Clinical trial NCT04945733
Conditions: Stomach Neoplasms Esophageal Neoplasms
Sponsor: Janssen Pharmaceutical K.K.
Start date: 2021-08-30; Completion date: 2023-07-03
Enrollment: 62 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to investigate the activity of amivantamab in gastric cancer (GC) and esophageal cancer (EC) participants (Phase 2a), and to characterize the preliminary antitumor activity of amivantamab in selected GC and EC population (Phase 2b).

Detailed description:

Arms: arm 1: Participants in Phase 2a GC cohorts will receive intravenous (IV) infusion of weight-based dose of amivantamab in 28-day cycles. Participants with body weight less than (\<) 80 kilograms (kg) will receive IV infusion of amivantamab 1,050 milligrams (mg) and participants with body weight greater than or equal to (\>=) 80 kg will receive IV infusion of amivantamab 1,400 mg once weekly in Cycle 1 and then every 2 weeks in subsequent cycles (on Days 1 and 15 of each cycle), followed by additional dosing based on body weight if recommended by clinical trial management team (CTMT) (amivantamab 1750 mg for body weight \<80 kg and 2100 mg for body weight \>=80 kg as IV infusion) every 2 weeks on Days 1 and 15 of 28 day cycle. Phase 2b GC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts. arm 2: Participants in Phase 2a EC cohorts will receive IV infusion of weight-based dose of amivantamab in 28-day cycles. Participants with body weight \<80 kg will receive IV infusion of amivantamab 1,050 mg and participants with body weight \>=80 kg will receive IV infusion of amivantamab 1,400 mg once weekly in Cycle 1 and then every 2 weeks in subsequent cycles (on Days 1 and 15 of each cycle) followed by additional dosing based on body weight if recommended by CTMT (amivantamab 1750 mg for body weight \<80 kg and 2100 mg for body weight \>=80 kg as IV infusion) every 2 weeks on Days 1 and 15 of 28 day cycle. Phase 2b EC expansion cohorts will be initiated if activity is observed within Phase 2a cohorts.
Interventions: intervention 1: Amivantamab
Intervention descriptions: intervention 1: Amivantamab will be administered intravenously.

Protocol documents:
Prot_000.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
1
Status: Approved,  Date:  16 August 2022
Janssen Pharmaceutical K.K.*
Clinical Protocol
Protocol Title
A Phase 2, Open-label Study of Amivantamab in Subjects With Previously Treated
Advanced or Metastatic Gastric or Esophageal Cancer
Protocol 61186372GIC2001; Phase 2
AMENDMENT 2
Amivantamab  JNJ-61186372
*This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used
throughout the protocol to represent Janssen Pharmaceutical K.K.
Status: 
Approved
Date: 
16 August 2022
Prepared by: Janssen Pharmaceutical K.K
EDMS number: 
EDMS-RIM-208737, 3.0
GCP Compliance:  This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory
requirements.
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or
otherwise.
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
2
Status: Approved,  Date:  16 August 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 2 
16-Aug-2022
Amendment 1 
10-Nov-2021
Original Protocol 
16-Apr-2021
Amendment 2 (16 August 2022)
Overall Rationale for the Amendment: The overall purpose of the amendment is to allow for potential
exploration of higher dose levels of amivantamab based on emerging data and per recommendation of the
CTMT. Toxic epidermal necrolysis (TEN) is added in the suggested algorithm for management of rash.
Additionally, some clarifications and corrections to the text are included.
The changes made to the clinical protocol 61186372GIC2001 as part of Protocol Amendment 2 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.9 Appendix 9: Protocol Amendment History.
Section Number 
and Name
Description of Change 
Brief Rationale
Synopsis -
NUMBER OF
PARTICIPANTS
 
 
A maximum of approximately 302 participants will
be enrolled in the combined Phase 2a and Phase 2b
populations, in the event the efficacy observed in
both Phase 2a cohorts warrants full enrollment in
their respective Phase 2b cohorts.
Approximately, 41 response evaluable participants
will be enrolled in each of Phase 2a GC and EC
arms (including extension cohort). The Phase 2b
GC expansion or EC expansion cohorts will
evaluate the antitumor activity of amivantamab in
GC and EC patients, using biomarker selection. If
activated, approximately 100 participants will be
enrolled in each of the Phase 2b cohorts.
If the CTMT recommends exploration of higher
doses, approximately 20 response evaluable
participants will be enrolled in each cohort of
Phase 2a.
To allow for the potential
exploration of higher dose levels of
Amivantamab based on emerging
data and per recommendation of the
CTMT.
1.2. Schema - 
Figure 1
Added below text in footnote:
If the CTMT recommends exploration of higher
dose levels, approximately 20 response evaluable
participants with expression of EGFR and/or cMet
will be enrolled in each dose cohort.
To enable
implementation/exploration of
higher dose levels of amivantamab
in Phase 2a.
4.1. Overall Design 
A maximum of approximately 302 participants will
be enrolled in the combined Phase 2a and Phase 2b
populations, in the event the efficacy observed in
both Phase 2a cohorts warrants full enrollment in
their respective Phase 2b cohorts.
Based on emerging data, the CTMT may also
recommend exploration of higher doses of
amivantamab.
To enable
implementation/exploration of
higher dose levels in Phase 2a.
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
3
Status: Approved,  Date:  16 August 2022
Section Number 
and Name
Description of Change 
Brief Rationale
9.2. Sample Size 
Determination 
In each dose cohort of phase 2a, approximately 
20 response evaluable participants will be 
additionally enrolled if the CTMT recommends
exploration of higher doses. The probability to
observe 4 or more response (ORR >= 20%) is
89% assuming ORR of 30%.
To provide statistical rationale for
sample size.
9.5. Interim 
Analysis 
An interim analysis was added in higher dose 
levels in Phase 2a.  
To monitor the efficacy at higher
dose levels in Phase 2a.
4.3. Justification for 
Dose 
Added rationale, safety review procedure for 
higher dose levels in Phase 2a. 
To conduct safety review with
close monitoring at higher dose
levels in Phase 2a.
6.1. Study 
Treatment 
Administered 
Dosage Level(s) 
Based on the participant's body weight at 
screening: 1,050 mg (if body weight is <80 kg) or
1400 mg (if body weight is ≥80 kg)
Additional higher dosing, if recommended by
the CTMT, will also be based on the
participant’s body weight: 1,750 mg (if body
weight is <80 kg) or 2,100 mg (if body weight is
≥80 kg)
 
Dosing Instructions
Amivantamab will be administered intravenously
in 28 day cycles as follows:
• Cycle 1: Once weekly (with the first dose split
over Day 1 [350 mg] and Day 2 [700 mg if
body weight is <80 kg or 1,050 mg if body
weight is ≥80 kg]). For additional higher
dosing, once weekly (with the first dose split
over Day 1 [350 mg] and Day 2 [1.400 mg if
body weight is <80 kg or 1,750 mg if body
weight is ≥80 kg]).
• Cycles 2+: Day 1 and 15 of each cycle
Defined potential higher dose level
in Phase 2a.
6.6. Dose 
Modification 
Guidance 
Added dose modification criteria for amivantamab 
for the 1,750/2,100 mg dosing. 
To provide guidance regarding dose
modification for potential higher
doses.
5.1. Inclusion 
Criteria 
Duration of contraception from the last dose was 
changed from 6 months to 3 months. 
To align the management
guidelines in the protocol with
other studies within the
amivantamab program.
6.6.2. Rash related 
Adverse Events – 
Table 7 
Severe bullous, blistering, or exfoliating skin 
conditions including toxic epidermal necrolysis 
(TEN) are added in the suggested algorithm for 
management of rash. 
To align the management guideline
in the protocol with other studies
within the amivantamab program
and in accordance with health
authorit y requests.
Synopsis - 
STATISTICAL 
METHODS 
 
No hypothesis testing is planned in Phase 2a. 
Objective response rate (ORR) will be calculated
for response evaluable population. Other efficacy
measurements will be also assessed.
Clarification
1.3. Schedule of 
Activities (SoA) - 
Table 1
On the Demography line, x was added in pre- 
screening.
On the Demography line, added below text in note:
Note: In Pre-screening, only Age and gender will
be collected.
Clarification
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
4
Status: Approved,  Date:  16 August 2022
Section Number 
and Name
Description of Change 
Brief Rationale
1.3. Schedule of 
Activities (SoA) - 
Table 1 
Footnote h was updated: 
Phase 2a participants: Tumor biopsy at screening
and C2D15 are mandatory. (must be collected even
if the first disease assessment shows disease
progression). Tumor biopsy sample after disease
progression from the most recent treatment can
replace the screening biopsy, if available. For
additional higher dosing, tumor biopsy at
C2D15 is mandatory, if clinically feasible (It is
not necessary for participants with one target
lesion only.)
To allow enrollment of participants
for whom repeated biopsy is not
clinically feasible.
4.1.2. Treatment 
Phase 
Added below text: 
For additional higher dosing in Phase 2a, post-
treatment biopsy at C2D15 will be mandatory, if
clinicall y feasible.
To allow enrollment of participants
for whom repeated biopsy is not
clinically possible.
6.1. Study 
Treatment
Administered
Added below bold text: 
Amivantamab will be administered intravenously
using the escalating infusion rate regimen as
specified in the IPPI. At the discretion of the
investigator, the infusion rate can be slower, but
not faster than specified in the IPPI. The product
must be infused via a peripheral vein for all Cycle
1 doses; infusion via central line is allowed for
subsequent dosin  g startin  g with the C2D1 dose.
Clarified dosing procedure.
8.3.6. Disease- 
related Events and
Disease-related 
Outcomes Not 
Qualifying as 
Adverse Events or 
Serious Adverse
Events
Added below bold text: 
 
