Conditions: Head and Neck Cancer Squamous Cell Carcinoma Non-small Cell Lung Cancer Gastric Cancer Esophageal Cancer Pancreas Cancer Bladder Cancer Renal Cell Carcinoma Melanoma Triple-negative Breast Cancer Ovarian Cancer Colo-rectal Cancer Fallopian Tube Cancer
Keywords: Camidanlumab tesirine
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 78
Healthy volunteers: no

Brief summary:
This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

Detailed description:
This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose expansion part. The duration of the study participation for each participant was defined as the time from the date of signed written informed consent to the completion of the followup period, withdrawal of consent, loss to follow-up, or death, whichever occurs first.

The study was include a Screening Period (of up to 21 days), a Treatment Period (with cycles of 3 weeks for a Q3W dosing regimen), and a Follow-up Period (approximately every 12 week visits) for up to 1 year after treatment discontinuation.

Arms:
arm 1: In Part 1 (dose escalation) participants received escalating doses of ADCT-301 as monotherapy.

Camidanlumab tesirine is administered as a 30-minute intravenous (IV) infusion on Day 1 of each cycle. Participants treated with camidanlumab tesirine as monotherapy, in the initial dose cohort will receive 20 μg/kg Q3W and the highest dose was 150 μg/kg Q3W. arm 2: In Part 1 (dose escalation) participants received escalating doses of ADCT-301 in combination with pembrolizamab as combination therapy.

In Part 2 (dose expansion), participants received ADCT-301 in combination with pembrolizamab as combination therapy at the dose identified in Part 1 (dose escalation).

Participants treated with camidanlumab tesirine in combination with pembrolizumab, in the initial dose cohort received 30 μg/kg Q3W of camidanlumab tesirine.

Pembrolizumab was administered as a 30 minute IV infusion at a fixed dose of 200 mg (starting 1 hour after the end of the camidanlumab tesirine infusion).

Interventions: intervention 1: ADCT-301 intervention 2: Pembrolizumab
Intervention descriptions: intervention 1: intravenous infusion intervention 2: intravenous infusion

Protocol document:
Prot_000.pdf: 
Protocol Number: ADCT-301-103 
 
Official Title: A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-
301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors 
NCT Number: NCT03621982 
 
Document Date: 14 February 2022 






ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
ADCT-301-103 
Protocol Amendment 8 
Confidential 
Page 3 
 
DECLARATION OF INVESTIGATOR 
I have read and understood all sections of the protocol entitled: “A Phase 1b, Open-label, 
Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, 
Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as 
Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors” 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 8, dated 14 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 SA 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 
 
 
 
 
 
 
 
Printed Name of Institution 


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TABLE OF CONTENTS 
TABLE OF CONTENTS .......................................................................................................... 4 
LIST OF TABLES .................................................................................................................... 9 
LIST OF FIGURES .................................................................................................................. 9 
LIST OF ABBREVIATIONS ................................................................................................. 10 
SUMMARY OF CHANGES .................................................................................................. 15 
LIST OF PRIOR PROTOCOL VERSIONS ........................................................................... 16 
PROTOCOL SYNOPSIS ........................................................................................................ 18 
SCHEDULE OF EVENTS ..................................................................................................... 28 
1 
INTRODUCTION AND BACKGROUND ................................................................... 36 
1.1 
Targeting CD25 in Tumor Microenvironment ...............................................................36 
1.2 
Description of Investigational Study Drug .....................................................................36 
1.3 
Safety and Efficacy of Camidanlumab Tesirine in Clinical Studies ..............................37 
1.3.1 
ADCT-301-001 ...........................................................................................................38 
1.3.2 
ADCT-301-002 ...........................................................................................................38 
1.3.3 
ADCT-301-201 ...........................................................................................................39 
1.3.4 
ADCT-301-103 ...........................................................................................................39 
1.4 
Pembrolizumab ...............................................................................................................39 
1.5 
Safety and Efficacy of Pembrolizumab ..........................................................................40 
2 
STUDY RATIONALE ................................................................................................... 41 
2.1 
Selected Tumor Types ....................................................................................................41 
2.1.1 
Rationale for the Selection of Indications for the Combination in the Dose-Escalation 
Part ..............................................................................................................................42 
2.1.2 
Rationale for the Selection of MSI-H/dMMR Patients in the Dose-Expansion .........42 
2.2 
Rationale for Study Design ............................................................................................43 
2.3 
Rationale for Dose Selection ..........................................................................................43 
2.3.1 
Dose of Camidanlumab Tesirine as Monotherapy ......................................................43 
2.3.2 
Dose of Camidanlumab Tesirine in combination with Pembrolizumab .....................43 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................. 45 
4 
STUDY DESIGN ........................................................................................................... 48 
4.1 
Overview ........................................................................................................................48 
4.1.1 
Dose-Escalation ..........................................................................................................48 
4.1.2 
Dose-Expansion ..........................................................................................................50 


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4.1.3 
Safety Oversight by the Dose-Escalation Steering Committee ..................................50 
4.2 
Study Periods ..................................................................................................................51 
4.2.1 
Screening Period .........................................................................................................51 
4.2.2 
Treatment Period .........................................................................................................51 
4.2.3 
End of Treatment ........................................................................................................51 
4.2.4 
Follow-up Period ........................................................................................................51 
4.2.5 
End of Study ...............................................................................................................51 
4.3 
Study Stopping Rules .....................................................................................................52 
4.3.1 
Camidanlumab Tesirine as Monotherapy ...................................................................52 
4.3.2 
Camidanlumab Tesirine in Combination with Pembrolizumab ..................................52 
5 
PATIENT POPULATION ............................................................................................... 53 
5.1 
Inclusion Criteria ............................................................................................................53 
5.2 
Exclusion Criteria ...........................................................................................................55 
5.3 
Screening Failures ..........................................................................................................57 
5.4 
Discontinuation ..............................................................................................................58 
5.4.1 
Discontinuation from Study Drug ..............................................................................58 
5.4.2 
Discontinuation from the Study ..................................................................................58 
5.4.3 
Loss to Follow-Up ......................................................................................................59 
5.5 
Patient Replacements .....................................................................................................59 
6 
TREATMENT ................................................................................................................ 60 
6.1 
Study Drugs ....................................................................................................................60 
6.1.1 
Camidanlumab Tesirine ..............................................................................................60 
6.1.2 
Pembrolizumab ...........................................................................................................60 
6.2 
Management of Clinical Supplies ..................................................................................60 
6.2.1 
Packaging and Storage ................................................................................................60 
6.2.2 
Preparation and Administration ..................................................................................60 
6.2.2.1 
Camidanlumab Tesirine ........................................................................................ 60 
6.2.2.2 
Pembrolizumab ..................................................................................................... 61 
6.2.3 
Accountability .............................................................................................................61 
6.3 
Camidanlumab Tesirine as Monotherapy Dosing ..........................................................61 
6.4 
Camidanlumab Tesirine Combination with Pembrolizumab Dosing .............................62 
6.5 
Dose-Limiting Toxicities ................................................................................................64 
6.6 
Dose Delays and Modifications .....................................................................................65 


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6.6.1 
Dose Delays and Modifications for Camidanlumab Tesirine .....................................65 
6.6.1.1 
Camidanlumab Tesirine Dose Modification Guidelines: General Toxicities ....... 66 
6.6.1.2 
Guidelines for Dose Modification: Specific Non-hematologic Toxicities ............ 66 
6.6.1.3 
Guidelines for Dose Modification: Specific Hematologic Toxicities ................... 69 
6.6.1.4 
Guidelines for Dose Modification: Specific Neurologic Toxicities ...................... 69 
6.6.1.5 
Guidelines for Dose Modification: Specific Skin Toxicities ................................ 69 
6.6.1.6 
Principles of Camidanlumab Tesirine Rechallenge .............................................. 73 
6.6.2 
Dose Delays and Modifications for Pembrolizumab ..................................................74 
6.6.2.1 
General rules ......................................................................................................... 74 
6.6.2.2 
Holding Recommendations ................................................................................... 74 
6.6.2.3 
Principles of Pembrolizumab Rechallenge ........................................................... 74 
6.7 
Overdose Management ...................................................................................................75 
6.8 
Treatment Compliance ...................................................................................................75 
6.9 
Premedication and Supportive Care ...............................................................................75 
6.9.1 
Premedication for Camidanlumab Tesirine ................................................................75 
6.9.2 
Premedication for Pembrolizumab .............................................................................75 
6.9.3 
Treatment of Edema and Pleural Effusion ..................................................................75 
6.9.4 
Treatment and Prophylaxis of Infusion-Related Hypersensitivity Reactions .............76 
6.9.5 
Consideration for Skin Toxicity ..................................................................................76 
6.9.5.1 
Camidanlumab Tesirine ........................................................................................ 76 
6.9.5.2 
Pembrolizumab ..................................................................................................... 76 
6.9.6 
Diagnostic, Work-up, and Management of Polyradiculopathy/ Guillain-Barré 
Syndrome ....................................................................................................................77 
6.9.7 
Other Supportive Care ................................................................................................78 
6.10 Concomitant Medications and Procedures .....................................................................78 
6.10.1 Permitted During Study ..............................................................................................78 
6.10.2 Prohibited During Study .............................................................................................78 
6.10.3 Varicella Zoster Virus Prophylaxis .............................................................................78 
7 
STUDY ASSESSMENTS AND PROCEDURES .......................................................... 79 
7.1 
Informed Consent ...........................................................................................................79 
7.2 
Demographics and Baseline Characteristics ..................................................................79 
7.3 
Efficacy Assessments .....................................................................................................79 
7.4 
Safety Assessments ........................................................................................................80 


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7.4.1 
Physical Examination .................................................................................................80 
7.4.2 
ECOG Performance Status .........................................................................................81 
7.4.3 
Height and Weight ......................................................................................................81 
7.4.4 
Vital Signs ...................................................................................................................81 
7.4.5 
Laboratory Tests .........................................................................................................81 
7.4.6 
Pregnancy Test ............................................................................................................83 
7.4.7 
ECG ............................................................................................................................83 
7.5 
Pharmacokinetics, 
 and Immunogenicity .......................................85 
7.5.1 
Pharmacokinetics ........................................................................................................86 
7.5.2 
Immunogenicity ..........................................................................................................89 
 
 
 
 
 
 
8 
ADVERSE EVENTS ..................................................................................................... 93 
8.1 
Definition of Adverse Events, Serious Adverse Events, and Adverse Events of Special 
Interest ............................................................................................................................93 
8.1.1 
Adverse Events of Special Interest .............................................................................93 
8.2 
Eliciting and Reporting Adverse Events/Adverse Events of Special Interest/Serious 
Adverse Events ...............................................................................................................94 
8.3 
Assessment of Severity ..................................................................................................95 
8.4 
Assessment of Causality .................................................................................................95 
8.5 
Regulatory Reporting .....................................................................................................95 
8.6 
Pregnancy Reporting ......................................................................................................95 
9 
STATISTICAL CONSIDERATIONS ............................................................................ 97 
9.1 
Sample Size Calculation .................................................................................................97 
9.2 
Analysis Populations ......................................................................................................97 
9.3 
Interim Analysis .............................................................................................................97 
9.4 
Final Analysis .................................................................................................................97 
9.5 
Demographics and Baseline Characteristics ..................................................................97 
9.6 
Exposure to Treatments ..................................................................................................98 
9.7 
Efficacy Analyses ...........................................................................................................98 
9.7.1 
Overall Response Rate ................................................................................................98 
9.7.2 
Duration of Response .................................................................................................98 


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9.7.3 
Progression-Free Survival ..........................................................................................98 
9.7.4 
Overall Survival ..........................................................................................................98 
9.8 
Safety Analyses ..............................................................................................................98 
9.8.1 
Adverse Events ...........................................................................................................99 
9.8.2 
Clinical Laboratory Results ........................................................................................99 
9.8.3 
Additional Safety Assessments ...................................................................................99 
9.9 
Pharmacokinetic Analyses ............................................................................................100 
9.10 Immunogenicity Analyses ............................................................................................100 
 
10 
DATA MANAGEMENT AND QUALITY ASSURANCE .......................................... 102 
11 
ETHICAL, REGULATORY, AND STUDY MANAGEMENT CONSIDERATIONS 103 
11.1 Regulatory and Ethical Conduct of the Study ..............................................................103 
11.2 Independent Ethics Committee or Institutional Review Board ....................................103 
11.3 Patient Information and Consent ..................................................................................103 
11.4 Confidentiality ..............................................................................................................103 
11.5 Financial Disclosure and Obligations ..........................................................................104 
11.6 Study Conduct ..............................................................................................................104 
11.7 Protocol Amendments ..................................................................................................104 
11.8 Monitoring of the Study ...............................................................................................104 
11.9 Records Retention ........................................................................................................104 
11.10 Publications ..................................................................................................................105 
12 
REFERENCE LIST ...................................................................................................... 106 
 




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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 
BOR 
best overall response 
BP 
blood pressure 
BID 
twice daily 
β-HCG 
human chorionic gonadotropin 
 
 
 
 
C1D1 
Cycle 1 Day 1 
CFR 
Code of Federal Regulations 
cHL 
classical Hodgkin Lymphoma 
CHPi 
checkpoint inhibitor 
CI 
confidence interval 
CL 
clearance 
Cmax 
maximum concentration 
CMV 
cytomegalovirus 


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Abbreviation 
Definition 
CNS 
central nervous system 
CR 
complete response 
CRO 
contract research organization 
CSF 
cerebrospinal fluid 
CSR 
clinical study report 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CTLA-4 
cytotoxic T-lymphocyte associated protein 4 
COVID-19 
Coronavirus disease 19 
DESC 
dose-escalation steering committee 
DLT 
dose limiting toxicity 
DNA 
deoxyribonucleic acid 
DOR 
duration of response 
DRESS 
drug reaction with eosinophilia and systemic symptoms 
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 
EU 
European Union 
FDA 
Food and Drug Administration 
FIH 
first-in-human  
GBS 
Guillain-Barré syndrome 
G-CSF 
granulocyte colony stimulating factor 
GCP 
Good Clinical Practice 
 
 
GGT 
gamma glutamyl transferase 
GI 
gastrointestinal 


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Abbreviation 
Definition 
h 
hour 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HIV 
HL 
human immunodeficiency virus 
Hodgkin lymphoma 
HSV1 
herpes simplex virus 1 
HSV2 
herpes simplex virus 2 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
iCPD 
immune-confirmed progressive disease 
iCR 
immune-complete response 
IEC 
independent ethics committee 
IL 
interleukin 
imRECIST 
immune-modified Response Evaluation Criteria in Solid Tumors 
INR 
international normalized ratio 
iPR 
immune-partial response 
IRB 
institutional review board 
iRECIST 
immune-RECIST (modified RECIST 1.1 for immune-based 
therapeutics) 
irRC 
immune-related Response Criteria 
irRECIST 
immune-related Response Evaluation Criteria In Solid Tumors 
iSD 
immune-stable disease 
iUPD 
immune-unconfirmed progressive disease 
IV 
intravenous 
IVIg 
intravenous immunoglobulin 
MedDRA 
Medical Dictionary for Regulatory Activities 
min  
minute 
mmHg 
millimeters of mercury 
MMR 
mismatch repair 
MRI 
magnetic resonance imaging 
MSI 
microsatellite instability 


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Abbreviation 
Definition 
MSS 
microsatellite stability 
MTD 
maximum tolerated dose 
NHL 
NSCLC 
non-Hodgkin lymphoma 
non-small cell lung cancer 
ORR 
overall response rate 
OS 
overall survival 
PBD 
pyrrolobenzodiazepine 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PD-1 
programmed death 1 
PD-L1 
programmed death-ligand 1 
PFS 
progression-free survival 
PK 
PLEX 
pharmacokinetic(s) 
plasma exchange 
PR 
partial response 
PTT 
partial thromboplastin time 
QT 
QTcB 
measure between Q wave and T wave in the electrocardiogram 
Bazett correction of the QT measure 
QTcF 
Fridericia correction of the QT measure 
Q3W 
every 3 weeks 
RBC 
red blood cell 
RDE 
recommended dose for expansion 
RECIST 
Response Evaluation Criteria In Solid Tumors 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SD 
stable disease 
SoC 
standard of care 
SoE 
Schedule of Events 
sCD25 
soluble CD25 
SJS 
Stevens-Johnson syndrome 
SmPC 
Summary of Product Characteristics 


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Abbreviation 
Definition 
 
 
TEAE 
treatment-emergent adverse event(s) 
Teff 
effector T cell 
TEN 
Topic epidermal necrolysis 
TGF-β 
Tumor growth factor beta 
Thalf 
apparent terminal elimination half-life 
 
 
TLS 
tumor lysis syndrome 
Tmax 
time to maximum concentration 
TNBC 
triple negative breast cancer 
Treg 
regulatory T cell 
TSH 
thyroid stimulating factor 
ULN 
upper limit of normal 
US 
United States 
Vd 
volume of distribution 
VZV 
varicella zoster virus 
WBC 
white blood cell 
WHO 
World Health Organization 
WOCBP 
women of childbearing potential 


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SUMMARY OF CHANGES 
The primary reason for Protocol Amendment 8 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 
recently revised half-life value of camidanlumab tesirine. 
• 
In Section 5.1, Inclusion criterion 11: 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 who are 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 2) have been revised accordingly. 
• In addition, revisions to the protocol text have also been applied to the synopsis section. 




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Versions 
Version Date 
Rationale for Changes  
Protocol 
Amendment 1 
20 June 2018 
The basis for Protocol Amendment 1 (20 June 2018) is the 
request from the Food and Drug Administration (FDA) to 
modify the study stopping rules to be consistent with the 
recent comments from the FDA related to the studies 
ADCT-301-001 and ADCT-301-002. 
Original 
Protocol 
11 May 2018 
 
 










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• 
Part 2 Dose-expansion camidanlumab tesirine in combination with 
pembrolizumab: 
- 
Group 1: One of the indications identified in Part 1, for which 
at least 1 response (PR or CR) was seen. 
- 
Group 2: Patients with advanced solid tumors and 
MSI-H/dMMR status, who have received a prior regimen 
containing PD-1/PD-L1 inhibitors, for which the best response 
was CR, PR, or SD ≥4 months, and then progressed while 
under treatment with the PD-1/PD-L1 inhibitor-based regimen 
Note: A maximum of 4 patients with the same indication will 
be allowed in this basket group. 
4. Patients who are refractory to or intolerant of existing therapy(ies) 
known to provide clinical benefit for their condition. 
5. Patients with advanced/metastatic cancer, with measurable disease as 
determined by RECIST v1.1 or immune-related Response Criteria 
(irRC)/ immune-related Response Evaluation Criteria In Solid Tumors 
(irRECIST)/ immune-related Response Evaluation Criteria In Solid 
Tumors (iRECIST)/ immune-modified Response Evaluation 
Criteria in Solid Tumors (imRECIST) as per Investigator discretion. 
Note 1: Lytic bone lesions or mixed lytic-blastic lesions, with 
identifiable soft tissue components, that can be evaluated by cross 
sectional imaging techniques such as computed tomography (CT) or 
magnetic resonance imaging (MRI) can be considered as measurable 
lesions ONLY if the soft tissue component meets the definition of 
measurability per RECIST. 
Note 2: If immediate prior therapy contains an immune-therapy 
component, progression has to meet criteria as defined in 
irRC/irRECIST/iRECIST/imRECIST as per Investigator discretion.  
6. A) For camidanlumab tesirine as monotherapy: Patient must have a 
site of disease amenable to biopsy and be willing to undergo fresh 
biopsy procedures (minimum 3 passes each) prior to first dose, 
according to the treating institution's guidelines. 
B) Patients included in the paired-biopsy cohort must in addition be 
willing to undergo fresh biopsy procedures (minimum 3 passes each) 
after receiving at least one dose of study drug. 
C) For camidanlumab tesirine in combination with pembrolizumab:  
Patient must either have a site of disease amenable to biopsy and must 
provide fresh tumor biopsy prior to C1D1, or have sufficient available 
archival tumor tissue (biopsied after their last disease progression, and 
in the situation where the patient has received no additional anti-cancer 
therapy between their progression and C1D1). Patients must also be 
willing to undergo fresh biopsy procedures (minimum 3 passes each) 
after receiving at least 1 dose of study treatment, according to the 
treating institution's guidelines. 
7. ECOG performance status 0-1. 
8. Patient with life expectancy ≥3 months as per Investigator assessment. 


