADCT-301-001 Phase 1 trial 
in HL patients and the anticipated recruitment projections, an interim analysis for futility is not 
warranted. 
2.2 Rationale for Dose Selection 
Doses ranging from 3 µg/kg Q3W up to 300 µg/kg Q3W were planned to be investigated in 
the FIH camidanlumab tesirine clinical study ADCT-301-001, which target CD25-positive 
tumors (Section 1.3); the highest dose level tested as of 14 April 2019 was 150 µg/kg Q3W 
and the MTD had not been reached. The recommended dose for Phase 2 for HL has been 
determined as 45 µg/kg Q3W dosed for 2 cycles, followed by 30 µg/kg Q3W. 
The decision for initial dosing at the 45 µg/kg Q3W dose level is based on a number of 
considerations including: 
1) the favorable ORR (87%) and CR rate (49%) together with an acceptable safety profile 
2) the high fraction of patients with cHL who could tolerate at least 2 cycles of 
camidanlumab tesirine before an AE leading to a dose delay/modification occurred 
3) the ability to manage some of the severe TEAEs at this dose level 
Given that the attribution of toxicity to disease itself can be variable, it is recognized that a 
relatively high incidence of severe TEAEs in the relapsed/refractory lymphoma population is 
not uncommon. 
Dose reduction from 45 to 30 µg/kg following 2 cycles of camidanlumab tesirine Q3W 
treatment would provide lower dose intensity, while still being an active dose (ORR 56%), 
which can mitigate the frequency and severity of AEs foreseen in patients treated with 45 µg/kg 
beyond 2 cycles.  


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 28 of 87 
Continued dosing at a reduced dose of 30 µg/kg with demonstrated antitumor activity is 
expected to decrease the necessity for dose delay/modification due to toxicity and thus increase 
the duration of response (DOR). 
Therefore, the safety profile of camidanlumab tesirine administered as 45 µg/kg Q3W for 
2 cycles, then 30 µg/kg Q3W thereafter is considered a reasonable regimen to investigate in 
patients with cHL, which can optimize potential response to treatment while maintaining an 
acceptable degree of manageable toxicity. 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 29 of 87 
3 Study Objectives and Endpoints 
Study objectives and associated endpoints are presented below in Table 2. 
Table 2 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Evaluate the efficacy of single agent camidanlumab tesirine 
in patients with relapsed or refractory HL 
• ORR according to the 2014 Lugano classification as determined by central 
review in all-treated patients 
Secondary 
Characterize additional efficacy endpoints of camidanlumab 
tesirine 
• DOR defined as the time from the first documentation of tumor response to 
disease progression or death 
• CR rate defined as the percentage of treated patients with a best overall 
response (BOR) of CR 
• Relapse-free survival (RFS) defined as the time from the documentation of 
CR to disease progression or death 
• Progression-free survival (PFS) defined as the time from first dose of study 
drug until the first date of either disease progression or death due to any cause 
• Overall survival (OS) defined as the time from first dose of study drug until 
death due to any cause 
• Fraction of patients receiving hematopoietic stem cell transplant (HSCT). 
Characterize the safety profile of camidanlumab tesirine 
• Frequency and severity of AEs and SAEs 
• Changes from Baseline of safety laboratory values, vital signs, 
Eastern Cooperative Oncology Group (ECOG) performance status, and 12-
lead electrocardiograms (ECGs) 
Characterize the PK profile of camidanlumab tesirine 
• Concentrations and PK parameters of camidanlumab tesirine total antibody, 
PBD-conjugated antibody, and unconjugated warhead SG3199  
Evaluate the immunogenicity of camidanlumab tesirine 
• Frequency of confirmed positive anti-drug antibody (ADA) responses, their 
associated ADA titers and, if applicable, neutralizing activity to 
camidanlumab tesirine after treatment with camidanlumab tesirine 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 30 of 87 
Objectives 
Endpoints 
Evaluate the impact of camidanlumab tesirine treatment on 
health-related quality of life (HRQoL) 
• Change from Baseline in HRQoL as measured by EuroQoL–5 
Dimensions – 5 Levels (EQ-5D-5L) and Functional Assessment of Cancer 
Therapy – Lymphoma (FACT-Lym) 
Exploratory 
Assess the pharmacodynamic effects of camidanlumab 
tesirine 
• Changes in levels of immunologically relevant biomarkers in blood such as 
but not limited to IL-2, IL-10, and soluble CD25 (sCD25)  
Characterize tumor and tumor-associated non-tumor cells 
(TANT), as well as immunological relevant parameters in 
tumor tissue 
• Measurement of CD25(+) tumor cells and TANT in baseline tumor tissue 
• Measurement of tumor infiltrating lymphocytes (TILs) and other 
immunologically relevant parameters in baseline tumor tissue 
Evaluate genetic alterations characterizing HL and their 
evolution upon camidanlumab tesirine treatment  
• Detect HL alterations in plasma circulating free DNA (cfDNA) prior, during, 
and after camidanlumab tesirine treatment, including at disease progression 
• Monitor residual disease prior to camidanlumab tesirine treatment and upon 
disease progression 
Explore exposure-response relationships affecting safety and 
efficacy of camidanlumab tesirine 
• Relation between exposure (camidanlumab tesirine dose, PK metrics) and 
selected efficacy and safety endpoints  
Explore correlations between clinical activity or safety of 
camidanlumab tesirine and tumor and/or blood biomarkers 
• Relation between tumor and/or blood biomarkers and selected efficacy and 
safety endpoints 
 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 31 of 87 
4 Study Design 
4.1 Overview 
This is a Phase 2, multi-center, open-label, single-arm study.  
The duration of the study participation for each patient is defined as the time from the date of 
signed written informed consent to the completion of the follow-up period, withdrawal of 
consent, loss to follow-up, or death, whichever occurs first. 
The study will include a Screening Period (of up to 28 days), a Treatment Period (cycles of 
3 weeks), and a Follow-up Period (approximately every 12-week visits) for up to 3 years from 
End of Treatment (EOT) (Section 4.2). 
An independent Data and Safety Monitoring Board (iDSMB) will be established to ensure the 
safety of patients enrolled in this study (Section 8.7). 
4.2 Study Periods 
4.2.1 Screening Period 
Informed consent must be obtained for each patient and documented with a signed informed 
consent form (ICF) prior to any study procedures. Procedures that are performed as part of 
standard of care may be used to satisfy screening requirements if they are performed in the 
appropriate window. 
The Screening Period is from 28 days to 1 day prior to the start of the study drug. The screening 
assessments should be performed within this period in order to assess the eligibility of the 
patient against the inclusion and exclusion criteria (Sections 5.1 and 5.2, respectively). 
See Section 5.3 for the information to be collected on screening failures. 
4.2.2 Treatment Period 
The treatment period starts on the date when a patient receives the first dose of study drug and 
continues until the EOT visit. 
A treatment cycle is defined as 3 weeks (i.e., 21 days). 
Patients may continue treatment for up to 1 year or until disease progression, unacceptable 
toxicity, or other discontinuation criteria (Section 5.4), whichever occurs first. 
Additionally, patients benefiting clinically at 1 year may continue treatment after a case by 
case review with the Sponsor. 
4.2.3 End of Treatment 
An EOT visit should be performed as soon as possible after the decision to discontinue the 
study drug, preferably within 30 days after last dose of study drug, and before initiation of any 
new anticancer treatment. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 32 of 87 
When EOT coincides with a scheduled visit, the scheduled visit will become EOT. 
4.2.4 Follow-up Period 
All patients, regardless of disease status, will be followed every 12 weeks for up to 3 years 
from EOT, or until withdrawal of consent, loss to follow-up, or death, whichever occurs first. 
When disease assessments are not planned for a follow-up visit, the visit can be done by phone. 
4.2.5 End of Study 
The end of study occurs at the last scheduled visit/procedure for the last patient, unless the 
study is terminated earlier by Sponsor. The death date should be considered as the end of study 
(EOS) date for an individual patient whose survival status was informed at any later contact 
date. 
4.3 Study Stopping Rules 
This study has no formal study stopping rule. 
However, upon a confirmed case of GBS/polyradiculopathy of any grade, other ≥Grade 3 
relevant severe neurologic toxicity, or other ≥Grade 3 potentially immune-mediated toxicity, 
the sponsor will calculate the overall incidence rate of such events in the study. The 
denominator used to calculate this rate will be the number of patients who have received at 
least 2 doses of study drug for GBS/polyradiculopathy of any grade and at least 1 dose of study 
drug for other ≥Grade 3 relevant severe neurologic and potentially immune-mediated toxicities.  
• Should the incidence of GBS/polyradiculopathy of any grade reach an incidence 
threshold of >8.1% (8.1% being the incidence of GBS/polyradiculopathy cases of any 
grade observed in the HL population of the ADCT-301-001 Phase 1 study at 45 µg/kg), 
enrollment will be paused while a comprehensive safety review is completed and the 
iDSMB convenes to advise on study continuation based on their assessment of 
benefit-risk. 
• Should the incidence of other ≥Grade 3 relevant severe neurologic toxicity and 
potentially immune-mediated toxicity reach an incidence threshold of >10.0% (10.0% 
being consistent with observations made for checkpoint inhibitors; Brahmer, 2018 and 
Davies, 2017), enrollment will be paused while a comprehensive safety review is 
completed and the iDSMB convenes to advise on study continuation based on their 
assessment of benefit-risk. 
All ongoing patients who could receive clinical benefit will be allowed to continue on the study 
after being informed of the new safety information and consenting to continuation. 
The Sponsor will notify Regulatory Agencies if the threshold has been exceeded and 
enrollment has been paused. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 33 of 87 
5 Patient Population 
Patients must meet all inclusion criteria and none of the exclusion criteria to be eligible for the 
study. All criteria have to be assessed at Screening, unless otherwise specified (e.g., criterion 
to be confirmed within 28 days to 1 day prior to the start of study drug on Cycle 1, Day 1 
[C1D1]). 
5.1 Inclusion Criteria 
1. Written informed consent must be obtained prior to any procedures. 
2. Male or female patients aged 18 years or older. 
For US sites only: Male or female patients aged 16 years or older. 
3. Pathologic diagnosis of cHL. 
4. Patients with relapsed or refractory cHL, who have received at least 3 prior lines of 
systemic therapy (or at least 2 prior lines in HSCT ineligible patients) including 
brentuximab vedotin and a checkpoint inhibitor approved for cHL (e.g., nivolumab or 
pembrolizumab). 
Note 1: Receipt of HSCT to be included in the number of prior therapies needed to 
meet eligibility. 
Note 2: The reason(s) for HSCT ineligibility must be documented in patient medical 
records/source documents and eCRF. 
5. Measurable disease as defined by the 2014 Lugano Classification. 
6. Availability of formalin-fixed paraffin-embedded (FFPE) tumor tissue block 
(or minimum 10 freshly cut unstained slides if block is not available). 
Note 1: Any biopsy since initial diagnosis is acceptable, but if several samples are 
available, the most recent sample is preferred. 
Note 2: If a sufficient amount of tissue is not available, a fresh biopsy may be taken, 
provided the procedure is not deemed high-risk and is clinically feasible, and provided 
it is approved locally. 
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2. 
8. Adequate organ function as defined by Screening laboratory values within the 
following parameters: 
a. Absolute neutrophil count (ANC) ≥ 1.0 × 103/µL (off growth factors at least 72 h). 
b. Platelet count ≥ 75 × 103/µL without transfusion in the past 2 weeks. 
c. ALT, AST, or GGT ≤ 2.5 × the upper limit of normal (ULN) if there is no liver 
involvement; ALT or AST ≤ 5 × ULN if there is liver involvement. 
d. Total bilirubin ≤ 1.5 × ULN (patients with known Gilbert’s syndrome may have a 
total bilirubin up to ≤ 3 × ULN with direct bilirubin ≤ 1.5 × ULN). 
e. Blood creatinine ≤ 3.0 × ULN or calculated creatinine clearance ≥ 30 mL/min by 
the Cockcroft-Gault equation. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 34 of 87 
Note: A laboratory assessment may be repeated a maximum of two times during the 
Screening Period to confirm eligibility. 
9. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days 
prior to start of study drug for women of childbearing potential. 
10. Women of childbearing potential (WOCBP)* must agree to use a highly effective** 
method of contraception from the time of giving informed consent until at least 
9.5 months after the last dose of camidanlumab tesirine. Men with female partners who 
are of childbearing potential must agree to use a condom when sexually active or 
practice total abstinence from the time of giving informed consent until at least 6.5 
months after the patient receives his last dose of camidanlumab tesirine. 
* Women of childbearing potential are defined as sexually mature women who have 
not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; 
or who have not been postmenopausal. A postmenopausal state is defined as no 
menses for 12 months without an alternative medical cause. A high follicle 
stimulating hormone (FSH) level in the postmenopausal range may be used to 
confirm a postmenopausal state in women not using hormonal contraception or 
hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, 
a single FSH measurement is insufficient. 
** Highly effective forms of birth control are methods that achieve a failure rate of less 
than 1% per year when used consistently and correctly. Highly effective forms of 
birth control include: hormonal contraceptives associated with inhibition of 
ovulation (oral, injectable, patch, and intrauterine devices), male partner sterilization, 
or total abstinence from heterosexual intercourse, when this is the preferred and 
usual lifestyle of the patient.  
Note: The double-barrier method (e.g., synthetic condoms, diaphragm, or cervical cap 
with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, 
symptothermal, postovulation), withdrawal (coitus interruptus), lactational amenorrhea 
method, and spermicide-only are not acceptable as highly effective methods of 
contraception. 
 
5.2 Exclusion Criteria 
1. Previous treatment with camidanlumab tesirine. 
2. Participation in another investigational interventional study. Being in follow-up of 
another investigational study is allowed. 
3. Known history of hypersensitivity to or positive serum human anti-drug antibody 
(ADA) to a CD25 antibody. 
4. Allogenic or autologous HSCT within 60 days prior to start of study drug. 
5. Active graft-versus-host disease (GVHD), except for non-neurologic symptoms as a 
manifestation of mild (≤ Grade 1) chronic GVHD.  
6. Post-HSCT lymphoproliferative disorders. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 35 of 87 
7. Active second primary malignancy other than non-melanoma skin cancers, 
non-metastatic prostate cancer, in situ cervical cancer, ductal or lobular carcinoma in 
situ of the breast, or other malignancy that the Sponsor’s medical monitor and 
Investigator agree and document should not be exclusionary. 
8. History of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic 
progressive 
sclerosis 
[scleroderma], 
systemic 
lupus 
erythematosus, 
Sjögren’s syndrome, autoimmune vasculitis [e.g., Wegener’s granulomatosis]) 
(subjects with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, hypophysitis 
due to autoimmune condition only requiring hormone replacement may be enrolled). 
9. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy 
including Guillain-Barré syndrome and myasthenia gravis) or other central nervous 
system autoimmune disease (e.g., poliomyelitis, multiple sclerosis). 
10. History of recent infection (within 4 weeks of C1D1) considered to be caused by one 
of the following pathogens: HSV1, HSV2, VZV, EBV, CMV, measles, Influenza A, 
Zika virus, Chikungunya virus, mycoplasma pneumonia, Campylobacter jejuni, 
enterovirus D68, or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 
Note: An influenza test and a pathogen-directed SARS-CoV-2 test (such as polymerase 
chain reaction [PCR]) are mandatory and must be negative before initiating study 
treatment (tests to be performed 3 days or less prior to dosing on C1D1; an additional 
2 days are allowed in the event of logistical issues for receiving the results on time). 
11. Patients who are carriers of human immunodeficiency (HIV) virus, hepatitis B virus 
(HBV), or hepatitis C virus (HCV), and require anti-viral therapy or prophylaxis. 
Note: Serology testing is mandatory for patients with unknown status. 
12. History of Stevens-Johnson syndrome or toxic epidermal necrolysis. 
13. Failure to recover ≤ Grade 1 (Common Terminology Criteria for Adverse Events 
version 4.0 [CTCAE v4.0]) from acute non-hematologic toxicity (except ≤ Grade 2 
neuropathy or alopecia), due to previous therapy, prior to screening. 
14. HL with central nervous system involvement, including leptomeningeal disease. 
15. Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or 
pleural effusion that is either requiring drainage or associated with shortness of breath). 
16. Breastfeeding or pregnant. 
17. Significant 
medical 
comorbidities, 
including 
uncontrolled 
hypertension 
(blood pressure [BP] ≥ 160/100 mmHg repeatedly), unstable angina, congestive heart 
failure (greater than New York Heart Association class II), electrocardiographic 
evidence of acute ischemia, coronary angioplasty or myocardial infarction within 
3 months prior to screening, severe uncontrolled atrial or ventricular cardiac 
arrhythmia, poorly controlled diabetes, or severe chronic pulmonary disease. 
18. Major surgery, radiotherapy, chemotherapy, or other anti-neoplastic therapy, 
within 14 days prior to start of study drug, except shorter if approved by the Sponsor. 
19. Use of any other experimental medication within 30 days prior to start of study drug. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 36 of 87 
20. Any live vaccine within 4 weeks prior to start of study drug and planned live vaccine 
administration after starting study drug. 
21. Congenital long QT syndrome, or a corrected QTc interval of ≥ 480 ms, at screening 
(unless secondary to pacemaker or bundle branch block). 
22. Any other significant medical illness, abnormality, or condition that would, in the 
Investigator’s judgment, make the patient inappropriate for study participation or put 
the patient at risk. 
 