An event such as disease progression, which is part
of the natural course of the disease under study,
does not need to be reported as an AE or SAE
term.
Clarification
10.3.5. Procedures 
Modified below bold text: 
Disease progression does not need to be reported
as an adverse event or serious adverse event term.
Clarification
Throughout the 
protocol 
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted.
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
5
Status: Approved,  Date:  16 August 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................. 2
TABLE OF CONTENTS .......................................................................................................................... 5 
LIST OF IN-TEXT TABLES AND FIGURES ............................................................................................ 7
1. 
PROTOCOL SUMMARY ................................................................................................................ 9
1.1. 
Synopsis ..................................................................................................................................... 9
1.2. 
Schema .................................................................................................................................... 11
1.3. 
Schedule of Activities (SoA) ...................................................................................................... 12
2. 
INTRODUCTION .......................................................................................................................... 16
2.1. 
Background............................................................................................................................... 16
2.1.1. 
Gastric and Esophageal Cancer............................................................................................. 16
2.1.2. 
Role of EGFR and cMet in Gastric and Esophageal Cancer ................................................... 17
2.1.3. 
Clinical Studies of Amivantamab ............................................................................................ 18
2.2. 
Study Rationale......................................................................................................................... 19
2.3. 
Benefit-risk Assessment ............................................................................................................ 20
2.3.1. 
Risks for Study Participation .................................................................................................. 20
2.3.2. 
Benefits for Study Participation .............................................................................................. 20
2.3.3. 
Benefit-risk Assessment for Study Participation ...................................................................... 20
3. 
OBJECTIVES AND ENDPOINTS ................................................................................................. 21
4. 
STUDY DESIGN ........................................................................................................................... 21
4.1. 
Overall Design .......................................................................................................................... 21
4.1.1. 
Screening Phase (Pre- and Full Screening) ............................................................................ 23
4.1.2. 
Treatment Phase ................................................................................................................... 23
4.1.3. 
Follow-up Phase (Applicable to Phase 2b Only) ..................................................................... 24
4.2. 
Scientific Rationale for Study Design ......................................................................................... 24
4.2.1. 
Study-specific Ethical Design Considerations ......................................................................... 25
4.3. 
Justification for Dose ................................................................................................................. 25
4.4. 
End of Study Definition .............................................................................................................. 26
5. 
STUDY POPULATION ................................................................................................................. 26
5.1. 
Inclusion Criteria ....................................................................................................................... 27
5.2. 
Exclusion Criteria ...................................................................................................................... 30
5.3. 
Lifestyle Considerations ............................................................................................................ 34
5.3.1. 
Activity ................................................................................................................................... 34
5.4. 
Screen Failures ......................................................................................................................... 34
6. 
STUDY TREATMENT AND CONCOMITANT THERAPY .............................................................. 34
6.1. 
Study Treatment Administered .................................................................................................. 34
6.2. 
Preparation/Handling/Storage/Accountability ............................................................................. 36
6.3. 
Measures to Minimize Bias: Randomization and Blinding .......................................................... 36
6.4. 
Study Treatment Compliance .................................................................................................... 37
6.5. 
Dose Delay Guidance ............................................................................................................... 37
6.6. 
Dose Modification Guidance ...................................................................................................... 37
6.6.1. 
Infusion-related Reactions ..................................................................................................... 39
6.6.2. 
Rash-related Adverse Events ................................................................................................. 41
6.6.3. 
Paronychia ............................................................................................................................ 43
6.6.4. 
Liver Chemistry Abnormalities ................................................................................................ 43
6.6.5. 
Pulmonary Toxicity ................................................................................................................ 45
6.7. 
Treatment of Overdose ............................................................................................................. 45
6.8. 
Concomitant Therapy ................................................................................................................ 45
6.8.1. 
Amivantamab Pre-infusion and Post-infusion Medications ...................................................... 46
6.8.1.1. 
Amivantamab Pre-infusion Medications ............................................................................... 46
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
6
Status: Approved,  Date:  16 August 2022
6.8.1.2. 
Amivantamab Post-infusion Medications ............................................................................. 46
6.8.2. 
Prohibited or Restricted Medications and Therapies ............................................................... 47
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL ........................................................................................... 47
7.1. 
Discontinuation of Study Treatment ........................................................................................... 47
7.2. 
Participant Discontinuation/Withdrawal From the Study ............................................................. 48
7.2.1. 
Withdrawal From the Use of Research Samples .................................................................... 48
7.3. 
Lost to Follow-up ....................................................................................................................... 49
8. 
STUDY ASSESSMENTS AND PROCEDURES ............................................................................ 49
8.1. 
Efficacy Assessments ............................................................................................................... 50
8.1.1. 
Disease Assessments ............................................................................................................ 50
8.2. 
Safety Assessments .................................................................................................................. 51
8.2.1. 
Physical Examinations ........................................................................................................... 52
8.2.2. 
Vital Signs ............................................................................................................................. 52
8.2.3. 
Electrocardiograms ................................................................................................................ 52
8.2.4. 
ECOG Performance Status .................................................................................................... 53
8.2.5. 
Clinical Safety Laboratory Assessments ................................................................................. 53
8.2.6. 
Pregnancy Testing ................................................................................................................. 54
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting...................................... 54
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information ............................................................................................................................ 54
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events ......................................... 55
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ..................................................... 55
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ........................................... 55
8.3.5. 
Pregnancy ............................................................................................................................. 55
8.3.6. 
Disease-related Events and Disease-related Outcomes Not Qualifying as Adverse
Events or Serious Adverse Events ......................................................................................... 56
8.3.7. 
Adverse Events of Special Interest ......................................................................................... 56
8.4. 
Pharmacokinetics ...................................................................................................................... 56
8.4.1. 
Evaluations ............................................................................................................................ 56
8.4.2. 
Analytical Procedures ............................................................................................................ 57
8.4.3. 
Pharmacokinetic Parameters and Evaluations........................................................................ 57
8.5. 
Pharmacogenomics .................................................................................................................. 57
8.6. 
Biomarkers ............................................................................................................................... 57
8.7. 
Immunogenicity Assessments ................................................................................................... 58
8.8. 
Medical Resource Utilization and Health Economics.................................................................. 58
9. 
STATISTICAL CONSIDERATIONS .............................................................................................. 58
9.1. 
Statistical Hypotheses ............................................................................................................... 59
9.2. 
Sample Size Determination ....................................................................................................... 59
9.3. 
Populations for Analysis Sets .................................................................................................... 59
9.4. 
Statistical Analyses ................................................................................................................... 60
9.4.1. 
General Considerations ......................................................................................................... 60
9.4.2. 
Primary Endpoint ................................................................................................................... 60
9.4.2.1. 
Objective Response Rate.................................................................................................... 60
9.4.3. 
Secondary Endpoints ............................................................................................................. 61
9.4.3.1. 
Disease Control Rate .......................................................................................................... 61
9.4.3.2. 
Duration of Response ......................................................................................................... 61
9.4.3.3. 
Time to Response ............................................................................................................... 61
9.4.3.4. 
Progression-free Survival .................................................................................................... 61
9.4.3.5. 
Overall Survival................................................................................................................... 61
9.4.4. 
Safety Analyses ..................................................................................................................... 62
9.4.5. 
Other Analyses ...................................................................................................................... 63
9.5. 
Interim Analysis......................................................................................................................... 64
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ........................... 65
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
7
Status: Approved,  Date:  16 August 2022
10.1. 
Appendix 1: Abbreviations ......................................................................................................... 65
10.2. 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations ....................................... 67
10.2.1. 
Regulatory and Ethical Considerations ................................................................................... 67
10.2.2. 
Financial Disclosure ............................................................................................................... 70
10.2.3. 
Informed Consent Process ..................................................................................................... 70
10.2.4. 
Data Protection ...................................................................................................................... 71
10.2.5. 
Long-term Retention of Samples for Additional Future Research ............................................ 72
10.2.6. 
Committees Structure ............................................................................................................ 72
10.2.7. 
Publication Policy/Dissemination of Clinical Study Data .......................................................... 73
10.2.8. 
Data Quality Assurance ......................................................................................................... 74
10.2.9. 
Case Report Form Completion ............................................................................................... 74
10.2.10. Source Documents ................................................................................................................ 75
10.2.11. Monitoring.............................................................................................................................. 76
10.2.12. On-site Audits ........................................................................................................................ 76
10.2.13. Record Retention ................................................................................................................... 77
10.2.14. Study and Site Start and Closure ........................................................................................... 77
10.3. 
Appendix 3: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting ........................................................................................................................... 79
10.3.1. 
Adverse Event Definitions and Classifications ........................................................................ 79
10.3.2. 
Attribution Definitions ............................................................................................................. 80
10.3.3. 
Severity Criteria ..................................................................................................................... 80
10.3.4. 
Special Reporting Situations .................................................................................................. 81
10.3.5. 
Procedures ............................................................................................................................ 81
10.3.6. 
Product Quality Complaint Handling ....................................................................................... 82
10.3.7. 
Contacting Sponsor Regarding Safety, Including Product Quality ........................................... 83
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ...................................................................... 84
10.5. 
Appendix 5: Eastern Cooperative Oncology Group (ECOG) Performance Status ....................... 86
10.6. 
Appendix 6: New York Heart Association Criteria ...................................................................... 87
10.7. 
Appendix 7: MDRD formula for eGFR........................................................................................ 88
10.8. 
Appendix 8: Study Conduct During a Natural Disaster ............................................................... 89
10.9. 
Appendix 9: Protocol Amendment History.................................................................................. 90
11. REFERENCES ............................................................................................................................. 95
INVESTIGATOR AGREEMENT ............................................................................................................ 98
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schedule of Activities for Study Procedures/Assessments .................................................... 12
Table 2: 
Sample Collection Times for Pharmacokinetics, Immunogenicity, and
Pharmacodynamics for Amivantamab .................................................................................. 15
Table 3: 
Guidance for Amivantamab Dose Delay and Modification for Toxicities (Other Than
Rash, Paronychia, Infusion-related Reaction, or Pulmonary Toxicity) .................................... 38
Table 4: 
Dose Modification for Amivantamab (1050mg/1400mg starting dose) ................................... 38
Table 5: 
Dose Modification for Amivantamab (1750mg/2100mg starting dose)* .................................. 38
Table 6: 
Management of Infusion-related Reactions ........................................................................... 40
Table 7: 
Suggested Algorithm for Management of Rash ..................................................................... 42
Table 8: 
Amivantamab Pre-infusion Medications ................................................................................ 46
Table 9: 
Amivantamab Post-infusion Medications .............................................................................. 47
Table 10: Clinical laboratory assessments ........................................................................................... 53
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
8
Status: Approved,  Date:  16 August 2022
FIGURES
Figure 1: Schematic Overview of the Study ......................................................................................... 11
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
9
Status: Approved,  Date:  16 August 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Phase 2, Open-label Study of Amivantamab in Subjects With Previously Treated Advanced or Metastatic
Gastric or Esophageal Cancer
Amivantamab, also known as JNJ-61186372, is a low fucose, fully human immunoglobulin G1
(IgG1)-based bispecific antibody directed against the epidermal growth factor (EGF) and tyrosine-protein
kinase mesenchymal epithelial transition (cMet) receptors, shows activity against tumors with
overexpressed wild type EGF receptor (EGFR) and activation of the cMet pathway. By inhibiting EGFR
and cMet signaling functions, amivantamab may disrupt these signaling pathways, thereby preventing
tumor growth and progression. Furthermore, the presence of high levels of EGFR and cMet on the surface
of tumor cells allow for targeting of these cells for destruction by immune effector cells, through
antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis mechanisms.
OBJECTIVES AND ENDPOINTS
The primary objective is to investigate the activity of amivantamab in gastric cancer (GC) and esophageal
cancer (EC) participants (Phase 2a) and to characterize the preliminary antitumor activity of amivantamab
in selected GC and EC population (Phase 2b), based on Objective response rate by investigator (per
Response Evaluation Criteria in Solid Tumors [RECIST] 1.1).
Hypothesis
Amivantamab will exhibit anti-tumor activity in participants with GC or EC expressing any level of EGFR,
cMET, or both proteins.
OVERALL DESIGN
This is an open-label, multicenter, multi-arm Phase 2 interventional study in participants with previously
treated advanced or unresectable GC or EC. Participants with gastric/gastroesophageal junction (GEJ) or
EC who express varying degrees of EGFR, cMet, or both as determined by immunohistochemistry (IHC)
locally or centrally will be enrolled in the Phase 2a cohorts. If activity is observed within Phase 2a cohorts,
the corresponding Phase 2b expansion cohorts will be initiated.
The safety and conduct of the study will be monitored on an ongoing basis by the clinical trial management
team (CTMT) in conjunction with the coordinating investigators.
The study will include a screening phase, a treatment phase, and a follow-up phase. Participants must
complete screening procedures within 28 days before Cycle 1 Day 1 (C1D1). Imaging of disease sites will
occur at regular intervals, as defined in the Schedule of Activities (Table 1), until documented objective
clinical or radiographic disease progression or until the participant meets another criterion for
discontinuation of study treatment.
The treatment phase for each participant will begin on C1D1 and continue as 28-day cycles until the
end-of-treatment (EOT) visit, approximately 30 days after the last dose of study treatment. This study will
be conducted in an outpatient setting. However, in-hospital observation, from C1D1 until Cycle 1 Day 8
(C1D8) is permitted during the Phase 2a cohorts to allow close monitoring, at the discretion of the
investigator. Participants who discontinue study treatment for any reason will be followed for subsequent
therapy, disease status (applicable only if participants discontinue treatment due to reasons other than
progressive disease), and survival in the follow-up phase. The follow-up phase applies only to Phase 2b
participants and starts after the EOT visit and continues until the end of study, death, lost to follow-up, or
withdrawal of consent from participation in the study, whichever comes first. The end of study will occur
after all participants have discontinued therapy with study treatment and have at least 6 months of follow-
up or have discontinued from the study.
NCT04945733


Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
10
Status: Approved,  Date:  16 August 2022
NUMBER OF PARTICIPANTS
A maximum of approximately 302 participants will be enrolled in the combined Phase 2a and Phase 2b
populations, in the event the efficacy observed in both Phase 2a cohorts warrants full enrollment in their
respective Phase 2b cohorts.
Approximately, 41 response evaluable participants will be enrolled in each of Phase 2a GC and EC arms
(including extension cohort). The Phase 2b GC expansion or EC expansion cohorts will evaluate the
antitumor activity of amivantamab in GC and EC patients, using biomarker selection. If activated,
approximately 100 participants will be enrolled in each of the Phase 2b cohorts.
If the CTMT recommends exploration of higher doses, approximately 20 response evaluable participants
will be enrolled in each cohort of phase 2a.
TREATMENT GROUPS AND DURATION
At study initiation, study treatment in Phase 2a cohorts will be administered in 28-day cycles, until disease
progression or until the participant meets another criterion for discontinuation of study treatment.
Description of study treatment
Dosage Level(s)
Based on the participant's body weight at screening: 1,050 mg (if body weight is
<80 kg) or 1400 m  g (if body weight is ≥80 kg)
Dosing Instructions 
Amivantamab will be administered intravenously in 28-day cycles as follows:
 Cycle 1: Once weekly (with the first dose split over Day 1 [350 mg] and Day 2
[700 mg if body weight is <80 kg or 1,050 mg if body weight is ≥80 kg]).
 Cycles 2+: Day 1 and 15 of each cycle
IP Packaging and 
Labeling
Study treatment will be provided in 7 mL glass vials, with 350 mg/vial
As there are investigations ongoing assessing different amivantamab formulations and schedules,
participants in Phase 2b cohorts may receive amivantamab according to a different schedule or route of
administration. Any such change would only be made after approved protocol amendment.
EFFICACY EVALUATIONS
Tumor response will be assessed by radiographic image assessments according to RECIST Version 1.1
guidelines, as defined in the Schedule of Activities.
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Blood samples will be collected from all participants receiving amivantamab for the measurement of serum
amivantamab for pharmacokinetic (PK) analyses. Serum samples will be collected and analyzed for
antibodies to amivantamab using a validated immunoassay. All samples collected for immune response
analysis will also be evaluated for amivantamab serum concentration to ensure appropriate interpretation
of immunogenicity data. Other immunogenicity analyses may be performed to further characterize any
immune responses generated.
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Blood samples collected at screening and during the study may be evaluated for circulating tumor DNA
(ctDNA) to evaluate molecular alterations to track response to treatment and understand mechanisms of
resistance to amivantamab. Blood samples and tissue samples may also be evaluated for other biomarkers
to evaluate molecular alterations and track response to amivantamab.
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SAFETY EVALUATIONS
The safety of amivantamab will be assessed by physical examinations, Eastern Cooperative Oncology
Group (ECOG) criteria for performance status, laboratory tests, vital signs, electrocardiograms, monitoring
of adverse events (AEs), and concomitant medication usage.
STATISTICAL METHODS
No hypothesis testing is planned in Phase 2a. Objective response rate (ORR) will be calculated for response
evaluable population. Other efficacy measurements will be also assessed.
The statistical hypothesis in Phase 2b is that amivantamab monotherapy will lead to ORR higher than 15%
(ie, H0 ≤15% vs Ha >15%) in patients with GC or EC, selected on the basis of expression of EGFR, cMet,
or both. This threshold is based on historical studies for approved third line (3L) regimens for GC
(11.2%-13.6%) and efficacy of approved second line (2L) regimens for EC (approximately 15%).
For Phase 2b part, a z test with normal approximation will be used to compare the ORR with 15%. An
interim futility analysis is planned in each of subpopulation of GC and EC arm approximately 12 weeks
after 50 participants received the first infusion. Multiplicity caused by subpopulation selection at the interim
analysis will be controlled by closed testing procedure and weighted statistics. Details will be described in
statistical analysis plan (SAP).
Safety data will be summarized for all participants who receive at least 1 dose of study treatment.
Data for PK, immunogenicity, and biomarkers will be summarized for participants who receive at least
1 dose of study treatment and provide an evaluable measurement for that endpoint at least once
post-baseline.
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
*At least 20 participants with IHC2+ or higher and at least 10 participants with cMet expression will be enrolled.
†Participants without expression of EGFR and cMet
If the CTMT recommends exploration of higher dose levels, approximately 20 response evaluable participants with
expression of EGFR and/or cMet will be enrolled in each dose cohort.
 