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9. Adequate organ function as defined by screening laboratory values 
within the following parameters: 
a. Absolute neutrophil count (ANC) ≥1.5 × 103/µL (off growth 
factors at least 72 hours). 
b. Platelet count ≥100 × 103/µL without transfusion in the past 
10 days. 
c. Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed). 
d. 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. 
e. 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). 
f. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance 
≥60 mL/min by the Cockcroft-Gault equation. 
Note: A laboratory assessment may be repeated a maximum of two 
times during the Screening period to confirm eligibility. 
10. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test 
within 7 days prior to start of study drug for women of childbearing 
potential (WOCBP). 
11. 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 
or 4 months after last dose of pembrolizumab, whichever is the latest. 
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 or 4 months after last dose of pembrolizumab, whichever is 
the latest. 
Exclusion Criteria: 
1. Participation in another investigational interventional study. 
2. Prior therapy with a CD25 (IL-2R) antibody. 
3. Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody. 
4. Patients with prior solid organ or allogeneic bone marrow transplant. 
5. 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]) (patients with vitiligo, type 1 
diabetes mellitus, residual hypothyroidism, hypophysitis due to 
autoimmune condition only requiring hormone replacement may be 
enrolled). 
6. 
History 
of 
neuropathy 
considered 
of 
autoimmune 
origin 
(e.g., polyradiculopathy including Guillain-Barré syndrome and 
myasthenia gravis) or other central nervous system (CNS) 
autoimmune disease (e.g., poliomyelitis, multiple sclerosis). 


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7. History of recent infection (within 4 weeks of C1D1) caused by a 
pathogen known to be associated with GBS, for example: herpes 
simplex virus 1/2 (HSV1, HSV2), varicella zoster virus (VZV), 
Epstein-Barr virus (EBV), cytomegalovirus (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). 
8. Known seropositive and requiring anti-viral therapy for human 
immunodeficiency (HIV) virus, hepatitis B virus (HBV), or 
hepatitis C virus (HCV). Note: Testing is not mandatory to be eligible 
but should be considered in patients with high risk for these infections; 
testing is mandatory if status is unknown. 
9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis. 
10. Failure to recover to ≤Grade 1 (Common Terminology Criteria for 
Adverse 
Events 
version 
4.0 
[CTCAE 
v4.0]) 
from 
acute 
non-hematologic toxicity (to ≤Grade 2 for neuropathy or alopecia), 
due to previous therapy, prior to screening. 
11. Symptomatic CNS metastases or evidence of leptomeningeal disease 
(brain MRI or previously documented cerebrospinal fluid [CSF] 
cytology). Previously treated asymptomatic CNS metastases are 
permitted provided that the last treatment (systemic anticancer therapy 
and/or local radiotherapy) was completed ≥4 weeks prior to Day 1 
except usage of low dose of steroids on a taper (i.e., up to 10 mg 
prednisone or equivalent on Day 1 and consecutive days is permissible 
if being tapered down). Patients with discrete dural metastases are 
eligible. 
12. 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). 
13. Active diarrhea CTCAE Grade 2 or a medical condition associated 
with chronic diarrhea (such as irritable bowel syndrome, inflammatory 
bowel disease). 
14. Active infection requiring systemic antibiotic therapy. 
15. Active 
bleeding 
diathesis 
or 
significant 
anticoagulation 
(international normalized ratio [INR] ≥2.0). 
16. Breastfeeding or pregnant. 


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17. Significant 
medical 
comorbidities, 
including 
uncontrolled 
hypertension (blood pressure [BP] ≥160 mmHg systolic and/or 
≥110 mmHg diastolic repeatedly with or without anti-hypertensive 
medication), unstable angina, congestive heart failure (greater than 
New York Heart Association class II), electrocardiographic evidence 
of acute ischemia, coronary angioplasty or myocardial infarction 
within 6 months prior to screening, severe uncontrolled atrial or 
ventricular cardiac arrhythmia, poorly controlled diabetes, active 
ulceration of the upper gastrointestinal (GI) tract or GI bleeding, or 
severe chronic pulmonary disease. 
18. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic 
therapy within 14 days prior to start of study drug (C1D1), 
except shorter if approved by the Sponsor. For cytotoxic agents that 
have major delayed toxicity, e.g., mitomycin C and nitrosoureas, 
4 weeks is indicated as washout period. For patients receiving 
systemic anticancer immunotherapies (as opposed to intralesional) 
that lead to activation of Teffs and/or increase the Teff/Treg ratio, such 
as anti-PD-1 antibodies, 4 weeks are indicated as the washout period. 
19. Use of any other experimental medication within 14 days prior to start 
of study drug (C1D1). 
20. Patients requiring concomitant immunosuppressive agents or chronic 
treatment with corticosteroids except: 
• 
replacement dose steroids in the setting of adrenal 
insufficiency 
• 
topical, inhaled, nasal, and ophthalmic steroids are allowed 
21. Planned live vaccines within 30 days prior to the first dose of study 
treatment and during study treatment 
22. Congenital long QT syndrome, or a corrected QTcF interval of 
≥480 ms, at screening (unless secondary to pacemaker or bundle 
branch block). 
23. 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. 
24. 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. 
25. For patients treated with camidanlumab tesirine in combination with 
pembrolizumab: patients intolerant to checkpoint-inhibitor or with a 
history of the following ≥Grade 3 immune-related adverse events: 
hepatitis, renal, ocular, neurologic, cardiovascular, rheumatologic, 
and hematologic 
26. For patients treated with camidanlumab tesirine in combination with 
pembrolizumab: patients with a history of non-infectious pneumonitis 
related to prior systemic treatment and that require treatment with 
steroids within the last 6 months prior to enrolment. 


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Camidanlumab tesirine (ADCT-301) 
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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 21 days), 
a Treatment Period (with cycles of 3 weeks for every 3 week [Q3W] 
dosing regimen), and a Follow-up Period (approximately every 12-week 
visits) for up to 1 year from end of treatment visit. 
Patients may continue treatment for up to 1 year or until disease 
progression, unacceptable toxicity, or other discontinuation criteria, 
whichever occurs first. Patients benefiting clinically at 1 year may continue 
treatment after a case-by-case review with the Sponsor. 
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: CT or MRI 
Safety Assessments: 
• 
Physical examination, including neurological examination 
• 
ECOG Performance status 
• 
Height and weight 
• 
Vital signs 
• 
Laboratory tests (hematology, chemistry, coagulation, thyroid 
function, urinalysis, and as applicable, additional microbiological 
studies) 
• 
Pregnancy test, if applicable 
• 
12-Lead ECG (triplicate) 
• 
AEs/SAEs, graded according to CTCAE version 4.0. 
• 
DLTs (dose-escalation only) 
Other Assessments: 
• 
Blood sampling for PK, ADA, 
  
 
 
Study Drug, Dosage, 
and Mode of 
Administration: 
Camidanlumab tesirine is administered as a 30-minute intravenous (IV) 
infusion on Day 1 of each cycle. 
Patients treated with camidanlumab tesirine as monotherapy, in the initial 
dose cohort will receive 20 µg/kg Q3W and the highest dose possibly 
tested will be 300 µg/kg Q3W.  
Patients treated with camidanlumab tesirine in combination with 
pembrolizumab, in the initial dose cohort will receive 30 µg/kg Q3W of 
camidanlumab tesirine. The highest dose possibly tested of camidanlumab 
tesirine in combination with pembrolizumab, will be the highest dose 
investigated and deemed safe, of camidanlumab tesirine as monotherapy. 
Pembrolizumab at dose of 200 mg Q3W will be administered on Day 1 of 
each cycle starting from Cycle 1 onwards (dosing schedule 1). If 
unacceptable toxicity occurs during Cycle 1, dosing Schedule 2, where 
pembrolizumab administration may start at Cycle 2, may be investigated 
in new enrolled patients.  


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 8 
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When given concomitantly, camidanlumab tesirine will be administered 
prior to pembrolizumab, and separated by 1 hour. 
Patients, who tolerate the combination and are in disease control, would be 
allowed to receive additional cycles of camidanlumab tesirine in 
combination with pembrolizumab, starting from Cycle 5. Additional 
administration of camidanlumab tesirine can be given per protocol upon 
informing the Sponsor. 
Additional administration of camidanlumab tesirine concomitantly with 
pembrolizumab, will be given as follow: 2 consecutive Cycles every 
2 Cycles (2 Cycles on, 2 Cycles off schedule), starting from Cycle 5 for up 
to a year (i.e., Cycle 5 and 6, Cycle 9 and 10, Cycle 13 and 14, Cycle 17 
and 18) if there is no delay in the planned treatment schedule, or, in case 
of delay in the administration of pembrolizumab, after respecting a 
minimum of 63 days (9 weeks) between the last dose of camidanlumab 
tesirine and the first dose of the 2 subsequent additional administrations of 
camidanlumab tesirine. Between these cycles, patients should receive 
pembrolizumab as a single agent. 
Sample Size: 
Approximately 95 patients; Part 1 may enroll approximately 65 patients 
and Part 2 will enroll approximately 30 patients. 
Statistical 
Considerations: 
Safety and tolerability analyses will be presented descriptively. 
ORR with 95% CI from treated patients will be presented descriptively. 
Duration of response, PFS, and OS will be analyzed in Kaplan-Meier 
approach. 
 


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Camidanlumab tesirine (ADCT-301) 
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SCHEDULE OF EVENTS 
Table 1. 
Schedule of Events Every 3 Weeks (Q3W) Dosing Schedule: Camidanlumab Tesirine as Monotherapy 
 
Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
(up to 1 year from EOT) 
(1 cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
–21 to –1 
1 
3 and 5 8 
15 
1 
81 
 
 
Informed consent 
11.3 
X 
 
 
 
 
 
 
 
 
Eligibility criteria 
5.1 
5.2 
X 
 
 
 
 
 
 
 
 
Demography and Baseline 
Characteristics 
7.2 
X 
 
 
 
 
 
 
 
 
Medical/Cancer history 
7.2 
X 
 
 
 
 
 
 
 
 
Fresh tumor tissue collection 
7.5.3.2 
X prior to 1st dose 
(from non-target lesion) 
Optional biopsy prior to C2D1 (-1 wk window)2 and 
preferentially from the same site as the Baseline biopsy. 
This biopsy is mandatory for paired-biopsy cohorts. 
 
Disease assessment 
7.3 
X3 
6 weeks and 12 weeks after C1D1, then every 12 wks3 
X3 
Every 12 wks from EOT 
until disease progression4 
Physical examination, 
incl. neurological examination 
and check for infection 
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 
X 
 
Vital signs (BP, HR, RR, Temp) 
7.4.4 
X 
X6 
X 
X 
X 
X5 
X 
X 
 
Hematology and Chemistry 
7.4.5 
X 
X 
 
X 
X 
X 
X 
X 
 
Coagulation and Urinalysis  
7.4.5 
X 
X 
 
 
 
 
 
X 
 
Viral detection, if applicable6 
7.4.5 
X 
X 
 
 
 
X 
 
X 
 
Recommendation for VZV 
prophylaxis 
6.10.3 
For all enrolled patients 
 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
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Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
(up to 1 year from EOT) 
(1 cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
–21 to –1 
1 
3 and 5 8 
15 
1 
81 
 
 
Influenza and SARS-CoV-2 
7.4.5 
3-5 days 
or less 
prior to 
dosing on 
C1D1 
 
 
 
 
 
 
 
 
Pregnancy test, if applicable 
7.4.6 
X 
On C1D1, thereafter on D1 of every other cycle 
X 
X7 
12-lead ECG8,9 
7.4.7 
Table 6 
X 
X 
(Pre, EOI, Post) 
X 
D3 only 
X 
X 
C3 and C4 (Pre, 
Post), 
C5 (Pre), then every 
other cycle (Pre)  
 
X 
 
Premedication  
6.9.1 
 
D-1 to D2 
 
 
 
D-1 to D2 
 
 
 
Camidanlumab tesirine 
Administration 
6.3 
 
X 
 
 
 
X 
 
 
 
PK sample10 
7.5.1 
Table 8 
 
X 
(Pre, EOI, Post) 
X 
X 
X 
C3 and C4 (Pre, 
Post),  
then every cycle 
(Pre) 
 
X 
 
ADA sample11 
7.5.2 
Table 8 
 
X (Pre) 
 
 
X 
C1 only 
C3, C4, and C5 
(Pre), then every 
other cycle (Pre) 
 
X12 
 
Additional microbiological 
studies 
7.4.5 
In case of suspicion of infection and GBS 
Concomitant medications 
6.10 
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 


ADC Therapeutics 
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Protocol Amendment 8 
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Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
(up to 1 year from EOT) 
(1 cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
–21 to –1 
1 
3 and 5 8 
15 
1 
81 
 
 
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; C=cycle; 
; 
 
; D=day; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; EOI=end of infusion; EOT=end of treatment; 
GBS=Guillain-Barré syndrome, 
; HR=heart rate; ICF=informed consent form; iRECIST=immune-RECIST; 
PK=pharmacokinetic; Q3W=every three weeks; RR=respiratory rate; SAE=serious adverse event; SARS-CoV-2=severe acute respiratory syndrome 
coronavirus 2; Temp=temperature; VZV=varicella zoster virus; wk=week. 
1  After completion of 4 treatment cycles, the Day 8 visit is not required unless clinically indicated.  
2  Timing of on-treatment biopsy and other 
 sample(s) may be adjusted based on emerging evidence. 
3  Imaging performed within 4 weeks prior to C1D1 (beyond the screening period) can be accepted as the Screening (Baseline) assessment, 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 8 weeks of EOT, it does not need 
to be repeated at EOT. Confirmation of progression should be performed as per iRECIST, i.e., 4 to 8 weeks after the first progressive disease assessment; if 
progression is not confirmed, disease assessment should continue as originally planned. 
4  Disease assessments to be performed in patients having discontinued study drug for reasons other than disease progression or initiation of other anti-cancer 
therapy. 
5  Vital signs to be measured pre, during (only BP and heart rate), and at EOI. During infusion, BP and HR will be measured every 30 minutes. 
6  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). 
7  A pregnancy test should be performed ≥6.5 months after the last dose of camidanlumab tesirine. 
8  Pre-dose is preferably 2 hours prior to start of infusion of camidanlumab tesirine during Cycle 1 Day 1, and within 30 minutes prior to PK sample for Cycle 2 
Day 1. EOI is to be done within 10 minutes prior to EOI. Post-dose is 4 hours from the start of infusion of camidanlumab tesirine. 
9  Pre-dose is within 30 minutes prior to PK sample. Post-dose is 4 hours from the start of infusion of camidanlumab tesirine. 
10  Pre-dose is preferably 2 hours prior to start of infusion of camidanlumab tesirine. EOI is to be done within 5 to 10 minutes prior to EOI. Post-dose is 4 hours 
from the start of infusion of camidanlumab tesirine. 
11  Pre-dose is within 2 hours prior to start of infusion of camidanlumab tesirine. Post-dose is 4 hours from the start of infusion of camidanlumab tesirine. 
12  Patients who test positive for ADAs will be requested to supply additional ADA samples. 
 
 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 8 
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Visit Scheduling Windows:  
• 
Treatment Period: C1D1 is the reference day, D3 and D5: visit day ± 1 day (combined D3 and D5 visit is not allowed), otherwise visit day ± 2 days 
• 
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) 
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Protocol Amendment 8 
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Table 2. 
Schedule of Events Every 3 Weeks (Q3W) Dosing Schedule: Camidanlumab Tesirine in combination with 
Pembrolizumab 
 
Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
up to 1 year from EOT
(1 cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
–21 to –1 
1 
3 and 5 8 
15 
1 
81 
 
 
Informed consent 
11.3 
X 
 
 
 
 
 
 
 
 
Eligibility criteria 
5.1 
5.2 
X 
 
 
 
 
 
 
 
 
Demography and Baseline 
Characteristics 
7.2 
X 
 
 
 
 
 
 
 
 
Medical/Cancer history 
7.2 
X 
 
 
 
 
 
 
 
 
Fresh tumor tissue collection2 
7.5.3.2 
X prior to 1st dose 
(from non-target lesion) 
Biopsy prior to C3D12 and preferentially from the same site as 
the Baseline biopsy. 
 
MMR/MSS/MSI3 
5.1 
X 
 
 
 
Disease assessment 
7.3 
X4 
6 weeks and 12 weeks after C1D1, then every 9 wks4 
X3 
Every 9 wks from EOT 
until disease 
progression5 
Physical examination, 
incl. skin examination, 
neurological examination and 
check for infection 
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 
X 
 
Vital signs (BP, HR, RR, Temp) 
7.4.4 
X 
X (Pre, EOI)6 
X 
X 
X 
X (Pre, EOI)6 
X 
X 
 
Hematology and Chemistry 
7.4.5 
X 
X 
 
X 
X 
X 
X 
X 
 
Thyroid function test 
7.4.5 
 
X 
 
 
 
X (Cycle 3 and every 
other Cycle) 
 
X 
 
Coagulation and Urinalysis  
7.4.5 
X 
X 
 
 
 
 
 
X 
 
Viral detection, if applicable7 
7.4.5 
X 
X 
 
 
 
X 
 
X 
 
Recommendation for VZV 
prophylaxis 
6.10.3 
For all enrolled patients 
 


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Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 8 
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Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
up to 1 year from EOT
(1 cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
–21 to –1 
1 
3 and 5 8 
15 
1 
81 
 
 
Influenza and SARS-CoV-2 
7.4.5 
3-5 days 
or less 
prior to 
dosing on 
C1D1 
 
 
 
 
 
 
 
 
Pregnancy test, if applicable 
7.4.6 
X 
X 
 
 
 
X 
 
X 
X8 
12-lead ECG 
7.4.7 
Table 7 
X 
X 
(Pre, EOI, 
Post)9 
 
 
 
C3, C5 and every other 
Cycle (Pre)9 
 
X 
 
Camidanlumab tesirine 
premedication  
6.9.1 
 
D-1 to D2 
 
 
 
D-1 to D210 
 
 
 
Camidanlumab tesirine 
Administration 
6.4 
 
X 
 
 
 
X, starting Cycle 511 
 
 
 
Pembrolizumab administration 
6.4 
 
X12 
 
 
 
X 
 
 
 
PK sample13 
7.5.1 
Table 9 
 
X 
(Pre, EOI, Post) 
X 
X 
X 
C3, C4, C5, C6, C7 
then every other cycle 
(Pre) 
 
X 
 
ADA sample14 
7.5.2 
Table 9 
 
X (Pre) 
 
 
X 
C1 only 
C3, C4, C5, C6, C7 
then every other cycle 
(Pre) 
 
X15 
X15 
Additional microbiological 
studies 
7.4.5 
In case of suspicion of infection and GBS 
Concomitant medications 
6.10 
From ICF signature date or D-14, whichever is earlier, until 30 days after last dose of study treatment 
Adverse events 
8 
AE/SAEs from ICF signature date until 30 days after last dose of study treatment; thereafter, related SAEs only 


ADC Therapeutics 
Camidanlumab tesirine (ADCT-301) 
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Protocol Amendment 8 
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Protocol 
Section Screening 
Treatment Period 
Follow-up Period 
up to 1 year from EOT
(1 cycle = 21 days) 
 
 
Cycle 1 and Cycle 2 (C1 and C2) 
C3 and beyond 
EOT 
Every 12 weeks (wks) 
Day (D) 
 
–21 to –1 
1 
3 and 5 8 
15 
1 
81 
 
 
1st New anticancer treatment 
4.2.3 
 
 
 
 
 
 
 
X 
X 
Survival 
4.2.4 
 
 
 
 
 
 
 
X 
X 
Abbreviations: ADA=anti-drug antibody; (S)AE=serious adverse event; BP=blood pressure; 
; 
 
; D=day; DESC=dose-escalation meeting committee; ECG=electrocardiogram; ECOG=Eastern Cooperative Oncology Group; EOI=end of 
infusion; EOT=end of treatment; GBS=Guillain-Barré syndrome, 
; HR=heart rate; ICF=informed consent form; 
MMR=mismatch repair; MSI=microsatellite instability; MSS=microsatellite stability; PK=pharmacokinetic; RR=respiratory rate; SAE=serious adverse event; 
SARS-CoV-2=severe acute respiratory syndrome coronavirus; Temp=temperature; VZV=varicella zoster virus; wk=week. 
1  
After completion of Cycle 4, the Day 8 visit is not required unless clinically indicated.  
2  
Timing of biopsy may be adjusted based on emerging evidence. The on-treatment biopsy should be performed between Cycle 2 Day 8 and Cycle 2 Day 15, 
before the disease assessment. For patients with sufficient available archival tumor tissue prior to C1D1 (biopsied after their last disease progression, and 
in the situation where the patient has received no anti-cancer therapy between their progression and C1D1), a fresh biopsy prior to C1D1 may not be needed. 
This archived tissue will be used in lieu of the fresh biopsy and the screening window will not apply to this sample obtained routinely prior to ICF signature. 
3  
In Dose-escalation, for patients with NSCLC or melanoma, PD-L1 expression is requested; MMR/MSS/MSI status is not required. In Dose-escalation, for 
patients with colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube cancer, pancreatic cancers: if MMR/MSS/MSI status is not available at 
signature of the informed consent, the test should be performed before C1D1. In Dose-expansion, for patients enrolled in Group 1, if MMR/MSS/MSI 
status is not available at signature of the informed consent, the test should be performed before C1D1. In Dose-expansion, for patients enrolled in Group 2, 
MSI-H/dMMR status must be available prior to ICF signature. 
4  
Imaging performed within 4 weeks prior to C1D1 (beyond the screening period) can be accepted as the Screening (Baseline) assessment, and the same 
assessment method should be used throughout the study. During the treatment period, imaging will be performed 6 weeks (42 days ±7 days) after C1D1, 
but prior to C3D1, and 12 weeks (84 days ±7 days) after C1D1, but prior to C5D1, then every 9 weeks (63 days ±14 days) until EOT. 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 9 weeks (63 days ± 14 days) until 1 year from EOT. Disease assessments should be performed at the timepoints specified even if study 
drug dosing is delayed. If a scan has been performed within 8 weeks of EOT, it does not need to be repeated at EOT. Confirmation of progression should 
be performed as per iRECIST, i.e., 4 to 8 weeks after the first progressive disease assessment; if progression is not confirmed, disease assessment should 
continue as originally planned. 
5  
Disease assessments to be performed in patients having discontinued study treatment for reasons other than disease progression or initiation of other 
anti-cancer therapy. 
6  
Vital signs will be done pre-dose, at end of infusion of camidanlumab tesirine and at end of infusion of pembrolizumab. 