5.3 Screening Failures 
Patients who signed the ICF but were found not eligible for the study prior to receiving study 
drug are defined as screening failures. 
For these patients, only limited information will be collected in the electronic case report form 
(eCRF): 
- 
Informed consent 
- 
Demographics 
- 
Inclusion/exclusion criteria 
- 
SAE and/or death occurring during the Screening Period 
- 
Screening failure details 
 
5.4 Re-screening Procedures 
A patient who did not meet the eligibility criteria (screening failure) may be considered for 
re-screening. Decision for re-screening must be confirmed by the Sponsor/Medical monitor. 
A re-screened patient should be assigned a new patient number. 
5.5 Discontinuation 
The reason for discontinuation and the date of discontinuation will be collected for all patients. 
Note: Once discontinued from the study for any reason, patients are not permitted to be 
re-enrolled. 
5.5.1 Discontinuation from Study Drug 
A patient may be discontinued from the study drug for any of the following reasons: 
• 
Planned for HSCT 
• 
Major protocol deviation 
• 
Discontinuation of the study by the Sponsor 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 37 of 87 
A patient must be discontinued from the study drug for any of the following reasons: 
• 
Investigator’s decision 
• 
Patient decision 
• 
Disease progression (radiographic and/or clinical) based on Investigator’s assessment  
• 
Unacceptable toxicity 
• 
Pregnancy 
• 
Death 
 
IMPORTANT: Study drug discontinuation is not to be automatically considered as 
withdrawal from the study. Patients discontinuing the study drug will be asked to perform an 
EOT visit (Section 4.2.3) and continue with the Follow-up period (Section 4.2.4) as per 
protocol. 
The investigational site should make every effort to complete follow-up per protocol. 
If patients are unable to return to the site, patient status (including, but not limited to, survival 
status) may be obtained by site staff via phone, email, or mail. 
5.5.2 Discontinuation from the Study  
A patient may be discontinued from the study for any of the following reasons: 
• 
Withdrawal of consent 
• 
Investigator/Sponsor decision 
• 
Death 
• 
Loss to follow-up (Section 5.5.3) 
• 
Study completion 
 
If a patient withdraws informed consent for the study, no additional study data will be collected. 
The Sponsor may continue to use previously collected medical research data prior to the 
withdrawal consistent with the original authorization. 
The study may be terminated at any time, for any reason, by the Sponsor. Patients still receiving 
study drug should have an EOT visit as described in Section 4.2.3 and Schedule of Events 
(SoE) (Table 1). 
5.5.3 Loss to Follow-up 
Patients who fail to return for protocol follow-up are to be contacted by the investigative site. 
Following a minimum of two documented unsuccessful telephone calls, the investigative site 
should send a registered letter to the patient in a final attempt to ensure protocol compliance. 
5.6 Patient Replacements 
No patients will be replaced. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 38 of 87 
6 Treatment 
6.1 Study Drug 
Camidanlumab tesirine will be provided as a lyophilized white to off-white powder in 2 mL 
glass vials (5 mg camidanlumab tesirine per vial) and stored at 2°C to 8°C. The lyophilized 
camidanlumab tesirine is formulated in 20 mM histidine, 175 mM sucrose, and 
0.04% polysorbate 20, at pH 6.0. Prior to use, the study drug is reconstituted with 1.2 mL of 
sterile water for injection to deliver 1.0 mL at a concentration of 5 mg/mL. After reconstitution, 
the vial should be gently swirled (do not shake the vial) to ensure complete dissolution and 
homogeneity, and visually inspected prior to use. Sterile water for injection is to be provided 
by study sites. 
Additional study drug description is included in the pharmacy manual. 
6.2 Management of Clinical Supplies 
Detailed instructions regarding study drug shipment, handling, storage, preparation, and 
administration are included in the pharmacy manual. 
6.2.1 Packaging and Storage 
The study drug will be supplied by the Sponsor through the designated packaging, labeling, 
and distribution center.  
All study drugs must be stored according to the pharmacy manual, in a secure area. 
The lyophilized formulation of camidanlumab tesirine should be protected from long-term 
exposure to light and stored refrigerated (2°C to 8°C). Light protection is not required for dose 
preparation and during administration of the diluted drug in the IV bag. 
6.2.2 Preparation and Administration  
The study drug solution at a concentration of 5 mg/mL will be the basis for the preparation of 
the infusion solution. The amount of the product to be diluted will depend on the dose level 
and the body mass of the patient. Of note, a cap on the administered dose is to be applied for 
patients with a body mass index ≥35 kg/m2. Additional details are included in the pharmacy 
manual. 
Administration of camidanlumab tesirine will be performed by the Investigator or a qualified 
designee according to the pharmacy manual. 
Camidanlumab tesirine is administered as a 30-minute intravenous (IV) infusion on Day 1 of 
each cycle. 
Variations in infusion times due to minor differences in IV bag overfill/underfill and the 
institution’s procedure for flushing chemotherapy lines will not result in protocol deviation. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 39 of 87 
Extravasation of camidanlumab tesirine may be associated with local irritation, swelling, pain, 
or tissue damage. The IV infusion site should be monitored for signs of IV infiltration or drug 
extravasation, and patients should be instructed to report immediately any signs of IV 
infiltration or drug extravasation during or after the infusion. Suspected extravasation of 
camidanlumab tesirine should be managed according to institutional protocol for management 
of extravasation of cytotoxic chemotherapy. 
For patients who have a central line, administration of camidanlumab tesirine via this central 
line should be considered. 
6.2.3 Accountability 
The Investigator or designee will maintain accurate records of receipt of all study drugs, 
including dates of receipt. In addition, accurate records will be kept regarding when and how 
much study drug is dispensed and used by each patient in the study. Reasons for departure 
from the expected dispensing regimen must also be recorded. All study drugs will be reconciled 
and retained or destroyed according to applicable regulations. 
6.3 Camidanlumab Tesirine Dosing 
Camidanlumab tesirine will be administered at a dose of 45 µg/kg Q3W for 2 cycles, 
then 30 µg/kg for subsequent cycles. 
Refer to Section 6.7 for premedication and supportive care. 
6.4 Dose Delays and Modifications 
The Investigator may suspend camidanlumab tesirine dosing for up to 21 days, for any patient 
who experiences any toxicity of any grade. 
Resumption of dosing with camidanlumab tesirine after any suspension, even when longer than 
21 days, is at the discretion of the Investigator, on assessment of the patient’s clinical condition 
and whether or not the patient is deriving potential clinical benefit from treatment with 
camidanlumab tesirine. 
The Investigator may also suspend camidanlumab tesirine dosing for any patient scheduled for 
HSCT in the near future, and resumption of dosing is only allowed if the patient has not 
received in the meantime any chemotherapy-based mobilization/conditioning therapy or 
HSCT. 
Management of toxicities, when considered to be at least possibly related to camidanlumab 
tesirine, must be performed according to: 
• Section 6.4.1 for general events (i.e., not specified in the below sections), 
• Section 6.4.2 for specific non-hematologic events, 
• Section 6.4.3 for specific hematologic events, 
• Section 6.4.4 for specific neurologic events, 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 40 of 87 
• Section 6.4.5 for specific skin events. 
 
6.4.1 Guidelines for Dose Modification: General 
AE Grade 
Camidanlumab Tesirine Management Guideline 
1/2 
No dose adjustment is required. 
3/4 
First Occurrence: 
• Hold camidanlumab tesirine until improvement to ≤ Grade 1 or Baseline.  
• If improvement to ≤ Grade 1 or Baseline occurs prior to the next scheduled dose, 
proceed with the originally planned camidanlumab tesirine dose level. 
• If improvement to ≤ Grade 1 or Baseline occurs > 21 days from the last scheduled 
(but missed) camidanlumab tesirine dose, continue camidanlumab tesirine and 
reduce from 45 to 30 µg/kg or from 30 to 20 µg/kg. 
Second Occurrence: 
• Hold camidanlumab tesirine until improvement to ≤ Grade 1 or Baseline, reduce 
from 45 to 30 µg/kg or from 30 to 20 µg/kg. 
Third Occurrence: 
Permanently discontinue camidanlumab tesirine. 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 41 of 87 
6.4.2 Guidelines for Dose Modification: Specific Non-hematologic 
Toxicities 
Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Infusion-related 
reactions 
 
1 
 
The infusion rate may be decreased or temporarily interrupted 
to permit resolution of the event. If the total time for dilution 
into the IV bag and infusion takes longer than 4 hours, the 
remaining solution of camidanlumab tesirine will be discarded 
and the dosing will continue with the assigned dose at the next 
scheduled dosing visit. 
Please refer to Section 6.7.3 for treatment recommendation. 
2 
Interrupt camidanlumab tesirine infusion to permit resolution 
of the event. If the event resolves within the total time of 
4 hours after dilution into the IV bag and infusion time, resume 
camidanlumab tesirine infusion at 50% of the prior infusion 
rate, still not exceeding the total of 4 hours after infusion has 
restarted. 
If the resolution takes longer than the total 4 hours, the 
remaining solution of camidanlumab tesirine will be 
discarded, and the dosing will continue with the assigned dose 
at the next scheduled dosing visit at 50% of the prior infusion 
rate. 
Please refer to Section 6.7.3 for treatment recommendation. 
3 
Permanently discontinue camidanlumab tesirine. However, if 
the AE resolves within 24 hours after onset (with or without 
clinical management), dosing may continue with the assigned 
dose at the next scheduled dosing visit at 50% of the prior 
infusion rate.  
Please refer to Section 6.7.3 for treatment recommendation. 
4 
Permanently discontinue camidanlumab tesirine. 
AST, ALT, or GGT 
abnormalities 
 
or 
 
Edema 
 
or 
 
Effusion  
 
2/3 
First Occurrence: 
• Hold camidanlumab tesirine until improvement to 
≤ Grade 1 or Baseline.  
• If improvement to ≤ Grade 1 or Baseline occurs prior to 
the next scheduled dose, proceed with the originally 
planned camidanlumab tesirine dose level. 
• If improvement to ≤ Grade 1 or Baseline occurs > 21 days 
from the last scheduled (but missed) camidanlumab 
tesirine dose, reduce from 45 to 30 µg/kg or from 30 to 
20 µg/kg. 
Second Occurrence: 
• Hold camidanlumab tesirine until improvement to 
≤ Grade 1 or Baseline.  
• If improvement to ≤ Grade 1 or Baseline occurs, reduce 
from 45 to 30 µg/kg or from 30 to 20 µg/kg. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 42 of 87 
Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Third Occurrence: 
Permanently discontinue camidanlumab tesirine. 
4 
First Occurrence: 
• Hold camidanlumab tesirine until improvement to
≤ Grade 1 or Baseline.
• If improvement to ≤ Grade 1 or Baseline occurs, continue
camidanlumab tesirine and reduce from 45 to 30 µg/kg or
from 30 to 20 µg/kg.
Second Occurrence: 
Permanently discontinue camidanlumab tesirine. 
Hy’s law (AST and/or 
ALT > 3 × ULN and 
bilirubin > 2 × ULN) 
- 
Permanently discontinue camidanlumab tesirine. 
Hy’s law defined as: AST and/or ALT > 3 × ULN and 
bilirubin > 2 × ULN, and without initial findings of cholestasis 
(ALP activity < 2 × ULN) and no other reason that could 
explain the combination of increased transaminases and serum 
total bilirubin, such as viral hepatitis A, B, or C, preexisting or 
acute liver disease, or another drug capable of causing the 
observed injury. 
Autoimmune toxicities 
(e.g., hyperthyroidism, 
hypothyroidism, 
hepatitis, other 
endocrinopathies) 
≥ 1 
Need to be followed at least weekly to quickly detect 
deterioration 
and 
modify 
dosing 
as 
per 
general 
recommendations in Section 6.4.1 (can be done by telephone 
unless symptoms worsen). 
Consider using ASCO guidelines for management of immune-
mediated toxicities (Brahmer, 2018), or local guidelines. 
Specific guidelines for management of hyperthyroidism, 
hypothyroidism, 
and 
hepatitis 
are 
provided 
in 
the 
Appendix 13.5. 
Selected Types of 
Infection: HSV1, 
HSV2, VZV, EBV, 
CMV, measles, 
Influenza A, Zika 
virus, Chikungunya 
virus, mycoplasma 
pneumonia, 
Campylobacter jejuni, 
enterovirus D68, or 
SARS-CoV-2. 
Any 
Grade 
No dose adjustment is required; however, hold camidanlumab 
tesirine. Re-dosing must be delayed so that there is at least a 
4-week window between symptom resolution and the next
dose of camidanlumab tesirine.
If there is suspicion that a patient may have contracted the 
coronavirus disease COVID-19 (e.g., recent contacts with 
persons who tested positive and/or recent symptoms of 
respiratory tract infection and/or recent loss of smell and/or 
taste), a pathogen-directed SARS-CoV-2 test, such as 
polymerase chain reaction (PCR), should be performed. If the 
patient tests positive, a repeat test should be conducted 7 to 
14 days later. If the patient repeatedly tests positive without 
having developed symptoms, dosing may proceed at the 
discretion of the Investigator. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 43 of 87 
6.4.3 Guidelines for Dose Modification: Specific Hematologic Toxicities 
Consider use of granulocyte colony-stimulating factor (G-CSF) as per institutional guidelines 
or as per American Society of Clinical Oncology (ASCO) guidelines for neutropenia/febrile 
neutropenia. 
For anemia, consider use of erythropoietin as per institutional guidelines. 
If a patient experiences hematologic toxicity of ≥ Grade 3 neutropenia or thrombocytopenia, 
camidanlumab tesirine must be held until the toxicity resolves to ≤ Grade 2. 
6.4.4 Guidelines for Dose Modification: Specific Neurologic Toxicities 
Patients experiencing any new neurological toxicities and/or new onset of pain refractory to 
common pain medications ≥ Grade 1, not explained by previous medical history, that could be 
linked to or may be an early indicator of polyradiculopathy/GBS, such as ascending (bilateral) 
sensory loss or motor weakness, need to be immediately evaluated by a neurologist and dosing 
of camidanlumab tesirine must be held until polyradiculopathy/GBS is ruled out. Please refer 
to Section 6.7.5 for management of polyradiculopathy/GBS, especially for the 
recommendation of prompt initiation of therapy upon reasonable suspicion of 
polyradiculopathy/GBS. Should further clinical, radiologic, or laboratory evidence support the 
diagnosis of polyradiculopathy/GBS with Level 1 diagnostic certainty (Section 6.7.5 and 
Appendix 13.2), treatment with camidanlumab tesirine must be permanently discontinued.  
Patients with ≥ Grade 3 neurologic toxicities defined as peripheral sensory and peripheral 
motor neuropathies and not explained by previous medical history must have treatment with 
camidanlumab tesirine permanently discontinued. 
Other new neurological findings not explained by previous medical history with an increase of 
≥ 1 Grade over Baseline will result in dose delay; dosing may be resumed after resolution to 
Baseline, at the Investigator’s discretion. The patient must be carefully monitored at least 
weekly until such resolution (can be done by telephone unless symptoms worsen). 


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6.4.5 Guidelines for Dose Modification: Specific Skin Toxicities 
Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Maculopapular rash 
 
or 
 
Photosensitivity 
rash 
 
or 
 
Pruritus 
 
or  
 
Xerosis 
 
or  
 
Hyperpigmentation 
 
1 
No dose adjustment is required and monitor for change in 
severity. 
Topical treatment to affected areas is indicated:  
- 
maculopapular rash, photosensitivity rash, or pruritus: 
high potency topical steroid cream (e.g., clobetasol 
propionate 0.05%, halobetasol propionate 0.05%) 
- 
xerosis or hyperpigmentation: consider ammonium lactate 
12% or urea 20% BID. 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report). 
2 
 
No dose adjustment is required and monitor for change in 
severity. 
Topical treatment to affected areas is indicated:  
- 
maculopapular rash or photosensitivity rash: high potency 
topical steroid cream (e.g., clobetasol propionate 0.05%, 
halobetasol propionate 0.05%). 
- 
pruritus: high potency topical steroid cream and consider 
oral antipruritic (e.g., hydroxyzine, gabapentin, or 
pregabalin).  
- 
xerosis or hyperpigmentation: consider ammonium lactate 
12% or urea 20% BID. 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report). 
In case these Grade 2 rashes become intolerable, Grade 3 
recommendations may be applied. 
3 
Hold camidanlumab tesirine until improvement to ≤ Grade 1 or 
Baseline and consider dermatology consult. 
Topical treatment to affected areas is indicated and consider 
systemic corticosteroid treatment e.g., prednisone 0.5 mg/kg for 
10 days:  
- 
maculopapular rash or photosensitivity rash: high potency 
topical steroid cream (e.g., clobetasol propionate 0.05%, 
halobetasol propionate 0.05%) and consider prednisone 
0.5 mg/kg for 10 days. 
- 
pruritus: 
high 
potency 
topical 
steroid 
cream 
(e.g., clobetasol 
propionate 
0.05%, 
halobetasol 
propionate 0.05%) and consider oral antipruritic (e.g., 
hydroxyzine, gabapentin, or pregabalin).  
- 
xerosis or hyperpigmentation: consider ammonium lactate 
12% or urea 20% BID; and triamcinolone 0.1% cream 
BID. 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report); if reactions do not improve, 
then: 
First Occurrence: 
• If improvement to ≤ Grade 1 or Baseline occurs prior to the 
next scheduled dose, proceed with the originally planned 
camidanlumab tesirine dose level. 
• If improvement to ≤ Grade 1 or Baseline occurs 
> 21 days from the last scheduled (but missed) 
camidanlumab tesirine dose, reduce from 45 to 30 µg/kg or 
from 30 to 20 µg/kg.  
Second Occurrence: 
• If improvement to ≤ Grade 1 or Baseline occurs, reduce 
from 45 to 30 µg/kg or from 30 to 20 µg/kg. 
Third Occurrence: 
Permanently discontinue camidanlumab tesirine. 
4 
Hold camidanlumab tesirine until improvement to ≤ Grade 1 or 
Baseline and consider dermatology consult. 
Topical treatment to affected areas is indicated and consider 
systemic corticosteroid treatment, e.g., prednisone 0.5 mg/kg for 
10 days:  
- 
maculopapular rash or photosensitivity rash: high potency 
topical steroid cream (e.g., clobetasol propionate 0.05%, 
halobetasol propionate 0.05%) and consider prednisone 
0.5 mg/kg for 10 days. 
- 
pruritus: 
high 
potency 
topical 
steroid 
cream 
(e.g., clobetasol 
propionate 
0.05%, 
halobetasol 
propionate 0.05%) and consider oral antipruritic (e.g., 
hydroxyzine, gabapentin, or pregabalin).  
- 
xerosis or hyperpigmentation: consider ammonium lactate 
12% or urea 20% BID; and triamcinolone 0.1% cream 
BID. 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report); if reactions do not improve, 
then: 
First Occurrence: 
• If improvement to ≤ Grade 1 or Baseline occurs, continue 
camidanlumab tesirine and reduce from 45 to 30 µg/kg or 
from 30 to 20 µg/kg. 
Second Occurrence: 
Permanently discontinue camidanlumab tesirine. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Blistering rash 
1 
No dose adjustment is required and monitor for change in 
severity. Consider dermatology consult 
Topical treatment to affected areas is indicated, e.g., silvadene 
1% cream BID and consider laboratory testing for blistering 
disorder 
(VZV/HSV 
and 
bacterial 
infection; 
bullous 
pemphigoid; pemphigus). 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report). 
 