Abbreviations: cMET=tyrosine-protein kinase mesenchymal-epithelial transition; DCR=disease control rate;
EC=esophageal cancer; ECOG PS=Eastern Cooperative Oncology Group performance status; EGFR=epidermal
growth factor receptor; GC=gastric cancer; IHC=immunohistochemistry; OS=overall survival; PFS=progression-
free survival; Ph=Phase; PK=pharmacokinetics.
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g. 
Screening will include, at a minimum, height, weight, general appearance, and an examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities,
musculoskeletal system, lymphatic system, and nervous system. On Day 1 of each cycle, body weight as well as directed physical examination of involved organs
and other body systems will be performed as indicated, with clinically significant abnormalities reported as adverse events.
h. 
Whenever possible, nontarget lesions should be biopsied rather than target lesions. Biopsy of a target lesion is allowed for the pre-treatment sample, but baseline
disease assessment must occur a minimum of 1 week after the biopsy procedure. The sponsor’s medical monitor must give approval prior to the biopsy of a target
lesion at baseline. During the study, biopsy of a target lesion is not allowed unless disease progression has occurred.
Phase 2a participants: Tumor biopsy at screening and C2D15 are mandatory. (must be collected even if the first disease assessment shows disease progression).
Tumor biopsy sample after disease progression from the most recent treatment can replace the screening biopsy, if available. For additional higher dosing, tumor
biopsy at C2D15 is mandatory, if clinically feasible (It is not necessary for participants with one target lesion only.)
Phase 2b participants: Tumor biopsy at screening is mandatory and on-treatment biopsy is optional.
Phase 2a and 2b participants: Post-progression biopsy (within 30 days of disease progression but before the next anticancer therapy) is requested if clinically
feasible.
i. 
Applicable to participants in Phase 2b only by participant visit or call
j. 
If the initiation of the subsequent anticancer therapy is required prior to EOT, EOT must be completed prior to the initiation of the subsequent anticancer therapy.
k. 
If the imaging data is obtained within 28 days prior to the initiation of study treatment (C1D1), it is not necessary to repeat the imaging tests.
l. 
If performed within 72 hours of the first Amivantamab dose, the assessment does not have to be repeated for C1D1.
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2. 
INTRODUCTION
Amivantamab, also known as JNJ-61186372, is a low fucose, fully human immunoglobulin G1
(IgG1)-based bispecific antibody directed against the EGF and tyrosine-protein kinase
mesenchymal epithelial transition (cMet) receptors and shows activity against tumors with
overexpressed wild type epidermal growth factor receptor (EGFR) and activation of the cMet
pathway. By inhibiting EGFR and cMet signaling functions, amivantamab may disrupt these
signaling pathways, thereby preventing tumor growth and progression, as demonstrated in
preclinical models of tumors driven by activated EGFR or activated MET signaling, or
simultaneous activation of either pathway. Furthermore, the presence of high levels of EGFR and
cMet on the surface of tumor cells allow for targeting of these cells for destruction by immune
effector cells, through antibody-dependent cellular cytotoxicity and antibody-dependent cellular
phagocytosis mechanisms.
For the most comprehensive nonclinical and clinical information regarding amivantamab, refer to
the latest version of the Investigator's Brochure (IB) and Addenda for amivantamab.
The term “study treatment” throughout the protocol, refers to study drug as defined in Section 6.1,
Study Treatment Administered.
The term "sponsor" used throughout this document refers to the entities listed in the Protocol
Supplementary Information page(s), which will be provided as a separate document.
The term "participant" throughout the protocol refers to the common term "subject".
2.1. 
Background
2.1.1. 
Gastric and Esophageal Cancer
Gastric Cancer
Cancer is a leading cause of death worldwide. Gastric cancer (GC) is the fifth most common cancer
worldwide and over 1 million new cases were reported worldwide in 2018. (Ferlay 2018) Gastric
cancer is highly prevalent in Asian countries accounting for approximately 75% of new cases in
2018 and is the third (male)/fourth (female) most prevalent cancer in Japan. (Ferlay 2018) Majority
of patients exhibit adenocarcinoma histology. The treatment regimen depends on the type of cancer
(eg, histology), the stage of the cancer at diagnosis, and the presence of molecular biomarkers (eg,
human epidermal growth factor receptor 2 (HER2) amplification, Programmed death-ligand 1
expression, and microsatellite instability). Treatment commonly includes surgery and
chemotherapy. In patients with metastatic disease, National Comprehensive Cancer Network
(NCCN) guidelines recommend HER2, programmed death-ligand 1, and microsatellite instability
testing. (NCCN Guidelines 2020) Likewise Japanese gastric cancer association guidelines
recommend HER2 testing prior to the initiation of initial systemic chemotherapy. (Japanese gastric
cancer 
treatment 
guidelines 2018) 
The 
first 
line 
treatment 
generally 
includes
fluoropyrimidine+cisplatin or oxaliplatin±trastuzumab (depending on HER2 status). The
combination therapy with S-1 is also recommended in Japan. (Japanese gastric cancer treatment
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guidelines 2018) The observed overall response rate for the guideline-recommended initial
treatment ranged between 35% to 68% (Bang 2010; Kurokawa 2014) with the median progression-
free survival (mPFS) of approximately 6 months. (Bang 2010; Kurokawa 2014; Koizumi 2008;
Ohtsu 2011; Yamada 2015; Yoon 2016) Available treatment options after first line treatment are
limited. 
The 
NCCN 
recommendations 
are 
chemotherapy 
as 
a 
single 
agent,
ramucirumab+paclitaxel, immune checkpoint inhibitor, or fluorouracil+irinotecan. Similar to
NCCN guidelines, the recommended second line (2L) and third line (3L) treatments are
ramucirumab+paclitaxel (2L), nivolumab (3L), or irinotecan (3L) per the Japanese guidelines.
(Japanese gastric cancer treatment guidelines 2018) The reported overall response rate from the
Phase 3 studies for 2L and 3L treatments are limited to 11% to 28% with the mPFS of 1.6 to 4.4
months. (Wilke 2014; Hironaka 2013; Kang 2017) Furthermore, 5-year survival rate is only 7.0%
and the median overall survival (OS) merely exceeds a year among stage IV patients. (Gastric
Cancer [Type of Cancer] 2020)
Esophageal Cancer
Esophageal cancer (EC) is the eighth most common cancer worldwide and ranked sixth among all
cancers in mortality in 2018. (Ferlay 2018) Similar to GC, EC is highly prevalent in Asian
countries accounting for over 75% of new cases in 2018. (Ferlay 2018) Squamous cell carcinoma
and adenocarcinoma are 2 major histologies of primary ECs. However, predominant EC histology
varies between geographical regions. The predominant histology observed among the Caucasian
population is adenocarcinoma whereas squamous histology predominates Asian countries.
(Chen 2017) Treatment commonly includes surgery, radiation therapy, chemoradiation therapy,
and chemotherapy. The NCCN guideline recommendations for the first line therapies are identical
to GC regimens due to the nature of histological similarities. (NCCN Guidelines 2020) Clinical
data of esophageal squamous cell carcinoma, which is the predominant histology in Asian
countries, are limited to mostly Phase 2 studies. The reported overall response rate of
chemotherapy as a single agent is 15%~40%. The recommended regimen in Japan for the first line
treatment is considered fluorouracil+cisplatin. (Vijayaraghavan 2020, Waddell 2013, Wang 2007,
Wilke 2014, Xu 2016, Yamada 2015, Yano 2003, Yoon 2016). The overall response rate and
mPFS from 2 phase 2 studies of this combination were reported to be 35% to 35.9% and 3.5 to
6.2 months, respectively. (Muro 2004; Kato 2011) There are no recommended 2L treatments per
Japanese guidelines and single agent chemotherapy is often used with the reported mPFS of 1.5 to
3.9 months. (Muro 2004; Kato 2011; Kudo 2017) A recent Phase  3 study evaluating
pembrolizumab versus chemotherapy in patients with advanced/metastatic adenocarcinoma or
squamous cell carcinoma of the esophagus as 2L therapy (KEYNOTE-181) had led to the
regulatory approval in Japan for the patients with PD-1 combined positive score ≥10. Even with
this targeted therapy, observed overall response rate and mPFS are limited to 17% and 1.5 months,
respectively. (Kudo 2017)
2.1.2. 
Role of EGFR and cMet in Gastric and Esophageal Cancer
Receptor tyrosine kinases (RTK) are involved in the regulation of many processes in mammalian
development, cell function, and tissue homeostasis. Dysregulation of RTKs has been implicated
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in the development of numerous human cancers, and various RTKs are targets for both approved
and experimental anticancer therapies.
Epidermal growth factor receptor, an RTK in the HER family, is normally expressed in tissues of
epithelial, mesenchymal, and neuronal origin. Binding of any of its 7 ligands, including EGF,
induces diverse cellular responses, including differentiation, proliferation, migration, and survival.
(Olayioye 2000) cMet is also an RTK, expressed in normal epithelial cells (Prat 1991), with a role
in growth and homeostasis, including embryonic development, angiogenesis, and wound healing.
(Sattler 2011) cMet is activated by a single specific ligand, hepatocyte growth factor, also known
as scatter factor.
Overexpression and mutations of the EGFR and cMet receptors have been linked to tumorigenesis
and malignancy, as well as poor prognosis in several types of cancer. (Birchmeier 2003;
Hyner 2005; Yano 2003) It is reported that approximately 25% and 50% of GC patients express
EGFR or cMet, respectively. (Fuse 2016) Likewise approximately 60% to 70% and 45% to 70%
of EC patients express EGFR or cMet, respectively. (Hanawa 2006; Gibault 2005) The expression
of EGFR or cMet has been implicated as a poor prognostic factor in GC   (Aydin 2014; Gao 2013;
Galizia 2007; Atmaca 2012; Fuse 2016) and EC (Wang 2007; Brand 2011; Ozawa 2015).
Furthermore, co-expression of EGFR and cMet has been reported to have significantly worse OS
in squamous cell carcinoma of esophagus. (Xu 2016)
Despite numerous agents targeting EGFR (including anti-EGFR antibodies and EGFR tyrosine
kinase inhibitors [TKIs]) having been used as a standard of care for many cancers, including
colorectal cancer, non-small cell lung cancer (NSCLC), and head and neck cancer, no EGFR-
directed therapy is available for gastric or ECs. Previous studies have failed to show efficacy of
cetuximab and panitumumab, anti-EGFR antibodies, for the treatment of GC or gefitinib, EGFR
tyrosine kinase inhibitor, in EC in non-biomarker selected population. (Lordick 2013;
Waddell 2013; Dutton 2014) A more recent study evaluating nimotuzumab, anti-EGFR antibody,
in combination with irinotecan for GC patients with EGFR expression has also been shown to be
unsuccessful. (Satoh 2015) The clinical experience of cMet-targeted therapy is less extensive. The
studies evaluating the efficacy of rilotumumab or onartuzumab, anti-cMet antibodies, in GC failed
to show clinical benefit. However, post-hoc retrospective analysis of these studies has implicated
clinical benefit in an EGFR or cMet overexpressing population, implying the clinical activity of
anti-EGFR and anti-cMet treatments in the subset of GC or EC population. (Iveson 2014;
Satoh 2015)
2.1.3. 
Clinical Studies of Amivantamab
The safety and efficacy of amivantamab as a monotherapy has been previously described in
patients 
with 
NSCLC 
in 
the 
first-in-human 
Phase 
1 
CHRYSALIS 
study
(Study 61186372EDI1001). Study 61186372EDI1001 includes both a dose-escalation phase
(Part 1: subjects with advanced NSCLC) and a dose-expansion phase (Part 2: subjects with
advanced EGFR-mutated or cMET-mutated NSCLC, after standard of care therapy). Part 1 of the
study includes a chemotherapy combination arm for participants with advanced NSCLC who are
eligible for treatment with standard of care carboplatin and pemetrexed. Part 2 of the study includes
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expansion cohorts for amivantamab monotherapy in populations with unmet clinical need,
including NSCLC characterized by the following: 1) Cohort C: EGFR resistance mutations (eg,
C797S and others) and previous treatment with a third-generation EGFR TKI; 2) Cohort D: EGFR
Exon 20ins disease and no previous treatment with an EGFR TKI with known activity in
Exon 20ins disease; 3) Cohort MET-1: EGFR mutation with MET mutation or amplification of ≥3
copy number and previous treatment with any EGFR TKI; and 4) Cohort MET-2: Primary MET
Exon 14 skipping mutation. Study 61186372EDI1001 also carried out initial safety and efficacy
exploration of amivantamab in combination with lazertinib, a 3rd generation EGFR TKI, as well
as amivantamab with carboplatin and pemetrexed chemotherapy combination. Please refer to IB
for further details regarding the experience with amivantamab in these combinations.
Based on early activity observed within the EFGR Exon20ins population, amivantamab was
awarded Breakthrough Therapy Designation by the United States Food and Drug administration
(FDA) and China Center for Drug Evaluation for the treatment of patients with EGFR Exon20ins
NSCLC, after progression on prior platinum-based chemotherapy.
In November 2020, the first biologic license application was submitted to United States (US) FDA
for the treatment of patients with EGFR Exon20ins NSCLC after prior progression on platinum-
based chemotherapy and is currently under review. Additional global regulatory submissions are
ongoing.
2.2. 
Study Rationale
Gastric and ECs have been known to express EGFR and cMet and the expression of these proteins
have corelated with poor prognosis. Although many agents targeting EGFR are part of standard of
care for many tumor types, no anti-EGFR or anti-cMet therapy has been approved in GC or EC.
As a bispecific duobody capable of engaging the extracellular domains of both EGFR and cMet
receptors, amivantamab has a unique mechanism of action that suggests it has the potential to
control EGFR-expressed and/or cMet-expressed GC and EC patients. Amivantamab has
demonstrated in vitro and in vivo pre-clinical activities against tumors with the EGFR or cMet
amplified GC and EC models (Vijayaraghavan 2020). Furthermore, clinical experience of
amivantamab in NSCLC has shown clinical benefit against broad-spectrum of EGFR and cMet
aberrations, including EGFR protein overexpression and cMet amplifications.
This study aims to evaluate the clinical activity of amivantamab as a monotherapy in GC (including
GEJ cancer) and EC patients who had received at least 2 prior lines (GC/GEJ participants) or at
least 1 prior line (EC participants) of standard therapy. The Phase 2a cohorts will initially
investigate the anti-tumor activity of amivantamab in participants with documented expression of
either EGFR, cMet, or both as evaluated by immunohistochemistry (IHC). Approximately 30
participants with any expression level of EGFR, cMet, or both proteins will be enrolled in each of
the Phase 2a cohort. However, based on the prior experiences investigating anti-EGFR and anti-
cMet antibodies in gastroesophageal cancers, at least 20 participants expressing IHC 2+ or higher
(defined as participants expressing EGFR IHC 2+ or above and/or cMet IHC 2+ or above) will be
enrolled. The clinical trial management team (CTMT) may allow additional enrollment in Phase
2a cohorts to achieve this minimal enrollment. Moreover, at least 10 participants expressing any
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level of cMet protein will be enrolled in each of Phase 2a cohort to better characterize the
contribution of cMet in amivantamab activity. If activity is demonstrated in the Phase 2a cohorts,
Phase 2a extension cohorts investigating participants without expression of EGFR and cMet, may
open for enrollment upon agreement with the CTMT. The Phase 2b cohorts will investigate the
clinical activity of amivantamab in selected patient population based on the Phase 2a data.
2.3. 
Benefit-risk Assessment
2.3.1. 
Risks for Study Participation
The safety and tolerability of amivantamab monotherapy was shown in the Phase 1
Study 61186372EDI1001 (Section 2.1.3) in NSCLC patients. Amivantamab was generally well
tolerated without any occurrence of dose limiting toxicities (DLTs). However, given that the
available clinical data are limited to NSCLC participants, unforeseen safety risks associated with
the study treatments are possible in GC or EC participants. This study protocol includes the
following elements to mitigate risks for study participants:
 The CTMT in conjunction with the coordinating investigator will review the safety and
conduct of Phase 2a periodically.
 Participants will be monitored closely for safety throughout the study (refer to Section 8.2),
per the scheduled assessments outlined in the Schedule of Activities (Table 1).
 Dose modification guidance is provided to manage toxicities that occur during the study (refer
to Section 6.5 and Section 6.6), including specific guidance for infusion-related reactions
(IRRs), rash, interstitial lung disease (ILD), liver test abnormalities, or paronychia.
Amivantamab is generally safe and well tolerated based on the data mentioned above.
2.3.2. 
Benefits for Study Participation
Although many agents targeting EGFR have been approved and are part of standard of care for
many tumor types, no anti-EGFR or anti-cMet therapy has been approved in GC or EC.
Amivantamab has demonstrated significant activity as monotherapy for the treatment of NSCLC,
receiving Breakthrough Therapy Designation by the US FDA and China Center for Drug
Evaluation, based on an overall response rate of 41% in subjects with EGFR Exon20ins disease,
after prior treatment with platinum-based chemotherapy. Consistent with the unique mechanism
of action of amivantamab, activity was observed in subjects with diverse EGFR mutations, as well
as in subjects with amplification of MET and overexpressed EGFR.
It is anticipated that using this therapeutic targeted approach with amivantamab as a single agent
in either advanced GC (including GEJ cancer) or EC participants may provide benefit to these
participants.
2.3.3. 
Benefit-risk Assessment for Study Participation
Considering the measures taken to minimize risk to participants of this study (refer to
Section 2.3.1), the potential risks of amivantamab are justified by the anticipated benefits that may
be afforded to participants with advanced GC or EC (refer to Section 2.3.2). More detailed
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information about the known and expected benefits and risks of amivantamab may be found in the
IB and Addenda for amivantamab.
3. 
OBJECTIVES AND ENDPOINTS
Objectives 
Endpoints
Primary
 
To investigate the activity of amivantamab in
gastric cancer (GC) and esophageal cancer
(EC) participants (Phase 2a)
 
To characterize the preliminary antitumor
activity of amivantamab in selected GC and EC
population (Phase 2b)
 
Objective 
response 
rate, 
as 
determined 
by
investigator, according to the Response Criteria in
Solid Tumors (RECIST) Version 1.1.
Secondary
 
To assess additional measures of clinical
benefits with amivantamab
 
Disease control rate (DCR), duration of response
(DoR), time to response (TTR), progression-free
survival (PFS), and overall survival (OS; Phase 2b
only).
 