ADC Therapeutics 
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Protocol Amendment 8 
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Page 35 
 
7  
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).  
8  
A pregnancy test should be performed ≥9.5 months after the last dose of camidanlumab tesirine or ≥4 months after last dose of pembrolizumab, whichever 
is the latest. 
9  
Pre-dose is preferably within 2 hours prior to the start of infusion of camidanlumab tesirine. EOI is within 10 minutes prior to the end of infusion of 
camidanlumab tesirine. Post-dose is 4 hours from the start of infusion of camidanlumab tesirine. 
10  Only when camidanlumab tesirine is administered.  
11  Additional administration of camidanlumab tesirine is allowed for patients who tolerate the combination and are in disease control after the first tumor 
assessment. Additional camidanlumab tesirine administration concomitantly to pembrolizumab would be given as follow: 2 consecutive Cycles every 
2 Cycles, starting from Cycle 5 up to a year (i.e., Cycle 5 and 6, Cycle 9 and 10, Cycle 13 and 14, Cycle 17 and 18) if there is no delay in the planed 
treatment schedule, or, in case of delay in the administration of pembrolizumab, after respecting a minimum of 63 days (9 weeks) between the last dose of 
camidanlumab tesirine and the first dose of the 2 subsequent additional administrations of camidanlumab tesirine. Between these cycles, patients should 
receive pembrolizumab as a single agent. 
12  Alternative Schedules may be investigated based on observed safety and efficacy data, as assessed by the DESC: pembrolizumab from Cycle 2 onwards 
(Schedule 2). When administered on the same day, camidanlumab tesirine is to be administered prior to pembrolizumab separated by 1 hour (or more if 
clinically indicated). 
13  Pre-dose is preferably 2 hours prior to the start of infusion of camidanlumab tesirine or 2 hours prior to the start infusion of pembrolizumab, in visits 
without camidanlumab tesirine administration. EOI is to be done within a window of 5 minutes prior to EOI to 10 minutes after EOI. Post-dose is 4 hours 
from the start of infusion of camidanlumab tesirine. Collection of PK is stopped if camindanlumab tesirine administration is discontinued. 
14  Pre-dose is within 2 hours prior to the start of infusion of camidanlumab tesirine or 2 hours prior to the start infusion of pembrolizumab, in visits without 
camidanlumab tesirine administration. Collection of ADA is stopped if camindanlumab tesirine administration is discontinued. 
15  Patients who test positive for ADAs will be requested to supply additional ADA samples. 
 
 
 
 
 
Visit Scheduling Windows:  
• 
Treatment Period: C1D1 is the reference day, D3 and D5: visit day ± 1 day (combined D3 and D5 visit is not allowed), otherwise visit day ± 2 days 
• 
EOT: as soon as possible after decision to discontinue the study treatment, preferably within 30 days after last dose of study treatment, and before initiation 
of any new anticancer treatment  
• 
Follow-up Period: visit day ± 14 days 
 


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1 INTRODUCTION AND BACKGROUND 
1.1 
Targeting CD25 in Tumor Microenvironment 
Advances in immunotherapies have added agents to the available armamentarium for the 
treatment of cancer, with novel modes of action. Some of these treatments are checkpoint 
inhibitors (CHPi); cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed 
death 1 (PD-1)/programmed death-ligand 1 (PD-L1) antibodies being the “first-generation” of 
immune CHPi (Burugu, 2017; Wolchok, 2017; Hodi, 2010).  
One of the mechanisms of anti-CTLA-4 is the activation of antitumor immunity by promoting 
T-cell proliferation. On the other hand, the PD-1/PD-L1 axis supports tumor immune evasion 
in many cancers, and blockade of this interaction using monoclonal antibodies against PD-1 or 
PD-L1 can lead to restoration of effector T cell (Teff) functions (Sasidharan Nair, 2018; 
Facciabene, 2012). 
While single agent anti-CTLA-4 ipilimumab led to a response rate of around 10% in the 
malignant melanoma registration trial, single agent PD-1 CHPi pembrolizumab lead to an 
overall response rate (ORR) of >30% and single agent PD-1 CHPi nivolumab to a similar ORR 
at the recommended dose in a similar patient population (Johnson, 2017; Franklin, 2017; 
Hamid, 2017). The combination of ipilimumab with nivolumab further improved response 
rates and median progression free survival, but at the cost of added toxicity (Orloff, 2016). 
Also, in other solid tumor indications, PD-1/PD-L1 CHPi only work in about a third of patients 
or less as a monotherapy. 
Activating effects of CHPi on CD8(+) cytotoxic T cells (in this context synonymous with Teff) 
are thought to be compromised by the local tumor milieu that suppresses T cell function 
(e.g., humoral factors such as tumor growth factor beta [TGF-β]), and CD25(+)FoxP3(+) 
regulatory T cells (Tregs) are known to contribute to this immunosuppressive effect 
(Sasidharan Nair, 2018; Tanaka, 2017). 
One of the factors with particular impact on the effect of tumor eradication through the immune 
system is the intra-tumoral balance of Teffs versus Tregs (Sasidharan Nair, 2018; 
Quezada, 2008). Therefore, attempts are made to either increase the amount of CD8(+) Teffs 
(Bentebibel, 2017; Charych, 2016) or decrease the amount of CD25(+) Tregs. Support for the 
latter concept stems from publications on preclinical models (Arce Vargas, 2017) and clinical 
investigations (Diab, 2017; Baine, 2015; Fong, 2014). Furthermore, since CTLA-4 is 
expressed on Tregs, the efficacy of ipilimumab can in part be attributed to its effect on Tregs, 
not just on Teffs, where it is also expressed (Tanaka, 2017; Romano, 2015), lending further 
support to the hypothesis of achieving clinical benefit through Treg suppression. 
Thus, depleting or inhibiting CD25(+) Tregs may offer stand alone or additional therapeutic 
benefit in combination with other agents in immune-oncology, such as CHPi. 
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. 


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Figure 1. 
Schematic Representation and Chemical Structure of Camidanlumab 
Tesirine 
Abbreviations: Ala=alanine; PABA=para-aminobenzoic acid; PEG=polyethylene glycol; HuMax-TAC=human 
monoclonal antibody being studied; Val, valine. 
 
Camidanlumab tesirine binds with picomolar affinity to human CD25. After binding and 
internalization, camidanlumab tesirine is transported to the lysosomes, where the 
protease-sensitive linker is cleaved and unconjugated PBD dimers (SG3199) are released 
inside the target cell. The released PBD dimers bind in the minor groove of DNA in a 
sequence-selective manner, and form highly cytotoxic DNA interstrand cross-links. 
The cross-links result in a stalled DNA replication fork, blocking cell division and causing cell 
death (Hartley, 2011). The cross-links formed by PBD dimers are relatively non-distorting to 
the DNA structure, making them hidden to repair mechanisms (Adair, 2012; Beck, 2017).  
1.3 
Safety and Efficacy of Camidanlumab Tesirine in Clinical Studies 
This is the first clinical trial of camidanlumab tesirine in solid tumors and preliminary safety 
and efficacy data are available; safety and efficacy data are also available from two Phase 1 
studies and one Phase 2 study in hemato-oncology indications (ADCT-301-001, 
ADCT-301-002, and ADCT-301-201). 
As of 04 Aug 2021, a total 338 patients have been treated across the entire camidanlumab 
tesirine monotherapy development program. There were 14 (4.2%) patients that experienced 
treatment-emergent Guillain-Barré syndrome (GBS)/polyradiculopathy across the entire 
camidanlumab tesirine development program within the 4 studies described below. This 
included 13 classical Hodgkin Lymphoma (cHL) subjects and one subject with non-Hodgkins 
lymphoma. No cases of GBS/polyradiculopathies have been observed in ADCT-301-103 at 
the time of the Protocol Amendment 7.  
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. 


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Additional details may be found in the current camidanlumab tesirine (ADCT-301) 
Investigator’s Brochure (IB). 
1.3.1 
ADCT-301-001 
ADCT-301-001 is a first-in-human (FIH) Phase 1 dose-escalation study of camidanlumab 
tesirine in patients with relapsed or refractory Hodgkin lymphoma (HL) and 
non-Hodgkin lymphoma (NHL), who have failed or are intolerant to established therapies, or 
have no other treatment options available. 
ADCT-301-001 showed significant activity of camidanlumab tesirine with an acceptable 
safety profile in patients with HL. Anti-tumor effects have also been demonstrated in NHL 
patients, but the number of patients in specific sub-populations is considerably less compared 
to the HL population. 
A total of 133 patients received at least 1 infusion of camidanlumab tesirine. Up to 150 µg/kg 
every 3 weeks (Q3W) was tested and the maximum tolerated dose (MTD) had not been reached. 
Treatment-emergent adverse events (TEAEs) were reported in 132 out of 133 (99.2%) patients 
treated with camidanlumab tesirine. The most frequently reported TEAEs (≥20% overall), 
regardless of grade or relationship, included: fatigue (38.3%); pyrexia (32.3%); rash 
maculo-papular (28.6%); diarrhea (26.3%); cough and gamma glutamyl transferase (GGT) 
increased (22.6%); nausea (21.1%); anemia (20.3%). 
Serious adverse events (SAEs), irrespective of causality, were reported in 74 (55.6%) out of 
133 patients.  
Out of 41 evaluable patients at the dose of 45 µg/kg Q3W, 18 (43.9%) achieved complete 
response (CR) and 14 (34.1%) achieved partial response (PR), for an ORR of 78.0%, as per 
Investigator evaluation. 
1.3.2 
ADCT-301-002 
ADCT-301-002 is a Phase 1 dose-escalation study of camidanlumab tesirine in patients with 
relapsed or refractory CD25(+) acute myeloid leukemia/acute lymphoblastic leukemia, 
who have failed or are intolerant to established therapies, or have no other treatment options 
available.  
A total of 35 patients received at least 1 infusion of camidanlumab tesirine in the 
dose-escalation portion of the study. The recommended dose for Part 2 has not been identified. 
The most frequently reported TEAEs (≥20%), across dosing regimens and regardless of grade 
or relationship, included: fatigue (31.4%); febrile neutropenia (25.7%); decreased appetite, 
nausea, GGT increased and pneumonia (22.9% each); diarrhea, hypocalcemia, and pyrexia 
(20.0% each). 
Two of the 35 patients (one each in the 30 µg/kg QW and 37.5 µg/kg QW groups) treated had 
a CR with incomplete hematologic recovery. All other patients had no response or progressive 
disease (PD). 


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1.3.3 
ADCT-301-201 
ADCT-301-201 is a multicenter, open-label, single-arm Phase 2 study in patients with relapsed 
or refractory HL. As of data cut-off date (26 March 2021), 117 patients have been treated. 
The most frequently reported TEAEs (≥20%), regardless of grade or relationship included: 
fatigue (36.8%), maculopapular rash (28.2%), nausea (27.4%), pyrexia (26.5%), anemia 
(20.5%) (Zinzani, 2021). Preliminary data are indicating that ORR was reported at 66.3% 
(Zinzani, 2021); data are maturing. 
1.3.4 
ADCT-301-103 
As of 14 April 2021, enrolment in the monotherapy part was completed; 44 patients were 
treated with camidanlumab tesirine monotherapy in Part 1 at 8 dose levels ranging from 20 to 
150 µg/kg administered on a 3-week treatment cycle and the MTD has not been reached.  
The most frequently reported TEAEs (≥20% overall), regardless of grade or relationship, 
included: nausea (40.9%), fatigue and decreased appetite (36.4% each), constipation (29.5%), 
abdominal pain (27.3%), rash (22.7%). (Puzanov, 2021).  
The TEAEs that have been assessed as Grade ≥3 were reported in 31 out of 44 (70.5%) patients. 
The most common Grade ≥3 TEAEs (observed in at least 5% of patients overall), regardless 
of relationship, included anemia (11.4%), abdominal pain, rash and pulmonary embolism 
(6.8% each). 
Grade 3 autoimmune AE (colitis, immune-mediated adverse event, systemic inflammatory 
response syndrome) and grade 3 neurologic AE (dysphagia and asthenia), regardless of 
relationship, were observed in 6.8% and 4.5% of the patients, respectively.  
Best overall responses were stable disease (SD) for 11 patients (25%) and progressive disease 
(PD) for 23 patients (52.3%); 2 patients were not evaluable (4.4%) and 8 (18.2%) had no 
post-baseline evaluation due to death (11.4%) or clinical progression (6.8%).  
Some patients with paired biopsies showed decreased Tregs and increased Teffs:Tregs ratio in 
the local tumor environment, supporting a therapeutic rationale for the treatment of advanced 
solid tumors with camidanlumab tesirine in combination with other immune-modulating 
therapies (Puzanov, 2020). 
At the time of this Protocol Amendment 7, the study is enrolling patients receiving 
camidanlumab tesirine in combination with pembrolizumab. 
1.4 
Pembrolizumab 
Pembrolizumab is a potent, highly selective, humanized monoclonal antibody (mAb) of the 
immunoglobulin G 4 kappa isotype that binds to the PD-1 receptor and directly blocks the 
interaction between PD-1 and its ligands (PD-L1 and PD-L2), thereby enhancing tumor 
regression and ultimately immune rejection. Pembrolizumab has an acceptable safety profile 
and has been approved for treatments of patients across a number of indications. 
Additional information may be found, as applicable, in the US Package Insert/EU Summary 
of Product Characteristics (PI/SmPC) of pembrolizumab. 


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1.5 
Safety and Efficacy of Pembrolizumab 
Most common adverse reactions (reported in ≥20% of patients) were:  
• Pembrolizumab as a single agent: fatigue, musculoskeletal pain, decreased appetite, 
pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain, and 
abdominal pain. 
• Pembrolizumab in combination with chemotherapy: fatigue/asthenia, nausea, 
constipation, diarrhea, decreased appetite, rash, vomiting, cough, dyspnea, pyrexia, 
alopecia, peripheral neuropathy, mucosal inflammation, and stomatitis. 
 
Immune-related adverse reactions, including severe and fatal cases, have occurred in patients 
receiving pembrolizumab. Most immune-related adverse reactions occurring during treatment 
with pembrolizumab were reversible and managed with interruptions of pembrolizumab, 
administration of corticosteroids and/or supportive care. Immune-related adverse reactions 
have also occurred after the last dose of pembrolizumab. 
Pembrolizumab has been approved as single agent or in combination for the treatment of 
various malignancies in the US and EU including melanoma, non-small-cell lung cancer 
(NSCLC), head and neck squamous cell carcinoma, small cell lung cancer, classical HL, 
primary mediastinal large B-cell lymphoma, urothelial carcinoma, microsatellite instability-H, 
gastric cancer, esophageal cancer, cervical cancer, hepatocellular carcinoma, Merkel cell 
carcinoma, and renal carcinoma. The responses observed in these indications (ORR) ranged 
from 13% till 59%.  
Additional information may be found, as applicable, in the US Package Insert/EU PI/SmPC of 
pembrolizumab. 


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2 STUDY RATIONALE 
Literature evidence indicates that one of the factors with particular impact on the effect of 
tumor eradication through the immune system appears to be the intra-tumoral balance of 
Teffs versus Tregs (Section 1.1).  
Sur301, a PBD dimer-based ADC directed against mouse CD25 (anti-CD25 antibody 
stochastically conjugated to the PBD linker drug SG3249) showed strong and durable 
anti-tumor activity in the MC38 and CT26 syngeneic models, two mouse colon 
adenocarcinoma-derived model with intra-tumoral Treg infiltration (Arce Vargas, 2017). 
When tested as single dose at either 0.5 or 1 mg/kg, sur301 showed complete tumor eradication 
in 8/8 mice at the end of the study (on Day 59). Interestingly, when a low dose of sur301 
(0.1 mg/kg, single dose) was combined with an anti-PD-1 monoclonal antibody, the resulting 
anti-tumor activity was synergistic in both MC38 and CT26 models as shown by their 
coefficient of drug interaction (0.268 and 0.285, respectively) (Zammarchi, 2018; Wu, 2012). 
Moreover, when the tumor-free survivor animals from both studies were re-challenged with 
new cells, no tumors formed, indicating that the animals had developed an immunologic 
memory.  
Targeting Tregs to enhance the efficacy of CHPi has been demonstrated to be safe, as observed 
in the combination of nivolumab and mogamulizumab (Doi, 2019). 
Therefore, camidanlumab tesirine as a single agent or in combination with an anti-PD-1 
monoclonal antibody is a candidate for targeting and selectively depleting CD25(+) Tregs in 
tumor infiltrates. Moreover, the intra-tumor release of camidanlumab tesirine PBD warhead 
may cause bystander killing of neighboring tumor cells (Flynn, 2016) and also trigger 
immunogenic cell death response, which will in turn strengthen the immune response against 
tumor cells (Rios-Doria, 2017). 
2.1 
Selected Tumor Types 
The following tumor entities have been shown to harbor a large number of tumor-infiltrating 
Treg cells or for which it is known that Treg cells are involved in the tumor growth, and 
therefore are selected for this study (Sasidharan Nair, 2018; Tanaka, 2017): colorectal 
(Zhang, 2015; Hu, 2017; Scurr, 2017), head and neck squamous cell carcinoma 
(Schaefer, 2004), NSCLC (Wolf, 2003; Woo, 2002; Woo, 2001), gastric and esophageal 
cancers (Ichihara, 2003; Sasada, 2003), pancreas (Hiraoka, 2006; Tang, 2014; Jang 2017)., 
bladder (Parodi, 2016; Horn, 2013), renal cell carcinoma (Santagata, 2017; Asma, 2015), 
melanoma (Ménétrier-Caux, 2012), triple negative breast cancer (TNBC) (Plitas, 2016; 
Gobert, 2009; Ménétrier-Caux, 2012; Liyanage, 2002), prostate cancer (Wu, 2019), and 
ovarian cancer (Sato, 2005; Curiel, 2004). 
In addition, indications approved for CHPi, like non-small cell lung cancer and melanoma, 
(Section 1.5) may also benefit from the combination of CHPi with camidanlumab tesirine, 
which may prime the immune system to become responsive to immunotherapy for efficiently 
targeting the tumor. When already exposed to checkpoint inhibitors in a prior line of treatment, 
Tregs may be responsible for the development of resistance (Fares, 2019) which may be 
overcome by treatment with camidanlumab tesirine. 