2/3 
Hold camidanlumab tesirine until improvement to ≤ Grade 1 or 
Baseline and consider dermatology and wound care consult.  
Topical treatment to affected areas is indicated, e.g., silvadene 
1% cream BID, and consider laboratory testing for blistering 
disorder 
(VZV/HSV 
and 
bacterial 
infection; 
bullous 
pemphigoid; pemphigus) and consider systemic corticosteroid 
treatment, e.g., prednisone 0.5 mg/kg for 10 days. 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report); if reactions do not improve, 
then: 
First Occurrence: 
• If improvement to ≤ Grade 1 or Baseline occurs prior to the 
next scheduled dose, proceed with the originally planned 
camidanlumab tesirine dose level. 
• If improvement to ≤ Grade 1 or Baseline occurs > 21 days 
from the last scheduled (but missed) camidanlumab tesirine 
dose, continue camidanlumab tesirine and reduce from 45 
to 30 µg/kg or from 30 to 20 µg/kg. 
Second Occurrence: 
• If improvement to ≤ Grade 1 or Baseline occurs, reduce 
from 45 to 30 µg/kg or from 30 to 20 µg/kg. 
Third Occurrence: 
Permanently discontinue camidanlumab tesirine. 
 
4 
Hold camidanlumab tesirine until improvement to ≤ Grade 1 or 
Baseline and consider dermatology consult. 
Topical treatment to affected areas is indicated, e.g., silvadene 
1% cream BID, and consider laboratory testing for blistering 
disorder 
(VZV/HSV 
and 
bacterial 
infection; 
bullous 
pemphigoid; pemphigus) and consider systemic corticosteroid 
treatment, e.g., prednisone 0.5 mg/kg for 10 days. 
Reassessment every 2 weeks is indicated (either by healthcare 
professional or patient self-report); if reactions do not improve, 
then: 
First Occurrence: 
• If improvement to ≤ Grade 1 or Baseline occurs, continue 
camidanlumab tesirine and reduce from 45 to 30 µg/kg or 
from 30 to 20 µg/kg. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Second Occurrence: 
Permanently discontinue camidanlumab tesirine. 
 
6.5 Overdose Management 
An overdose is any dose of study drug given to a patient that exceeds the maximum dose 
described in the protocol by 15% or more. Any overdose, with or without associated AEs, must 
be promptly (i.e., within 24 hours after the time site personnel first learn about the event) 
reported to the Sponsor. 
There are no data available to determine what the effects of overdose are and whether they can 
be reversed. Symptomatic treatment and standard supportive care measures for the 
management of any observed toxicity should be applied. 
If feasible, a sample for PK analysis should be taken as close as possible to the overdose event. 
6.6 Treatment Compliance 
Administration of the study drug will be performed by the Investigator or a qualified designee; 
therefore, compliance will be verified by the study drug administration information. 
6.7 Premedication and Supportive Care 
6.7.1 Premedication 
Unless contraindicated, administer dexamethasone 4 mg orally twice daily (BID), or 
equivalent, the day before camidanlumab tesirine administration (if possible), the day of 
camidanlumab tesirine administration (give at least 2 hours prior to administration when not 
given the day before; otherwise any time prior to administration), and the day after 
camidanlumab tesirine administration. 
[For Italy Sites Only: Prednisone 25 mg BID is the only equivalent to the dexamethasone 
4 mg BID dose permitted as alternative premedication. The dosing schedule of dexamethasone 
and prednisone is the same.] 
Patients who experience an infusion-related hypersensitivity reaction will receive the 
alternative premedication regimen specified in Section 6.7.3. 
6.7.2 Treatment of Edema and Pleural Effusion 
Spironolactone at standard doses should be administered for patients with weight gain greater 
than 1 kg from C1D1, new or worsening edema, and/or new or worsening pleural effusion. 
The dose of spironolactone may be titrated as clinically indicated. Additional diuretic support 
may be added if there is further increase in weight, edema, or pleural effusion. 
Additionally, patients should be advised to monitor their weight on a daily basis, at around the 
same time (preferably in the morning), and to notify the study site if they gain > 1 kg 
(2.2 pounds) over Baseline. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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6.7.3 Treatment and Prophylaxis of Infusion-Related Hypersensitivity 
Reactions 
Medications for the treatment of severe hypersensitivity reactions, including anaphylaxis, 
should be available for immediate use and may be administered according to site standard 
treatment protocols.  
Any patient who experiences an infusion-related hypersensitivity reaction should receive 
prophylactic treatment in subsequent cycles according to the guidelines below or per 
institutional standard of care: 
• On Day 1 of each cycle, patients will be instructed to take dexamethasone 20 mg orally 
12 and 6 hours before the start of the camidanlumab tesirine infusion. When necessary, 
12 and 6 hours before the first infusion may be defined as “immediately before sleeping” 
and “immediately after waking up.” 
• On Day 1 of each cycle, patients will be given diphenhydramine hydrochloride 50 mg IV 
30 minutes before the start of the camidanlumab tesirine infusion. 
• On Day 1 of each cycle, patients will be given ranitidine (or equivalent) 50 mg IV 
30 minutes before the start of the camidanlumab tesirine infusion. 
• For 2 days following administration of camidanlumab tesirine on Day 1, patients are to 
take dexamethasone 4 mg orally BID. 
 
6.7.4 Consideration for Skin Toxicity 
Skin toxicity has been reported in patients receiving camidanlumab tesirine for hematologic 
malignancies. Often, the toxicities manifested as rash were reported in sun exposed areas; it is 
therefore recommended that precautions are taken to avoid exposure of skin to sunlight, even 
through glass (e.g., use of sun protective clothing and sunglasses, sunscreen with a sun 
protection factor ≥ 30 applied every 2 hours, avoidance of being outside with no protection). 
Also, fragrance-free detergents and soaps are recommended. 
Consideration should be given to corticosteroid therapy in patients who develop clinically 
significant skin toxicity (guidelines for dose modification in Section 6.4.5). 
Photographs of skin toxicity may be taken for documentation purposes at the discretion of the 
Investigator provided the patient has given consent.  


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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6.7.5 Diagnostic, Work-up, and Management of Polyradiculopathy/ 
Guillain-Barré Syndrome  
It is strongly recommended starting prompt management of polyradiculopathy/GBS with either 
intravenous immunoglobulin (IVIg) 0.4 g/kg/day for 5 days or plasma exchange (PLEX) once 
diagnosis of polyradiculopathy/GBS has been considered by a neurologist; this could be at 
CTCAE Grade 2 symptoms for neuropathy or Score 1 as per GBS disability scale 
(Appendix 13.3). It has to be considered that manifestation of polyneuropathy can be variable. 
Diagnostic workup should include: 
• Neurology consultation 
• Magnetic resonance imaging (MRI) spine with and without contrast to rule out 
compressive lesion and evaluate for nerve root enhancement or thickening 
• Electrodiagnostic studies (nerve conduction studies) 
• Serologic test for SARS-CoV-2 (Alberti, 2020; Toscano, 2020; Zhao, 2020) 
• Pulmonary function tests 
• Lumbar puncture: cerebrospinal fluid (CSF) typically has albuminocytologic 
dissociation, i.e., protein elevation disproportionate to white blood cells (WBCs—
although note that CSF WBCs are often elevated in GBS associated with immune 
checkpoint inhibitors) 
• Serum antibody testing for GBS (ganglioside antibodies) when possible 
 
Management includes: 
• IVIg or PLEX as above  
• If IVIg and/or PLEX do not result in improvement, consider using steroids (Gu, 2017)  
• Admission to inpatient unit with capability for rapid transfer to intensive care unit-level 
monitoring 
• Frequent focused neurological examination (at least twice daily) 
• Frequent pulmonary function monitoring 
• Monitoring for autonomic dysfunction 
• Non-opioid management of neuropathic pain  
• Treatment of constipation/ileus 
• Anticoagulation 
• Physical therapy 
 


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Camidanlumab tesirine (ADCT-301) 
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6.7.6 Other Supportive Care 
Although the study patient population has a low risk for development of tumor lysis syndrome 
(TLS) compared to patients with acute disease (Cairo, 2010), patients should be observed for 
development of TLS and treated according to site standard treatment protocols. 
As testing in animals showed testicular toxicity (atrophy with reduced spermatogenesis), 
male patients are advised to consider cryopreservation of sperm prior to treatment with 
camidanlumab tesirine, where applicable. 
The iDSMB recommended VZV prophylaxis according to institutional guidelines for all 
patients enrolled in this study (whether already receiving camidanlumab tesirine or newly 
enrolled). 
6.8 Concomitant Medications and Procedures 
Medications (except for the study drug) and procedures will be recorded in the eCRF starting 
from the ICF signature date or from 14 days prior to C1D1, whichever is earlier, and continuing 
until 30 days after last dose of study drug. 
6.8.1 Permitted During Study 
Medications or procedures for the clinical care of the patient, including management of AEs, 
are permitted during the study, except for those listed in Section 6.8.2.  
Hematopoietic growth factors are permitted as per ASCO guidelines (Smith, 2006).  
6.8.2 Prohibited During Study 
• Other anticancer therapy during the Treatment Period (including palliative radiotherapy), 
with the exception of hormonal therapy for maintenance treatment of breast and prostate 
cancer. 
• Other investigational agents during the Treatment Period. 
• Live vaccines during the Treatment Period and for 3 months after last dose of study drug. 
 


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Camidanlumab tesirine (ADCT-301) 
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7 Study Assessments and Procedures 
7.1 Informed Consent 
Informed consent, as documented by a signed and dated ICF, must be obtained prior to 
performing any study procedures. Results (e.g., from laboratory tests or radiographic 
evaluations, etc.) obtained prior to the date of informed consent but within the allowed 
timeframe for screening may be used for determination of patient eligibility only if obtained 
as part of standard care. For additional details, please refer to Section 11.3. 
7.2 Demographics and Baseline Characteristics 
These assessments include: 
• Demographic information such as age, gender, ethnicity, and race (to the extent allowed 
by local regulations). 
• Cancer medical history, which includes a complete history of all surgeries and significant 
diagnoses, and all cancer treatment, including surgery, radiation therapy, chemotherapy, 
etc. 
• Immune-related adverse events of prior checkpoint inhibitors. 
• Any other relevant medical history. Importantly, according to the iDSMB 
recommendation patients with signs or symptoms of Grade 2 neuropathy should be 
examined by a neurologist at Screening. 
• Collection of information on prior medications used from ICF signature date or at least 
within 14 days prior to camidanlumab administration, whichever is earlier. 
 
7.3 Efficacy Assessments 
Disease assessments will occur as per SoE (Table 1) until progression.  
Screening (Baseline) imaging must be performed within 4 weeks prior to C1D1. 
During the treatment period, imaging will be performed 6 weeks and 12 weeks after C1D1, 
then every 9 weeks until EOT. Week 6 imaging should be performed within 1 week prior to 
C3D1 and Week 12 imaging should be performed within 1 week prior to C5D1. All other 
imaging should be performed within ±2 weeks of the scheduled time point. 
Disease assessments should take place at the timepoints specified even if study drug dosing is 
delayed. 
During the follow-up period, patients who discontinued study drug for reasons other than 
disease progression or initiation of other anti-cancer therapy will have imaging performed 
every 12 (± 2) weeks until 1 year from EOT, then every 6 months until disease progression, up 
to 3 years from EOT; when patients discontinue the study drug because they are planned to 
undergo a HSCT or to receive CAR-T therapy, imaging will continue the same way. 
Moreover, HSCT information such as but not limited to type of HSCT, conditioning therapy 


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should be recorded in the eCRF. Likewise for CAR-T therapy, the type of CAR-T used 
including conditioning therapy should be recorded in the eCRF. 
If a scan has been performed within 6 weeks of EOT, it does not need to be repeated at EOT. 
Additional disease assessments may be obtained, if clinically indicated. 
Positron emission tomography-computed tomography (PET-CT) of the neck/chest/abdomen/ 
pelvis and other areas of known disease or newly suspected disease, as well as a clinical 
examination for lymphoma, will be performed. If it is known that the tumor is tracer-avid, the 
baseline CT as part of the PET-CT does not have to be performed with contrast medium; 
however, if the tumor is not tracer-avid, diagnostic CT should be used and contrast medium 
considered, however patients who have a contraindication to CT IV contrast medium should 
have MRI examinations performed instead. The assessment method determined to identify 
sites of disease at Baseline (i.e., PET-CT, CT, MRI) should be used for all subsequent 
assessments. 
Patients whose tumor is not PET-avid should have a bone marrow biopsy as part of their 
baseline staging and disease assessment if clinically appropriate. 
The patient’s response to treatment will be determined according to the 2014 Lugano 
Classification Criteria (Appendix 13.4) as CR, PR, stable disease (SD), or progressive disease 
(PD). Upon indication of clinical progression (non-radiographic), a radiographic disease 
assessment to confirm the PD is expected, if clinically indicated, in order to ensure appropriate 
data collection toward the primary endpoint of this protocol. 
Images will be obtained according to local site imaging requirements and will be submitted for 
a central/independent review. Central imaging review will be performed using two blinded 
independent reviewers with adjudication by a third blinded independent reviewer in cases of 
discordance. Submission instructions for the central/independent review will be provided in a 
separate manual. 
7.4 Safety Assessments  
Safety will be assessed based on the procedures in the subsection below. AEs/SAEs collection 
and reporting is described in Section 8. 
Unless otherwise specified, all safety assessments on dosing days will be done prior to study 
drug administration. 
7.4.1 Physical Examination 
Physical examinations will be performed according to institutional standards and will include 
whole body skin examination.  
Physical examinations will also include a neurological examination of strength, sensation, and 
deep tendon reflexes. In addition, patients will be asked whether they are or have been 
experiencing subjective neurologic symptoms (at screening or since the last visit), such as 
blurred vision, muscle weakness, or paresthesia, and the response must be documented in the 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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CRF; refer to Section 6.4.4 for dose modification due to specific neurologic toxicities and 
Section 6.7.5 for details on polyradiculopathy/GBS management. This examination does not 
need to be conducted by a neurologist. Neurologic consultation needs to be obtained for any 
abnormal findings not explained by previous medical history (e.g., a patient with left sided 
weakness known to be a result of a previous cerebrovascular accident would not need to see a 
neurologist as part of this study) that could be linked to or may be an early indicator of 
polyradiculopathy/GBS, such as ascending (bilateral) sensory loss, motor weakness, or new 
onset of pain, which is refractory to common pain medications and with or without any 
additional neurological deficiencies. 
The examination must include a determination if the patient has had any recent infection. 
At the discretion of the Investigator, evaluation of any reported infection must be conducted to 
rule out infection with a microorganism that may be associated with autoimmune or 
neurological disease(s) as specified in the exclusion criteria (Section 5.2) and Section 7.4.5. 
7.4.2 ECOG Performance Status 
ECOG performance status grades are presented in Appendix 13.1 and will be captured as per 
SoE (Table 1). 
7.4.3 Height and Weight 
Height and weight will be measured as per SoE (Table 1). 
Additional measurements will be performed if clinically indicated. 
Patients should monitor their weight at home to detect potential edema/effusions. 
Refer to Section 6.7.2 for further details. 
7.4.4 Vital Signs 
Vital signs will be measured as per SoE (Table 1). 
Vital signs include the measurements of arterial BP (systolic and diastolic), heart rate (HR), 
respiratory rate, and body temperature and will be performed according to the institutional 
standards. 
For Day 1 of each cycle, vital signs are to be measured before the start of the camidanlumab 
tesirine infusion and at the end of infusion (example in Figure 2). 
7.4.5 Laboratory Tests 
Samples will be collected at the time points specified as per SoE (Table 1) and will be analyzed 
locally. Additional sample(s) may be collected and analyzed if clinically indicated. The C1D1 
laboratory test(s) can be waived if the laboratory test(s) for eligibility was done within 3 days 
of C1D1. 
Hematology: WBCs with 5-part differential (neutrophils, eosinophils, basophils, lymphocytes, 
and monocytes), platelet count, hemoglobin, and hematocrit. 