To confirm the safety of amivantamab in
participants with gastric or esophageal cancers
(ECs)
 
Adverse events defined by the National Cancer
Institute Common Terminology Criteria for Adverse
Events (NCI-CTCAE) Version 5.0 in participants
treated with amivantamab
 
To assess the pharmacokinetics (PK) and
immunogenicity of amivantamab following
multiple intravenous dose administrations
 
Serum PK parameters including but not limited to
maximum serum concentration (Cmax), time to reach
the maximum serum concentration (Tmax), area under
the 
curve 
(AUC)(t1-t2), 
AUCtau, 
plasma/serum
concentration immediately prior the next study
treatment administration (Ctrough), and accumulation
ratio; incidence of anti-amivantamab antibodies
Exploratory
 
Explore biomarkers predictive of clinical response and resistance to amivantamab in blood and tumor tissue
 
Explore the relationship between serum PK and pharmacodynamic (PD) markers (eg, soluble EGFR and
cMet)
 
Determine whether amivantamab can impact the anti-tumor immune response or microenvironment
Refer to Section 8, STUDY ASSESSMENTS AND PROCEDURES for evaluations related to
endpoints.
HYPOTHESIS
Amivantamab will exhibit anti-tumor activity in participants with GC or EC expressing any level
of EGFR, cMET, or both proteins.
4. 
STUDY DESIGN
4.1. 
Overall Design
This is an open-label, multicenter, multi-arm Phase 2 interventional study in participants with
previously treated advanced or unresectable GC or EC who are 20 years or older (or the legal age
of consent in the jurisdiction in which the study is taking place). The participants with gastric/GEJ
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or EC who express varying degrees of EGFR, cMet, or both as determined by IHC locally or
centrally will be enrolled in the GC cohort or EC cohort. If activity is demonstrated in the Phase
2a cohorts, Phase 2a extension cohorts investigating participants without expression of EGFR and
cMet, may open for enrollment upon agreement with the CTMT. If activity is observed within the
Phase 2a cohorts, the corresponding Phase 2b GC or EC expansion cohorts will be initiated to
evaluate the antitumor activity of amivantamab in selected GC and EC participants based upon the
prospective assessment of IHC during Phase 2a (schematic overview is Section 1.2).
A maximum of approximately 302 participants will be enrolled in the combined Phase 2a and
Phase 2b populations, in the event the efficacy observed in both Phase 2a cohorts warrants full
enrollment in their respective Phase 2b cohorts. Approximately, 30 response evaluable participants
will be enrolled in each of Phase 2a GC and EC arm. However, based on the prior experiences
investigating anti-EGFR and anti-cMet antibodies in gastroesophageal cancers, at least 20
participants expressing IHC 2+ or higher (defined as participants expressing EGFR IHC 2+ or
above or cMet IHC 2+ or above) will be enrolled. Moreover, at least 10 participants expressing
any level of cMet protein (IHC1+ or above) will be enrolled in each Phase 2a cohort to better
characterize the contribution of cMet in amivantamab activity. The CTMT may allow additional
enrollment in the Phase 2a cohorts to achieve this minimal enrollment, if these criteria aren’t met
in the initial 30 evaluable subjects. If activity is demonstrated in the Phase 2a cohorts, Phase 2a
expansion cohorts investigating a maximum of 11 participants without any expression of EGFR
and cMet, may open for enrollment upon agreement with the CTMT. The CTMT will assess the
data and may recommend additional participants to be enrolled for further characterization if 2 or
more responses are observed in each of Phase 2a GC or EC extension cohorts. Based on emerging
data, the CTMT may also recommend exploration of higher doses of amivantamab. The Phase 2b
GC expansion or EC expansion cohorts will evaluate the antitumor activity of amivantamab in GC
and EC patients, using biomarker selection based upon Phase 2a results. If activated,
approximately 100 participants will be enrolled in each of the Phase 2b cohorts.
The safety and conduct of the study will be monitored by the CTMT in conjunction with the
coordinating investigators. In general, the CTMT will monitor the conduct of the study and review
study data in an ongoing basis. The CTMT may recommend and decide on modifications in the
study conduct which may include, but are not restricted to, changes in  (1) study treatment
administration dose/schedule, (2) patient population based on the emerging biomarker data,
(3) allowing further enrollment or terminate enrollment of a specific subpopulation to better
characterize the specific population (eg, enrollment of IHC 2+/3+ or EGFR and cMet double
positive population), (4) opening of Phase 2a extension cohorts and (5)-PK or biomarker sampling
times. All decisions made by the CTMT will be documented in a CTMT decision document. The
Independent Ethics Committee/Institutional Review Board (IEC/IRB) will be notified for all
CTMT decisions, if required. The recommendations of the CTMT may be instituted by the study
team, pending protocol amendment, as long as they are consistent with the benefit-risk and fall
within the populations already reviewed and approved by the health authority (HA) and local IRBs.
All the CTMT documentation will be maintained in the sponsor’s study master file and, as
applicable, in the investigator’s study files. If unexpected safety findings are identified, the CTMT
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will assess the safety data in a prompt manner. The study will include a screening phase
(Section 4.1.1), a treatment phase (Section 4.1.2), and a follow-up phase (Section 4.1.3).
4.1.1. 
Screening Phase (Pre- and Full Screening)
The participant must sign an informed consent form (ICF) at the beginning of the full screening
phase, before the first study-related activity is conducted. During the full screening period,
participants will be evaluated for eligibility for study participation. Participants must complete all
screening procedures within 28 days of C1D1. Pre-treatment biopsy will be collected for all
participants in Phase 2a and Phase 2b. The tumor IHC result regardless of the local or central must
be obtained and confirmed for the eligibility prior to C1D1. If the central tumor IHC is used for
the eligibility prior to the initiation of the study treatment and the central results are not completed
during the screening period, the screening period can be extended by 14 days. However, all other
assessments must still meet timing criteria relative to C1D1 or must be repeated.
If an assessment was performed as part of the participant’s routine clinical evaluation and not
specifically for this study, it needs not be repeated after signed ICF has been obtained provided
the assessments fulfill the study requirements and are performed within the specified timeframe
prior to C1D1.
An optional pre-screening period with corresponding ICF is offered to facilitate molecular
characterization of archived tumor biopsy sample, prior to signing of full study ICF. The
participant may sign pre-screening ICF and submit archival sample before completion of the
previous therapy. If IHC assay is performed locally, enrollment should be considered with
reference to the scoring criteria used in the central IHC assay.
If there is a discrepancy between the local and central IHC assay, the study treatment may be
continued at the investigator discretion.
4.1.2. 
Treatment Phase
The treatment phase for a participant will begin on C1D1 and continue as 28-day cycles until the
EOT visit, approximately 30 days after the last dose of study treatment. If the initiation of the
subsequent anticancer therapy is required prior to EOT, EOT must be completed prior to the
initiation of the subsequent anticancer therapy. This study will be conducted in an outpatient
setting. However, in-hospital observation, from C1D1 until C1D8 is permitted in the Phase 2a
(including Phase 2a extension cohorts) to allow close monitoring at the discretion of the
investigator. Study treatment will continue until documented clinical or radiographic (RECIST
Version 1.1) disease progression or until the participant meets another criterion for discontinuation
of study treatment.
Disease assessments will occur as close as possible to the start of treatment (baseline screening
scans), 6 weeks (+1 week) after the first dose of study treatment, then every 6 weeks (±1 week)
for the first 12 months and then every 12 weeks (±1 week) until objective radiographic disease
progression or withdrawal of consent.
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At each study visit during the treatment phase, participants will undergo safety evaluations,
including physical examinations and assessment of adverse events (AEs), vital signs, concomitant
medication usage, and clinical laboratory parameters. Participants will also have blood samples
drawn for assessment of PK and immunogenicity parameters and for biomarker evaluations, at
selected visits. Post-treatment biopsy, circulating tumor DNA (ctDNA), and biomarker at C2D15
as well as per the Schedule of Activities (Section 1.3) will be collected on C2D15 (±1 day) from
all participants in Phase 2a. For additional higher dosing in Phase 2a, post-treatment biopsy at
C2D15 will be mandatory, if clinically feasible.
4.1.3. 
Follow-up Phase (Applicable to Phase 2b Only)
Participants who discontinue study treatment will be followed for subsequent therapy, disease
status (applicable only if participants discontinuing treatment due to reasons other than progressive
disease, to confirm disease progression date), and survival in the follow-up phase. This phase starts
from the EOT visit assessment will be done every 12 weeks (±14 days) after the last dose of study
treatment or disease progression (whichever occurs first) and continues until the end of study,
death, lost to follow-up, or withdrawal of consent from participation in the study, whichever comes
first. If the information is obtained via telephone contact, written documentation of the
communication must be available for review in the source documents. If the participant has died,
the date and cause of death will be collected and documented on the electronic case report form
(eCRF). Investigators may recontact the participant to obtain long-term follow-up information
regarding the participant's safety or survival status as noted in the ICF.
A diagram of the study design is provided in Section 1.2, Schema.
4.2. 
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Treatment Groups
This is an open-label non-randomized study; therefore, no blinding or randomization is applied.
Clinical Pharmacology Assessments
Serum samples will be collected and analyzed for amivantamab concentrations, and estimation of
basic PK parameters from this concentration-time data will be performed and reported.
Immunogenicity (antibodies to amivantamab, also termed anti-drug antibody) will be evaluated
for potential impact on PK. Pharmacokinetic profiles and parameters will be assessed relative to
clinical safety, efficacy, pharmacokinetic (PD) (soluble EGFR and cMet), and exploratory
biomarker data, as available.
Biomarker Collection
In Phase 2a: Pre-treatment tumor samples will be assessed by IHC for EGFR and Met expression
levels on the tumor. On-treatment tumor samples in Phase 2a and, if collected in Phase 2b, will be
assessed for changes in the expression of markers of pathway inhibition including, but not limited
to, EGFR and MET. Tissue samples collected may be tested by next-generation sequencing or
another methodology to identify genetic alterations which may predict response or resistance to
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amivantamab. These include, but are not limited to, mutations, insertions, or amplification of the
EGFR and MET genes and other genes of interest.  Tumor tissue may also be evaluated for
additional biomarkers (DNA, RNA, and/or protein) relevant to GC or EC or the mechanism of
action of amivantamab, including immune cell activity.
Circulating tumor DNA from screening blood samples will be analyzed to characterize baseline
EGFR and cMet mutational status. Biomarker samples (tumor and blood) will be collected to
evaluate the mechanism of action of amivantamab, to help explain inter-participant variability in
clinical outcomes, and to help identify population subgroups that respond to amivantamab. The
goal of the biomarker analyses is to evaluate the drug-clinical response relationship and
mechanisms of resistance to amivantamab.
In addition, blood samples may be evaluated for biomarkers (DNA, RNA, and/or protein) which
may be related to amivantamab response.
4.2.1. 
Study-specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and during
the study, participants will be given any new information that may affect their decision to continue
participation. They will be told that their consent to participate in the study is voluntary and may be
withdrawn at any time with no reason given and without penalty or loss of benefits to which they
would otherwise be entitled. Only participants who are fully able to understand the risks, benefits,
and potential AEs of the study and provide their consent voluntarily will be enrolled.
The total blood volume to be collected is considered to be an acceptable amount of blood to be
collected over this time period from the population in this study based upon the standard of the
Japanese Red Cross blood donation and American Red Cross. (Japanese Red Cross Society;
American Red Cross)
4.3. 
Justification for Dose
Amivantamab was generally well tolerated in a Phase 1 study (Study 61186372EDI1001) up to
the dose of 1750 mg, with no dose limiting toxicities reported during dose escalation and no
maximum tolerated dose identified in lung cancer participants. Based on the totality of exposure,
safety, and efficacy data, the recommended Phase 2 dose was determined to be 1050 mg for body
weight <80 kg and 1400 mg for body weight ≥80 kg, administered by IV infusion in 28 day cycles:
once weekly in Cycle 1 (with a split dose on Days 12), and then every 2 weeks in subsequent
cycles. The recommended Phase 2 dose achieved a complete soluble target saturation throughout
dosing for the EGFR and cMet in the lung cancer participants. The observed safety profile of
amivantamab is consistent with EGFR and cMet inhibition and majority of treatment emergent
adverse events (TEAEs) were Grade 1 to 2 in severity. Therefore, administering the same dosing
regimen to GC or EC participants is considered appropriate.
Based on observed PK, safety, and efficacy data, the CTMT may recommend exploration of higher
dosing of amivantamab. In the monotherapy dose escalation of amivantamab in Study
61186372EDI1001, doses up to 1,750 mg were assessed. In this study, participants who received
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1,750 mg had a body weight (BW) <80 kg, and the observed exposure was similar to model-
estimated exposures achieved with weight-based dosing of 1,750 mg/2,100 mg for participants
weighing <80 kg and ≥80 kg, respectively. At the maximum assessed dose, there were no dose-
limiting toxicities (DLTs) observed, and a maximum tolerated dose (MTD) was not established.
The need for exploration of higher dose levels, and which dose(s) to assess, will be dependent
upon the clinical activity observed at the current dose (1,050 mg [BW<80 kg]/1,400 mg
[BW≥80 kg]), exposure-response data, and safety data. Based upon these data, the CTMT may
recommend exploration of the following doses: 1,750 mg [body weight < 80 kg]/2,100 mg [body
weight ≥ 80 kg]. For evaluation of potential higher doses, the CTMT will convene after 3 subjects
have completed 1 cycle of treatment, to review safety and tolerability. Based on the data reviewed,
the CTMT may recommend continuation of the cohort to approximately 20 response evaluable
participants. Safety will be closely monitored for all study participants, with ongoing review of
safety during regularly scheduled CTMT meetings.
4.4. 
End of Study Definition
End of Study Definition
The end of study will occur after all participants have discontinued therapy with study treatment
and have at least 6 months of follow-up or have discontinued from the study. The data cutoff for
the clinical study report (CSR) will be 6 months after the first dose of last participant in the
Phase 2b. Participants on-treatment at the time of analysis will continue to receive study treatment
and those who are in follow-up will continue to be followed.
Study Completion Definition
Phase 2a: A participant will be considered to have completed the study if:
 The participant has died
 The participant has met all of the following:
o Documented radiographic disease progression
o Completed the EOT assessment
o Completed protocol-required AE follow-up
 Note: In case a subsequent therapy is initiated without documented radiographic disease
progression, then it will be considered the study completion.
Phase 2b: A participant will be considered to have completed the study if the participant died
before the EOT.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 28 days before administration of the
study treatment. Refer to Section 5.4, Screen Failures for conditions under which the repeat of any
screening procedures is allowed.
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The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed.
5.1. 
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. 
Participant must be ≥20 years of age (or the legal age of consent in the jurisdiction in
which the study is taking place).
2. 
Criterion modified per Amendment 1:
2.1. Participant tumor must express either EGFR, cMet, or both as determined by
either local or central IHC assay (IHC 1+ or above). A copy of the de-identified
pathology report, or equivalent information, for IHC analysis must be submitted
during the screening period if local IHC test was used for the eligibility
determination.
Phase 2a extension cohorts: Participant tumor must lack expression of EGFR and
MET as determined by either local or central IHC assessment. A copy of the de-
identified pathology report, or equivalent information, for IHC analysis must be
submitted during the screening period if local IHC test was used for the eligibility
determination.
3. 
Participant must have histologically or cytologically confirmed gastric (including GEJ)
or EC that is locally advanced, unresectable, or metastatic, and not eligible for curative
treatment.
Gastric or GEJ Cancer Only
a. Must be refractory or ineligible to at least 2 prior lines of standard of care
systemic therapy. Prior therapies must include fluoropyrimidine- and
platinum-based chemotherapy. Participants with known HER2 expression
must have had HER2-targeting therapy as part of the prior therapy.