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2.1.1 
Rationale for the Selection of Indications for the Combination in the Dose-
Escalation Part 
Six potential tumor indications have been selected for the dose-escalation of camidanlumab 
tesirine in combination with pembrolizumab: colorectal cancer, gastric/esophageal cancer, 
ovarian cancer, pancreatic cancer, melanoma, and NSCLC. 
The first four indications listed are known to be “cold” tumors (Bonnaventura, 2019) with high 
unmet needs, for which immunotherapy does not show high activity (Chi, 2020; Le, 2015; 
Matulonis, 2019), except for the MSI-H/dMMR patients (Le, 2017; Le, 2020; Marabelle, 2019). 
Use of camidanlumab tesirine could help to enhance activity of CHPi in these indications by 
increasing the ratio Teff:Treg. 
Melanoma and NSCLC are known to be “hot” tumors (Vareki, 2020), with immunotherapy 
already established in front-line therapy. However, most of the patients treated with an 
immunotherapy progressed while receiving such therapy or after the end of the immunotherapy 
treatment. Regulatory T lymphocytes may be involved in the acquired resistance to CHPi 
(Saleh, 2019). By depleting Tregs with camindanlumab tesirine, any resistance to CHPi could 
be overcome. 
2.1.2 
Rationale for the Selection of MSI-H/dMMR Patients in the Dose-Expansion 
In the Dose-expansion, Group 2 will enroll patients with MSI-H/dMMR status, who have 
received prior CHPi therapy with best response being stable disease or better, and then 
progressed. 
MSI-H/dMMR tumors carry hundrends to thousands of somatic mutations encoding for 
potential neoantigens, and can therefore be recognized by the immune system, as demonstrated 
by their high levels of lymphocytic infiltration, these characteristics render these tumors 
susceptible to reactivation of antitumor response via PD-1/PD-L1 inhibition (Dudley, 2016; 
Lee, 2016; Marabelle, 2019).  
While, in general, MSI-H/dMMR tumors benefit from CHPi therapy, there are still between 
40 to 80% patients carrying MSI-H/dMMR tumors that do not respond to anti-PD1/PD-L1 
based therapies (Marabelle, 2019).  
Primary and acquired resistance to anti-PD-1/PD-L1 of MSI-H/dMMR tumors can be triggered 
by several factors. Primary resistance in MSI-H/dMMR patients treated with PD-1/PD-L1 
inhibitors could be due, among other things, to genetic factors (Sahin, 2019; Grasso, 2018; 
Amodio, 2021), degree of microsatellite instability impacting the insertion-deletion tumor 
mutational load (Mandal, 2019), lower Tumor Mutational Burden and consequent lower level 
of T cell infiltration in non-responders (Loupakis, 2020), as well as misdiagnosis of 
MSI-H/dMMR status (Cohen, 2019; Loupakis, 2020); in these patients the addition of 
camindanlumab tesirine is not expected to render tumors sensitive to a PD-1 inhibitor. On the 
other hand, the enrollment of patients that showed some degree of sensitivity to prior 
PD-1/PD-L1 inhibition should increase chances to select MSI-H/dMMR patients whose 
tumors can be recognized and attacked by the immune system, upon treatment with 
pembrolizumab plus camindanlumab tesirine. It is conceivable that, in at least some of these 
patients, the acquired resistance to prior PD-1/PD-L1 inhibitor could be due to increased Tregs 
infiltration and to their inhibitory activity on anti-tumor immune response. The depletion of 
Tregs by camindanlumab tesirine could therefore restore sensitivity to PD-1/PD-L1 inhibitors 


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in some of these patients, increasing the confidence that any eventual efficacy signal observed 
is due to the combination and not solely to pembrolizumab activity. 
2.2 
Rationale for Study Design 
The dose-escalation portion of this study (Part 1) is designed to establish a safe and tolerated 
dose and dosing schedule of camidanlumab tesirine as monotherapy, and camidanlumab 
tesirine in combination with pembrolizumab, for further testing in patients with advanced solid 
tumors infiltrated by Tregs. The dose(s) and dosing schedule(s) identified in Part 1 will be 
tested in the dose-expansion portion of the study (Part 2) to further characterize the safety and 
evaluate preliminary efficacy in the study population. 
Part 1 will utilize a 3+3 dose-escalation design and be under the oversight of a Dose-Escalation 
Steering Committee (DESC). 
Part 2 will include patients who are likely to respond based on Part 1 preliminary efficacy 
results in order to further assess safety and tolerability of the recommended dose(s)/schedule(s). 
2.3 
Rationale for Dose Selection 
2.3.1 
Dose of Camidanlumab Tesirine as Monotherapy 
Doses ranging from 3 µg/kg Q3W up to 300 µg/kg Q3W were planned to be investigated in 
the FIH camidanlumab tesirine clinical studies ADCT-301-001 and -002, which target 
CD25(+) tumors (Section 1.3); the highest dose level tested in these studies was 150 µg/kg 
Q3W and the MTD had not been reached. In order to minimize the dose levels to be 
investigated and start with a dose with potential antitumor activity, this study will investigate 
dose levels between 20 µg/kg and 300 µg/kg Q3W. 
At the 20 µg/kg dose level, approximately 30% tumor shrinkage was observed in a HL patient 
(03-002) in study ADCT-301-001; lower dose levels appear to be sub-therapeutic. 
Thus, 20 µg/kg Q3W has been selected as a starting dose as it represents a dose level that has 
previously been shown to be safe (in HL and NHL patients) and is slightly below the predicted 
therapeutic dose in solid tumors. 
2.3.2 
Dose of Camidanlumab Tesirine in combination with Pembrolizumab 
Pembrolizumab dose is established at 200 mg every 3 weeks.  
In the pembrolizumab/camidanlumab tesirine combination, the pembrolizumab dose will be 
kept constant at 200 mg; and will be combined with escalating doses of camidanlumab tesirine, 
in Part 1 (dose-escalation).  
Clinical dose selection for camidanlumab tesirine for the combination with pembrolizumab is 
based on clinical efficacy and safety data from relapsed/refractory Classical Hodgkin 
Lymphoma (cHL) patients and patients with solid tumors. The clinical starting dose for the 
FIH trial (ADCT-301-001) with camidanlumab tesirine was 3 µg/kg. At 13 µg/kg a partial 
response was observed in a cHL patient, with lower dose levels appearing sub-therapeutic 
when given as a single agent. In the same trial, a 50% overall response rate was observed in 
cHL patients at 30 µg/kg (Collins, 2019). 
In murine preclinical model, a single dose of sur301 at 0.5 mg/kg was shown to have strong 
and durable anti-tumor activity when used as a monotherapy. The human equivalent dose of 


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0.5 mg/kg is 40 µg/kg. On this trial ADCT-301-103, camidanlumab tesirine at a dose-level of 
45 µg/kg, has not resulted in any responses, suggesting that the human equivalent dose 
calculation likely underestimates a similarly efficacious dose in human, supporting a higher 
starting dose compared to FIH study ADCT-301-001. 
Based on the above, 30 µg/kg is the proposed starting dose for the combination with 
pembrolizumab. At this dose, camidanlumab tesirine is associated with a favorable clinical 
safety profile in solid tumor indications, whereas in cHL patients a 50% response rate and 
acceptable safety was observed. 
In this study, investigating camidanlumab tesirine alone in advanced solid tumors patients, 
preliminary data of peripheral blood analyses indicate a dose related increase in CD4+ cells 
and to lesser extend CD8+ cells mirrored by dose dependent decrease of Treg in CD45+ 
lymphocyte population and leading to an increase of Teff/Treg ratio. Such immunological 
effects are thought to be supportive of anti-tumoral efficacy (Tanaka, 2017). 
These effects are shown at dose of 30 µg/kg and above. 
Camidanlumab tesirine, at the starting dose of 30 µg/kg, will be administered first for 2 cycles 
to perform its immunotherapy priming effect; pembrolizumab is intended to be given from the 
start to benefit of the potential synergistic effect seen in the non-clinical studies.  
In order to minimize the dose levels to be investigated and start with a dose with potential 
antitumor activity, this study will investigate dose of camidanlumab tesirine in combination 
with pembrolizumab between 30 µg/kg and the highest dose level of camidanlumab tesirine as 
monotherapy shown to be safe. 
A sequential dosing regimen may be implemented to mitigate overlapping toxicities at the 
discretion of the DESC.  
 


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3 STUDY OBJECTIVES AND ENDPOINTS 
Study objectives and associated endpoints are presented below in Table 3. 
Table 3. 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
Characterize the safety and tolerability of 
camidanlumab tesirine as monotherapy and 
camidanlumab tesirine in combination with 
pembrolizumab, 
and 
to 
identify 
the 
recommended dose(s) and schedule(s) for 
future studies in patients with selected 
advanced solid tumors 
• Frequency and severity of adverse events (AEs) and serious adverse events (SAEs) for patients treated with 
camidanlumab tesirine as monotherapy and for patients treated with camidanlumab tesirine in combination 
with pembrolizumab 
• Changes from Baseline of safety laboratory values, vital signs, Eastern Cooperative Oncology Group (ECOG) 
performance status, and 12-lead electrocardiograms (ECGs) for patients treated with camidanlumab tesirine as 
monotherapy and for patients treated with camidanlumab tesirine in combination with pembrolizumab 
• Frequency of dose interruptions and dose reductions for patients treated with camidanlumab tesirine as 
monotherapy and for patients treated with camidanlumab tesirine in combination with pembrolizumab 
• Incidence of dose limiting toxicities (DLTs) (dose-escalation only) for patients treated with camidanlumab 
tesirine as monotherapy and for patients treated with camidanlumab tesirine in combination with 
pembrolizumab 
Secondary 
Evaluate 
the 
preliminary 
anti-tumor 
activity of camidanlumab tesirine as 
monotherapy and camidanlumab tesirine in 
combination with pembrolizumab 
• Overall response rate (ORR) according to the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, 
for patients treated with camidanlumab tesirine as monotherapy and for patients treated with camidanlumab 
tesirine in combination with pembrolizumab 
• Duration of response (DOR) defined as the time from the first documentation of tumor response to disease 
progression as per RECIST v 1.1, or death for patients treated with camidanlumab tesirine as monotherapy and 
for patients treated with camidanlumab tesirine in combination with pembrolizumab 
• Progression-free survival (PFS) defined as the time between start of treatment and the first documentation of 
recurrence, progression, as per RECIST v 1.1, or death for patients treated with camidanlumab tesirine as 
monotherapy and for patients treated with camidanlumab tesirine in combination with pembrolizumab 
• Overall survival (OS) defined as the time between the start of treatment and death from any cause for patients 
treated with camidanlumab tesirine as monotherapy and for patients treated with camidanlumab tesirine in 
combination with pembrolizumab 


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Objectives 
Endpoints 
Evaluate the pharmacokinetic (PK) profile 
of camidanlumab tesirine as monotherapy 
and camidanlumab tesirine in combination 
with pembrolizumab 
• Concentrations and PK parameters of camidanlumab tesirine total antibody, PBD-conjugated antibody, and 
unconjugated warhead SG3199 in serum 
Evaluate 
the 
immunogenicity 
of 
camidanlumab tesirine as monotherapy and 
camidanlumab tesirine in combination with 
pembrolizumab 
• Frequency of confirmed positive anti-drug antibody (ADA) responses, their associated titers and, if applicable, 
neutralizing activity to camidanlumab tesirine after treatment with camidanlumab tesirine 


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4 STUDY DESIGN 
4.1 
Overview 
This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a 
dose-expansion part.  
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 21 days), a Treatment Period (with cycles 
of 3 weeks for a Q3W dosing regimen), and a Follow-up Period (approximately every 12-week 
visits) for up to 1 year from End of Treatment (EOT) visit (Section 4.2).  
See study diagram in Appendix 13.6. 
4.1.1 
Dose-Escalation 
Dose-escalation cohorts:  
In the dose-escalation part, patients will receive escalating doses of camidanlumab tesirine as 
monotherapy, or escalating doses of camidanlumab tesirine in combination with 
pembrolizumab, guided by a 3+3 design. 
For each dose level (Section 6.3 and Section 6.4), if none of the first 3 patients at that dose 
level experience a DLT, new patients may be entered at the next higher dose level. If 1 of 
3 patients experiences a DLT, up to 3 more patients are to be treated at that same dose level. 
If none of the additional 3 patients at that dose level experience a DLT, new patients may then 
be entered at the next higher dose level. However, if 1 or more of the additional 3 patients 
experiences a DLT, then no further patients are to be started at that dose level and the preceding 
dose is identified as the MTD. The MTD, therefore, is defined as the highest dose level at 
which none of the first 3 treated patients, or no more than 1 of the first 6 treated patients, 
experience a DLT.  
If the starting dose of camidanlumab tesirine in combination with pembrolizumab is not 
tolerated, two lower doses could be investigated (Section 6.4). In such cases, if a DLT is 
observed in the first 3 patients enrolled in dose level -1, 3 additional patients will be enrolled; 
if 2 DLTs are observed out of these 6 patients, dose will be de-escalated to dose level -2.  
Camidanlumab tesirine as monotherapy: The DLT (see Section 6.5 for further details) 
observation period for dose-escalation will be 21 days following the first study drug 
administration. 
Camidanlumab tesirine in combination with pembrolizumab: The DLT (see Section 6.5 for 
further details) observation period for dose-escalation will start at the time of first 
administration of pembrolizumab and will end 21 days following this first administration of 
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Different dosing schedules of camidanlumab tesirine in combination with pembrolizumab may 
be tested in the dose-escalation part: 
• Schedule 1: Administration of camidanlumab tesirine for the first 2 cycles with 
concomitant administration of pembrolizumab starting at the first cycle (additional 
administrations of camindanlumab tesirine according to a schedule with 2 cycles 
off – 2 cycles on, if there is no delay in the planed treatment schedule, or, in case of 
delay in the administration of pembrolizumab, after respecting a minimum of 63 days 
(9 weeks) between the last dose of camidanlumab tesirine and the first dose of the 
2 subsequent additional administrations of camidanlumab tesirine; between these 
Cycles, patients should receive pembrolizumab as a single agent) 
• Schedule 2: Administration of camidanlumab tesirine for the first 2 cycles with 
concomitant administration of pembrolizumab in the second cycle followed by 
pembrolizumab monotherapy thereafter (additional administrations of camindanlumab 
tesirine upon informing the Sponsor) 
• The dose-escalation part will start with Schedule 1, then: 
o Schedule 2 may be initiated if dose level -1 and dose level -2 used in Schedule 1 
are presenting safety concerns (e.g., significant overlapping toxicities) and 
investigation of Schedule 1 is stopped.  
o Other Schedules may be investigated based on observed safety and efficacy data.  
 
No intra-patient dose-escalation is allowed in this regular dose-escalation part of the study. 
The number of dose levels will depend on the emergent toxicity profile of camidanlumab 
tesirine and will be decided by the DESC (Section 4.1.3); PK 
 may 
also inform decision making. 
The DESC may expand enrollment at doses below the current dose level being evaluated as 
part of the dose-escalation process; additional patients, of the same indication, may only be 
added at dose levels that are equal or higher to the dose level for which at least 1 patient with 
documented PR or CR has been observed. No more than 10 patients in total can be treated at 
such dose level unless ≥3 of the 10 patients have documented PR or CR. 
The dose-escalation part will be completed once the recommended dose(s) (and schedule[s]) 
for expansion (RDE)/MTD has been identified. Dose-escalation cohorts may enroll 
approximately 48 patients. 
Paired-biopsy cohorts: Separately, paired-biopsy cohorts will enroll patients, only treated with 
camidanlumab tesirine as monotherapy, who will be undergoing two mandatory biopsies, one 
pre- and one on-treatment biopsy, 
 
. These cohorts will be introduced at dose levels that have been deemed 
safe during escalation and will be composed of a maximum of 3 patients per dose level, 
irrespective of the indication and whether or not preliminary antitumor response(s) were seen 
at that dose level. In order to allow patients to benefit from trial participation, one intra-patient 
dose-escalation (after the mandatory on-treatment biopsy has been obtained) to the highest 
dose level determined to be safe at that point will be performed, unless deemed by the 


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Investigator not to be in the best interest of the patient. Paired-biopsy cohorts may enroll 
approximately up to 17 patients. 
Overall, Part 1 may enroll approximately 65 patients. 
4.1.2 
Dose-Expansion 
Two groups are planned in the dose-expansion part (Part 2): 
• Group 1: an indication for which camidanlumab tesirine in combination with 
pembrolizumab was shown in Part 1 to have preliminary activity. 
• Group 2: a basket group of patients with advanced solid tumors and MSI-H/dMMR 
status, who have received a prior regimen containing a PD-1/PD-L1 inhibitor, for which 
the best response was CR, PR, or SD ≥4 months, and then progressed while under 
treatment with a PD-1/PD-L1 inhibitor based regimen; no more than 4 patients with 
the same indication are allowed in this basket group. 
 
Part 2 will enroll approximately 30 patients, approximately 16 patients in Group 1 and 14 in 
Group 2. 
4.1.3 
Safety Oversight by the Dose-Escalation Steering Committee 
A DESC will be responsible for safety monitoring and overall supervision of the study. 
Membership of the DESC will include: 
• Medical Monitor(s) (Sponsor and/or designee)  
• Investigator(s) from each participating site  
• Ad hoc members (e.g., project manager, study coordinator(s), regulatory 
representative(s), 
pharmacovigilance 
representative(s), 
biostatistician(s), 
clinical pharmacologist(s), etc.) 
 
In general, the DESC will make any substantial decisions regarding the conduct of the study, 
such as: 
• Monitor the safety of the study and review its progress at monthly intervals or more 
frequent intervals as required. 
• Determine dose levels to be administered and the RDE/MTD based on assessment of 
safety findings in all patients and determination of DLTs in dose-escalation cohorts. 
• Provide input into protocol changes, when required. 
• Determine if it is appropriate to maintain a Q3W schedule or test other dosing regimens. 
• Determine whether adjustment in timing of on-treatment biopsy and other 
 
sample(s) is needed based on emerging evidence. 
 


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Each DESC meeting and the decisions made will be documented in writing and provided to all 
participating DESC members and Investigators. Meeting documents may be submitted to 
IRBs/IECs or competent authorities according to institutional or local requirements. 
The DESC may be maintained during Part 2 (expansion) of the study to continue to monitor 
and evaluate patient safety, but the frequency of meetings can be adjusted. 
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 (SoC) may be used to satisfy screening requirements if they are performed in 
the appropriate window. 
The screening period is from 21 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 end of treatment visit.  
A treatment cycle is defined as 3 weeks (i.e., 21 days). 
After completion of Cycle 4, the Day 8 visit is not required unless clinically indicated.  
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. 
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 1 year 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 date of last visit/contact in the study or date of death, whichever occurs last, will be 
considered as the end of study (EOS) for an individual patient. 
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. 


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4.3 
Study Stopping Rules 
4.3.1 
Camidanlumab Tesirine as Monotherapy 
The investigation of camidanlumab tesirine as monotherapy will be stopped if any of the 
following circumstances occur: 
• Two or more patients develop polyradiculopathy/GBS (Level 1 of diagnostic certainty; 
Appendix 13.2). Continuation of patients who have shown clinical benefit will be 
discussed with relevant regulatory authority(ies) if this stopping rule is applied. 
• After 10 patients have been dosed, ≥30% of patients experience a specific Grade 4 or 
higher non-hematologic treatment emergent AE. 
 