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Chemistry: ALT, AST, GGT, ALP, amylase, lipase, total bilirubin (conjugated and 
unconjugated bilirubin only when total bilirubin is abnormal), sodium, potassium, chloride, 
phosphorus/phosphate, calcium, magnesium, blood urea nitrogen or urea, carbon 
dioxide/bicarbonate, creatinine, creatine phosphokinase, total protein, albumin, glucose, and 
lactate dehydrogenase. 
Coagulation: partial thromboplastin time (PTT)/activated PTT (aPTT) and INR. 
Urinalysis: pH, specific gravity, protein, WBCs, red blood cell (RBCs), ketones, glucose, and 
bilirubin. 
Urinalysis may be performed by dipstick. Abnormal findings will be followed up with a 
microscopic evaluation and/or additional assessments as clinically indicated. A microscopic 
evaluation consists at a minimum of WBC and RBC quantitation per high power field, as well 
as semi-quantitative assessment of other cells and substances, if present, such as epithelial cells, 
bacteria, and crystals (“few,” “moderate,” “many”). Other evaluations depending on 
microscopic findings may be added. 
Thyroid function tests: Thyroid-stimulating hormone (TSH); reflex free T4 (FT4) and/or free 
triiodothyronine (FT3), as applicable, only when TSH is abnormal. 
Influenza and SARS-CoV-2: An influenza test and a pathogen-directed SARS-CoV-2 test 
(such as PCR) must be performed and be negative for eligibility purposes. 
Viral detection: Seropositive patients for, or with prior history of, HIV, HBV, or HCV not 
receiving antiviral therapy at screening will be monitored during the study (not needed if 
seropositivity is only due to vaccination). 
Additional microbiological studies: Pathogens of interest are: HSV1, HSV2, VZV, EBV, 
CMV, measles, Influenza A, Zika virus, Chikungunya virus, mycoplasma pneumonia, 
Campylobacter jejuni, enterovirus D68, and SARS-CoV-2. 
Patients will be regularly examined and asked whether they have been suffering from or exhibit 
symptoms of an infection during their participation in the trial. If there is a reasonable suspicion 
that such infection could have been caused by one of the pathogens listed above, appropriate 
microbiological workup must be conducted. See Section 6.4.2 for dose delay recommendation 
upon confirmation of infection by one of these microorganisms. 
If there is suspicion that a patient may have contracted the coronavirus disease COVID-19 (e.g., 
recent contacts with persons who tested positive and/or recent symptoms of respiratory tract 
infection and/or recent loss of smell and/or taste), a pathogen-directed SARS-CoV-2 test, such 
as PCR, should be performed. If the patient tests positive, a repeat test should be conducted 
7 to 14 days later. If the patient repeatedly tests positive without having developed symptoms, 
dosing may proceed at the discretion of the Investigator. 


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7.4.6 Pregnancy Test 
A highly sensitive β-HCG test in urine or blood β-HCG test will be performed in WOCBP for 
eligibility (see Section 5.1) and throughout the study as per SoE (Table 1). 
The C1D1 pre-dose pregnancy test can be waived if the test for eligibility was done within 
7 days of C1D1. After starting the study drug, the interval between 2 consecutive pregnancy 
tests should be no more than 6 weeks. 
The EOT pregnancy test should be performed ≥9.5 months after the last dose of study drug 
(i.e., end of relevant systemic exposure considering 5 half-lives plus 6 months for other than 
aneugenic genotoxic compound). If the EOT visit is planned less than 9.5 months after the last 
dose of study drug, the patient will be asked either to come back to the site for a pregnancy test 
or she will be given a pregnancy kit to perform the test at home and the result collected over 
the phone. Both the phone contact and the result of the pregnancy test must be documented on 
source documents at the site. 
If a pregnancy test is positive, the study drug must be held pending confirmation. 
If the pregnancy is confirmed, camidanlumab tesirine treatment will be discontinued 
permanently for the patient. Refer to Section 8.6 for the handling of the patient and reporting 
the event. 
7.4.7 ECG 
Three consecutive (also called triplicate) 12-lead ECGs will be performed at defined 
timepoints throughout the study as per SoE (Table 1). Refer to Table 3 for the detailed schedule 
of ECGs. The ECGs will be performed after the patient is resting for at least 5 minutes. 
At timepoints coinciding with blood sample collection, including PK, ECGs should be taken 
prior to blood collection, and, when applicable, before vital signs measurements  
(example in Figure 2). If a patient experiences Torsade de Pointes, additional concomitant 
PK samples (i.e., unscheduled) should be collected. 
The ECGs will be submitted for a central review. Submission instructions for the central review 
will be provided in a separate manual. Assessments will include determination of heart rate 
and rhythm and the PR, QRS, QT, QTcF, and QTcB intervals. Eligibility and clinical decisions 
may be made based on the local ECG assessment. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
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Table 3 
Schedule for Triplicate ECG Collection 
Cycle 
Day 
ECG timepoint (window) 
Screening 
- 
Any time within 28 days prior to C1D1 
C1 
D1 
Predose (preferably within 2 h prior to start of infusion) 
EOI (within 10 min prior to EOI) 
Postdose* 4 h (± 15 min) 
D8 
Postdose* 168 h (± 48 h; but within 30 min prior to PK sample) 
D15 
Postdose* 336 h (± 48 h; but within 30 min prior to PK sample) 
C2 
D1 
Predose (within 30 min prior to PK sample) 
EOI (within 10 min prior to EOI) 
Postdose* 4 h (± 15 min) 
D8 
Postdose* 168 h (± 48 h; but within 30 min prior to PK sample) 
D15 
Postdose* 336 h (± 48 h; but within 30 min prior to PK sample) 
C3 and C4 
 
D1 
Predose (within 30 min prior to PK sample)  
EOI (within 10 min prior to EOI) 
C5, C7 … 
every other cycle 
D1 
Predose (within 30 min prior to PK sample) 
EOT 
 
Any time (but within 30 min prior to PK sample) 
Unscheduled 
 
Any time 
Abbreviations: C1D1, Cycle 1, Day 1; ECG, electrocardiogram; EOI, end of infusion; EOT, end of treatment; 
PK, pharmacokinetics. 
* Postdose timepoint is counted from start of infusion. 
 




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Camidanlumab tesirine (ADCT-301) 
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7.5.1 Pharmacokinetics 
The PK profile of camidanlumab tesirine PBD-conjugated antibody, total antibody, and 
unconjugated warhead SG3199 will be assessed in serum by a central laboratory designated 
by the Sponsor using validated bioanalytical methods. 
Up to 6 mL of whole blood will be collected as per Table 1 and Table 4. Blood should be 
drawn from a vein away from the one used for study drug infusion. 
The serum PK samples must be stored at ≤ -70°C. Please refer to the laboratory manual for 
detailed instructions regarding specimen handling and shipment. 
At timepoints coinciding with ECG collection, PK blood collection should occur immediately 
after the end of the ECG recording and, when applicable, after vital signs (example in Figure 2). 
If a patient experiences Torsade de Pointes, concomitant PK samples (e.g., unscheduled) 
should be collected. 
Table 4 
Sampling Schedule for PK and ADA 
Cycle 
Day PK timepoint (window) 
ADA timepoint (window) 
C1 
D1 
Predose (preferably within 2 h prior 
to start of infusion) 
EOI (-5 to +10 min) 
Postdose* 4 h (± 10 min) 
Predose (preferably within 2 h prior 
to start of infusion) 
 
D8 
Postdose* 168 h (± 48 h)  
- 
D15 Postdose* 336 h (± 48 h) 
Postdose* 336 h (± 48 h) 
C2 
D1 
Predose (within 2 h prior to start of 
infusion) 
EOI (-5 to +10 min) 
Postdose* 4 h (± 10 min) 
Predose (within 2 h prior to start of 
infusion) 
D8 
Postdose* 168 h (± 48 h) 
- 
D15 Postdose* 336 h (± 48 h) 
- 
C3, C4, C5, and 
C6 
D1 
Predose (within 2 h prior to start of 
infusion)  
EOI (-5 to +10 min) 
- 
C3, C5, … 
every other cycle 
D1 
- 
Predose (within 2 h prior to start of 
infusion) 
C7, C8, … 
every cycle 
D1 
Predose (within 2 h prior to start of 
infusion)  
- 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Cycle 
Day PK timepoint (window) 
ADA timepoint (window) 
EOT 
 
At any time during visit day 
At any time during visit day 
Unscheduled 
 
Any time 
Any time (if applicable, together 
with PK sample) 
Abbreviations: ADA, anti-drug antibody; EOI, end of infusion; EOT, end of treatment; PK, pharmacokinetics. 
* Postdose timepoint is counted from start of infusion. 
 
To understand the metabolic disposition of camidanlumab tesirine in humans, samples 
remaining after PK analysis is complete may be pooled among patients for potential metabolite 
identification.  
7.5.2 Immunogenicity 
Detection of ADAs will be performed by using a screening assay for identification of antibody 
positive samples/patients, a confirmation assay, and titer assessment. 
Up to 6 mL of whole blood will be collected as per Table 1 and Table 4. 
Blood should be drawn from a vein away from the one used for study drug infusion. 
For patients who test positive for ADA, additional ADA samples will be requested for testing 
every 12 weeks following the EOT visit until the ADA titer falls to a background level, as long 
as the patient is still on-study. 
The ADA samples must be stored at ≤ -70°C. Please refer to the laboratory manual for detailed 
instructions regarding specimen handling and shipment. 
7.5.3 Biomarkers 
7.5.3.1 Blood Samples for Biomarkers 
Blood samples for biomarkers analyses will be collected as per SoE (Table 1) and a more 
detailed presentation of soluble markers timepoints is provided in Table 5. 
Please refer to the laboratory manual for detailed instructions regarding specimen handling and 
shipment.  
Soluble Biomarkers: Up to 6 mL of blood for the quantification of immunologically relevant 
biomarkers (e.g., IL-2, IL-6, IL-8, IL-10, IFNγ, TNFα, sCD25, CCL17) will be taken at 
multiple timepoints. This will include analyses of biomarkers that may be predictive of or 
associated with GBS (at a minimum on C1D1 and C3D1 predose). 
cfDNA/gDNA: Up to 30 mL of whole blood will be taken at multiple timepoints for 
investigating genetic alterations characterizing Hodgkin lymphoma in cfDNA. gDNA will be 
analyzed to confirm the somatic origin of the genetic alterations and will be measured at 
predose C1D1 and EOT only. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 60 of 87 
Table 5 
Sampling Schedule for Soluble Biomarkers 
Cycle 
Day 
Timepoint (window) 
C1 
D1 
Predose (preferably within 2 h prior to start of infusion) 
Postdose* 4 h (± 10 min) 
D8 
Postdose* 168 h (± 48 h)  
D15 
Postdose* 336 h (± 48 h) 
C2 
D1 
Predose (within 2 h prior to start of infusion) 
Postdose* 4 h (± 10 min) 
D8 
Postdose* 168 h (± 48 h) 
D15 
Postdose* 336 h (± 48 h) 
C3 
D1 
Predose (within 2 h prior to start of infusion)  
EOI (within 10 min prior to EOI) 
C5, C7, … 
every other cycle 
D1 
Predose (within 2 h prior to start of infusion)  
EOT 
 
At any time during visit day 
Follow-up 
 
- 
Unscheduled 
 
Any time (if applicable, together with PK sample) 
Abbreviations: EOT, end of treatment; PK, pharmacokinetics. 
* Postdose timepoint is counted from start of infusion. 
 
7.5.3.2 
Tumor Tissue for Biomarkers 
Available tumor tissue will be collected to investigate potential predictive markers of clinical 
response. Any sample since initial diagnosis is acceptable, but if several samples are available, 
the most recent sample is preferred. Tumor tissue (FFPE block preferred) should be submitted 
once it has been determined that the patient meets all other eligibility criteria and is scheduled 
to proceed with study drug administration. 
Please refer to the laboratory manual for detailed instructions regarding specimen handling and 
shipment. 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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7.6 Health-Related Quality of Life (HRQoL) Questionnaires 
7.6.1 EuroQoL-5 Dimensions-5 Levels (EQ-5D-5L) 
The EQ-5D-5L is designed as an international, standardized, generic instrument for describing 
and evaluating QoL (EuroQoL Group, 1990). This questionnaire can be completed by patients 
≥12 years of age. The EQ-5D-5L consists of 2 parts: 
• The descriptive system: QoL is classified according to 5 dimensions: mobility, 
self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension 
comprises 5 levels of perceived problems (e.g., none, slight, moderate, severe, 
extreme). 
• The visual analog scale (VAS): patients are asked to indicate their health state today on 
a VAS with the endpoints labeled ‘the best health you can imagine’ (score 100) and 
‘the worst health you can imagine’ (score 0). Patients are asked to mark an “X” on the 
VAS to indicate their own health and then to report the score in a text box. If there is a 
discrepancy between where the patient has placed the X and the number he/she has 
written in the box, the number in the box is to be entered in the CRF together with a 
comment indicating the discrepancy. 
 
7.6.2 Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) 
The FACT-Lym is a lymphoma-specific subscale for the Functional Assessment of Cancer 
Therapy (FACT) questionnaire (Hlubocky, 2013). As this questionnaire has been validated for 
patients ≥18 years old; therefore, it will not be adminitered to patients <18 years old (age at 
screening). It consists of 15 specific items that are used together with the core 27-item 
questionnaire FACT-G. The patient is asked to respond to each item with a score of 0-4, where 
0 = not at all, 1 = a little bit, 2 = somewhat, 3 = quite a bit, and 4 = very much. A higher score 
indicates a worse level of QoL. 
 


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Camidanlumab tesirine (ADCT-301) 
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Date of Protocol Amendment 5: 16 February 2022 
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8 Adverse Events 
8.1 Definition of Adverse Events, Serious Adverse Events, and Adverse 
Events of Special Interest 
An AE is defined as any untoward medical occurrence in a patient or clinical investigation 
subject administered a pharmaceutical product, which does not necessarily have to have a 
causal relationship with this treatment. 
Test results collected during the study (e.g., laboratory values, physical examination, ECGs, 
etc.) or identified from review of other documents may constitute AEs if deemed clinically 
significant. 
An SAE is defined as any AE that: 
• results in death. 
• is life threatening. 
• requires inpatient hospitalization or prolongation of existing hospitalization 
(hospitalization for elective procedures or for protocol compliance is not considered an 
SAE). 
• results in persistent or significant disability/incapacity. 
• is a congenital anomaly/birth defect. 
• important medical events that do not meet the preceding criteria but based on 
appropriate medical judgment may jeopardize the patient or may require medical or 
surgical intervention to prevent any of the outcomes listed above. 
 