b. In case of progression within 24 weeks of prior adjuvant or neoadjuvant
chemotherapy, this therapy will be considered as 1 prior line of systemic
therapy for the purpose of meeting the eligibility criteria.
Esophageal Cancer Only
a. Must be refractory or intolerant to at least 1 prior line of systemic therapy.
Prior therapies must include fluoropyrimidine-, and platinum-based
chemotherapy (including chemoradiation therapy given as stage IV setting).
b. Participant who underwent a radical resection in conjunction with
chemotherapy including neo-adjuvant/adjuvant therapy or chemoradiation
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(including participants who underwent chemoradiation, if residual tumor
exists, followed by salvage surgery) whose recurrence was confirmed by
imaging within 24 weeks after the last dose of chemotherapy will be
considered as having received 1 line of prior systemic therapy for the purpose
of meeting the eligibility criteria.
Note: If prior combination therapy discontinued due to an AE, and then one of the
agents continued, this is considered to be “1 prior line” and not “2 prior lines.” The
change in dosage form (IV administration, oral administration) or dose reduction
without progression is considered to be “1 prior line” and not “2 prior lines.”
4. 
Participant must have measurable disease according to RECIST Version 1.1. If only
one measurable lesion exists, it may be used for the screening biopsy if the baseline
tumor assessment scans are performed ≥7 days after the biopsy.
5. 
Participant must have Eastern Cooperative Oncology Group (ECOG) performance
status 0 or 1 (refer to Section 10.5, Appendix 5: Eastern Cooperative Oncology Group
(ECOG) Performance Status).
6. 
Participant must have adequate organ and bone marrow function as follows, without
history of red blood cell transfusion or platelet transfusion within 7 days prior to the
date of the laboratory test.
a. Hemoglobin ≥8 g/dL
b. Absolute neutrophil count ≥1500/mm3, without use of granulocyte colony
stimulating factor (G-CSF) within 10 days prior to the date of the test
c. Platelets ≥75,000/mm3
d. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
≤3×upper limit of normal (ULN). If liver metastases are present, ≤5×ULN
e. Total bilirubin ≤1.5×ULN (participants with Gilbert’s syndrome can enroll if
direct bilirubin is within normal limits)
f. 
Calculated or measured glomerular filtration rate ≥40 mL/min using the
Modified Diet in Renal Disease (MDRD) equation (refer to Section 10.7,
Appendix 7: MDRD formula for eGFR)
7. 
Participant must have a tumor lesion amenable for biopsy and agree to protocol-defined
mandatory biopsies.
8. 
A woman of childbearing potential must have a negative urine or serum pregnancy test
within 72 hours prior to receiving the first dose of study treatment.
9. 
Criterion modified per Amendment 2:
9.1 A female participant must be as defined in Section 10.4, Appendix 4:
Contraceptive and Barrier Guidance) either of the following:
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a. Not of childbearing potential
b. Of childbearing potential and
o 
practicing true abstinence;
o 
or have a sole partner who is vasectomized;
o 
or practicing at least 1 highly effective user independent method of
contraception (see Section 10.4, Appendix 4: Contraceptive and Barrier
Guidance).
Participant must agree to continue the above throughout the study and for 3
months after the last dose of study treatment.
Note: If a woman becomes of childbearing potential after start of the study the
woman must comply with point (b.) as described above.
10.  
Criterion modified per Amendment 2:
10.1 A female participant must not be pregnant, breast-feeding, or planning to become
pregnant while enrolled in this study or within 3 months after the last dose of
study treatment (enrollment is not permitted even if a woman who is breast-
feeding stops breast-feeding).
11. 
Criterion modified per Amendment 2:
11.1 A male participant must wear a condom (with or without spermicidal
foam/gel/film/cream/suppository) when engaging in any activity that allows for
passage of ejaculate to another person during the study and for a minimum of 3
months after receiving the last dose of study treatment. His female partner, if of
childbearing potential, must also be practicing a highly effective method of
contraception (see Section 10.4, Appendix 4: Contraceptive and Barrier
Guidance).
If the male participant is vasectomized, he still must wear a condom (with or
without spermicidal foam/gel/film/cream/suppository), but his female partner is
not required to use contraception.
12. 
Criterion modified per Amendment 2:
12.1 A male participant must agree not to donate sperm for the purpose of reproduction
during the study and for a minimum of 3 months after receiving the last dose of
study treatment.
13. 
Criterion modified per Amendment 2:
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13.1 A male participant must agree not to plan to father a child while enrolled in this
study or within 3 months after the last dose of study treatment.
14. 
Participant must sign an ICF indicating that he or she understands the purpose of, and
procedures required for, the study and is willing to participate in the study.
15. 
Participant must be willing and able to adhere to the prohibitions and restrictions
specified in this protocol.
5.2. 
Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. 
Participant has an uncontrolled illness, including but not limited to the following:
a. Diabetes
b. Ongoing or active bacterial infection (includes infection requiring treatment
with antimicrobial therapy [participants will be required to complete
antibiotics 1 week before enrollment]), symptomatic viral infection, or any
other clinically significant infection
c. Active bleeding diathesis
d. Psychiatric illness/social situation that would limit compliance with study
requirements
2. 
Participant has had prior chemotherapy, targeted cancer therapy, immunotherapy, or
treatment with an investigational anticancer agent within 2 weeks or 4 half-lives
whichever is longer or had radiation therapy within 4 weeks before the first
administration of study treatment. For agents with long half-lives, the maximum
required time since last dose is 28 days. Toxicities from previous anticancer therapies
should have resolved to baseline levels or to Grade 1 or less, (except for alopecia or
post-radiation skin changes [any grade], Grade ≤2 peripheral neuropathy, and Grade ≤2
hypothyroidism stable on hormone replacement).
3. 
Participant has untreated brain metastases (a participant with definitively, locally treated
metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for
at least 2 weeks prior to the first administration of study treatment is eligible), history
of leptomeningeal disease or spinal cord compression that has not been treated
definitively with surgery or radiation. If brain metastases are diagnosed on screening
imaging, the participant may be rescreened for eligibility after definitive treatment.
4. 
Participant has a history of (non-infectious) ILD/pneumonitis that required steroids, or
has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out
by imaging at screening. GEJ or Esophageal cancer participants with history of radiation
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pneumonitis (defined as radiographically stable for 3 months prior to enrollment
without need of any treatment) may be enrolled.
5. 
Participant has an active malignancy (ie, progressing or requiring treatment change in
the last 12 months) other than the disease being treated under study. The only allowed
exceptions are:
a. Non-muscle invasive bladder cancer treated within the last 24 months that is
considered completely cured.
b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that
is considered completely cured.
c. Non-invasive cervical cancer treated within the last 24 months that is considered
completely cured.
d. Localized prostate cancer (N0M0):
o 
With a Gleason score of 6, treated within the last 24 months or untreated
and under surveillance,
o 
With a Gleason score of 3+4 that has been treated more than 6 months
prior to full study screening and considered to have a very low risk of
recurrence,
o 
Or history of localized prostate cancer and receiving androgen deprivation
therapy and considered to have a very low risk of recurrence.
e. Breast cancer:
o 
adequately treated lobular carcinoma in situ or ductal carcinoma in situ,
o 
or history of localized breast cancer and receiving antihormonal agents
and considered to have a very low risk of recurrence.
f. Malignancy that is considered cured with minimal risk of recurrence.
g. Phase 2a participants only: Participants with another malignancy may enroll if
any systematic treatment is considered not to become necessary by the
investigator for at least 6 months after the enrollment.
6. 
Participant has a history of clinically significant cardiovascular disease including, but
not limited to:
a. Diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks
prior to the first dose of study treatment or any of the following within
6 months prior to the first dose of study treatment: myocardial infarction,
unstable angina, stroke, transient ischemic attack, coronary/peripheral artery
bypass graft, or any acute coronary syndrome. Clinically non-significant
thrombosis, such as non-obstructive catheter-associated clots, are not
exclusionary.
b. Prolonged QTcF interval >480 msec or clinically significant cardiac
arrhythmia or electrophysiologic disease (eg, placement of implantable
cardioverter defibrillator or atrial fibrillation with uncontrolled rate).
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Note:  Participants with cardiac pacemakers who are clinically stable are
eligible.
c. Uncontrolled (persistent) hypertension: systolic blood pressure >180 mm Hg;
diastolic blood pressure >100 mm Hg
d. Congestive heart failure defined as New York Heart Association (NYHA)
class III-IV or Hospitalization for congestive heart failure (any NYHA class)
(refer to Section 10.6, Appendix 6: New York Heart Association Criteria)
within 6 months of study enrollment
e. Pericarditis/clinically significant pericardial effusion
f. 
Myocarditis
7. 
Participant has known allergies, hypersensitivity, or intolerance to excipients of
amivantamab (refer to the IB).
8. 
Participant has received study treatment (including investigational vaccines) within
6 weeks before enrollment except for the anticancer therapy described in the Exclusion
Criterion No. 2.
9. 
Participant has, or will have, any of the following:
a. An invasive operative procedure with entry into a body cavity, within 4 weeks
or without complete recovery before C1D1. Thoracentesis, if needed, and
percutaneous biopsy for baseline tumor tissue sample may be done less than
4 weeks prior to C1D1, as long as the participant has adequately recovered
from the procedure prior to the first dose of study treatment in the clinical
judgement of the investigator
b. Significant traumatic injury within 3 weeks before the start of C1D1 (unless
all wounds must be fully healed prior to Day 1)
c. Expected major surgery while the investigational agent is being administered
or within 6 months after the last dose of study treatment
10. 
Participant has at screening:
a. Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg)
Note: Participants with a prior history of HBV demonstrated by positive hepatitis
B core antibody are eligible if they have at screening 1) a negative HBsAg and 2)
a HBV DNA (viral load) below the lower limit of quantification, per local testing.
Participants with a positive HBsAg due to recent vaccination are eligible if HBV
DNA (viral load) is below the lower limit of quantification, per local testing.
b. Positive hepatitis C antibody (anti-HCV [hepatitis C virus])
Note: Participants with a prior history of HCV, who have completed antiviral
treatment and have subsequently documented HCV RNA below the lower limit of
quantification per local testing are eligible.
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c. Other clinically active infectious or non-infectious liver disease
11. 
Participant is known to be positive for human immunodeficiency virus (HIV), with 1 or
more of the following:
a. Not receiving highly active antiretroviral therapy (ART)
b. Had a change in ART within 6 months of the start of screening
c. Receiving ART that may interfere with study treatment (consult sponsor for
review of medication prior to enrollment)
d. CD4 count <350 at screening
e. Acquired immunodeficiency syndrome (AIDS)-defining opportunistic
infection within 6 months of start of screening
Not agreeing to start ART and be on ART >4 weeks plus having HIV viral load
<400 copies/mL at end of 4-week period (to ensure ART is tolerated and HIV
controlled).
12. 
Participant has received prior EGFR or cMet-directed therapies.
13. 
Any condition for which, in the opinion of the investigator, participation would not be
in the best interest of the participant (eg, compromise the well-being) or that could
prevent, limit, or confound the protocol-specified assessments.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening
and that the participant continues to meet criteria prior to dosing on C1D1. On C1D1, the
participant’s condition should be consistent with their baseline and the participant should have
taken regular prescribed medication(s), unless instructed otherwise by the study physician. If a
participant's status changes (including laboratory results or receipt of additional medical records)
after Screening but before the first dose of study treatment is given such that he or she no longer
meets all eligibility criteria, supportive treatment may be administered, if necessary, so that
eligibility criteria can be met and laboratory test(s) may be repeated once, to determine if the
participant qualifies for the study. If enrollment criteria are not met after further evaluation, the
participant should be excluded from participation in the study. Participants who are determined to
be eligible for the study due to changes in their condition after initially failing screening must sign
a new ICF. The required source documentation to support meeting the enrollment criteria are noted
in Section 10.2, Appendix 2: Regulatory, Ethical, and Study Oversight Considerations.
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5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study to be eligible for participation:
1. 
Refer to Section 6.8, Concomitant Therapy for details regarding prohibited and
restricted therapy during the study.
2. 
Agree to follow all requirements that must be met during the study as noted in the
Inclusion and Exclusion Criteria (eg, contraceptive requirements).
5.3.1. 
Activity
1. 
Agree to use sun protective measures (such as a hat, sunglasses, protective clothing,
sunscreen), limit prolonged exposure to natural sunlight, and avoid artificial sunlight
(tanning beds or phototherapy) from baseline until the last dose of study treatment. Use
broad-spectrum sunscreen (containing titanium dioxide or zinc oxide) with a skin
protection factor (SPF) ≥30.
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not enrolled into
the study, the date seen and age at initial informed consent will be used.
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened. Rescreened participants should be assigned a new participant number that is different
from the initial screening.
6. 
STUDY TREATMENT AND CONCOMITANT THERAPY
Refer to the Investigational Product Preparation Instructions (IPPI) or the study Site
Investigational Product and Procedures Manual (SIPPM) for detailed guidance on amivantamab
dosage and administration.
6.1. 
Study Treatment Administered
Study treatment administration must be captured in the source documents and the electronic case
report form (eCRF).
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Amivantamab is supplied for this study in a glass vial containing 350 mg/vial with concentration
of 50 mg/mL in a 7 mL vial. Amivantamab will be manufactured and provided under the
responsibility of the sponsor. Refer to the IB for a list of excipients. The IV infusion will be
prepared at the site in 250 mL of diluent (Refer to IPPI).
The initial dosage of amivantamab will be based on the participant's body weight at screening:
1,050 mg (if body weight is <80 kg) or 1,400 mg (if body weight is ≥80 kg). Additional higher
dosing, if recommended by the CTMT, will also be based on the participant’s body weight:
1,750 mg (if body weight is <80 kg) or 2,100 mg (if body weight is ≥80 kg). Qualified site
personnel will administer amivantamab as an IV infusion in 28-day cycles as follows:
Cycle 1: Once weekly (with the first dose split over Day 1 [350 mg] and Day 2 [700 mg if body
weight is <80 kg or 1,050 mg if body weight is ≥80 kg]). For additional higher dosing, once weekly
(with the first dose split over Day 1 [350 mg] and Day 2 [1.400 mg if body weight is <80 kg or
1,750 mg if body weight is ≥80 kg]).
Cycles 2+: Days 1 and 15 of each cycle
Amivantamab will be administered intravenously using the escalating infusion rate regimen as
specified in the IPPI. At the discretion of the investigator, the infusion rate can be slower, but not
faster than specified in the IPPI. The product must be infused via a peripheral vein for all Cycle 1
doses; infusion via central line is allowed for subsequent dosing starting with the C2D1 dose.
Infusion durations that exceed the planned length of time due to IV bag overfill, minor equipment
calibration factors, and/or participant factors not under the control of administering personnel will
not be considered protocol deviations. The actual infusion time should be accurately recorded.
Refer to IPPI for information describing the stability and administration of amivantamab.
Amivantamab must be administered according to the procedures described in the IPPI and clinical
protocol, under the supervision of qualified staff. Additional guidance is provided below:
 On Day 1 of each cycle, review results of hematology and chemistry laboratory assessments
before administering study treatment.
 Amivantamab must be diluted as described in the IPPI prior to infusion
 Do not mix or dilute amivantamab with other drugs.
 Amivantamab must not be administered as an IV push or bolus.
Dose and administration schedule may be adjusted based on CTMT recommendations during
Phase 2a part.
As there are investigations ongoing assessing different amivantamab formulations and schedules,
participants in Phase 2b cohorts may receive amivantamab according to a different schedule or
route of administration. Any such change would only be made after approved protocol amendment.
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Clinical Protocol 61186372GIC2001 Amendment 2
 