Furthermore, patient enrollment will be halted pending a safety analysis and review with the 
relevant regulatory authority(ies) if any patient in Part 1 or Part 2 experiences a 
Common Terminology Criteria for Adverse Events (CTCAE) Grade 5 AE, or 
two non-hematologic CTCAE Grade 4 AEs, which are not attributable to the underlying 
disease, and for which relationship to camidanlumab tesirine cannot be ruled out, within 
30 days of their last dose of camidanlumab tesirine. 
4.3.2 
Camidanlumab Tesirine in Combination with Pembrolizumab 
The investigation of camidanlumab tesirine in combination with pembrolizumab will be 
stopped if any of the following circumstances occur: 
• Two or more patients develop polyradiculopathy/GBS (Level 1 of diagnostic certainty; 
Appendix 13.2). Continuation of patients who have shown clinical benefit will be 
discussed with relevant regulatory authority(ies) if this stopping rule is applied. 
• After 10 patients have been dosed, ≥30% of patients experience a specific Grade 4 or 
higher non-hematologic treatment emergent AE. 
 
Furthermore, patient enrollment will be halted pending a safety analysis and review with the 
relevant regulatory authority(ies) if any patient in Part 1 or Part 2 experiences a CTCAE 
Grade 5 AE, or two non-hematologic CTCAE Grade 4 AEs, which are not attributable to the 
underlying disease, and for which relationship to camidanlumab tesirine or pembrolizumab 
cannot be ruled out, within 30 days of their last dose of camidanlumab tesirine or 
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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 21 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 patient aged 18 years or older. 
3. Pathologic diagnosis of solid tumor malignancy that is locally advanced or metastatic 
at time of Screening: 
• 
Part 1 Dose-escalation camidanlumab tesirine as monotherapy: 
Selected advanced solid tumors: colorectal, head and neck squamous cell 
carcinoma, non-small cell lung cancer, gastric and esophageal cancers, pancreas, 
bladder, renal cell carcinoma, melanoma, triple negative breast cancer, and 
ovarian/fallopian tube cancer. 
• 
Part 1 Dose-escalation camidanlumab tesirine in combination with pembrolizumab 
Selected advanced solid tumors: colorectal cancer, gastric-esophageal cancer, 
ovarian/fallopian tube cancer, pancreatic cancer, non-small cell lung cancer, and 
melanoma. 
Note: For colorectal cancer, gastric-esophageal cancer, ovarian/fallopian tube 
cancer, 
pancreatic 
cancers 
MMR/MSS/MSI 
status 
is 
mandatory. 
If MMR/MSS/MSI status is not available at signature of the informed consent, the 
test should be performed before C1D1. 
• 
Part 
2 
Dose-expansion 
camidanlumab 
tesirine 
in 
combination 
with 
pembrolizumab: 
- 
Group 1: One of the indications identified in Part 1, for which at least 1 response 
(PR or CR) was seen 
- 
Group 2: Patients with advanced solid tumors and MSI-H/dMMR status, who 
have received a prior regimen containing a PD-1/PD-L1 inhibitor, for which the 
best response was CR, PR, or SD ≥4 months, and then progressed while under 
treatment with the PD-1/PD-L1 inhibitor-based regimen 
Note: A maximum of 4 patients with the same indication will be allowed in this 
basket group. 
4. Patients who are refractory to or intolerant of existing therapy(ies) known to provide 
clinical benefit for their condition. 
5. Patients with advanced/metastatic cancer, with measurable disease as determined by 
RECIST v1.1 or immune-related Response Criteria (irRC)/ immune-related Response 
Evaluation Criteria In Solid Tumors (irRECIST)/ immune-related Response Evaluation 
Criteria In Solid Tumors (iRECIST)/ immune-modified Response Evaluation Criteria 
in Solid Tumors (imRECIST) as per Investigator discretion. 


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Note 1: Lytic bone lesions or mixed lytic-blastic lesions, with identifiable soft tissue 
components, that can be evaluated by cross sectional imaging techniques such as 
computed tomography (CT) or magnetic resonance imaging (MRI) can be considered 
as measurable lesions ONLY if the soft tissue component meets the definition of 
measurability per RECIST. 
Note 2: If immediate prior therapy contains an immuno-therapy component, 
progression has to meet criteria as defined in irRC/irRECIST/iRECIST/imRECIST as 
per Investigator discretion.  
6. A) For camidanlumab tesirine as monotherapy: Patient must have a site of disease 
amenable to biopsy and be willing to undergo fresh biopsy procedures (minimum 
3 passes each) prior to first dose, according to the treating institution's guidelines. 
B) Patients included in the paired-biopsy cohort must in addition be willing to undergo 
fresh biopsy procedures (minimum 3 passes each) after receiving at least 1 dose of 
study drug. 
C) For camidanlumab tesirine in combination with pembrolizumab: Patient must either 
have a site of disease amenable to biopsy and must provide fresh tumor biopsy prior to 
C1D1, or have sufficient available archival tumor tissue (biopsied after their last disease 
progression, and in the situation where the patient has received no additional 
anti-cancer therapy between their progression and C1D1). Patients must also be willing 
to undergo fresh biopsy procedures (minimum 3 passes each) after receiving at least 
1 dose of study treatment, according to the treating institution's guidelines. 
7. ECOG performance status 0-1. 
8. Patient with life expectancy ≥3 months as per Investigator assessment. 
9. Adequate organ function as defined by screening laboratory values within the following 
parameters: 
a. Absolute neutrophil count (ANC) ≥1.5 × 103/µL (off growth factors at least 
72 hours). 
b. Platelet count ≥100 × 103/µL without transfusion in the past 10 days. 
c. Hemoglobin ≥9 g/dL (5.6 mmol/L) (prior transfusion allowed). 
d. 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. 
e. 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). 
f. Blood creatinine ≤1.5 × ULN or calculated creatinine clearance (CL) 
≥60 mL/min by the Cockcroft-Gault equation. 
Note: A laboratory assessment may be repeated a maximum of two times during the 
Screening period to confirm eligibility. 
10. Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test within 7 days 
prior to start of study drug (C1D1) for women of childbearing potential (WOCBP). 


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11. 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 or 4 months after last dose of pembrolizumab, 
whichever is the latest. 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 or 4 months after last dose of pembrolizumab, 
whichever is the latest. 
* 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 (i.e., who have not menstruated at all) for at least 
1 year. 
** 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, 
post-ovulation), 
withdrawal 
(coitus 
interruptus), 
lactational 
amenorrhea method, and spermicide-only are not acceptable as highly effective 
methods of contraception. 
 
5.2 
Exclusion Criteria 
1. Participation in another investigational interventional study. 
2. Prior therapy with a CD25 (IL-2R) antibody. 
3. Known history of ≥Grade 3 hypersensitivity to a therapeutic antibody. 
4. Patients with prior solid organ or allogeneic bone marrow transplant. 
5. 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]) 
(patients with vitiligo, type 1 diabetes mellitus, residual hypothyroidism, 
hypophysitis due to autoimmune condition only requiring hormone replacement 
may be enrolled). 
6. History of neuropathy considered of autoimmune origin (e.g., polyradiculopathy 
including Guillain-Barré syndrome and myasthenia gravis) or other central nervous 
system (CNS) autoimmune disease (e.g., poliomyelitis, multiple sclerosis). 


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7. History of recent infection (within 4 weeks of C1D1) caused by a pathogen known 
to be associated with GBS, for example: herpes simplex virus 1/2 (HSV1, HSV2), 
varicella zoster (VZV), Epstein-Barr virus (EBV), cytomegalovirus (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). 
8. Known seropositive and requiring anti-viral therapy for human immunodeficiency 
(HIV) virus, hepatitis B virus (HBV), or hepatitis C virus (HCV). Note: Testing is 
not mandatory to be eligible but should be considered in patients with high risk for 
these infections; testing is mandatory if status is unknown. 
9. History of Stevens-Johnson syndrome or toxic epidermal necrolysis. 
10. Failure to recover to ≤Grade 1 (CTCAE version 4.0) from acute non-hematologic 
toxicity (to ≤Grade 2 for neuropathy or alopecia), due to previous therapy, prior to 
screening. 
11. Symptomatic CNS metastases or evidence of leptomeningeal disease (brain MRI or 
previously documented cerebrospinal fluid [CSF] cytology). Previously treated 
asymptomatic CNS metastases are permitted provided that the last treatment 
(systemic anticancer therapy and/or local radiotherapy) was completed ≥4 weeks 
prior to Day 1 except usage of low dose of steroids on a taper (i.e., up to 10 mg 
prednisone or equivalent on Day 1 and consecutive days is permissible if being 
tapered down). Patients with discrete dural metastases are eligible. 
12. 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). 
13. Active diarrhea CTCAE Grade 2 or a medical condition associated with chronic 
diarrhea (such as irritable bowel syndrome, inflammatory bowel disease). 
14. Active infection requiring systemic antibiotic therapy. 
15. Active bleeding diathesis or significant anticoagulation (international normalized 
ratio [INR] ≥2.0). 
16. Breastfeeding or pregnant. 
17. Significant 
medical 
comorbidities, 
including 
uncontrolled 
hypertension 
(blood pressure [BP] ≥160 mmHg systolic and/or ≥110 mmHg diastolic repeatedly 
with or without anti-hypertensive medication), unstable angina, congestive heart 
failure (greater than New York Heart Association class II), electrocardiographic 
evidence of acute ischemia, coronary angioplasty or myocardial infarction within 
6 months prior to screening, severe uncontrolled atrial or ventricular cardiac 
arrhythmia, 
poorly controlled 
diabetes, 
active 
ulceration 
of 
the 
upper 
gastrointestinal (GI) tract or GI bleeding, or severe chronic pulmonary disease. 


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18. Major surgery, radiotherapy, chemotherapy or other anti-neoplastic therapy within 
14 days prior to start of study drug (C1D1), except shorter if approved by the 
Sponsor. For cytotoxic agents that have major delayed toxicity, e.g., mitomycin C 
and nitrosoureas, 4 weeks is indicated as washout period. For patients receiving 
systemic anticancer immunotherapies (as opposed to intralesional) that lead to 
activation of Teffs and/or increase the Teff/Treg ratio, such as anti-PD-1 antibodies, 
4 weeks is indicated as the washout period.  
19. Use of any other experimental medication within 14 days prior to start of study drug 
(C1D1). 
20. Patients requiring concomitant immunosuppressive agents or chronic treatment with 
corticosteroids except: 
• replacement dose steroids in the setting of adrenal insufficiency 
• topical, inhaled, nasal, and ophthalmic steroids are allowed 
21. Planned live vaccine within 30 days prior to the first dose of study treatment and 
during study treatment 
22. Congenital long QT syndrome, or a corrected QTcF interval of ≥480 ms, at 
screening (unless secondary to pacemaker or bundle branch block). 
23. 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. 
24. 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. 
25. For patients treated with camidanlumab tesirine in combination with 
pembrolizumab: patients intolerant to checkpoint-inhibitor or with a history of the 
following ≥ Grade 3 immune-related adverse events: hepatitis, renal, ocular, 
neurologic, cardiovascular, rheumatologic, and hematologic. 
26. For patient treated with camidanlumab tesirine in combination with pembrolizumab: 
patients with a history of non-infectious pneumonitis related to prior systemic 
treatment and that require treatment with steroids within the last 6 months prior to 
enrolment. 
 
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 


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• SAE and/or death occurring during the screening period 
• Screening failure details (documenting primary reason for screen failure) 
 
A patient who did not meet the eligibility criteria (screening failure) may be considered for 
re‑screening. Decision for re-screening and C1D1 must be confirmed by the Sponsor/Medical 
monitor. A re-screened patient should be assigned a new patient number. 
Participants who are rescreened are required to sign a new ICF. 
Screen failed patients could be rescreened once.  
5.4 
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. 
5.4.1 
Discontinuation from Study Drug 
A patient may be discontinued from the study drugs for any of the following reasons: 
• Disease progression (radiographic or clinical) 
• Unacceptable toxicity 
• Patient’s decision 
• Major protocol deviation 
• Investigator’s decision 
• Discontinuation of the study by the Sponsor 
• 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. 
5.4.2 
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 


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• Loss to follow-up (Section 5.4.3) 
• Study completion 
 
If a patient withdraws informed consent for study participation, 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 and Table 2). 
5.4.3 
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. 
5.5 
Patient Replacements 
Any patient in Part 1 who discontinues before completion of the first treatment cycle, for any 
reason other than a DLT, is to be replaced. 


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6 TREATMENT 
The study drugs are camidanlumab tesirine and pembrolizumab. 
The study treatment refers either to camidanlumab tesirine as monotherapy or to 
camidanlumab tesirine in combination with pembrolizumab, as applicable.  
The start of a Cycle is defined as the administration of any of the study drugs. 
6.1 
Study Drugs 
6.1.1 
Camidanlumab Tesirine 
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.  
6.1.2 
Pembrolizumab 
Pembrolizumab will be provided as 100 mg/4 mL (25 mg/mL) liquid vial. After dilution, the 
liquid vial is clear to slightly opalescent, colorless to slightly yellow solution and is single-dose 
vial. Additional study drug description is included in the pharmacy manual. 
Individual patients will receive the same formulation for their entire treatment. 
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 at (2°C to 8°C [36°F to 46°F]).  
Unopened vials of pembrolizumab liquid must be stored at 2°C to 8°C (36°F to 46°F), 
protected from light and must not be frozen. 
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  
6.2.2.1 
Camidanlumab Tesirine 
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 


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mass index ≥35 kg/m2; these patients will be dose based on a body mass index of 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. 
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. 
6.2.2.2 
Pembrolizumab 
Pembrolizumab will be given as a fixed dose of 200 mg administered as a 30 minutes 
IV infusion (starting 1 hour after the end of the camidanlumab tesirine infusion).  
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. 
For patients who have a central line, administration of pembrolizumab via this central line 
should be considered. 
Please refer to prescribing information for further details, especially for monitoring of potential 
infusion reaction. 
6.2.3 
Accountability 
The Investigator, or designee, will maintain accurate records of receipt of all study drugs, 
including dates of receipt and conditions. 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 as Monotherapy Dosing 
In the dose-escalation portion of the study (Part 1), the initial dose of camidanlumab tesirine 
will be 20 µg/kg (Dose Level 1) every 3 weeks (Q3W), and the highest dose possibly tested 
will be 300 µg/kg Q3W or equivalent (e.g., 100 µg/kg every week). The dose-escalation 
procedure is described in Section 4.1.1.  
A patient should maintain the same treatment schedule throughout the duration of the trial. 
However, once RDE is identified, patients receiving lower or higher dose levels of 
camidanlumab tesirine enrolled in Part 1 may be offered continued treatment at RDE. 


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Additional lower and/or intermediate dose levels to the provisional dose levels (Table 4) may 
be implemented. Dose level -1 may be used in case antitumor responses/significant toxicities 
are seen at Dose Level 1. 
Table 4. 
Provisional Dose Levels in the Dose-Escalation (Part 1): Camidanlumab 
Tesirine as Monotherapy 
Dose Level* 
Dose of Cami 
-1 
10 µg/kg Q3W 
1 
20 µg/kg Q3W (starting dose) 
2 
30 µg/kg Q3W 
3 
45 µg/kg Q3W 
4 
60 µg/kg Q3W 
5 
80 µg/kg Q3W 
6 
100 µg/kg Q3W 
7 
125 µg/kg Q3W 
8 
150 µg/kg Q3W 
9 
200 µg/kg Q3W 
10 
250 µg/kg Q3W 
11 
300 µg/kg Q3W 
*  Additional or intermediate dose levels may be implemented during the study; however, the dose will not be 
higher than 300 µg/kg every 3 weeks (Q3W) or equivalent (e.g., 100 µg/kg every week [QW]).  
 
Refer to Section 6.8 for premedication and supportive care. 
6.4 
Camidanlumab Tesirine Combination with Pembrolizumab Dosing 
In the dose-escalation portion of the study (Part 1), the initial dose of camidanlumab tesirine 
will be 30 µg/kg (Dose Level 1) every 3 weeks (Q3W) for 2 cycles (on C1D1 and C2D1). 
The maximum dose possibly administered will be the highest dose of camidanlumab tesirine 
as monotherapy investigated and deemed to be safe. The dose-escalation procedure is 
described in Section 4.1.1.  
Pembrolizumab at dose of 200 mg Q3W will be administered on Day 1 of each cycle starting 
from Cycle 1 onwards (dosing schedule 1). 
If unacceptable toxicity (Section 6.5) occurs during Cycle 1 at dose level -1 and dose level -2, 
dosing Schedule 2, where pembrolizumab administration may start at Cycle 2, may be 
investigated in new enrolled patients. 
Patients who tolerate the study treatment (i.e., no liver enzyme increase ≥ Grade 2, no pleural 
effusion ≥ Grade 2, no edema ≥ Grade 2) and are in disease control (defined as disease control 
≥ SD) may receive additional doses of camidanlumab tesirine in combination with 
pembrolizumab, upon informing the Sponsor. 
Additional administrations of camidanlumab tesirine in combination with pembrolizumab will 
be given as follows: 2 consecutive Cycles every 2 Cycles (2 cycles on, 2 cycles off schedule), 


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starting from Cycle 5 up to a year (i.e., Cycle 5 and 6, Cycle 9 and 10, Cycle 13 and 14, 
Cycle 17 and 18) if there is no delay in the planed treatment schedule: Between these cycles, 
patients should receive pembrolizumab as a single agent.  
In case of delay in the administration of pembrolizumab, additional administrations of 
camidanlumab tesirine can be done after respecting a minimum of 63 days (9 weeks) between 
the last dose of camidanlumab tesirine and the first dose of the 2 subsequent additional 
administrations of camidanlumab tesirine. 
Study treatment is given up to a year. Continued administration of camidanlumab tesirine as 
monotherapy or camidanlumab in combination with pembrolizumab, or pembrolizumab alone 
after a year is to be discussed with the Sponsor.  
A patient should maintain the same treatment schedule throughout the duration of the trial. 
However, once RDE is identified, patients receiving lower or higher dose levels of 
camidanlumab tesirine enrolled in Part 1 may be offered continued treatment at RDE. 
Additional lower and/or intermediate dose levels to the provisional dose levels (Table 5) may 
be implemented (no change in pembrolizumab dose). 
If one study drug, camidanlumab tesirine or pembrolizumab, is put on hold or discontinued 
due to related toxicity, the other study drug could continue as single agent. 
In the dose-expansion portion of the study (Part 2), patients will be assigned to the RDE of 
camidanlumab tesirine in combination with pembrolizumab recommended from Part 1. 
The RDE selected for Part 2 will be based on review of all available study data and will be 
recommended by the DESC. 
Table 5. 
Provisional Dose Levels in the Dose-Escalation (Part 1): Camidanlumab 
Tesirine in Combination with Pembrolizumab 
Dose Level* 
Dose of Cami 
Dose of pembrolizumab 
-2 
13 µg/kg Q3W × 2 
200 mg Q3W 
-1 
20 µg/kg Q3W × 2 
200 mg Q3W 
1 
30 µg/kg Q3W × 2 
(starting dose) 
200 mg Q3W 
2 
45 µg/kg Q3W × 2 
200 mg Q3W 
3 
60 µg/kg Q3W × 2 
200 mg Q3W 
4 
80 µg/kg Q3W × 2 
200 mg Q3W 
5 
100 µg/kg Q3W × 2 
200 mg Q3W 
6 
125 µg/kg Q3W × 2 
200 mg Q3W 
7 
150 µg/kg Q3W × 2 
200 mg Q3W 
8 
200 µg/kg Q3W × 2 
200 mg Q3W 
9 
250 µg/kg Q3W × 2 
200 mg Q3W 
10 
300 µg/kg Q3W × 2 
200 mg Q3W 
*  Additional or intermediate dose levels may be implemented during the study; however, the dose will not be 
higher than the highest dose of camidanlumab tesirine as monotherapy every three weeks (Q3W) 
investigated and deemed safe. 
 