Adverse Events of Special Interest (AESIs) are significant AEs that are judged to be of special 
interest because of clinical importance, known class effects, or based on preclinical signals. 
Events considered to be AESIs are identified in Section 8.1.1. 
8.1.1 Adverse Events of Special Interest  
For this study the following adverse events, irrespective of seriousness and causality, are 
considered AESIs: 
• GBS (including variants such as acute motor and sensory axonal neuropathy) 
• Polyradiculopathy 
• Autonomic nervous system imbalance 
• Nerve palsy 
• ≥Grade 3 neurologic toxicities 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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• ≥Grade 3 immune-mediated toxicities. Of note, rashes will not be considered as 
immune-mediated skin toxicities, since they are well described toxicities of 
PBD-dimers; with exception for Stevens-Johnson syndrome, toxic epidermal 
necrolysis, acute generalized exanthematous pustulosis, exfoliative dermatitis, and 
drug reaction with eosinophilia and systemic symptoms. 
• Autoimmune-mediated events (such as, but not limited to, pneumonitis, hepatitis, 
colitis, endocrinopathies, type 1 diabetes mellitus, and nephritis/renal dysfunction) 
 
For all AESIs it is important to provide as much information as possible: e.g., time of onset 
(including changes in severity), duration of events, time to resolution, and relationship to 
camidanlumab tesirine. It is also important to specify if any AEs are autoimmune mediated. 
AESIs will be closely monitored and followed. 
8.2 Eliciting and Reporting Adverse Events/Adverse Events of Special 
Interest/Serious Adverse Events 
Patients will be instructed to contact the Investigator at any time after ICF signature if any 
symptoms develop. At each study visit, patients will be asked a non-leading question to elicit 
any medically related changes in their well-being. Patients may also report AEs voluntarily 
and they will be instructed to contact the Investigator between visits if any symptoms develop 
or worsen.  
All AEs will be reported starting when the patient provides written informed consent. 
Clinically significant medical conditions present at the time of ICF signature will be reported 
as medical history. Clinically significant medical conditions that start or worsen after ICF 
signature will be reported as AEs. 
All AEs, AESIs, and SAEs, regardless of relationship to study drug, will be reported from the 
time the patient signs the ICF until 30 days after the last dose of study drug; thereafter, only 
related SAEs will be reported [For German Sites Only: thereafter, only SAEs will be recorded 
(irrespective of the relationship to the study drug)]. The exception to this is patients who have 
responded to camidanlumab tesirine and undergo HSCT (either autologous or allogeneic) after 
permanent discontinuation of camidanlumab tesirine treatment without any intervening anti-
cancer therapy to treat relapsing disease (mobilization/conditioning treatment for HSCT is 
allowed) or who have received CAR-T as the immediate subsequent anticancer therapy 
(mobilization/conditioning treatment for CAR-T is allowed). These patients will have the 
following safety information reported until 180 days post-HSCT/post-CAR-T regardless of 
relationship to camidanlumab tesirine: 
• ≥ Grade 3 AEs suggestive of hepatic toxicity, veno-occlusive disease/sinusoidal 
obstruction syndrome, graft-versus-host disease, infectious complications, potentially 
immune-mediated adverse events, prolonged cytopenia(s), and pulmonary toxicity 
• In addition, for CAR-T therapy, any ≥ Grade 3 AEs of cytokine-release-syndrome and 
neurological toxicity 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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• SAEs 
• Death 
 
Whenever possible, AEs should be reported as a diagnosis rather than individual signs and 
symptoms. If no diagnosis is available or has been identified, then the primary symptom is 
reported. 
In general, the term ‘disease progression’ should not be used for reporting an AE/SAE. 
However, AEs/SAEs that are complications of disease progression should be reported. 
All AEs reported or observed during the study will be recorded on the AE page of the 
eCRF. Information to be collected will include event term, date of onset, assessment of severity 
(Section 8.3), seriousness (Section 8.1), relationship to study drug (Section 8.4), action taken 
with study drug, date of resolution of the event or ongoing (when no resolution by the end of 
the reporting period), any required treatment or evaluations, and outcome. 
New serious AESIs/SAEs and any recurrent episodes, progression, or complications of the 
original AESI/SAE must be reported to the pharmacovigilance department of the Sponsor or 
delegate (e.g., contract research organization [CRO]) within 24 hours after the time site 
personnel first learn about the event. Reporting will occur through the electronic data capture 
(EDC) system. 
Any recurrence of GBS/polyradiculopathy, irrespective of the relationship to study drug, has 
to be reported to the Sponsor, including when the recurrence occurs when the patient has 
already completed the study. The reporting of such events after the patient has completed the 
study will be captured via the Sponsor’s safety database and therefore will not impact database 
lock. 
Non-serious AESIs must be entered in the EDC system and reported to the Sponsor or delegate 
(e.g., CRO) within 48 hours after the time site personnel first learn about the event. 
8.3 Assessment of Severity 
All AEs will be graded according to CTCAE v4.0. For events not included in the CTCAE 
criteria, the severity of the AE is graded on a scale of 1 to 5 as shown in Table 6.  


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Table 6 
Definition of Severity Grades for CTCAE 
Grade 
Definition 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living (ADL).a 
3 
Severe or medically significant but not immediately life threatening; hospitalization 
or prolongation of hospitalization indicated; disabling; limiting self-care ADL.b 
4 
Life-threatening consequences; urgent intervention indicated. 
5 
Death related to adverse event. 
a. 
ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
b. 
Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking medications, 
and not bedridden.  
 
The AEs characterized as intermittent do not require documentation of onset and duration of 
each episode. 
8.4 Assessment of Causality 
The Investigator’s assessment of an AE’s relationship to study drug is an important part of 
safety reporting but is not a factor in determining whether an AE is reported. An AE will be 
assessed as related to study drug if there is a reasonable possibility of causal relationship with 
the use of the study drug. For SAEs, whenever possible, the Investigator should provide a 
rationale for the causality assessment.  
8.5 Regulatory Reporting 
Reporting of AEs to competent authorities and Independent Ethics Committees (IECs) will be 
consistent with local laws, regulations, guidelines, and requests. 
8.6 Pregnancy Reporting 
Any pregnancy in a patient that occurs from signing the ICF up to 9.5 months after the last 
dose of study drug, whichever occurs last, must be reported using the Pregnancy Report Form. 
Any pregnancy in a partner of a male patient that occurs from signing the ICF up to 6.5 months 
after last dose of study drug must be reported. Pregnancy must be reported within 24 hours 
after the site personnel first learn of the pregnancy. The pregnancy itself is not considered an 
AE. However, the pregnancy must be followed to determine outcome (including spontaneous 
miscarriage, elective termination, normal birth, or congenital abnormality) and status of mother 
and child, even if the patient discontinued from the study. Abortions (elective or spontaneous) 
must be reported as an SAE. 
Any SAE occurring in association with a pregnancy that is brought to the Investigator’s 
attention after the patient has completed the study and considered by the Investigator as 
possibly related to the study drug must be promptly reported in the same manner. 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Once pregnancy is confirmed in a study participant, study drug will be discontinued; 
see Section 7.4.6 for additional information. 
8.7 Independent Data and Safety Monitoring Board 
An iDSMB will primarily ensure the safety of patients enrolled in this study by providing 
expertise and recommendations for further study conduct and progress, which concern the 
continuation, modification, or termination of the study. 
The iDSMB will be composed of at least one clinician with immuno-oncology expertise and a 
biostatistician. The board will meet periodically to review data, and as soon as possible upon 
occurrence of polyradiculopathy/GBS and possibly other relevant ≥ Grade 3 autoimmune or 
neurologic toxicities (see Section 4.3) or other concerning safety issues. 
Details regarding the iDSMB responsibilities, authorities, and procedures will be included in 
a separate iDSMB charter. 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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9 Statistical Considerations 
Full details of the analysis plan, including a more technical and detailed elaboration of the 
statistical analyses, will be provided in the statistical analysis plan (SAP). Results for the 
exploratory/correlative analyses may be reported separately. 
9.1 Sample Size Calculation 
This study uses a single-arm design to test for an improvement in response rate in the HL 
population. A sample size of 100 will provide a robust population for safety evaluation and 
adequate precision for observed ORR in the expected range. For the test of efficacy, this study 
has > 98% power to distinguish between an active therapy with a 55% true response rate from 
a therapy with a response rate of 35% or less with a 1-sided alpha of 0.025. 
9.2 Analysis Populations 
• All-Treated Population: All patients who receive at least 1 dose of camidanlumab tesirine. 
This population will be used in the primary analyses of efficacy and safety. 
• Per-Protocol Population: All patients in the all-treated population without important 
protocol deviations, which will be further described in detail in the SAP. 
• The PK Population: All patients who receive study drug and have at least 1 pre- (C1D1) 
and 1 postdose valid assessment. 
• The Pharmacodynamic Population: All patients who receive study drug and have at least 
1 valid pharmacodynamics/biomarker assessment. 
9.3 Interim Analysis 
No formal interim analysis is planned. 
9.4 Final Analysis 
For primary and key secondary endpoints analyses, a database snapshot will be taken when all 
patients who achieve PR or CR have a minimum of 12 months follow-up after initial 
documented response (may be less for patients undergoing HSCT). All efficacy, safety, and 
PK endpoints will be analyzed and reported in the clinical study report (CSR). 
The exact binomial test will be used in the final analyses for the primary endpoint because of 
the practical consideration that accrual cannot be limited to exactly 100 patients (≤ 110 patients 
expected, see Table 7). 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
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Table 7 
Number of Responses Needed to Have 95% CI Low Bound of ORR >35% 
Total Patients Enrolled 
100 
102 
105 
108 
110 
Number of Responders 
45 
46 
47 
49 
49 
Lower Bound of 95% Exact CI 
35.03% 
35.22% 
35.05% 
35.76% 
35.07% 
 
Follow-up analyses will be performed when all the patients complete the study per protocol. 
The results will be reported in a CSR addendum. 
9.5 Demographics and Baseline Characteristics 
Demographics and Baseline characteristics, such as cancer history and medications history, 
will be summarized for the All-Treated Population. 
9.6 Exposure to Treatments 
Exposure to study drug, prior, and concomitant medications will be summarized for the 
All-Treated analysis set by dose level. Dose interruptions, reductions, and relative dose 
intensity will also be summarized. 
9.7 Efficacy Analyses 
Primary efficacy analyses will be based on response as determined by central review. 
Response reported by Investigators will be used for sensitivity analyses. 
9.7.1 Overall Response Rate 
The ORR will be defined as the proportion of patients with a best overall response (BOR) of 
CR or PR. The overall response category will be derived based on response assessment 
performed on or before the start of subsequent anti-cancer therapy. For the primary ORR 
analysis in the all-treated population, patients with a CR or PR will be counted as successes 
and all other patients (including those with missing response information) will be counted as 
failures. 
The percentage of ORR with its 95% confidence interval (CI) will be presented. In contrast to 
CR, PR, or PD, a BOR of SD can only be made after the patient is on-study for a minimum of 
35 days after the first dose of study drug. Any tumor assessment indicating SD before this time 
period will be considered as a non-evaluable for BOR if no assessment after this time period 
is available. 
9.7.2 Duration of Response 
The DOR will be defined among responders (CR or PR) as the time from the earliest date of 
first response until the first date of either disease progression or death due to any cause. 
The date of disease progression will be defined as the earliest date of disease progression based 
on central review. For patients who have not progressed or died at the time of the analysis, 
censoring will be performed using the date of the last valid disease assessment prior to 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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initiation of a new anticancer therapy (including HSCT). A sensitivity analysis of DOR is 
planned to be conducted in which the DOR for patients undergoing SCT is not censored at the 
last evaluable disease assessment prior to SCT. The data will be analyzed by the Kaplan-Meier 
method. The median DOR and 95% CI will be presented. DOR will be analyzed by response 
subgroup (CR, PR). Further details will be outlined in the SAP. 
9.7.3 Complete Response Rate 
Complete response rate (CRR) will be defined as the proportion of patients with a best overall 
response of CR. The percentage of CRR with its 95% CI will be presented. 
9.7.4 Relapse-free Survival 
The RFS will be defined among CR patients as the time from the earliest date of first complete 
response until the first date of either disease relapse or death due to any cause. The date of 
disease progression will be defined as the earliest date of disease progression based on central 
review. For patients who have not progressed or died at the time of the analysis, censoring will 
be performed using the date of the last valid disease assessment. The data will be analyzed by 
the Kaplan-Meier method. The median DOR and 95% CI will be presented. Further details 
will be outlined in the SAP. 
9.7.5 Progression-free Survival 
The PFS will be defined among all-treated patients as the time from first dose of study drug 
until the first date of either disease progression or death due to any cause. The date of disease 
progression will be defined as the earliest date of disease progression based on central review. 
For patients whose disease has not progressed at the time of the analysis, censoring will be 
performed using the date of the last valid disease assessment. The data will be analyzed by the 
Kaplan-Meier method. The median PFS time and 95% CI will be presented. Further details 
will be outlined in the SAP. 
9.7.6 Overall Survival 
Median OS will be defined as the time from the first dose of study drug until death due to any 
cause. For patients who have not died at the time of the analysis, censoring will be performed 
using the date the patient was last known to be alive. The data will be analyzed by the 
Kaplan-Meier method. The median OS and 95% CI will be presented. Further details will be 
outlined in the SAP. 
9.7.7 Patients Receiving Transplant 
The fraction of patients receiving HSCT following camidanlumab tesirine, and without any 
other anticancer therapy in between other than the therapies preparing for HSCT, will be 
summarized. 
9.8 Safety Analyses 
Safety analyses will be presented descriptively. 


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9.8.1 Adverse Events 
The focus of AE summarization will be on TEAEs. A TEAE is defined as an AE that occurs 
or worsens in the period extending from the first dose of study drug to 30 days after the last 
dose of study drug in this study or start of a new anticancer therapy/procedure, whichever 
comes earlier. 
All TEAEs will be summarized. Summary tables will be presented to show the number of 
patients reporting TEAEs by severity grade and corresponding percentages. A patient who 
reports multiple TEAEs within the same Preferred Term (or System Organ Class) is counted 
only once for that Preferred Term (or System Organ Class) using the worst severity grade. 
Separate summaries will be prepared for TEAEs classified as severe or life threatening 
(Grade 3 or higher); study drug-related AEs; AEs leading to treatment interruption, 
modification, or discontinuation; AESIs; serious AEs; and death. 
9.8.2 Clinical Laboratory Results 
Clinical hematology, coagulation panel, biochemistry, and urinalysis data will be summarized 
at each scheduled assessment. Shifts for clinical laboratory results that can be graded according 
to CTCAE v4.0 will be summarized by CTCAE grade. Shifts for other numeric laboratory 
results will be by high/normal/low flag. Shifts for all other laboratory results will be by 
normal/abnormal flag. 
Summaries by visit will include data from scheduled assessments, and all data will be reported 
according to the nominal visit date for which it was recorded. Unscheduled data will be 
included in “worst-case post Baseline” summaries, which will capture a worst case across all 
scheduled and unscheduled visits after the first dose of study drug. Further details will be 
provided in the SAP. 
9.8.3 Additional Safety Assessments 
The results of scheduled assessments of vital signs, physical examinations, ECOG performance 
status, and 12-lead ECGs will be summarized. All data will be reported according to the 
nominal visit date for which it was recorded (i.e., no visit windows will be applied). 
Unscheduled data will be included in “worst-case” summaries, which will capture a worst case 
across all scheduled and unscheduled visits after the first dose of study drug. All data will be 
listed. Further details will be provided in the SAP. 
9.9 Pharmacokinetic Analyses 
The PK profile will include determination of maximum concentration (Cmax), time to Cmax 
(Tmax), area under the concentration-time curve from time zero to the last quantifiable 
concentration (AUClast), area under the concentration-time curve from time zero to the end of 
the dosing interval (AUCtau), area under the concentration-time curve from time zero to infinity 
(AUCinf), apparent terminal elimination half-life (Thalf), clearance (CL), volume of distribution 
(Vss), and accumulation index (AI). 




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Results from ADA testing will include tabular summarization for number/proportion of 
patients with positive predose ADA response, number of patients with postdose ADA response 
only, and number of patients with positive ADA response at any time. The denominator will 
be the total number of patients tested for ADAs in the study. For patients exhibiting a positive 
ADA, PK, safety and efficacy correlates will be assessed and reported. 
9.11 Exploratory Analyses 
Exploratory analyses may be reported separately as an amendment to the CSR. 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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10 Data Management and Quality Assurance 
The Investigator will maintain accurate source documentation including patient medical 
records, laboratory reports, ECG strips, and patient diaries. 
Investigative site qualified personnel will enter patient data into an EDC system. The analysis 
data sets will be a combination of these data and data from other sources. 
Clinical data management will be performed in accordance with applicable standards and data 
cleaning procedures to ensure the integrity of the data (e.g., removing errors and 
inconsistencies in the data). AEs will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). Concomitant medications will be coded using the world health 
organization (WHO) Drug Dictionary. 
After database lock, each study site will receive information about all of their site-specific 
eCRF data as entered into the EDC system for the study, including full discrepancy and audit 
history. Additionally, a copy of study data from all sites will be created and sent to the Sponsor 
for storage. The CRO will maintain a duplicate copy for its records. In all cases, patient initials 
will not be collected or transmitted to the Sponsor. 
For detailed instruction on data entry procedures and timelines, please refer to the eCRF 
Completion Guidelines. 