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6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
All study treatment must be stored at controlled temperatures according to the requirements on the
label. Amivantamab must be protected from light prior to use. Refer to the pharmacy
manual/SIPPM for additional guidance on study treatment preparation, handling, and storage.
Accountability
The investigator is responsible for ensuring that all study treatment received at the site is
inventoried and accounted for throughout the study. The study treatment administered to the
participant must be documented on the treatment accountability form. All study treatment will be
stored and disposed of according to the sponsor's instructions. Study site personnel must not
combine contents of the study treatment containers.
Study treatment must be handled in strict accordance with the protocol and the container label and
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate
environmental conditions. Unused study treatment must be available for verification by the
sponsor's study site monitor during on-site monitoring visits. The return to the sponsor of unused
study treatment will be documented on the study treatment return form. When the study site is an
authorized destruction unit and study treatment supplies are destroyed on-site, this must also be
documented on the study treatment return form.
Potentially hazardous materials containing hazardous liquids, such as used ampules, needles,
syringes, and vials, should be disposed of immediately in a safe manner and therefore will not be
retained for treatment accountability purposes.
Study treatment should be dispensed under the supervision of the investigator or a qualified
member of the study site personnel, or by a hospital/clinic pharmacist. Study treatment will be
supplied only to participants participating in the study. Returned study treatment must not be
dispensed again, even to the same participant. Study treatment may not be relabeled or reassigned
for use by other participants. The investigator agrees neither to dispense the study treatment from,
nor store it at, any site other than the study sites agreed upon with the sponsor. Further guidance
and information for the final disposition of unused study treatments are provided in the study
reference manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Treatment Allocation
Procedures for Randomization
Randomization will not be used in this study. Participants will be assigned to treatment in the order
in which they qualify for this study.
Blinding
As this is an open-label study, blinding procedures are not applicable.
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6.4. 
Study Treatment Compliance
The study personnel at the study site will account for all study treatments dispensed and for
appropriate return. The certificates of delivery and return should be signed.
Amivantamab is to be prescribed only by the principal investigator or a qualified physician listed
as a subinvestigator on required forms. The study treatment may not be used for any purpose other
than that outlined in this protocol, including other human studies, animal investigations, or in vitro
testing. Amivantamab will be administered as an IV infusion by qualified study site personnel and
the details of each administration will be recorded in the eCRF (including date, start, and stop
times of the IV infusion and volume infused). Dispensing of all study treatment must also be
recorded in the participant’s source documents.
Administration of pre-infusion medications will be documented in the source documents and eCRF.
6.5. 
Dose Delay Guidance
In instances where treatment delay is indicated, treatment with amivantamab may be delayed until
recovery of toxicity to a level allowing continuation of therapy. A participant for whom treatment
was delayed should be assessed at least weekly to ensure adequate supportive care is being
administered and to assess for improvement of toxicity. For majority of clinically significant
toxicities dose delay and dose modifications should occur as per the guidelines described below
(Section 6.6). If dose delay is continued for more than 28 days, consult with the medical monitor
before restarting study treatment.
6.6. 
Dose Modification Guidance
Any dose/dosage adjustment should be overseen by medically qualified study site personnel
(principal or sub-investigator unless an immediate safety risk appears to be present). The following
guidance should be followed for dose delay and modification of the amivantamab based on the
toxicity grade of AEs other than IRRs (Section 6.6.1), rash (Section 6.6.2), paronychia
(Section 6.6.3), liver chemistry abnormalities (Section 6.6.4), and pulmonary toxicity
(Section 6.6.5). When possible, the medical monitor should be notified prior to dose modifications.
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Status: Approved,  Date:  16 August 2022
Table 3: 
Guidance for Amivantamab Dose Delay and Modification for Toxicities (Other Than Rash,
Paronychia, Infusion-related Reaction, or Pulmonary Toxicity)
Toxicity 
Gradea
Actionb 
Length of
Dose delayd 
Dose Modification of Amivantamab after Resolution of
Adverse Eventc
1 
None 
N/A
Continue at current dose level. Consider supportive care
according to local standards as appropriate.
2 
None or 
consider dose
delay 
≤7 days 
Restart at current dose level.
>7 days 
Consider restart at next lower dose level.
3 
Dose delay
≤7 days 
Restart at current dose level.
>7 days 
Restart at next lower dose level.
4 
Dose delay 
≤7 days 
Restart at next lower dose level
>7 days
Consider permanently discontinuing amivantamab. Participants
considered by the investigator and sponsor to be benefiting from
treatment may be continued at a lower dose upon satisfactory
resolution of the toxicity.
a. Per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
b. For all toxicities, consider supportive care according to protocol or local standards (if no protocol guidance
provided), as appropriate.
c. Resolution defined as: Grade ≤1 or back to baseline.
d. If dose dela y occurs for more than 1 cycle, contact the medical monitor to discuss retreatment.
 