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6.5 
Dose-Limiting Toxicities 
For the dose-escalation of camidanlumab tesirine as monotherapy, a DLT is defined as any of 
the following events, which occur during the 21 days following the first study drug 
administration period of Part 1 (excluding the paired-biopsy cohorts), except those that are 
clearly due to underlying disease or extraneous causes. 
For the dose-escalation of camidanlumab tesirine in combination with pembrolizumab, a DLT 
is defined as any of the following events, which occur during the 21 days following the first 
administration of pembrolizumab in Part 1, except those that are clearly due to underlying 
disease or extraneous causes. 
A hematologic DLT is defined as: 
Event 
Severity 
Febrile neutropenia or neutropenic infection 
≥Grade 3 
Neutropenia lasting >7 days 
≥Grade 4 
Thrombocytopenia 
≥Grade 4  
Thrombocytopenia with clinically significant bleeding 
≥Grade 3 
Thrombocytopenia requiring a platelet transfusion 
≥Grade 3 
Anemia 
≥Grade 4 
Anemia requiring transfusion 
≥Grade 3 
 
A non-hematologic DLT is defined as: 
Event 
Severity 
Hy’s law case  
Aspartate transaminase (AST) and/or alanine transaminase 
(ALT) >3 × upper limit normal (ULN) and bilirubin 
>2 × ULN, and without initial findings of cholestasis 
(serum alkaline phosphatase [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. 
Hypersensitivity/infusion-related 
reaction (regardless of premedication) 
≥Grade 3. A Grade 3 hypersensitivity/infusion related 
reaction that resolves within 24 hours after onset with 
appropriate clinical management does not qualify as a 
DLT. 
Radiculitis / Polyradiculopathy / GBS 
≥Grade 2 
All other non-hematologic toxicity  
≥Grade 3 
 


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The following conditions are not considered DLTs: 
Event 
Severity 
Fatigue 
Grade 3 for ≤7 days. 
Diarrhea, nausea, or vomiting 
Grade 3 in the absence of premedication that responds to 
therapy and improves by at least 1 grade within 3 days for 
Grade 3 events or to ≤Grade 1 within 7 days. 
Alkaline 
phosphatase 
(ALP) 
and 
gamma glutamyl transferase (GGT) 
Grade 3 ALP and GGT elevations, unless considered 
clinically relevant by the investigator.  
Serum lipase or serum amylase 
Grade 3 for ≤7 days if without clinical signs or symptoms 
of pancreatitis. 
Electrolyte abnormalities 
Grade 3 that normalizes within 48 hours (with or without 
medical intervention) and does not manifest themselves 
clinically; in such instances, a follow-up sample MUST be 
taken within 48 hours to check whether such normalization 
has occurred. 
 
A dose limiting toxicity is not a reason for treatment discontinuation.  
Patients who experience a DLT that resolves or stabilizes with appropriate medical 
management may continue treatment at the discretion of the Investigator in consultation with 
the Sponsor.  
6.6 
Dose Delays and Modifications 
When both camidanlumab tesirine and pembrolizumab have been dosed and an AE occurs with 
relationship to study treatment and requires study treatment hold, the resumption of study 
treatment can occur only with one study drug at a time. The second study drug may be resumed 
at the next planned Cycle. 
In the above situation, prior to the resumption of any study drugs, discussion should occur with 
the Sponsor. 
6.6.1 
Dose Delays and Modifications for Camidanlumab Tesirine 
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. 
Guidelines for management of toxicities, when considered to be at least possibly related to 
camidanlumab tesirine, are detailed: 
 in Section 6.6.1.1 for general toxicities (i.e., not specified in the below sections), 
 in Section 6.6.1.2 for specific non-hematologic toxicities, 
 in Section 6.6.1.3 for specific hematologic toxicities, 


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• in Section 6.6.1.4 for specific neurologic toxicities, 
• in Section 6.6.1.5 for specific skin toxicities. 
 
When a patient is treated with the combination of camidanlumab tesirine and pembrolizumab, 
the management of irAEs related to camidanlumab tesirine will follow the recommendations 
for the management of irAEs related to pembrolizumab in Table 14 (Appendix 13.4). 
6.6.1.1 
Camidanlumab Tesirine Dose Modification Guidelines: General Toxicities 
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, 
continue camidanlumab tesirine at the original assigned dose level in subsequent 
treatment cycles. 
If improvement to ≤Grade 1 or Baseline occurs >21 days from the last scheduled 
(but missed) camidanlumab tesirine dose, continue camidanlumab tesirine and reduce 
by 1 dose level from the original assigned dose in subsequent treatment cycles. 
Second 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, reduce 
by 1 dose level from the original assigned dose in subsequent treatment cycles. 
If improvement to ≤Grade 1 or Baseline occurs >21 days from the last scheduled 
(but missed) camidanlumab tesirine dose, continue camidanlumab tesirine and reduce 
by 2 dose levels from the original assigned dose in subsequent treatment cycles.  
Otherwise, camidanlumab tesirine should be permanently discontinued. 
Third Occurrence: 
Permanently discontinue camidanlumab tesirine. 
 
6.6.1.2 
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 6.9.4 for treatment recommendation. 


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Adverse Event 
Grade Camidanlumab Tesirine Management Guideline 
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 6.9.4 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 6.9.4 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, continue camidanlumab tesirine at the original 
assigned dose level in subsequent treatment cycles. 
If improvement to ≤Grade 1 or Baseline occurs >21 days from the 
last scheduled (but missed) camidanlumab tesirine dose, continue 
camidanlumab tesirine and reduce by 1 dose level from the 
original assigned dose in subsequent treatment cycles. 
Second 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, reduce by 1 dose level from the original assigned 
dose in subsequent treatment cycles. 
If improvement to ≤Grade 1 or Baseline occurs >21 days from the 
last scheduled (but missed) camidanlumab tesirine dose, continue 
camidanlumab tesirine and reduce by 2 dose levels from the 
original assigned dose in subsequent treatment cycles.  
Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
Third Occurrence: 
Permanently discontinue camidanlumab tesirine. 


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Adverse Event 
Grade Camidanlumab Tesirine Management Guideline 
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, continue camidanlumab tesirine and reduce by 
1 dose level from the original assigned dose in subsequent 
treatment cycles. 
If improvement to ≤Grade 1 or Baseline occurs >21 days from the 
last scheduled (but missed) camidanlumab tesirine dose, continue 
camidanlumab tesirine and reduce by 2 dose levels from the 
original assigned dose in subsequent treatment cycles. 
Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
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., 
hypothyroidism, 
hyperthyroidism, 
hepatitis, other 
endocrinopathies) 
≥1 
Need to be followed at least weekly to quickly detect deterioration 
and modify dosing as per general recommendations in 
Section 6.6.1.1 (can be done by telephone unless symptoms 
worsen). 
Consider using American Society of Clinical Oncology (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 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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6.6.1.3 
Guidelines for Dose Modification: Specific Hematologic Toxicities 
Consider use of granulocyte colony stimulating factor (G-CSF) as per institutional guidelines 
or as per ASCO guidelines for neutropenia/febrile neutropenia. Prophylactic G-CSF may not 
be used during the first cycle of camidanlumab tesirine. 
For anemia, consider use of erythropoietin as per institutional guidelines. 
6.6.1.4 
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 6.9.6 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 6.9.6 and 
Appendix 13.3), 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). 
6.6.1.5 
Guidelines for Dose Modification: Specific Skin Toxicities 
Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
Maculopapular rash 
 
or 
 
Photosensitivity rash 
 
or 
 
Pruritus 
 
or  
 
Xerosis 
 
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 BID (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 BID (e.g., clobetasol propionate 
0.05%, halobetasol propionate 0.05%). 


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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
or  
 
Hyperpigmentation 
 
- pruritus: high potency topical steroid cream BID 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 BID (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 BID 
(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 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 by 1 dose level from the original 
assigned dose in subsequent treatment cycles.  
Second Occurrence: 
• If improvement to ≤Grade 1 or Baseline occurs prior to the 
next scheduled dose, reduce by 1 dose level from the 
original assigned dose in subsequent treatment cycles. 
• If improvement to ≤Grade 1 or Baseline occurs >21 days 
from the last scheduled (but missed) camidanlumab 
tesirine dose, reduce by 2 dose levels from the original 
assigned dose in subsequent treatment cycles. 


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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
• Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
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 BID (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 BID 
(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 prior to the 
next scheduled dose, continue camidanlumab tesirine and 
reduce by 1 dose level from the original assigned dose in 
subsequent treatment cycles. 
• If improvement to ≤Grade 1 or Baseline occurs >21 days 
from the last scheduled (but missed) camidanlumab 
tesirine dose, reduce by 2 dose levels from the original 
assigned dose in subsequent treatment cycles.  
• Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
Second Occurrence: 
Permanently discontinue camidanlumab tesirine. 
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). 


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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
 
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, reduce by 1 dose level from the original 
assigned dose in subsequent treatment cycles.  
• Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
Second Occurrence: 
• If improvement to ≤Grade 1 or Baseline occurs prior to the 
next scheduled dose, reduce by 1 dose level from the 
original assigned dose in subsequent treatment cycles. 
• If improvement to ≤Grade 1 or Baseline occurs >21 days 
from the last scheduled (but missed) camidanlumab 
tesirine dose, reduce by 2 dose levels from the original 
assigned dose in subsequent treatment cycles. 
• Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
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: 


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Adverse Event 
Grade 
Camidanlumab Tesirine Management Guideline 
First Occurrence: 
• If improvement to ≤Grade 1 or Baseline occurs prior to the 
next scheduled dose, continue camidanlumab tesirine and 
reduce by 1 dose level from the original assigned dose in 
subsequent treatment cycles. 
• If improvement to ≤Grade 1 or Baseline occurs >21 days 
from the last scheduled (but missed) camidanlumab 
tesirine dose, reduce by 2 dose levels from the original 
assigned dose in subsequent treatment cycles.  
• Otherwise, camidanlumab tesirine should be permanently 
discontinued. 
Second Occurrence: 
Permanently discontinue camidanlumab tesirine. 
Abbreviations: BID=twice daily; HSV=herpes simplex virus; VZV=varicella zoster virus 
 
6.6.1.5.1 Severe Immune-Mediated Skin Adverse Events 
When a patient is treated with camidanlumab tesirine in combination with pembrolizumab, and 
there are cases of severe immune-mediated skin adverse events related to camidanlumab 
tesirine, the following recommendations for camindanlumab tesirine should be followed. 
These recommendations align with current guidances provided in the pembrolizumab 
prescribing information: 
- 
Grade 3 immune-mediated skin AE, drug reaction with eosinophilia and systemic 
symptoms (DRESS), suspected Stevens-Johnson syndrome (SJS), suspected toxic 
epidermal necrolysis (TEN): withhold treatment regimen 
- 
Grade 4 immune-mediated skin AE, DRESS, confirmed SJS, confirmed TEN: 
treatment regimen permanently discontinued 
 
6.6.1.6 
Principles of Camidanlumab Tesirine Rechallenge 
Exercise caution when considering resumption of camidanlumab tesirine after significant 
immune-related adverse events (irAEs) (≥Grade 2). Close follow-up should be performed 
when resuming camidanlumab tesirine to monitor recurrent symptoms: 
• If re-challenged and toxicity returns, permanently discontinue camidanlumab tesirine 
• Assess patient’s tumor status prior to rechallenge. If an objective response (complete 
or partial) to camidanlumab tesirine was achieved, resumption of camidanlumab 
tesirine may not be advisable due to risk of toxicity recurrence. Risks/benefits of 
restarting camidanlumab tesirine is to be discussed with Sponsor. 
 


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6.6.2 
Dose Delays and Modifications for Pembrolizumab 
6.6.2.1 
General rules 
Dose reduction or dose-escalation are not permitted. 
Management of immune-related AEs in patients treated with immune checkpoint inhibitor 
therapy, based on international guidelines (Brahmer, 2018; Haanen, 2017; Puzanov, 2017; 
NCCN, 2019) are shown in Appendix 13.4.  
Guidelines for management of toxicities, when considered to be at least possibly related to 
pembrolizumab, are detailed in Appendix 13.4. 
In the event of toxicity not relieved with optimal medical support, modifications in 
pembrolizumab administration include dose interruptions, delays in the start of the next cycle, 
and/or treatment discontinuation (refer to Section 6.6.2.2 and Appendix 13.4). 
In the event of a delay in initiation of a planned Cycle of Study treatment for >21 days, the 
Sponsor should be contacted to discuss continuing the patient on pembrolizumab. 
Pembrolizumab will be given at full dose when resumed after being held for toxicity. 
If pembrolizumab is held because of AEs >12 weeks beyond the last dose, then the patient will 
be discontinued from pembrolizumab and will be followed for safety. 
If pembrolizumab is discontinued due to significant irAE, camidanlumab tesirine could be 
continued, at lower dose level, after discussion with the Sponsor. 
Investigators should inform Sponsor in case of immune-related AEs of any grade. 
6.6.2.2 
Holding Recommendations 
If a patient experiences any Grade ≥3 toxicity, pembrolizumab must be held until the toxicity 
resolves to Grade 1 or less (Grade 1 or baseline for peripheral neuropathy).  
For the dose recommendations per prescribing information, please refer to Appendix 13.4. 
6.6.2.3 
Principles of Pembrolizumab Rechallenge 
Exercise caution when considering resumption of pembrolizumab after significant irAEs. 
Close follow-up should be performed when resuming pembrolizumab to monitor recurrent 
symptoms: 
• If re-challenged and toxicity returns, permanently discontinue pembrolizumab 
• Assess patient’s tumor status prior to rechallenge. If an objective response (complete 
or partial) to pembrolizumab was achieved, resumption of pembrolizumab may not be 
advisable due to risk of toxicity recurrence. Risks/benefits of restarting pembrolizumab 
is to be discussed with Sponsor. 
 
With some exceptions (see Appendix 13.4), resumption of pembrolizumab following Grade 2 
irAEs can be considered upon resolution to ≤Grade 1. 
Consult with organ-specific specialists prior to resumption of immunotherapy as appropriate 
following an immunotherapy hold due to irAEs. For organ-specific considerations for 
pembrolizumab rechallenge after a hold, refer to Appendix 13.4. 


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6.7 
Overdose Management 
For camidanlumab tesirine, the overdose is any dose given to a patient that exceeds the planned 
dose by 15% or more. 
For pembrolizumab, an overdose is defined as any dose exceeding 5 times the prescribed dose 
for pembrolizumab (i.e., ≥1000 mg). No specific information is available on the treatment of 
overdose of pembrolizumab.  
Any overdose, with or without associated AEs, drug should be held, and event must be 
promptly (i.e., within 24 hours after the time site personnel first learn about the event) reported 
to the Sponsor; in case of study treatment related AE, please refer to the dose delay and 
modification recommendation, listed in Section 6.6. 
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.  
6.8 
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.  
6.9 
Premedication and Supportive Care  
6.9.1 
Premedication for Camidanlumab Tesirine 
Unless contraindicated, administer dexamethasone 4 mg orally 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. 
Patients who experience an infusion-related hypersensitivity reaction will receive the 
alternative premedication regimen specified in Section 6.9.4. 
6.9.2 
Premedication for Pembrolizumab 
No premedication is required for pembrolizumab. 
6.9.3 
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 
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6.9.4 
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 SoC: 
• 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. 
 
6.9.5 
Consideration for Skin Toxicity 
6.9.5.1 
Camidanlumab Tesirine 
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 (for example, 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 6.6.1.5).  
Photographs of skin toxicity may be taken for documentation purposes at the discretion of the 
Investigator provided the patient has given consent for this specific assessment. 
6.9.5.2 
Pembrolizumab 
Immune-related severe skin reactions have been reported in patients receiving pembrolizumab. 
Patients should be monitored for suspected severe skin reactions and other causes should be 
excluded. Based on the severity of the adverse reaction, pembrolizumab should be withheld or 
permanently discontinued, and corticosteroids should be administered (see Appendix 13.4). 
Cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been 
reported in patients receiving pembrolizumab. For signs or symptoms of SJS or TEN, 
pembrolizumab should be withheld and the patient should be referred to a specialised unit for 
assessment and treatment. If SJS or TEN is confirmed, pembrolizumab should be permanently 
discontinued (see Appendix 13.4). 


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Caution should be used when considering the use of pembrolizumab in a patient who has 
previously experienced a severe or life-threatening skin adverse reaction on prior treatment 
with other immunestimulatory anticancer agents. 
6.9.6 
Diagnostic, Work-up, and Management of Polyradiculopathy/ Guillain-Barré 
Syndrome  
It is strongly recommended starting 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 would 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 
• 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: 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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6.9.7 
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. 
6.10 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. 
6.10.1 
Permitted During Study 
Medications or procedures for the clinical care of the patient, including management of AEs, 
bisphosphonates, are permitted during the study, except for those listed in Section 6.10.2.  
Hematopoietic growth factors are permitted as per ASCO guidelines (Smith, 2006). 
Prophylactic G-CSF may not be used during the first cycle of camidanlumab tesirine. 
Local radiotherapy for analgesic/palliative purposes or for lytic lesions at risk of fracture may 
be carried out if required after completion of the DLT evaluation period. Whenever possible, 
these patients should have a tumor assessment of the lesion(s) before they receive radiotherapy 
to rule out progression of disease. No dose modification of study medication is needed during 
radiotherapy. 
6.10.2 
Prohibited During Study 
• Other anticancer therapy during the Treatment period, 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 the last dose of study 
treatment 
 
6.10.3 Varicella Zoster Virus Prophylaxis 
In accordance with international guidelines related to infections in cancer patients 
(NCCN, 2020; Sandherr, 2006) VZV prophylaxis is recommended according to institutional 
guidelines for patients enrolled in this study, whether already receiving camidanlumab tesirine 
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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 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. 
• Collection of information on prior medications used from ICF signature date or at least 
within 14 days prior to camidanlumab tesirine administration, whichever is earlier. 
• Mutational status 
o For patients in the combination cohorts, mutational status includes as well PD-L1 
expression, mismatch repair (MMR) and microsatellite stability (MSS) or 
microsatellite instability (MSI) status (See Section 5.1).  
 In Dose-escalation, for patients with NSCLC or melanoma, PD-L1 expression 
is requested; MMR/MSS/MSI status is not required. 
 In Dose-escalation, for patients with colorectal cancer, gastric-esophageal 
cancer, ovarian/fallopian tube cancer, pancreatic cancers: if MMR/MSS/MSI 
status is not available at signature of the informed consent, the test should be 
performed before C1D1.  
 In Dose-expansion, for patients enrolled in Group 1, if MMR/MSS/MSI status 
is not available at signature of the informed consent, the test should be 
performed before C1D1.  
 In Dose-expansion, for patients enrolled in Group 2, MSI-H/dMMR status must 
be available prior to ICF signature (See Section 5.1). 
 
7.3 
Efficacy Assessments 
Disease assessments will occur as per SoE (Table 1 and Table 2) until progression.  
Imaging performed within 4 weeks prior to C1D1 can be accepted as the Screening (Baseline) 
assessment. 


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During the treatment period, imaging will be performed 6 weeks (42 days ±7 days) after C1D1, 
but prior to C3D1, and 12 weeks (84 days ±7 days) after C1D1, but prior to C5D1, then every 
12 weeks (84 days ±14 days) until EOT for patients treated with camidanlumab tesirine as 
monotherapy and every 9 weeks (63 days ±14 days) until EOT for patients treated with 
camidanlumab tesirine in combination with pembrolizumab. 
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 weeks (84 days ±14 days), for patients treated with camidanlumab tesirine as 
monotherapy, or every 9 weeks (63 days ±14 days) for patient treated with camidanlumab 
tesirine in combination with pembrolizumab, until 1 year from EOT.  
If a scan has been performed within 8 weeks of EOT, it does not need to be repeated at EOT.  
Additional disease assessments may be obtained, if clinically indicated.  
CT or MRI scans with contrast of the chest, abdominal and pelvic area or brain scans (CT or 
MRI with contrast), and bone scans or X-ray exam if clinically indicated, will be performed. 
For image acquisition specifications, including instruction in the event of allergy to contrast 
dye, refer to RECIST v1.1 (Specifications for Standard Anatomical Radiological Imaging). 
The same methods used at Baseline that identify sites of disease should be used uniformly for 
all subsequent assessments. Response to treatment will be determined by the Investigator as 
CR, PR, stable disease (SD), or progressive disease (PD) according to RECIST v 1.1. As per 
iRECIST (Seymour, 2017), the terminology “immune-” CR/PR/SD (iCR/iPR/iSD) will be 
used. In addition, confirmation of progression or immune-confirmed progressive disease 
(iCPD) should be performed as per iRECIST, i.e., 4 to 8 weeks after the first PD assessment 
or immune-unconfirmed progressive disease (iUPD), unless there is clear clinical deterioration 
which would prevent such confirmation. If progression is not confirmed, disease assessment 
should continue as originally planned. Clinically stable patients may at investigator discretion 
either interrupt or continue treatment until iCPD.  
Images will be obtained according to local site imaging requirements and may be provided to 
Sponsor for independent review as part of comparative analysis if required.  
7.4 
Safety Assessments  
Safety will be assessed based on the procedures in the subsection below. Adverse events/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.  
Depending on local practice, physical examination, ECOG, and laboratory testing could be 
done within 24 hours before dosing. 
7.4.1 
Physical Examination 
Physical examinations will be performed according to institutional standards and will include 
a whole-body skin examination.  