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Camidanlumab tesirine (ADCT-301) 
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Date of Protocol Amendment 5: 16 February 2022 
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11 Ethical, Regulatory, and Study Management Considerations 
11.1 Regulatory and Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, International Council for Harmonisation (ICH) Good Clinical 
Practice (GCP), and all applicable regulations. 
11.2 Independent Ethics Committee or Institutional Review Board 
Federal regulations and ICH guidelines require that approval be obtained from an Institutional 
Review Board (IRB)/IEC before participation of human patients in research studies. 
Before study onset, the protocol, informed consent, advertisements to be used for the 
recruitment of study patients, and any other written information regarding this study intended 
to be provided to the patient must be approved by the IRB/IEC. Documentation of all IRB/IEC 
approvals will be maintained by the site and will be available for review by the Sponsor or its 
designee. 
All IRB/IEC approvals should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title or protocol number or 
both, and the date approval or a favorable opinion was granted. 
The Investigator is responsible for obtaining continued review of the clinical research as 
specified by the IRB/IEC, at intervals not exceeding 1 year. The Investigator must supply the 
Sponsor or its designee with written documentation of continued review of the clinical research. 
11.3 Patient Information and Consent 
Informed consent in compliance with IRB/IEC and local regulations shall be obtained from 
each patient before performing any study procedures and will be documented with a signed 
IRB/IEC approved ICF. Before enrollment, each prospective patient will be given a full 
explanation of the study and be allowed to read the approved ICF. Once the Investigator is 
assured that the patient understands the implications of participating in the study, the patient 
will be asked to give consent to participate in the study and sign the ICF. The process for 
obtaining consent has to be documented at the institution. 
If the ICF is revised during the course of the study, all patients on-study, including those in 
follow-up, must sign the revised form, unless otherwise indicated by the IRB/IEC  
(local or global, as applicable). In such cases, the reason for not re-consenting the patient 
should be documented. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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11.4 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain patient confidentiality. All records will be kept in a secure storage 
area with limited access. Clinical information will not be released without the written 
permission of the patient, except as necessary for monitoring and auditing by the Sponsor, its 
designee, regulatory authorities, or the IRB/IEC. 
The Investigator and other study staff may not disclose or use for any purpose other than 
performance of the study any data, record, or other unpublished, confidential information 
disclosed to those individuals for the purpose of the study. Prior written agreement from the 
Sponsor or its designee must be obtained for the disclosure of any said confidential information 
to other parties. 
11.5 Financial Disclosure and Obligations 
Investigators are required to provide financial disclosure information to allow the Sponsor to 
submit the complete and accurate certification or disclosure statements as required under 
21 CFR 54 and local regulations. In addition, the Investigator must promptly update this 
information if any relevant changes occur during the course of the investigation and for 1 year 
following the completion of the study. 
11.6 Study Conduct 
The Investigator will conduct all aspects of this study in accordance with the principles of the 
current version of ICH E6 as well as all national, state, and local laws and regulations. 
Study personnel involved in conducting this study will be qualified by education training and 
experience to perform their respective tasks. Study information from this protocol will be 
posted on publicly available clinical study registers before enrollment of patients begins. 
11.7 Protocol Amendments 
Any change in the study plan requires a protocol amendment. All amendments to the protocol 
must be reviewed and approved following the same process as the original protocol before the 
amended protocol can be implemented. The Investigator will inform the governing IRB/IEC 
of all protocol amendments issued by the Sponsor in accordance with established IRB/IEC 
procedure. Only protocol amendments intended to eliminate an apparent immediate hazard to 
patient(s) may be implemented immediately, i.e., without IRB/IEC approval, but the 
circumstances of the change must be documented and submitted to the IRB/IEC. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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11.8 Monitoring of the Study 
All aspects of the study will be carefully monitored by the Sponsor or designee for compliance 
with GCP and applicable government regulations. 
Investigators and institutions involved in the study will permit study-related monitoring, audits, 
IRB/IEC review, and regulatory inspections by providing direct access to all study records. 
In the event of an audit, the Investigator agrees to allow the Sponsor, representatives of the 
Sponsor, or a regulatory agency access to all study records. 
The Investigator should promptly notify the Sponsor and the CRO of any inspections scheduled 
by any regulatory authorities and promptly forward copies of any inspection reports received 
to the Sponsor. 
11.9 Records Retention 
Essential documents should be retained for at least 15 years from the completion of the study 
(last patient last visit) or until at least 2 years after the last approval of a marketing application 
in an ICH region or until there are no pending or contemplated marketing applications in an 
ICH region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational study drug. However, these documents should be retained 
for a longer period if required by the applicable regulatory requirements or by an agreement 
with the Sponsor. It is the responsibility of the Sponsor to inform the Investigator/institution 
as to when these documents no longer need to be retained. 
11.10 Publications 
Following completion of the study, the results from the study may be reported publicly by 
making any oral public presentation and/or submitting or presenting a manuscript, abstract, or 
other materials relating to the Study at scientific meetings and/or to a publisher, reviewer, or 
other outside person in scientific journals (“Publication”), provided, however, that Publication 
of the results from an individual site shall not be made before the first multi-site Publication 
by Sponsor. The Sponsor shall coordinate the drafting, editing, authorship, and other activities 
related to study Publication and shall mutually agree with the Investigator(s) on the number, 
medium, forum, and timing for Publication. The Sponsor shall solicit input regarding contents 
of the Publication from all Investigators and in consultation with all sites. The Sponsor 
acknowledges the right of the Investigator(s) to publish the results of this study after the entire 
study has completed, but also reserves the right to a window to review the Publication for 
regulatory compliance as well as for protection of its intellectual property. In particular, the 
Sponsor may request to remove the Sponsor’s confidential information and suspend 
Publication for a certain period of time to protect the Sponsor’s intellectual property interest, 
as further set forth in the Clinical Trial Agreement with the clinical study site(s) and 
Investigator(s). 


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Camidanlumab tesirine (ADCT-301) 
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Date of Protocol Amendment 5: 16 February 2022 
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12 Reference List 
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perfect synergy. Expert Opin Biol Ther 2012; 12(9):1191-1206. 
Alberti P, Beretta S, Piatti M, Karantzoulis A, Piatti ML, Santoro P, et al. Guillain-Barré 
syndrome related to COVID-19 infection. Neurol Neuroimmunol Neuroinflamm 2020; 
7(4):e741. 
Beck A, Goetsch L, Dumontet C, Corvaïa N. Strategies and challenges for the next generation 
of antibody-drug conjugates. Nat Rev Drug Discov 2017; 16(5):315-337. 
Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, et al. 
Management of immune-related adverse events in patients treated with immune checkpoint 
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Oncol 2018; 36(17):1714-1768. 
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independently predicts early treatment failure of acute myeloid leukaemia (AML). 
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Recommendations for initial evaluation, staging, and response assessment of Hodgkin and 
non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol 2014; 32(27):3059-3068. 
CIOMS Working Group. Drug-Induced Liver Injury (DILI): Current Status and Future 
Directions for Drug Development and the Post-Market Setting. Geneva, 2020. 
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modulators and targeted agents in cancer. Br J Haematol 2017; 179(1):20-35. 
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Clinical 
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Hematology 2013b; 18(1):14-19. 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Geng 
H, 
Brennan 
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J Intern Med 2017; 281(3):247-260. 
Gu Y, Menzies AM, Long GV, Fernando SL, Herkes G. Immune mediated neuropathy 
following checkpoint immunotherapy. J Clin Neurosci 2017; 45:14-17. 
Hartley JA. The development of pyrrolobenzodiazepines as antitumour agents. 
Expert Opin Investig Drugs 2011; 20(6):733-744. 
Hlubocky FJ, Webster K, Cashy J, et al. The development and validation of a measure of 
health-related quality of life for non-hodgkin’s lymphoma: the functional assessment of cancer 
therapy−lymphoma (FACT-Lym). Lymphoma 2013; 2013:1-9. 
LeMaistre CF, Saleh MN, Kuzel TM, Foss F, Platanias LC, Schwartz G, et al. Phase I trial of 
a ligand fusion-protein (DAB389IL-2) in lymphomas expressing the receptor for interleukin-
2. Blood 1998; 91(2):399-405. 
Lim KH, Tefferi A, Lasho TA, Finke C, Patnaik M, Butterfield JH, et al. Systemic mastocytosis 
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Mehta-Shah N and Bartlett NL. Management of relapsed/refractory classical Hodgkin 
lymphoma in transplant-ineligible patients. Blood 2018; 131(15):1698-1703. 
Mottok A and Steidl C. Biology of classical Hodgkin lymphoma: implications for prognosis 
and novel therapies. Blood 2018; 131(15):1654-1665. 
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2 dose levels of denileukin diftitox for the treatment of cutaneous T-cell lymphoma. 
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Prince HM, Duvic M, Martin A, Sterry W, Assaf C, Sun Y, et al. Phase III placebo-controlled 
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Schnell R, Vitetta E, Schindler J, Barth S, Winkler U, Borchmann P, et al. Clinical trials with 
an anti-CD25 ricin A-chain experimental and immunotoxin (RFT5-SMPT-dgA) in Hodgkin's 
lymphoma. Leuk Lymphoma 1998; 30(5-6):525-537. 
Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, et al. Guillain-Barre syndrome 
and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation 
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Shao H, Calvo KR, Gronborg M, Tembhare PR, Kreitman RJ, Stetler-Stevenson M,et al. 
Distinguishing hairy cell leukemia variant from hairy cell leukemia: development and 
validation of diagnostic criteria. Leuk Res 2013; 37(4): 401-409. 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
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Shvidel L, Braester A, Bairey O, Rahimi-Levene N, Herishanu Y, Tadmor T, et al. 
Cell surface expression of CD25 antigen (surface IL-2 receptor alpha-chain) is not a prognostic 
marker in chronic lymphocytic leukemia: results of a retrospective study of 281 patients. 
Ann Hematol 2012; 91(10):1597-1602. 
Smith TJ, Khatcheressian J, Lyman GH, Ozer H, Armitage JO, Balducci L, et al. 2006 update 
of recommendations for the use of white blood cell growth factors: An Evidence-Based 
Clinical Practice Guideline. J Clin Oncol 2006; 24(19):3187-3205. 
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Immunohistochemical study of 166 cases. Am J Pathol 1987; 126(3):506-512. 
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Syndrome Associated with SARS-CoV-2. N Engl J Med 2020; 382:2574-2576. 
Waldmann TA, White JD, Carrasquillo JA, Reynolds JC, Paik CH, Gansow OA, et al. 
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SARS-CoV-2 infection: causality or coincidence? Lancet Neurol 2020; 19(5):383-384. 


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Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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13 Appendices 
13.1 Appendix: Eastern Cooperative Oncology Group Performance Status 
Performance status will be assessed using the ECOG performance status grades as indicated 
below: 
Grade 
Definition 
0 
Fully active, able to carry on all pre-disease performance without restriction 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of 
a light or sedentary nature, e.g., light house work, office work 
2 
Ambulatory and capable of all self-care but unable to carry out any work activities; 
up and about more than 50% of waking hours 
3 
Capable of only limited self-care; confined to bed or chair more than 50% of waking 
hours 
4 
Completely disabled; cannot carry on any self-care; totally confined to bed or chair 
5 
Dead 
Reference: Oken, 1982 
 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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13.2 Appendix: Clinical Case Definitions: Level 1 of Diagnostic Certainty 
for Guillain-Barré Syndrome (GBS) 
• Bilateral AND flaccid weakness of the limbs1, 2, 3 
AND 
• Decreased or absent deep tendon reflexes in weak limbs4 
AND 
• Monophasic illness pattern5 AND interval between onset and nadir of weakness 
between 12 h and 28 days AND subsequent clinical plateau6 
AND 
• Electrophysiologic findings consistent with GBS7 
AND 
• Cytoalbuminologic dissociation (i.e., elevation of CSF protein level above laboratory 
normal value AND CSF total white cell count < 50 cells/µL)8 
AND 
• Absence of an identified alternative diagnosis for weakness9 
Reference: Sejvar, 2011 
1. Weakness is usually, but not always, symmetric in nature, and usually has a pattern of progression from 
legs to arms (ascending). However, other patterns of progression may occur (e.g., beginning in the arms). 
The degree of weakness can range from mild to moderate to severe, i.e., complete paralysis. 
2. Respiratory or cranial nerve-innervated muscles may also be involved. 
3. It is important that strength be assessed in a manner that takes into account subject age, sex, and level of 
functioning. 
4. Decreased or absent tendon reflexes may also be seen in limbs without weakness. However, to meet case 
definition criteria, decreased or absent tendon reflexes must be observed in weak limbs. 
5. Fluctuations in level of weakness, before reaching nadir, or during the plateau or improvement phases, 
occur in some cases, usually associated with the use of disease-modifying therapies. Such fluctuations 
usually occur within the first 9 weeks after onset and are followed by eventual improvement. 
6. The eventual outcome is either stabilization at nadir OR subsequent improvement OR death. 
7. Electrophysiologic patterns consistent with polyneuropathy of the types described for GBS. 
Electrophysiologic studies performed sooner than 7 days after weakness onset may be normal and should 
thus be repeated at a later time if possible, and “normal” studies may occur in otherwise typical cases of 
GBS. However, cases with persistently “normal” studies will not meet Level 1 criteria. 
8. CSF (cerebrospinal fluid) protein concentrations should be elevated above what is considered normal 
reference values for the testing laboratory. CSF may be “normal” in otherwise typical cases of GBS; this 
is particularly true within the first week of illness. However, cases with persistently “normal” CSF, or CSF 
with ≥ 50 WBC, will not meet Level 1 criteria. 
9. If an alternative diagnosis explaining flaccid weakness/paralysis is present a diagnosis of Guillain–Barré 
syndrome is excluded. However, in many, if not most cases, a comprehensive documentation of testing 
for various other etiologies will either be incomplete or unavailable. These case definitions are provided 
to give guidance in the absence of detailed information on investigations for alternative etiologies of 
flaccid paralysis. 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 82 of 87 
13.3 Appendix: Guillain–Barré Syndrome Disability Scale 
Score 
Description 
0 
Healthy 
1 
Minor symptoms or signs of neuropathy but capable of manual work/capable of 
running 
2 
Able to walk without support of a stick (5 m across an open space) but incapable of 
manual work/running 
3 
Able to walk with a stick, appliance, or support (5 m across an open space) 
4 
Confined to bed or chair bound 
5 
Requiring assisted ventilation (for any part of the day or night) 
6 
Death 
Reference: Sejvar, 2011 


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Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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13.4 Appendix: Response Assessment of Hodgkin and Non-Hodgkin 
Lymphoma (Lugano Classification) 
Response/Site 
PET-CT-Based Response 
CT-Based Response 
Complete 
Complete metabolic response 
Complete radiologic response  
(all of the following) 
Lymph nodes and 
extralymphatic sites 
• Score 1, 2, or 3* with or without a residual 
mass on 5PS** 
Note: Uptake may be greater than normal 
mediastinum and/or liver in Waldeyer’s ring 
or extranodal sites with high physiologic 
uptake or with activation within spleen or 
marrow (e.g., with chemotherapy or myeloid 
colony-stimulating factors). In this 
circumstance, complete metabolic response 
may be inferred if uptake at sites of initial 
involvement is no greater than surrounding 
normal tissue even if the tissue has high 
physiologic uptake 
• Target nodes/nodal masses must regress to 
≤ 1.5 cm in LD 
• No extralymphatic sites of disease 
Nonmeasured lesion 
• Not applicable 
• Absent 
Organ enlargement 
• Not applicable 
• Regress to normal 
New lesions 
• None 
• None 
Bone marrow 
• No evidence of FDG-avid disease in 
marrow 
• Normal by morphology; if indeterminate, 
IHC negative 
Partial 
Partial metabolic response 
Partial remission  
(all of the following) 
Lymph nodes and 
extralymphatic sites 
• Score 4 or 5** with reduced uptake 
compared with baseline and residual 
mass(es) of any size. 
• At interim, these findings suggest 
responding disease. 
• At end of treatment, these findings indicate 
residual disease. 
• ≥ 50% decrease in SPD of up to 6 target 
measurable nodes and extranodal sites 
• When a lesion is too small to measure on 
CT, assign 5 mm × 5mm as the default 
value. 
• When no longer visible, 0 × 0 mm 
• For a node > 5 mm × 5 mm, but smaller 
than normal, use actual measurement for 
calculation 
Nonmeasured lesion 
• Not applicable 
• Absent/normal, regressed, but no increase 
Organ enlargement 
• Not applicable 
• Spleen must have regressed by > 50% in 
length beyond normal 
New lesions 
• None 
• None 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Response/Site 
PET-CT-Based Response 
CT-Based Response 
Bone marrow 
• Residual uptake higher than uptake in 
normal marrow but reduced compared with 
baseline (diffuse uptake compatible with 
reactive changes from chemotherapy 
allowed). If there are persistent focal 
changes in the marrow in the context of a 
nodal response, consideration should be 
given to further evaluation with MRI or 
biopsy or an interval scan 
• Not applicable 
No response or stable 
disease 
No metabolic response 
 
Stable disease 
Target nodes/nodal 
masses, extranodal 
lesions 
• Score 4 or 5 with no significant change in 
FDG uptake from baseline at interim or 
end of treatment 
• < 50% decrease from baseline in SPD of 
up to 6 dominant, measurable nodes and 
extranodal sites; no criteria for progressive 
disease are met 
Nonmeasured lesions 
• Not applicable 
• No increase consistent with progression 
Organ enlargement 
• Not applicable 
• No increase consistent with progression 
New lesions 
• None 
• None 
Bone marrow 
• No change from baseline 
• Not applicable 
Progressive disease 
Progressive metabolic disease 
Progressive disease  
(requires at least 1 of the following) 
Individual target 
nodes/nodal masses 
• Score 4 or 5 with an increase in intensity of 
uptake from baseline and/or 
• PPD progression 
Extranodal lesions 
• New FDG-avid foci consistent with 
lymphoma at interim or end of treatment 
assessment 
An individual node/lesion must be abnormal 
with: 
• LDi > 1.5 cm and 
• Increase by ≥ 50% from PPD nadir and  
• An increase in LDi or SDi from nadir 
0.5 cm for lesions ≤ 2 cm 
1.0 cm for lesions > 2 cm 
• In the setting of splenomegaly, the splenic 
length must increase by > 50% of the 
extent of its prior increase beyond baseline 
(e.g., a 15-cm spleen must increase to > 16 
cm). If no prior splenomegaly, must 
increase by at least 2 cm from baseline 
• New or recurrent splenomegaly 
Nonmeasured lesions 
• None 
• New or clear progression of preexisting 
nonmeasured lesions 


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Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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Response/Site 
PET-CT-Based Response 
CT-Based Response 
New lesions 
• New FDG-avid foci consistent with 
lymphoma rather than another etiology 
(e.g., infection, inflammation). If uncertain 
regarding etiology of new lesions, biopsy 
or interval scan may be considered 
• Regrowth of previously resolved lesions 
• A new node > 1.5 cm in any axis 
• A new extranodal site > 1.0 cm in any axis; 
if < 1.0 cm in any axis, its presence must 
be unequivocal and must be attributable to 
lymphoma 
• Assessable disease of any size 
unequivocally attributable to lymphoma 
Bone marrow 
• New or recurrent FDG-avid foci 
• New or recurrent involvement 
Abbreviations: 5PS, 5-point scale; CT, computed tomography; FDG, fluorodeoxyglucose; IHC, immunohistochemistry; 
LDi, longest transverse diameter of a lesion; MRI, magnetic resonance imaging; PET, positron emission tomography; PPD, 
cross product of the LDi and perpendicular diameter; SDi, shortest axis perpendicular to the LDi; SPD, sum of the product 
of the perpendicular diameters for multiple lesions. 
* A score of 3 in many patients indicates a good prognosis with standard treatment, especially if at the time of an interim 
scan. However, in trials involving PET where de-escalation is investigated, it may be preferable to consider a score of 3 as 
inadequate response (to avoid undertreatment). Measured dominant lesions: Up to six of the largest dominant nodes, nodal 
masses, and extranodal lesions selected to be clearly measurable in 2 diameters. Nodes should preferably be from disparate 
regions of the body and should include, where applicable, mediastinal and retroperitoneal areas. Non-nodal lesions include 
those in solid organs (e.g., liver, spleen, kidneys, lungs), GI involvement, cutaneous lesions, or those noted on palpation. 
Nonmeasured lesions: Any disease not selected as measured, dominant disease and truly assessable disease should be 
considered not measured. These sites include any nodes, nodal masses, and extranodal sites not selected as dominant or 
measurable or that do not meet the requirements for measurability but are still considered abnormal, as well as truly 
assessable disease, which is any site of suspected disease that would be difficult to follow quantitatively with measurement, 
including pleural effusions, ascites, bone lesions, leptomeningeal disease, abdominal masses, and other lesions that cannot 
be confirmed and followed by imaging. In Waldeyer’s ring or in extranodal sites (e.g., GI tract, liver, bone marrow), FDG 
uptake may be greater than in the mediastinum with complete metabolic response, but should be no higher than surrounding 
normal physiologic uptake (e.g., with marrow activation as a result of chemotherapy or myeloid growth factors). 
** PET 5PS: 1, no uptake above background; 2, uptake ≤ mediastinum; 3, uptake > mediastinum but ≤ liver; 
4, uptake moderately > liver; 5, uptake markedly higher than liver and/or new lesions; X, new areas of uptake unlikely to 
be related to lymphoma. 
Reference: Cheson, 2014 
 


ADC Therapeutics 
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Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
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13.5 Appendix: 
Management 
of 
Specific 
Autoimmune 
Toxicities: 
Hyperthyroidism, Hypothyroidism, and Hepatitis 
Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Hyperthyroidism 
1 
No dose adjustment is required.  
Close follow-up (at least weekly; by phone if stable) and 
monitoring of TSH, reflex FT4 and/or FT3 (as applicable), 
every 2-3 weeks, until it is clear whether there will be 
persistent hyperthyroidism (>6 weeks) or hypothyroidism. 
 
2 
Consider endocrine consultation. 
Dose delay is at the Investigator’s discretion. Rechallenge 
without dose adjustment is permitted. 
β-blocker (e.g., atenolol) for symptomatic relief, hydration, 
and supportive care may be needed. 
For persistent hyperthyroidism or clinical suspicion (e.g., 
ophthalmopathy or thyroid bruit), work-up for Graves disease 
and consider thionamide. 
 
3/4 
Endocrine consultation is indicated. 
Hold camidanlumab tesirine until improvement to ≤ Grade 1 
or Baseline with appropriate therapy. Rechallenge is then 
permitted as per General Guidelines for Dose Modification 
(Section 6.4.1). 
Give β-blocker (e.g., atenolol) for symptomatic relief.  
For severe symptoms or concern for thyroid storm, hospitalize 
patient and initiate prednisone 1-2 mg/kg/day or equivalent 
tapered over 1-2 weeks; consider also use of saturated 
solutions of potassium iodide or thionamide. 
Hypothyroidism 
1 
Asymptomatic; TSH generally <10 mIU/L. 
No dose adjustment is required.  
Close follow-up (at least weekly; by phone if stable) and 
monitoring of TSH, FT4/FT3 (as applicable) every 4-6 weeks. 
 
2 
TSH generally persists >10 mIU/L. 
Consider endocrine consultation. 
Dose delay is at the Investigator’s discretion. Rechallenge 
without dose adjustment is permitted. 
Give thyroid hormone supplementation in symptomatic 
patients with any degree of TSH elevation or in asymptomatic 
patients with TSH levels that persist >10 mIU/L. 
Monitor TSH, FT4/FT3 (as applicable) every 6-8 weeks while 
titrating hormone replacement to normal TSH. Thereafter, 
monitor TSH, FT4 and/or FT3 (as applicable) every 6 weeks 
during camidanlumab tesirine treatment or as needed for 
symptoms to ensure appropriate hormone replacement; repeat 
testing annually or as indicated by symptoms once stable. 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
Final ADCT-301-201 Clinical Protocol 
Protocol Amendment 5 
Date of Protocol Amendment 5: 16 February 2022 
Page 87 of 87 
Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
 
3/4 
Endocrine consultation is indicated. 
Hold camidanlumab tesirine until improvement to ≤ Grade 1 
or Baseline, or control with appropriate supplementation. 
Rechallenge is then permitted as per General Guidelines for 
Dose Modification (Section 6.4.1). 
May admit for IV therapy if signs of myxedema (bradycardia, 
hypothermia) 
Provide thyroid supplementation and reassessment as in Grade 
2. 
Hepatitis 
1/2 
Asymptomatic LFT elevations and Hy’s law should be 
managed per guidances given in the Section 6.4.2. 
Consider work-up for other causes of elevated liver enzymes 
(CIOMS Working Group consensus, 2020): e.g., viral 
hepatitis, alcohol history, iron study, thromboembolic event, 
liver ultrasound, cross-sectional imaging for potential liver 
metastasis. Antinuclear antibodies, antismooth muscle 
antibodies, and/or antineutrophil cytoplasmic antibodies 
testing can be considered if suspicion for primary 
autoimmune hepatitis.  
 
3 
Consider hepatology consult and biopsy. Work-up for 
alternative causes as in Grade 2. 
Permanently discontinue camidanlumab tesirine. 
Closely monitor chemistries (every 1-2 days). Consider 
inpatient monitoring for patients with AST/ALT > 8 x ULN 
and/or elevated total bilirubin > 3 x ULN.  
Immediately start corticosteroid 1-2 mg/kg 
methylprednisolone or equivalent; seek hepatology 
consultation. If corticosteroid refractory or no improvement 
after 3 days, consider additional treatments such as 
mycophenolate mofetil or azathioprine. 
Corticosteroid tapering can be attempted around 4-6 weeks; 
re-escalate if needed. 
 
4 
Consider hepatology consult and biopsy. Work-up for 
alternative causes as in Grade 2. 
Permanently discontinue camidanlumab tesirine. 
Monitor chemistries daily, consider inpatient monitoring. 
Administer 2 mg/kg/day methylprednisolone or equivalent, 
avoid use of infliximab. 
Corticosteroid tapering can be attempted around 4-6 weeks 
when symptoms improve to ≤ Grade 1 or Baseline; re-
escalate if needed. 
 

SAP_001.pdf: 
Protocol Number: ADCT-301-201 
 
Official Title: A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of 
Camidanlumab Tesirine (ADCT-301) in Patients with Relapsed or Refractory Hodgkin Lymphoma 
 
NCT Number: NCT04052997 
 
Document Date: 13 September 2022 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
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1 
 
This statistical analysis plan (SAP) describes the statistical methods to be used during the 
reporting and analyses of data collected under ADC Therapeutics Protocol ADCT-301-201.
This SAP should be read in conjunction with the study protocol and case report form (CRF). 
This version of the plan has been developed using the protocol amendment 1 dated 14 Jun 
2019 and CRF version 2.0 dated 23 Oct 2019. 


 
 
2 
 
2.1 
 
Evaluate the efficacy of single agent camidanlumab tesirine in patients with relapsed or 
refractory Hodgkin lymphoma (HL).   
2.2 
 
Characterize additional efficacy endpoints of camidanlumab tesirine 
Characterize the safety profile of camidanlumab tesirine 
Characterize the pharmacokinetic (PK) profile of camidanlumab tesirine 
Evaluate the immunogenicity of camidanlumab tesirine 
Evaluate the impact of camidanlumab tesirine treatment on health-related quality of 
life (HRQoL) 
2.3 
 
Assess the pharmacodynamic effects of camidanlumab tesirine 
Characterize tumor and tumor-associated nontumor cells (TANT), as well as 
immunological relevant parameters, in baseline tumor tissue 
Evaluate genetic alterations characterizing HL and their evolution upon 
camidanlumab tesirine treatment 
Explore exposure-response relationships affecting safety and efficacy of 
camidanlumab tesirine 
Explore correlations between clinical activity or safety of camidanlumab tesirine and 
tumor and/or blood biomarkers   
 


 
 
3 
 
This is a Phase 2, multi-center, open-label, single-arm study.  The study will enroll 
approximately 100 patients. 
Because of the considerable overall response rate (ORR) observed in the ADCT-301-001 
Phase 1 trial in HL patients and the anticipated recruitment projections, an formal interim 
analysis for futility is not warranted. 
3.1 
 
The primary hypothesis is that the overall response rate based on central review for patients 
treated with camidanlumab tesirine is significantly greater than 35% (i.e., H0
0.35 vs. 
Ha: p >0.35).  This hypothesis will be tested at a type I error of 0.05 (2-sided).   
Using nQuery exact test for single proportion, a sample size of 100 patients has >98% power 
to distinguish between an active therapy with a 55% true response rate from a therapy with a 
response rate of 35% or less with a 1-sided alpha of 0.025.  This sample size will provide 
adequate precision for the point estimate of ORR in the expected range and a robust 
population for safety evaluation.   
3.2 
 
This study is not randomized. 
3.3 
 
NA. 


 
 
4 
 
All analyses use SAS® version 9.4 or higher. All available data will be used in the analyses, 
and important data will be included in data listings, sorted by patient, and by visit within 
patient. Missing data will not be imputed, except via censoring in survival analyses and as 
otherwise specified. 
Unless otherwise noted, categorical data will be presented using counts and percentages, with 
the number of patients in the analysis population as the denominator for percentages. 
Percentages will be rounded to one decimal place, except 100% will be displayed without 
any decimal places and percentages will not be displayed for zero counts. Continuous data, 
unless otherwise noted, will be summarized using the number of observations (n), mean, 
standard deviation (std), median, minimum, and maximum. Minima and maxima will be 
rounded to the precision of the original value, and means, medians, and 95% confidence 
intervals (CIs) if presented will be rounded to 1 decimal place greater than the precision of 
the original value. The std will be rounded to 2 decimal places greater than the precision of 
the original value, up to a maximum of 3 decimal places.  
4.1 
 
4.1.1 
 
All patients who receive at least 1 dose of camidanlumab tesirine.  This population will be 
used in the primary analyses of efficacy and safety. 
4.1.2 
 
All patients in the all-treated population who met the inclusion/exclusion criteria, did not take
a prohibited concomitant treatment, nor had other protocol deviation which have important 
impact on efficacy results.  
4.1.3 
 
 
4.1.4 
 
 
4.1.5 
 
 


 
 
 
 
4.2 
 
The number and percentage of patients enrolled and treated in the study will be presented 
along with the number and percentage of patients in each analysis population. In addition, the 
number and percentage of patients who withdrew from study treatment and who discontinued 
the study for each reason will be tabulated. 
 
4.3 
 
 
1. Patients entered the study even though they did not satisfy the entry criteria 
2. Patients received a prohibited concomitant treatment during the study 
3. Patients who met criteria for mandatory withdrawal of study drug during the study 
but did not have study drug withdrawn 
4. Patients who received the wrong treatment or incorrect dose, specifically: 
-Actual dose of study drug was greater than 15% more or less than protocol defined 
planned dose level. 
-Patients started next cycle less than 18 days after Day 1 of the most recent treatment 
cycle. 
Important protocol deviations will be listed. 
4.4 
 
Demographic and baseline characteristics will be tabulated for the all-treated population. 
Variables include the following: 
Sex (female, male) 
Race (white, black or African American, Asian, American Indian or Alaska native, 
native Hawaiian or other Pacific Islander, other) 
Ethnicity (Hispanic or Latino, not Hispanic or Latino) 
Age (years) 
Age group (<55, 55 - 
- 
, (12-17 years, 18-64 years, 65-
84 years, 85 years) 
Height (cm) 
Weight (kg) 
Body mass index (BMI) (kg/m2) 


 
 
Eastern Cooperative Oncology Group (ECOG) performance status
Demographic and baseline characteristics data will be listed. 
4.5 
 
Cancer history will be presented for the all-treated population. Cancer history will include the 
following variables: 
Duration since diagnosis  
Classical Hodgkin lymphoma subtype (nodular sclerosis classical Hodgkin lymphoma 
[cHL], lymphocyte-rich cHL, mixed cellularity cHL, lymphocyte-depleted cHL, and 
other) 
Stage of disease at study entry (Stage I, II, III, IV; constitutional symptoms A, B; 
Subtype E, X, S) 
Cytogenetic analysis 
Immunophenotypic analysis (results available yes; CD15, CD30, PAX5, CD3, CD20, 
CD45, CD79a, BCL6, etc.)
Prior anticancer procedure or therapy will include the following variables: 
Number of lines of therapy/regimens per patient 
Response to the first line and/or most recent line of prior systematic therapy 
Any prior radiotherapy for the current malignancy (yes, no) 
Any prior surgery for the current malignancy (yes, no) 
Reason for stopping therapy (progression, lack of response, toxicity, completed 
treatment, partial or complete remission, other) 
Best response (complete response [CR], partial response [PR], stable disease [SD], 
progressive disease [PD], not evaluable [NE]) 
Any prior stem cell transplant (yes, no) 
Primary reason for transplant ineligibility prior to entering the study  
Type of transplant (allogenic, autologous, both, other) 
Medical and cancer history data will be listed. Results of cytogenetic analysis and 
immunophenotypic analysis will be listed. Tumor tissue biopsy collection will not be listed, 
but will be contained in datasets. 
Prior anticancer surgery, radiotherapy, systemic therapy, and stem cell transplant data will be 
listed. 
4.6 
All medications taken from the ICF signature date or within 14 days prior to Cycle 1 Day 1 
(C1D1), whichever is earlier, and until at least 30 days after last dose of study drug are to be 
reported in the CRF pages. 


 
 
All medications will be coded using the World Health Organization-Drug Dictionary (WHO-
DD). 
Prior medications are those the patient used prior to the first dose. Prior medications 
can be discontinued before the first dose or can be ongoing during the treatment 
phase.   
Concomitant medications are any treatments received by the patient concomitantly to 
any camidanlumab tesirine from the first dose to the last dose + 30 days. A given 
medication can be classified both as a prior medication and as a concomitant 
medication. Concomitant medications do not include medications started 30 days 
after the last dose.  
Any technical details related to computation, dates, and imputation for missing dates are 
described in Section 7. 
 
4.7 
 
4.7.1 
 
Camidanlumab tesirine exposure will be summarized for the all-treated population. Duration 
of treatment, total number of cycles dosed, total dose received (in µg and µg/kg), average 
dose per cycle (in µg and µg/kg), and relative dose intensity (actual dose taken / planned 
dose) will be tabulated. Patients will receive 45 µg/kg every 3 weeks (Q3W) for 2 cycles, 
then 30 µg/kg Q3W for subsequent cycles as planned. When actual weight adjusted dose is 
needed, the last available weight before each infusion will be used. 
kg/m2 will have their dose calculated based on an adjusted body weight as follows: 
Adjusted body weight in kg = 35 kg/m2 * (height in meters)2 
Dose administered at each infusion (µg) is calculated by concentrated investigational product 
(IP) volume (in mL)* 5 mg/mL *1000. For incomplete infusion, adjust the calculated 
prepared dose by multiplying a factor of (1- volume of dosing solution not administered [in 
mL]/ [50 + total volume of reconstituted solution] mL) for lyophilized formulation. The 
number of patients who received camidanlumab tesirine at each cycle will also be tabulated 
using frequency counts and percentages. 
Dose delays, interruptions, and reductions may also be analyzed if relevant. A cycle is 
delayed if it starts more than 2 days post- scheduled date. 
 
Exposure data and infusion details will be listed together. 
4.7.2 
Pre-medication and prophylactic medications for hypersensitivity will be listed only. 


 
 
4.7.3 
 
subsequent anticancer therapies or procedures including systemic therapy, 
conditioning/mobilization chemotherapy, CAR-T, transplant, or other (e.g. radiation), along 
with the start date of new anticancer therapy or procedure will be collected and listed only.
4.8 
 
The summary of safety results will be presented.  
General common rules 
All safety analyses will be performed on the all-treated population, unless otherwise 
specified, using the following common rules: 
The baseline value is defined as the last non-missing value or measurement taken up 
to the first dose in the study. 
The analyses of the safety variables will be essentially descriptive and no systematic 
testing is planned. 
If relevant, selected safety analyses will be summarized by age, sex, racial subgroups, 
and any pertinent subgroups.  
The toxicity grade according to the Common Terminology Criteria for Adverse 
Events (CTCAE) version 4.0 will be taken into account in the summary. For patients 
with multiple occurrences of the same event, the maximum grade is used. If a patient 
has both missing and non-missing severity grades for treatment-emergent adverse 
events (TEAEs) within the same preferred term (PT), the patient will be counted 
under the non-missing severity grade. 
4.8.1 
 
4.8.1.1 
 
The primary focus of adverse event reporting will be on TEAEs. An adverse event (AE) will 
be considered to be a TEAE if it begins or worsens on or after the first dose date and until 30 
days after the last dose date, or start of a new anticancer therapy/procedure, whichever comes 
earlier. 
An AE occurring before the first dose or more than 30 days after the last dose date or after 
the start of a new anticancer therapy/procedure will not be included in TEAE displays, but 
will be listed as non-TEAEs. 
 