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Physical examinations will also include a neurological examination of strength, sensation, and 
deep tendon reflexes. 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 should be documented; refer to 
Section 6.6.1.4 for dose modification due to specific neurologic toxicities and Section 6.9.6 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 the underlying disease or 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 or motor 
weakness, or new onset of pain, which is refractory to common pain medications with or 
without any additional neurological deficiencies. 
The examination must include a determination if the patient has had any 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). 
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 and Table 2).  
7.4.3 
Height and Weight 
Height and weight will be measured as per SoE (Table 1 and Table 2). 
Additional measurements will be performed if clinically indicated. 
Patients should monitor their weight at home to detect potential edema/effusions. 
Refer to Section 6.9.3 for further details. 
7.4.4 
Vital Signs 
Vital signs will be measured as per SoE (Table 1 and Table 2). 
Vital signs include the measurements of arterial BP (systolic and diastolic), heart rate, 
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). 
For patients treated with pembrolizumab, vital signs will be also collected at the end of infusion 
of pembrolizumab. 
7.4.5 
Laboratory Tests 
Samples will be collected at the time points specified as per SoE (Table 1 and Table 2) 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. 


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Hematology: WBCs with 5-part differential (neutrophils, eosinophils, basophils, lymphocytes, 
and monocytes), platelet count, hemoglobin, and hematocrit.  
Chemistry: ALT, AST, GGT, ALP, amylase, lipase, total bilirubin (conjugated and 
unconjugated bilirubin only when total bilirubin is abnormal), sodium, potassium, chloride, 
phosphate/phosphorus, 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 
(prothrombin time to be collected if INR is not available). 
Thyroid function: Thyroid-Stimulating Hormone (TSH); reflex free T4 and/or free T3, as 
applicable, only when TSH is abnormal. 
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. 
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). 
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. 
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, or 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 should be conducted, provided the availability of the test(s). See 
Section 6.6.1.2 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.  
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, all efforts should be made to keep the interval 
between two consecutive pregnancy tests no more than 6 weeks. 
If a pregnancy test is positive, the study drug must be held pending confirmation. 
If the pregnancy is confirmed, study treatment will be discontinued permanently for the 
patient. Refer to Section 8.6 for the handling of the patient and reporting the event. 
A pregnancy test is to be performed at the EOT visit. In addition, a pregnancy test should be 
performed ≥9.5 months after the last dose of camidanlumab tesirine (i.e., end of relevant 
systemic exposure considering 5 half-lives plus 6 months for other than aneugenic genotoxic 
compound [CTFG, 2020; FDA, 2019] or ≥4 months after the last dose of pembrolizumab, 
whichever is the latest. The patient will be asked either to come back to the site for a pregnancy 
test or she will be given a prescription for a pregnancy test. The result will be collected over 
the phone or will be faxed/emailed to the site. The contact with the patient and the result of the 
pregnancy test must be documented on source documents at the site. 
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 and Table 2). Refer to Table 6 for the 
detailed schedule of ECGs, for patients treated with camidanlumab tesirine as monotherapy.  
Refer to Table 7 for the detailed schedule of ECGs, for patients treated with camidanlumab 
tesirine in combination with pembrolizumab. 
ECGs will be performed after the patient has rested 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. 


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Table 6. 
Schedule for Triplicate ECG Collection (Q3W Schedule): Camidanlumab 
Tesirine as Monotherapy 
Cycle 
Day 
ECG timepoint (window) 
Screening 
- 
Any time within 21 days prior to C1D1 
C1 
D1 
Pre-dose (preferably within 2 h prior to start of infusion) 
EOI (within 10 min prior to EOI) 
Post-dose* 4 h (± 15 min) 
D3 
Post-dose* 48 h (± 24 h; but within 30 min prior to PK sample) 
D8 
Post-dose* 168 h (± 48 h; but within 30 min prior to PK sample) 
D15 
Post-dose* 336 h (± 48 h; but within 30 min prior to PK sample) 
C2 
D1 
Pre-dose (within 30 min prior to PK sample) 
EOI (within 10 min prior to EOI) 
Post-dose* 4 h (± 15 min) 
D3 
Post-dose* 48 h (± 24 h; but within 30 min prior to PK sample) 
D8 
Post-dose* 168 h (± 48 h; but within 30 min prior to PK sample) 
D15 
Post-dose* 336 h (± 48 h; but within 30 min prior to PK sample) 
C3 and C4 
 
D1 
Pre-dose (within 30 min prior to PK sample)  
Post-dose* 4 h (± 15 min) 
C5, C7  
every other cycle 
D1 
Pre-dose (within 30 min prior to PK sample) 
EOT 
 
Any time (but within 30 min prior to PK sample) 
Unscheduled 
 
Any time 
Abbreviations: C=cycle; D=day; ECG=electrocardiogram; EOI=end of infusion; EOT=end of treatment; h=hour; 
min=minutes; PK=pharmacokinetics; Q3W=every 3 weeks. 
* Post-dose timepoint is counted from start of infusion. 
 
Table 7. 
Schedule for Triplicate ECG Collection (Q3W Schedule): Camidanlumab 
Tesirine in combination with Pembrolizumab 
Cycle 
Day 
ECG timepoint (window) 
Screening 
- 
Any time within 21 days prior to C1D1 
C1 
D1 
Pre-dose (preferably within 2 h prior to start of infusion) 
EOI (within 10 min prior to EOI of camidanlumab tesirine) 
Post-dose* 4 h (± 15 min) 
C2 
D1 
Pre-dose (preferably within 2 h prior to start of infusion) 
EOI (within 10 min prior to EOI camidanlumab tesirine) 
Post-dose* 4 h (± 15 min) 
C3, C5, every other 
Cycle 
D1 
Pre-dose (preferably within 2 h prior to start of infusion) 
EOT 
 
Any time (but within 30 min prior to PK sample) 
Unscheduled 
 
Any time 
Abbreviations: C=cycle; D=day; ECG=electrocardiogram; EOI=end of infusion; EOT=end of treatment; h=hour; 
min=minutes; PK=pharmacokinetics; Q3W=every 3 weeks. 
* Post-dose timepoint is counted from start of infusion of camidanlumab tesirine 
 




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For detailed instructions related to central laboratory sample collection, labeling, processing, 
storage, or shipment refer to the appropriate laboratory manual(s).  
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 8 for the patients treated 
with camidanlumab tesirine as monotherapy, as per Table 2 and Table 9 for the patients treated 
with camidanlumab tesirine in combination with pembrolizumab. 
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) 
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Table 8. 
Sampling Schedule for PK and ADA (Q3W Schedule): Camidanlumab 
Tesirine as Monotherapy 
Cycle 
Day 
PK timepoint (window) 
ADA timepoint (window) 
C1 
D1 
Pre-dose 
(preferably within 2 h prior to start of 
infusion of camidanlumab tesirine) 
EOI of camidanlumab tesirine (-5 to +10 
min) 
Post-dose* 4 h (± 10 min) 
Pre-dose 
(preferably within 2 h prior to start of 
infusion of camidanlumab tesirine) 
 
D3 
Post-dose* 48 h (± 24 h)  
- 
D5 
Post-dose* 96 h (± 24 h) 
- 
D8 
Post-dose* 168 h (± 48 h)  
- 
D15 
Post-dose* 336 h (± 48 h) 
Post-dose* 336 h (± 48 h) 
C2 
D1 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine) 
EOI of camidanlumab tesirine (-5 to +10 
min) 
Post-dose* 4 h (± 10 min) 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine) 
D3 
Post-dose* 48 h (± 24 h)  
- 
D5 
Post-dose* 96 h (± 24 h) 
- 
D8 
Post-dose* 168 h (± 48 h) 
- 
D15 
Post-dose* 336 h (± 48 h) 
- 
C3 and C4 
D1 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine)  
Post-dose* 4 h (± 10 min) 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine) 
C5, C6, C7, 
every cycle 
D1 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine)  
 
C5, C7,  
every other cycle 
D1 
 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine) 
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; C=cycle; D=day; EOI=end of infusion; EOT=end of treatment; 
h=hour; min=minutes; PK=pharmacokinetics; Q3W=every 3 weeks. 
* 
Post-dose timepoint is counted from start of infusion of camidanlumab tesirine. 


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Table 9. 
Sampling Schedule for PK and ADA (Q3W Schedule): Camidanlumab 
Tesirine in combination with Pembrolizumab 
Cycle 
Day 
PK timepoint (window)1 
ADA timepoint (window)1 
C1 
D1 
Pre-dose 
(preferably within 2 h prior to start of 
infusion of camidanlumab tesirine) 
EOI of camidanlumab tesirine (-5 to +10 
min) 
Post-dose* 4 h (± 10 min) 
Pre-dose 
(preferably within 2 h prior to start of 
infusion of camidanlumab tesirine) 
 
D3 
Post-dose* 48 h (± 24 h)  
- 
D5 
Post-dose* 96 h (± 24 h) 
- 
D8 
Post-dose* 168 h (± 48 h)  
- 
D15 
Post-dose* 336 h (± 48 h) 
Post-dose* 336 h (± 48 h) 
C2 
D1 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine) 
EOI of camidanlumab tesirine (-5 to +10 
min) 
Post-dose* 4 h (± 10 min) 
Pre-dose 
(within 2 h prior to start of infusion of 
camidanlumab tesirine) 
D3 
Post-dose* 48 h (± 24 h)  
- 
D5 
Post-dose* 96 h (± 24 h) 
- 
D8 
Post-dose* 168 h (± 48 h) 
- 
D15 
Post-dose* 336 h (± 48 h) 
- 
C3, C4, C5, C6, C7 
then every other 
Cycle 
D1 
Pre-dose 
(within 2 h prior to start of infusion of 
study treatment)  
Pre-dose 
(within 2 h prior to start of infusion of 
study treatment) 
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; C=cycle; D=day; EOI=end of infusion; EOT=end of treatment; 
h=hour; min=minutes; PK=pharmacokinetics; Q3W=every 3 weeks. 
* 
Post-dose timepoint is counted from start of infusion of camidanlumab tesirine. 
1 
Upon consultation with the Sponsor, PK and ADA samples will not be collected anymore if camidanlumab 
tesirine is permanently discontinued and pembrolizumab continues as single agent. 
 
For patients treated with camidanlumab tesirine in combination with pembrolizumab, the 
collection of PK data will be stopped upon consultation with the Sponsor if camidanlumab 
tesirine administration is discontinued and pembrolizumab continues. 
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.  


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7.5.2 
Immunogenicity 
Detection of ADAs against camidanlumab tesirine 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 8 for the patients treated 
with camidanlumab tesirine as monotherapy, as per Table 2 and Table 9 for the patients treated 
with camidanlumab tesirine in combination with pembrolizumab. 
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.  
For patients treated with camidanlumab tesirine in combination with pembrolizumab, unless 
there is a penultimate observation of positive ADA response, no other collection of ADA data 
is necessary if camindanlumab tesirine administration is discontinued.  


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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 examinations, 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 judgement 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 AEs, irrespective of seriousness and causality, are considered 
AESIs (except those clearly attributed to pembrolizumab alone): 
• GBS (including variants such as acute motor and sensory axonal neuropathy) 
• Polyradiculopathy 
• Autonomic nervous system imbalance 
• Nerve palsy 
• ≥Grade 3 neurologic toxicities 
• ≥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 (Note: immune-mediated skin 
toxicities will need confirmatory skin biopsy) 


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• 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. 
Adverse events of special interest 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 drugs (camidanlumab tesirine 
and pembrolizumab), 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. 
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 serious 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. 


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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 version 4.0. 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 12.  
Table 12. 
Definition of Severity Grades for Common Terminology Criteria for 
Adverse Events 
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 participant that occurs from signing the ICF up to 9.5 months after the last 
dose of camidanlumab tesirine, or up to 4 months after the last dose of pembrolizumab, 
whichever is the latest, 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 the last dose 
of camidanlumab tesirine, or up to 4 months after the last dose of pembrolizumab, whichever 
is the latest, 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 


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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. 
Once pregnancy is confirmed in a study participant, study drug will be discontinued; 
see Section 7.4.6 for additional information.  




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9.6 
Exposure to Treatments 
Exposure to study drug, prior, and concomitant medications will be summarized for the Safety 
analysis set by dose level. Dose interruptions, reductions, and relative dose intensity will also 
be summarized. 
9.7 
Efficacy Analyses 
9.7.1 
Overall Response Rate 
The ORR by RECIST v 1.1 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. 
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 
Duration of response by RECIST 1.1 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. 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 for all responders and by response (CR/PR). The median duration of 
response and 95% CI will be presented. Further details will be outlined in the SAP. 
9.7.3 
Progression-Free Survival 
PFS will be defined 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. 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. 
9.7.4 
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. 
9.8 
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, whichever is 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); study drug-related AEs; AEs leading to treatment interruption, modification, or 
discontinuation; AESIs; SAEs; 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 version 4.0 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. 






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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). Adverse events 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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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 or the patient’s legally authorized representative 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 or their legally authorized representative before performing any study procedures 
and will be documented with a signed IRB/IEC approved ICF. Before enrollment, each 
prospective patient or his or her legally authorized representative 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/legally authorized representative understands the implications of 
participating in the study, the patient/legally authorized representative 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. 
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 (or the patient’s legal guardian), except as necessary for monitoring 
and auditing by the Sponsor, its designee, regulatory authorities, or the IRB/IEC. 


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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. 
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 


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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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SAP_001.pdf: 
Protocol Number: ADCT-301-103 
 
Official Title: A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-
301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors 
NCT Number: NCT03621982 
 
Document Date: 02 December 2021 


ADC Therapeutics 
ADCT-301 
ADCT-301-103 
SAP Final Version 
Page 1 of 23 
 
 
 
 
 
 
Statistical Analysis Plan 
 
 
 
 
A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor 
Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in 
Combination in Patients With Selected Advanced Solid Tumors 
 
PROTOCOL NO.: ADCT-301-103 
 
 
 
SAP Final No./ Date: 30 November 2021 
 
 
Statistician: 
 
 
 
 
 
  
Confidentiality Statement 
 
All financial and nonfinancial support for this study will be provided by ADC Therapeutics 
SA. The concepts and information contained in this document or generated during the study 
are considered proprietary and may not be disclosed in whole or in part without the expressed, 
written consent of ADC Therapeutics SA. The study will be conducted according to the 
International Conference on Harmonisation harmonised tripartite guideline E6(R1), Good 
Clinical Practice. 
 
 


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ADC Therapeutics 
ADCT-301 
ADCT-301-103 
SAP Final Version 
Page 3 of 23 
 
Table of Contents 
Table of Contents ...................................................................................................................... 3 
Glossary of Abbreviations......................................................................................................... 5 
1 Introduction ............................................................................................................................ 7 
2 Study Objectives .................................................................................................................... 8 
2.1 Primary Objectives ......................................................................................................8 
2.2 Secondary Objectives ..................................................................................................8 
 
3 Study Design .......................................................................................................................... 9 
3.1 Sample Size Consideration ..........................................................................................9 
3.2 Randomization .............................................................................................................9 
3.3 Modifications to the statistical section of the protocol ................................................9 
4 Statistical methods ............................................................................................................... 10 
4.1 Analysis Populations .................................................................................................10 
4.1.1 Safety Analysis Set .......................................................................................10 
4.1.2 DLT-evaluable Analysis Set ..........................................................................10 
4.1.3 Efficacy Analysis Set .................................................................................... 11 
4.1.4 Pharmacokinetics (PK) Analysis Set ............................................................ 11 
 
4.2 Patient Disposition ..................................................................................................... 11 
4.3 Protocol Deviations ................................................................................................... 11 
4.4 Demographic and Baseline Characteristics ...............................................................12 
4.5 Cancer History and Medical History .........................................................................12 
4.6 Prior and Concomitant Medications (other than anticancer therapies) .....................12 
4.7 Exposure to Treatment ...............................................................................................12 
4.7.1 Extent of Study Drug Exposure ....................................................................12 
4.7.2 Subsequent Anticancer Therapy or Procedure ..............................................15 
4.8 Efficacy Analyses ......................................................................................................15 
4.8.1 Overall Response Rate ..................................................................................15 
4.8.2 Duration of Response ....................................................................................16 
4.8.3 Duration of Stable Disease ............................................................................16 
4.8.4 Progression-Free Survival .............................................................................16 
4.8.5 Overall Survival ............................................................................................17 
 


ADC Therapeutics 
ADCT-301 
ADCT-301-103 
SAP Final Version 
Page 4 of 23 
 
4.9 Safety Analyses .........................................................................................................17 
4.9.1 Adverse Events..............................................................................................17 
4.9.1.1 Analyses of Adverse Events ......................................................... 17 
4.9.1.2 Dose-Limiting Toxities ................................................................ 19 
4.9.1.3 Serious Adverse Events ............................................................... 19 
4.9.1.4 Deaths .......................................................................................... 19 
4.9.1.5 Adverse Events of Special Interest .............................................. 19 
4.9.2 Laboratory Data ............................................................................................19 
4.9.3 Electrocardiogram .........................................................................................20 
4.9.4 Vital Signs .....................................................................................................20 
4.9.5 ECOG Performance Status ...........................................................................20 
4.9.6 Physical Examinations ..................................................................................20 
4.9.7 Pregnancy Test ..............................................................................................20 
5 Final Analysis....................................................................................................................... 21 
6 Data handling conventions ................................................................................................... 22 
6.1 General conventions ..................................................................................................22 
6.1.1 Missing data ..................................................................................................22 
6.1.2 Unscheduled visits ........................................................................................22 
6.1.3 Duplicated visits ............................................................................................22 
7 Reference List ...................................................................................................................... 23 




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SAP 
Statistical analysis plan 
SD 
Stable disease 
SOC 
System organ class 
std 
Standard deviation 
TEAE 
Treatment-emergent adverse event 
 
 
WHODRUG DD 
World Health Organization Drug Dictionary  
 
 


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1 Introduction 
This statistical analysis plan (SAP) describes the statistical methods to be used during the 
reporting and analysis of data collected under ADC Therapeutics Protocol ADCT-301-103. 
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 7 dated 2 
September 2021.  


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2 Study Objectives 
2.1 Primary Objectives  
 
Characterize the safety and tolerability of camidanlumab tesirine as monotherapy and 
camidanlumab tesirine in combination with pembrolizumab, and to identify the 
recommended dose(s) and schedule(s) for future studies in patients with selected advanced 
solid tumors 
2.2 Secondary Objectives 
 
Evaluate the preliminary anti-tumor activity of camidanlumab tesirine as monotherapy and 
camidanlumab tesirine in combination with pembrolizumab 
 
Evaluate the pharmacokinetic (PK) profile of camidanlumab tesirine as monotherapy and 
camidanlumab tesirine in combination with pembrolizumab 
 
Evaluate the immunogenicity of camidanlumab tesirine as monotherapy and 
camidanlumab tesirine in combination with pembrolizumab 


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3 Study Design 
This is a Phase 1b, multi-center, open-label study with a dose-escalation part and a dose-
expansion part. 
In the dose-escalation part (Part 1), patients will receive escalating doses of camidanlumab 
tesirine as monotherapy, or escalating dose of camidanlumab tesirine in combination with 
pembrolizumab, guided by a 3+3 design. 
Additionally, in the dose-escalation part for camidanlumab tesirine as monotherapy, separate 
paired-biopsy cohorts have been included: 
 
The paired-biopsy cohorts will enroll patients, treated only with camidanlumab tesirine as 
monotherapy, who will be undergoing two mandatory biopsies, one pre- and one 
on-treatment biopsy, to better understand effects of camidanlumab tesirine on tumor tissue 
biomarkers. These cohorts will be introduced at dose levels that have been deemed safe 
during escalation. In order to allow patients to benefit from trial participation, one intra-
patient dose escalation (after the mandatory on-treatment biopsy has been obtained) to the 
highest dose level determined to be safe at that point will be performed, unless deemed by 
the Investigator not to be in the best interest of the patient. 
Two groups are planned in the dose-expansion part (Part 2): 
 
Group 1: an indication for which camidanlumab tesirine in combination with 
pembrolizumab at the doses shown in Part 1 to have preliminary activity. 
 