 
 
 
 
 
Overview of TEAEs, summarizing number of TEAE and number (%) of patients with 
any 
-
TEAE 
-
Related TEAE (including possibly related, probably related, or related) 
-
Any TEAE Grade 3  
-
Serious TEAE  
-
TEAE leading to death 
-
TEAE leading to permanent treatment withdrawal 
-
TEAE leading to camidanlumab tesirine delay or reduction or interruption (if 
applicable) 
-
TEAE with at least one infusion related reaction 
-
TEAE of special interest 
All 
Grade 3 by PT, showing number (%) of patients with at least one TEAE, 
sorted by decreasing incidence of PTs 
All post-treatment/treatment-emergent AEs of special interest by PT, showing 
number (%) of patients with at least one TEAE of special interest, sorted by 
decreasing incidence of PTs 
All TEAEs by primary System Organ Class (SOC) and PT, showing number (%) of 
patients with at least one TEAE, sorted by SOC in alphabetic agreed order and 
decreasing incidence of PTs within SOC. This sorting order will be applied to all 
other tables, unless otherwise specified. 
All TEAEs by primary SOC, PT and Maximal CTCAE grade, showing number (%) 
of patients with at least one TEAE, sorted by SOC in alphabetic agreed order and 
decreasing incidence of PTs within SOC. This sorting order will be applied to all 
other tables, unless otherwise specified. 
All TEAEs 
rade 3 by primary SOC, PT and Maximal CTCAE grade 
All related TEAEs by primary SOC, PT and Maximal CTCAE grade (including 
possibly related, probably related, or related) 
All TEAEs leading to treatment withdrawal by primary SOC, PT and Maximal 
CTCAE grade 
All TEAEs leading to dose delay by primary SOC, PT and Maximal CTCAE grade 


 
 
All TEAEs leading to dose reduction by primary SOC, PT and Maximal CTCAE 
grade 
All TEAEs leading to infusion interruption by primary SOC, PT and Maximal 
CTCAE grade 
All TEAEs with fatal outcome by primary SOC, PT and Maximal CTCAE grade 
All Serious TEAEs by primary SOC, PT and Maximal CTCAE grade 
All infusion related reaction TEAEs by primary SOC, PT and Maximal CTCAE 
grade 
All post-treatment/treatment-emergent AEs of special interest by primary SOC, PT 
and Maximal CTCAE grade 
Summary of grouped post-treatment/treatment-emergent AEs selected by 
Standardised MedDRA Query (SMQ), ADCT modified SMQ, pre-specified SOC will 
also be provided by Grouped PT term, and Maximal CTCAE grade.  
Summary of TEAEs will also be provided by demographic factors including: sex, age 
group, race, disease subtype if appropriate. 
Time to onset of certain types of AEs will be summarized or presented using Kaplan-
Meier plot if appropriate. 
AE of special interest (AESI) is defined in the study protocol. Potential AESIs are 
identified per the pre-specified list of preferred or lower level terms based on 
customization of SMQs which satisfying the conditions as defined in protocol (level 1 
adjudication). Final AESIs are identified through the review of individual potential 
AESIs by clinical team (level 2 adjudication). 
All TEAEs, all serious adverse events (SAEs), all TEAEs leading to treatment 
withdrawal, all TEAEs leading to dose reduction, all TEAEs leading to dose delay, all 
TEAEs considered infusion related reactions, all TEAEs with fatal outcome and non-
TEAEs will be listed.  
4.8.1.2 
 
 
Number (%) of patients who died during the study and reasons for death 
Number (%) of patients who died within 30 days after the last dose of study drug 
(excluding those who died after taking any subsequent anticancer therapy/procedure) 
and reasons for death 
4.8.1.3 
 
The following analysis will be performed for patients who have responded to camidanlumab
tesirine and undergo HSCT (either autologous or allogeneic) after permanent discontinuation 


 
 
of camidanlumab tesirine treatment (without any intervening anticancer therapy to treat 
relapsing disease but mobilization/conditioning treatment for HSCT is allowed) or who have 
received CAR-T as the immediate subsequent anticancer therapy (mobilization/conditioning 
treatment for CAR-T is allowed) (i.e., patient in SCT population/CAR-T population) .  The 
data will include the following information reported until 180 days post-HSCT/post-CAR-T
regardless of relationship to camidanlumab tesirine. 
Summary of 
Grade 3 suggestive of hepatic toxicity, veno-occlusive 
disease/sinusoidal obstruction syndrome, graft-versus-host disease, infectious 
complications, potentially immune-mediated adverse events, prolonged cytopenia(s), 
and pulmonary toxicity 
In addition for CAR-T patients, summary of 
 AEs of cytokine-release-
syndrome and neurological toxicity  
SAEs by primary SOC, PT and Maximal CTCAE grade 
Number (%) of patients who died after HSCT/CAR-T and reasons for death 
4.8.2 
 
Laboratory data of hematology, biochemistry, and coagulation up the end of study visit will 
be reported in SI units.  
Descriptive statistics (mean, standard deviation, median, and range) will be calculated for the 
raw data and for their changes from baseline at each scheduled assessment for hematology, 
biochemistry, coagulation. All results will be summarized using shift from baseline. Shifts 
for clinical laboratory results that can be graded according to CTCAE version 4.0 will be 
summarized by CTCAE grade. 
Summaries by visit will include data from scheduled assessments, and all data will be 
reported according to the nominal visit date for which it was recorded. Unscheduled data will 
-
all scheduled and unscheduled visits after the first dose of study treatment. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
All laboratory data, including urinalysis, and as applicable, serology, viral detection, and/or
additional microbiological studies will be listed. Pregnancy test results will not be listed, but 
will be included in datasets. 
4.8.3 
 
Descriptive statistics (mean, standard deviation, median and range) for ECG data will be 
calculated for the raw data and for their changes from baseline at each scheduled assessment.
The following abnormal QTc (including QTcF and QTcB) will be reported by a frequency 
table: 
 At any post-baseline with absolute value 


 
 
>450 - <=480 ms 
>480 - <=500 ms 
> 500 ms 
 
 
 
Summary analyses will include data up to the start of subsequent anticancer therapy/procedure.
All ECG data will be listed, both for quantitative data and for overall impression. 
4.8.4 
 
Descriptive statistics (mean, standard deviation, median, and range) for vital signs data, 
including systolic and diastolic blood pressure, heart rate, respiration rate, and body 
temperature will be calculated for the raw data and for their changes from baseline at each 
scheduled assessment. 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
All vital signs data will be listed together with body weight. 
4.8.5 
 
Descriptive statistics (mean, standard deviation, median and range) will be calculated for the 
raw data and for their changes from baseline at each scheduled assessment. 
 
ECOG performance score data will be listed. 
4.8.6 
 
Physical examination will be performed according to protocol. Clinically significant findings 
from the physical examinations will be recorded as medical history (prior to first 
administration of camidanlumab tesirine) or AEs (subsequent to first administration of 
camidanlumab tesirine). 
Body weight will be listed together with vital signs. 
4.9 
 
Disease assessment will be performed according to protocol. The endpoints described in this 
section, if not mentioned specifically, use the independent reviewer
according to
the 2014 Lugano Classification criteria before the start of subsequent anticancer therapy or 
procedure.  


 
 
Tumor assessment data (target lesions, non-target lesions, new lesions lesions, overall 
response, SUV max, Deauville score, etc.) will be listed. A separate listing will contain 
derived data for duration of response (DOR), relapse-free survival (RFS), progression-free 
survival (PFS), and Overall survival (OS). 
4.9.1 
 
Overall response rate is defined as the proportion of patients who achieve either CR or PR as 
best overall response (BOR) as determined by central review according to the 2014 Lugano 
Classification criteria before the start of subsequent anticancer therapy or procedure. For the 
primary ORR analysis in the all-treated population, patients with a CR or PR will be counted 
as successes and all other patients (including those with missing response information) will 
be counted as failures. 
The order of overall response category is: CR, PR, SD, NE, PD (including disease 
recurrence/ relapse). The overall response category will be derived based on response 
assessment performed on or before the start of subsequent anticancer therapy/procedure. 
Patients without documented subsequent anticancer therapy and/or with missing start date of 
anticancer therapy will be considered as not having received subsequent anticancer therapy.
A BOR of SD can only be made after the patient is on-study for a minimum of 35 days after 
the first dose of study drug.  Any tumor assessment indicating SD before this time period will 
be considered as NE for BOR if no assessment after this time period is available.   
The overall response rate and the corresponding 95% two-sided exact CI will be presented. 
Subgroup analysis may be provided for disease subtype, disease stage, age group, sex, 
country, response to the first line and/or most recent line of prior systematic therapy (relapse: 
CR+PR vs. refractory: SD+PD vs. other: NE + missing), and other relevant variables.
Percent change from baseline in the sum of product of the perpendicular diameters (SPD) for 
target lesions will be presented for available data in the all-treated population . These data 
will also be displayed as a waterfall plot, with vertical bars representing the sorted values of 
best percent reduction for each patient.  
A sensitivity analysis of ORR determined by the independent reviewer
will be 
conducted for the per-protocol population if relevant. 
A sensitivity analysis of ORR will be conducted in which best overall response is determined 
by investigators. 
4.9.2 
 
Duration of response will be defined for patients with CR or PR only as the interval between 
the date of initial documentation of a response and the date of the first documented evidence 
of progressive disease based on independent radiographic assessment or death, whichever 
occurs first. Clincal progression at EOT/EOS without radiographic assessment could be 
considered as an event in a sensitivity analysis. Patients who have the event after the start of 
subsequent anticancer therapy/procedure, or are progression-free and alive at the time of 


 
 
clinical cut-off, or have unknown status, will be censored at the last valid tumor assessment 
on or before the start of subsequent anticancer therapy/procedure or clinical cut-off time.  
Patients with no post-baseline disease assessment will be censored on Day 1. 
Duration of response will be estimated and displayed for the all-treated population using 
Kaplan-Meier methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented.
A sensitivity analysis of DOR will be conducted in which the DOR for patients undergo SCT 
will not be censored at SCT. 
A sensitivity analysis of DOR per investigator assessments will also be conducted. 
Subgro
 
4.9.3 
 
 
4.9.4 
 
  
4.9.5 
 
 
Patients with no post-baseline disease assessment will be censored on Day 1. 
RFS will be estimated and displayed for the all-treated population using Kaplan-Meier 
methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 


 
 
A sensitivity analysis of RFS will be conducted in which RFS for patients undergo SCT will 
not be censored at SCT. 
 
4.9.6 
 
Progression-free survival is defined as the interval between the date of the first dose and the 
date of the first disease progression based on independent radiographic assessment or death, 
whichever occurs first. Clincal progression at EOT/EOS without radiographic assessment 
could be considered as an event in a sensitivity analysis. Patients who have the event after the 
start of subsequent anticancer therapy/procedure, or who are progression-free and alive at the 
time of clinical cut-off, or have unknown status, will be censored at the time of their last 
valid disease assessment on or before the start of subsequent anticancer therapy/procedure or 
clinical cut-off.  
Patients with no post-baseline disease assessment will be censored on Day 1. 
PFS will be estimated and displayed for the all-treated population using Kaplan-Meier 
methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 
A sensitivity analysis of PFS will be conducted in which the PFS for patients undergo SCT 
will not be censored at SCT. 
 
4.9.7 
 
Overall survival is defined as the interval between the date of the first dose and the date of 
death from any cause. Patients who are known to be alive as of their last known status will be 
censored at their date of last contact. Patients who are lost to follow-up will be censored at 
the date the patient is last known to have been alive. The last confirmed alive date is the 
latest of the following: study visit date, telephone contact date, end of study last confirmed 
alive date, follow-up systemic (anticancer) therapy end date or start date (if ongoing or end 
date is missing), local or central radiologist scan date, or other date in the clinical database.
OS will be estimated and displayed for the all-treated population using Kaplan-Meier 
methods (SAS® PROC LIFETEST). A Kaplan-Meier plot will be presented. 
4.9.8 
 
Total tumor volume will be summarize if data are available. 
4.9.9 
 
The fraction of patients receiving HSCT following camidanlumab tesirine, and without any 
other anticancer therapy in between other than the therapies preparing for HSCT, will be 
summarized. 


 
 
4.10 
 
Scoring of QoL  data and methods for handling of missing items or missing assessments will 
be based on 
 
4.10.1 
 
EQ-5D-5L is designed as an international, standardized, generic instrument for describing 
and evaluating QoL.  The EQ-5D-5L consists of two parts: 
The descriptive system: QoL is classified according to five dimensions: mobility, self 
care, usual activities, pain/discomfort, and anxiety/depression.  Each dimension 
comprises five levels of perceived problems (e.g., none, slight, moderate, severe, 
extreme). 
The visual analog scale (VAS): patients are asked to indicate their health state today 
 
on the VAS to indicate their own health and then to report the score in a text box.  If 
there is a discrepancy between where the patient has placed the X and the number 
he/she has written in the box, the number in the box is to be entered in the CRF 
together with a comment indicating the discrepancy. 
Individual dimension responses will be summarized at each scheduled assessment with 
frequency counts and percentage of patients.  
Descriptive statistics (mean, standard deviation, median and range) of actual values and 
changes from baseline will be presented at each scheduled assessment for the EQ-VAS.
 
 
Summary analyses will include data up to the start of subsequent anticancer 
therapy/procedure. 
 


 
 
4.10.2 
 
 
The FACT-Lym questionnaire includes subscales for physical well-being (PWB, 7 items),
social/ family well-being (SWB, 7 items), emotional well-being (EWB, 6 items), functional
well-being (FWB, 7 items) and additional concerns (Lymphoma Subscale, LymS, 15 items).
The FACT-Lym scoring guide identifies those negatively stated items that must be reversed 
before being added to obtain subscale totals. Negatively stated items are reversed by 
summed to a total, which is the subscale score. For all FACT-Lym scales and symptom
indices, the higher score is associated with the better quality of life. The scores in the 
following items need to be reversed: 
Physical well-being: all individual items 
Social/family well-being: none 
Emotional well-
 
Functional well-being: none 
Additional concerns: all individual items 
 
 
FACT_Lym Trial Outcome Index (TOI, score range: 0-116) = PWB + FWB + LymS
FACT_G Total Score (score range: 0-108) = PWB + SWB + EWB + FWB 
FACT_Lym Total Score (score range: 0-168) = PWB + SWB + EWB + FWB + 
LymS 
 


 
 
 
 
 
data listing for each individual item, the subscale scores and the composite scores will be
presented for each subject at each visit. 
5 
 
No formal interim analysis is planned. 
6 
 
 


 
 
7 
 
 
 
 
  
 


 
 
8 
 
8.1 
 
8.1.1 
 
 
 
If dates are completely missing, no imputation will be made.  
For any partial date with missing year, no imputation will be made. 
For missing initial diagnosis date, if only day is missing, then the 1st of the month 
will be used; if only year is present, then Jan 1st will be used. If such imputed date for 
initial diagnosis is on or after date of first dose, then date of first dose - 1 will be used. 
If the imputed date is for an AE start date and is in the same year and month as but 
before the first dose date, then the first dose date will be used, or if the imputed AE 
start date is after the AE end date, then the AE end date will be used. If the imputed 
date is for an AE start date and is in the same year and month as but after the last dose 
date + 30 days, then the last dose date + 30 days will be used. 
If a medication date or time is missing or partially missing, so it cannot be determined 
whether it was taken prior or concomitantly, it will be considered as a prior and 
concomitant medication. 
If the imputed date is for a date of death and is before the last date that the patient is 
known to be alive, the latter date will be used. 
If the date part is missing for new anticancer therapy, the month and year will be used 
for comparison with disease assessment. 
 
 
 
 


 
 
8.1.2 
 
 
8.1.3 
 
 
If more than 1 assessment occurs during the same nominal visit, select the record 
closest to the nominal day for that visit. 
If there are 2 assessments that are equidistant from the nominal day, the data of the 
assessment after the scheduled study day will be used. 
The last measurement will be used if multiple measurements are taken on the same 
day. 
 
 






 
 
HL 
Hodgkin lymphoma 
HSCT 
Hematopoietic stem cell transplant 
iDSMB 
Independent Data and Safety Monitoring Board 
IP 
Investigational product 
MedDRA 
Medical Dictionary for Regulatory Activities 
NE 
Not evaluable 
ORR 
Overall response rate 
OS 
Overall survival 
PD 
Progressive disease 
PFS 
Progression-free survival 
PK 
Pharmacokinetic 
PP 
Per-protocol 
PR 
Partial response 
PT 
Preferred term 
Q3W 
Every 3 weeks 
QTc 
Corrected QT interval 
RFS 
Relapse-free survival 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCT 
Stem cell transplant 
SD 
Stable disease 
SMQ 
Standardised MedDRA Query 
SOC 
System organ class 
SPD 
Sum of product of the perpendicular diameters  
std 
Standard deviation 
TANT 
Tumor-associated nontumor cells 
TEAE 
Treatment-emergent adverse event 
WHODRUG DD 
World Health Organization Drug Dictionary