Group 2: a basket group of patients with advanced solid tumors and MSI-H/dMMR status, 
who have received a prior regimen containing a PD-1/PD-L1 inhibitors, for which the best 
response was CR, PR, or SD ≥4 months, and then progressed while under treatment with 
the PD-1/PD-L1 inhibitor based regimen; no more than 4 patients with the same indication 
(tunour type) are allowed in this basket group. 
3.1 Sample Size Consideration 
Approximately 95 patients; Part 1 may enroll approximately 65 patients and Part 2 will enroll 
approximately 30 patients, approximately 16 patients in Group 1 and 14 in Group 2. 
3.2 Randomization 
Not applicable. 
3.3 Modifications to the statistical section of the protocol  
Not applicable. 


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4 Statistical methods  
No hypothesis testing will be performed in this study. 
All analyses will use SAS® version 9.4 or higher.  
Unless otherwise stated, tables, listings, and figures will be broken down by monotherapy and 
combination therapy and then by dose level in dose-escalation part, and by group in dose-
expansion part. Additional tables broken down by indication and by indication at recommded 
dose for expansion (RDE) will be specificied in later sections. All data will be provided in 
listings. Tables and figures are based on the defined analysis population. 
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 
1 decimal place and not be displayed for zero counts.  
Continuous data 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.  
CI will be two-sided and use α=0.05 (i.e., 95% CIs), unless otherwise specified. For exact 
estimates, the CI will be calculated using the Clopper–Pearson exact method. For Kaplan-
Meier estimates, the CI will be calculated using the Greenwood’s formula with 
(complementary) log-log transformation. 
Kaplan-Meier plots will be provided along with Kaplan-Meier estimates. 
The Baseline value is defined as the last non-missing value or measurement taken prior to the 
first dose of study drug. 
4.1 Analysis Populations  
4.1.1 Safety Analysis Set 
All patients who receive study drugs. 
4.1.2 DLT-evaluable Analysis Set 
Patients in Part 1who receive study drug. However, this set excludes: 
 Patients in Part 1 who discontinue from the study during the dose limiting toxicity 
(DLT) period (see Protocol Section 6.5) without experiencing a DLT 


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 Patients in Part 1 enrolled in the paired-biopsy cohort 
 Additional patients in Part 1, of same indication, enrolled at a dose level equal or higher 
to the dose level for which at least 1 patient with documented PR or CR has been 
observed 
4.1.3 Efficacy Analysis Set 
All patients who receive at least 1 dose of study drug (refer to Protocol Section 6), have valid 
baseline disease assessment(s), and at least one valid post baseline disease assessment.  Patients 
who do not have a post baseline assessment due to early clinical progression or death (after 
receiving study drug) will also be included. 
4.1.4 Pharmacokinetics (PK) Analysis Set 
All patients who receive study drugs and have at least 1 pre-(C1D1) and 1 post-dose valid PK 
assessment. 
  
 
4.2 Patient Disposition 
Enrolled subjects include all patients who signed informed consent forms. All subjects enrolled, 
including screen fails, will be summarized. Subjects who discontinued treatment and 
discontinued from the study will be summarized, along with the primary reasons for 
discontinuation. The disposition summary will be based on the Safety Analysis Set. 
Patient disposition data will be listed.  
4.3 Protocol Deviations 
All protocol deviations will be determined prior to database lock and will be agreed upon by a 
review of individual subject data. Major protocol deviation criteria will be established and 
subjects with major protocol deviations will be identified and documented before the database 
lock for the primary analysis. 
The number and percentage of patients with any important clinical study report (CSR)- 
reportable protocol deviation will be summarized overall and by type of deviation. The pre-
defined important CSR-reportable protocol deviations are listed below; in addition, any other 
protocol deviations deemed by ADCT medical to be important CSR-reportable deviations will 
be included in the summary.  
 Patient entered the study even though they did not satisfy the entry criteria 


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 Patient received a prohibited concomitant treatment during the study 
 Patient who met criteria for mandatory study drug discontinuation during the study 
but did not have study drug withdrawn 
 Patient who received the wrong treatment or incorrect dose, including dose not 
specified in the protocol and actual dose of study drug was greater than 15% more or 
less than protocol planned dose. 
Important protocol deviations will be summarized and listed. 
4.4 Demographic and Baseline Characteristics 
Demographic and baseline characteristics will be tabulated for the Safety Analysis Set.  
Demographic and baseline characteristics data will also be listed. 
4.5 Cancer History and Medical History 
Cancer history, prior radiotherapy, prior cancer surgery, and prior system treatments will be 
tabulated for the Safety Analysis Set.  
Cancer history, including each tumor type, medical history, prior radiotherapy, prior cancer 
surgery, and prior system treatments will be listed. 
4.6 Prior and Concomitant Medications (other than anticancer therapies) 
All medications will be recorded in the CRF 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. 
All medications will be coded using the World Health Organization-Drug Dictionary (WHO-
DD) version 2018 March 01. 
Prior and concomitant medications will be listed. 
4.7 Exposure to Treatment 
4.7.1 Extent of Study Drug Exposure 
Study drug exposures will be based on the Safety Analysis Set.  
A treatment cycle is defined as 3 weeks (i.e., 21 days).  
For patients receiving camidanlumab tesirine as monotherapy, camidanlumab tesirine will be 
administered as an intravenous (IV) infusion on Day 1 of each cycle starting from Cycle 1 
onwards. 


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For patients receiving camidanlumab tesirine in combination with pembrolizumab, 
camidanlumab tesirine will be administered for 2 cycles (on C1D1 and C2D1), and 
pembrolizumab at a dose of 200 mg Q3W will be administered on Day 1 of each cycle starting 
from Cycle 1 onwards (dosing schedule 1). If unacceptable toxicity (Protocol section 6.5) 
occurs during Cycle 1 at dose level -1 and dose level -2, dosing schedule 2, where 
pembrolizumab administration may start at Cycle 2, may be investigated in newly enrolled 
patients. 
Patients who tolerate the study treatment (i.e., no liver enzyme increase ≥ Grade 2, no pleural 
effusion ≥ Grade 2, no edema ≥ Grade 2) and are in disease control (defined as disease control 
≥ SD) may receive additional doses of camidanlumab tesirine in combination with 
pembrolizumab, upon informing the Sponsor. 
Additional administrations of camidanlumab tesirine in combination with pembrolizumab will 
be given as follows: 2 consecutive Cycles every 2 Cycles (2 cycles on, 2 cycles off schedule), 
starting from Cycle 5 up to a year (i.e., Cycle 5 and 6, Cycle 9 and 10, Cycle 13 and 14, Cycle 
17 and 18) if there is no delay in the planed treatment schedule: Between these cycles, patients 
should receive pembrolizumab as a single agent 
Study treatment is given for up to a year. Continued administration of camidanlumab tesirine 
as monotherapy or camidanlumab in combination with pembrolizumab, or pembrolizumab 
alone after a year will be discussed with the Sponsor in the context of the likely risk benefit 
assessment for each individual patient. The dose amounts of camidanlumab tesirine 
monotherapy are given according to Protocol section 6.3 and for the combination with 
pembrolizumab according to Protocol section 6.4.  
Duration of treatment (days) is calculated as date of last treatment – date of first treatment + 1. 
 Camidanlumab tesirine 
Dose administered at each infusion (µg) of camidanlumab tesirine is calculated by 
concentrated investigational product (IP) volume (in mL) * 5 mg/mL * 1000. For cases of  
incomplete infusion, adjust the calculated prepared dose by multiplying a factor of (1- volume 
of dosing solution not administered [in mL]/ 50 mL). If volume of dosing solution not 
administered is missing, then adjust the calculated prepared dose by multiply the factor of (end 
time – start time [in minutes])/30 minutes. 
Relative dose intensity (%) for camidanlumab tesirine is calculated as 100 * [total weighted 
adjusted dose received (µg/kg) / total planned dose (µg/kg)], where total planned dose is 
number of cycles should be for camidanlumab tesirine dosing during treatment * protocol 
planned dose (µg/kg) per cycle. 
Table 1 Target study day for camidanlumab tesirine 


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Study Visit 
Target 
Study 
Day 
when 
Camidanlumab 
Tesirine 
as 
Monotherapy 
Target 
Study 
Day 
when 
Camidanlumab 
Tesirine 
in 
Combination with Pembrolizumab 
C1D1 
1 
1 
C2D1 
22 
22 
C3D1 
43 
NA 
C4D1 
64 
NA 
C5D1 
85 
85 
C6D1 
106 
106 
C7D1 
127 
NA 
C8D1 
148 
NA 
C9D1 
169 
169 
C10D1 
190 
190 
C11D1 
211 
NA 
C12D1 
232 
NA 
C13D1 
253 
253 
C14D1 
274 
274 
C15D1 
295 
NA 
C16D1 
316 
NA 
C17D1 
337 
337 
C18D1 
358 
358 
Note: If patients receive doses beyond C18, target study day at each cycle will be calculated 
by adding 21 days from target study day in the previous cycle. 
Duration of treatment, number of cycles dosed, total dose received (µg), total weight adjusted 
dose received (µg/kg), average dose per cycle (µg/kg), dose modification, delay, reduction, 
and interruption, and relative dose intensity for camidanlumab tesirine will be summarized. 
 Pembrolizumab 
Dose administered at each infusion (mg) of pembrolizumab is fixed at 200 mg as a 30 minutes 
IV infusion (starting 1 hour after the end of the camidanlumab tesirine infusion), and dose 
modifications are not expected. For incomplete infusion, adjust the calculated prepared dose 
by multiplying a factor of (1- volume of dosing solution not administered [in mL]/ 50 mL). If 
volume of dosing solution not administered is missing, then adjust the calculated prepared dose 
by multiply the factor of (end time – start time [in minutes])/30 minutes. 
Relative dose intensity (%) for pembrolizumab is calculated as 100 * [total dose received (mg) 
/ total planned dose (mg)], where total planned dose is number of cycles should be for 
pembrolizumab dosing during treatment * 200 (mg) per cycle. 


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Duration of treatment, number of cycles dosed, total dose received (mg), average dose per 
cycle (mg), dose delay, reduction, and interruption, and relative dose intensity for 
pembrolizumab will be summarized. 
Exposure data and infusion details in both camidanlumab tesirine and pembrolizumab will be 
listed. 
4.7.2 Subsequent Anticancer Therapy or Procedure 
Patients’ subsequent anticancer therapies or procedures including systemic therapy, radiation, 
transplant, or other, along with the start date of new anticancer therapy or procedure will be 
listed. 
4.8 Efficacy Analyses 
Efficacy analyses will be based on the Efficacy Analysis Set. 
Derived efficacy endpoints and tumor assessment data will be listed. 
4.8.1 Overall Response Rate 
An objective responder is defined as any patient who had a best overall response (BOR) of CR 
or PR per RECIST 1.1. Overall response rate (ORR) is defined as the proportion of objective 
responders.  
For the analysis of ORR, 
 The category of BOR includes complete response (CR), partial response (PR), stable 
disease (SD), progressive disease (PD), and inevaluable (NE). 
 Overall responses derived for BOR must be assessed on or before the start of 
subsequent anti-cancer therapy or procedure. 
 A BOR of SD requires the patient on-study for a minimum of 35 days after the first 
dose of study drug. A patient with SD only before this time will be considered as NE.  
 For patients who do not have post-baseline assessment due to early clinical progression 
or death (after receiving study drug), they will be categorized separately from patients 
with assessments. 
Disease control rate (DCR) is defined as the proportion of objective responders and patients 
with SD at least 35 days after the first dose of study drug. 
The ORR and DCR and their 95% two-sided exact CIs will be presented. Time to first response 
and time to BOR will aso be summarized. 
BOR will also be presented by indication and by indication at RP2D. In addition, extent of 
study drug exposure will be summarized according to BOR category. 


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4.8.2 Duration of Response 
Duration of response (DoR) is defined among objective responders (CR or PR per RECIST 
1.1) as the time from the earliest date of first response until the first date of either disease 
progression (based on radiographic or clinical progression at end of treatment [EOT]/end of 
study [EOS]) or death due to any cause.  
The censoring rules for DoR are as follow: 
 For patients who are still alive at the time of analysis and without objective evidence 
of progression, patients will be censored at the last tumor assessment. 
 For patients who receive subsequent anti-cancer therapy or procedure prior to disease 
progression or death, patients will be censored at the last tumor assessment on or prior 
to subsequent therapy or procedure. 
 A sensitivity analysis might be considered:if a clinical disease progression or toxicity 
is observed without radiographic tumor progression assessment being confirmed, then 
the patient will be censored at the last tumor assessment.  
The DoR will be estimated by Kaplan-Meier method. The median DoR and its 95% two-sided 
CI will be presented. 
DoR will also be presented by indication and by indication at RP2D. 
4.8.3 Duration of Stable Disease 
Duration of stable disese (DoSD) is defined among patients of SD per RECIST 1.1 as the time 
from first dose of study drug until disease progression (based on radiographic or clinical 
progression at end of treatment [EOT]/end of study [EOS]) or death due to any cause.  
The censoring rules for DoR in Section 4.8.2 apply to DoSD. 
The DoSD will be estimated by Kaplan-Meier method. The median DoSD and its 95% two-
sided CI will be presented. 
DoSD will be presented by dose, by indication, and by indication at RP2D. 
4.8.4 Progression-Free Survival 
Progression-Free Survival (PFS) is defined as the time from first dose of study drug until 
disease progression (based on radiographic or clinical progression at end of treatment 
[EOT]/end of study [EOS]) or death due to any cause, whichever occurs first.  
The censoring rules for PFS are as follow: 
 For patients who are still alive at the time of analysis and without objective evidence 
of progression, patients will be censored at the last tumor assessment. 




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A treatment-emergent AE (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, whichever is earlier.  
AEs will be coded according to MedDRA Version 22.0, and the severity of the toxicities will 
be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for 
Adverse Events (CTCAE) Version 4.0, where applicable. 
The summary of overall TEAEs includes: 
 TEAEs 
 Drug-related TEAEs 
 Grade ≥3 TEAEs 
 Drug-related Grade ≥3 TEAEs 
 Serious Adverse Events (SAEs) 
 Drug-related SAEs 
 TEAEs leading to dose delayed, reduced or interrupted (camidanlumab tesirine or 
pembrolizumab) 
 TEAEs leading to discontinuation of camidanlumab tesirine or pembrolizumab 
 TEAEs leading to death 
 Infusion related reactions 
The incidence of TEAEs will be summarized by system organ class (SOC) and preferred term 
(PT). A subject will be counted only once within a SOC and PT, even if the subject experienced 
more than one AE within a specific SOC and PT. Below TEAEs will be summarized in the 
same fashion:  
 Drug-related TEAEs by SOC and PT 
 Grade ≥3 TEAEs by SOC and PT 
 Drug-related Grade ≥3 TEAEs by SOC and PT 
 The most common TEAEs (≥ 10% incidence) by PT 
 TEAEs by SOC, PT and maximum CTCAE grade 
 TEAEs by relationship to study drug, maximum CTCAE grade, SOC and PT 
Listing of all AEs, including non-TEAEs, will be provided. Besides, TEAEs leading to dose 
reduced, delayed or interrupted (camidanlumab tesirine or pembrolizumab), TEAEs leading to 
discontinuation of camidanlumab tesirine or pembrolizumab, and TEAEs leading to death will 
also be provided. 
Details on classification of AEs with missing or partial onset dates are provided in Section 6. 


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4.9.1.2 Dose-Limiting Toxities 
Definition of DLT is referred to the Protocol section 6.5. DLTs will be summarized in each 
dose level in the dose-escalation part for the DLT-evaluable Analysis Set.  
Listings of DLTs will be provided. 
4.9.1.3 Serious Adverse Events 
A post-dose AE is defined as an AE during treatment that occurs or worsens from the first dose 
of study drug.  
Below SAEs will be summarized in both TEAE and post-dose AE: 
 SAEs by PT 
 SAEs by SOC and PT 
 SAEs by SOC, PT and maximum CTCAE grade 
Listings of SAEs will be provided. 
4.9.1.4 Deaths 
Listing of all deaths will be provided. 
4.9.1.5 Adverse Events of Special Interest 
Definition of AESI is referred to the Protocol section 8.1.1.  
Below AESIs will be summarized in both TEAE and post-dose AE: 
 AESIs by PT 
 AESIs by SOC and PT 
 AESIs by SOC, PT and maximum CTCAE grade 
Listings of AESIs will be provided. 
4.9.2 Laboratory Data 
Laboratory data for hematology, chemistry, and coagulation will be summarized for the actual 
values and the change from baseline value at each scheduled assessment. In addition, all data 
will be graded according to the NCI CTCAE Version 4.0, and summarized by baseline and 
maximum post-baseline CTCAE grade, including unscheduled visits. Shift tables will 
summarize the shift from baseline grade to maximum post-baseline CTCAE grade. 


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Listings of laboratory data for hematology, chemistry, and coagulation will be provided. In 
addition, listings of urinalysis, thyroid function testing, influenza testing, SARS-CoV-2 testing, 
and any microbiological tests performed will also be provided. 
4.9.3 Electrocardiogram 
Electrocardiogram (ECG) data will be summarized for the actual values and the change from 
baseline value at each scheduled assessment. Shift tables will summarize the shift from 
baseline to End of Treatment and worst post-baseline visit in ECG interpretation (categorized 
as normal; abnormal, not clinically significant; and abnormal, clinically significant). 
Corrected QT interval by Fredericia (QTcF)  will be summarized by categories as follows: 
 QTcF interval > 450 ms 
 QTcF interval > 480 ms 
 QTcF interval > 500 ms 
 QTcF interval increases from baseline > 30 ms 
 QTcF interval increases from baseline > 60 ms 
Listings of ECG data will be provided from both local and central reads of the data. 
4.9.4 Vital Signs 
Vital signs data, including weight, will be summarized for the actual values and the change 
from baseline value at each scheduled assessment.  
Listings of vital signs data, including height and weight, will be provided. 
4.9.5 ECOG Performance Status 
ECOG performance status will be summarized at each scheduled assessment. Shift tables will 
summarize the shift from baseline to End of Treatment and to the worst post-baseline visit in 
ECOG performance status. 
Listing of ECOG performance status will be provided. 
4.9.6 Physical Examinations 
Listing of physical examinations will be provided. 
4.9.7 Pregnancy Test 
Listing of pregnancy test results, if applicalble, will be provided. 
 


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5 Final Analysis 
All efficacy and safety endpoints will be analyzed and reported in the clinical study report 
(CSR). Results of PK analysis, immunogenicity analysis, 
will be 
reported separately. 


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6 Data handling conventions 
6.1 General conventions 
6.1.1 Missing data 
In general, missing data including dates will be treated as missing and no data imputation will 
be applied, unless otherwise specified. Data that are potentially spurious or erroneous will be 
queried and examined during the review of the study data. 
If there are partial or missing dates for an AE, then it will be considered as a TEAE. If the 
assessment of the relationship of an AE to study drug is missing, then the relationship will be 
as possibly related. 
If the severity/grade is missing for one of the treatment emergent occurrences of an AE, the 
maximal severity of the remaining occurrences will be considered. If the severity is missing 
for all the occurrences a “missing” category will be added in summary table. 
6.1.2 Unscheduled visits 
Unscheduled visit measurements of laboratory data, vital signs, and ECG will be used for 
computation of baseline and worst values and/or grades. Re-windowing for unscheduled visits 
will not be performed. 
6.1.3 Duplicated visits 
Depending on the statistical analysis method, single values may be required for each analysis 
window. For example, change from baseline by visit usually requires a single value per visit. 
Unless otherwise noted throughout the rest of this document, when a single value is needed, 
the following rule(s) will be used: 
 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. 


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7 Reference List