In case a dose modification is necessary, the study treatment will be administered as follows:
 
If the CTMT recommends exploration of higher doses of amivantamab and a dose modification
is necessary, the study treatment will be administered as follows:
 
Table 5: 
Dose Modification for Amivantamab (1750mg/2100mg starting dose)*
Dosage Level
Amivantamab
Participant <80 kg
Participant ≥80 kg
0 (startin  g dose) 
1750 m  g Q2W 
2100 m  g Q2W 
-1 
1400 m  g Q2W 
1750 m  g Q2W
-2 
1050 m  g Q2W 
1400 m  g Q2W 
-3 
Discontinue 
Discontinue
*Will be explored per CTMT recommendation
Q2W=ever y 2 weeks (eg, Da y 1 and Da y 15 of each 28-da y cycle)
The following sections provide additional guidance for the prevention, monitoring, and
management of toxicities that have been reported with amivantamab.
Table 4: 
Dose Modification for Amivantamab (1050mg/1400mg starting dose)
Dosage Level
Amivantamab
Participant <80 kg 
Participant ≥80 kg
0 (startin  g dose) 
1050 m  g Q2W 
1400 m  g Q2W
-1 
700 m  g Q2W 
1050 m  g Q2W
-2 
350 m  g Q2W 
700 m  g Q2W 
-3 
Discontinue 
Discontinue
Q2W=ever y 2 weeks (eg, Da y 1 and Da y 15 of each 28-da y cycle)
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Status: Approved,  Date:  16 August 2022
6.6.1. 
Infusion-related Reactions
Infusion-related reactions have been commonly observed during treatment with amivantamab,
predominantly with the first exposure on C1D1, and typically within the first 90 minutes of the
infusion. The majority of IRRs are Grade 1 or 2. Refer to Summary of Data and Guidance for
Investigators in the current version of the IB for amivantamab. The guidelines described here are
related to the safe administration of amivantamab during initial dosing.
During the amivantamab infusions, participants should be clinically monitored at regular intervals
(including an assessment prior to the start of infusion) as specified in the Schedule of Activities
(Table 1). The monitoring should include heart rate, blood pressure, temperature, respiratory rate,
and oxygen saturation measurements.
Particularly with the initial dose (C1D1 and C1D2), participants should be educated on 1) the
likelihood of experiencing an IRR with the initial dose, 2) the symptoms to anticipate (which
include chills, dyspnea, chest discomfort, fever, flushing, among others), 3) that they should alert
nursing staff if they experience these symptoms, and 4) that the experience of an IRR will not
preclude further therapy with amivantamab. Participants must be monitored closely for early signs
and symptoms indicative of an acute IRR. Even with mild symptoms, the study treatment infusion
should be interrupted immediately when the initial dose is administered (ie, C1D1 or C1D2), as
described in the tables below, to prevent more serious grade IRRs from occurring. Trained clinical
personnel should be prepared to intervene in the event of IRRs. Resources necessary for
resuscitation (ie, agents such as epinephrine, aerosolized bronchodilator, IV antihistamines, IV
corticosteroids; medical equipment such as oxygen, airway management equipment including
suction, and a defibrillator) must be readily available.
Prevention of Infusion-related Reactions
Required prophylaxis for IRRs is described in Section 6.8.1.
Treatment of Infusion-related Reactions
Participants who experience early symptoms of IRRs, manifesting as fever, chills, rigors,
bronchospasm, headache, rash, pruritus, arthralgia, hypo- or hypertension or other symptoms, must
have their amivantamab infusion interrupted, if indicated, and the symptoms managed according
to the recommendations provided in Table 6. With the initial dose of amivantamab (C1D1 and
C1D2), interrupting the infusion should be considered even with mild symptoms to prevent more
severe manifestations of IRR. All Grade 3 or 4 IRRs should be reported within 24 hours to the
medical monitor.
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Status: Approved,  Date:  16 August 2022
Table 6: 
Management of Infusion-related Reactions
Toxicity Grade* 
Treatment 
Premedication 
at
Subsequent Dosing
Grade 1 
Mild reaction 
Monitor participant as medically indicated until recovery 
from symptoms. If occurring with initial dose (ie, C1D1 
or C1D2), consider early infusion interruption to prevent 
more severe symptoms.
Antihistamine, antipyretic,
and glucocorticoid, as per
Table 8.
Grade 2  
Mild 
to 
moderate 
reaction; 
therapy 
or 
infusion interrupted 
but responds promptly to 
symptomatic treatment 
Interrupt infusion 
If 
clinically 
indicated, 
start 
IV 
fluids; 
give 
diphenhydramine 50 mg (or equivalent) IV and/or 
paracetamol (acetaminophen) 650 to 1,000 mg; consider
corticosteroids and bronchodilator therapy; monitor 
participant closely until recovery from symptoms 
 
First interruption for infusion-related reaction:
Restart infusion at 50% of the rate at the time of
interruption: if no further evidence of infusion-related
reaction after 30 minutes, the rate may be increased to
100% of the infusion rate at the time of interruption;
monitor participant closely.
 
Second interruption for infusion-related reaction:
Stop and consider discontinuation of further study
treatment at that visit; administer diphenhydramine 50 mg
IV or equivalent and monitor participant until resolution
of symptoms. The amount of study treatment infused
must be recorded in the eCRF. If continuing
administration after the second interruption, restart
infusion at 50% of the rate at the time of the second
interruption. If no further evidence of infusion-related
reaction after 30 minutes, the rate may be increased to
100% of the infusion rate at the time of interruption;
monitor participant closely.
Antihistamine, antipyretic,
and glucocorticoid, as per
Table 8.
 
Consider meperidine if
participant 
experiences
chills and rigors.
Grade 3 or 4 
Severe reaction 
 
Grade 3: prolonged (ie, 
not rapidly responsive to 
symptomatic medication 
and/or brief interruption 
of infusion); recurrence 
of symptoms following
initial 
improvement; 
hospitalization indicated 
for 
other 
clinical 
sequelae 
(eg, 
renal 
impairment, pulmonary 
infiltrates) 
 
Grade 
4: 
life- 
threatening; pressor or
ventilator 
support
indicated
Stop infusion  
Start IV saline infusion; recommend bronchodilators, 
supplemental oxygen; epinephrine 0.2 to 1 mg of a 1:1000 
solution for subcutaneous administration or 0.1 to 
0.25 mg of a 1:10000 solution injected slowly for IV 
administration, and/or diphenhydramine 50 mg IV with 
methylprednisolone 100 mg IV (or equivalent), as needed 
(other drugs as appropriate).  
 
Participant should be monitored until the investigator is
comfortable that the symptoms will not recur.
Investigators should follow their institutional guidelines
for the treatment of anaphylaxis. In the case of late-
occurring hypersensitivity symptoms (eg, appearance of
a localized or generalized pruritus within 1 week after
treatment), symptomatic treatment may be given (eg, oral
antihistamine, or corticosteroids), as appropriate.
Based on severity of
symptoms, 
consider
permanent discontinuation
of 
study 
treatment.
Consultation with Medical
Monitor required before
continuing 
with
subsequent dosing.
eCRF=electronic case report form; IRR=infusion-related reaction; IV=intravenous.
*Per National Cancer Institute - Common Terminology Criteria for Adverse Events Version 5.0
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Status: Approved,  Date:  16 August 2022
6.6.2. 
Rash-related Adverse Events
The prevention and management of EGFR inhibitor-induced rash-related TEAEs can be conducted
in accordance with local institutional guidelines or according to the recommendations below.
Prophylaxis Recommendations
The prophylactic regimen can be managed according to local practice and guidelines; however,
these should include the following:
 Avoid exposure to sunlight.
 Wear protective clothing (including hat, sunglasses, etc).
 Use broad-spectrum sunscreen with an SPF of ≥30 and reapply as necessary. Ultraviolet A
light can penetrate glass; therefore, sunscreen should also be worn indoors and in vehicles if
exposed to direct sunlight. Recommended active sunscreen ingredients are zinc oxide and/or
titanium dioxide.
 Apply alcohol-free emollient cream or ointments (eg, glycerin, cetomacrogol, or
ceramide-based cream) or skin moisturizer on dry areas of the body. These topical agents can
be applied on a daily basis starting on Day 1 and more often as needed. Ideal time for
application is after bathing. Creams and ointments are preferred over gels, lotions and oils.
Reactive Management Recommendations
It is strongly recommended that participants who develop rash/skin toxicities receive evaluations
for management on the specific AE.
 Consider consultation with a dermatologist, especially if the rash is Grade 3, atypical in
appearance or distribution, or does not improve within 2 weeks (for Grade 2 rash).
 Initiate a topical corticosteroid (cream or ointment) twice daily
 
Examples to use for face: betamethasone valerate 0.05%, hydrocortisone valerate 0.2%,
or desonide 0.05%
 
Examples to use for body: betamethasone valerate 0.1%, triamcinolone acetonide 0.1%
 If not already initiated for prophylaxis, initiate systemic antibiotic (such as doxycycline
100 mg twice daily, minocycline 100 mg twice daily, or cephalexin 500 mg twice daily), or
increase the dosing if already administered.
 If an associated skin infection is suspected, obtain bacterial and fungal cultures followed by
adjustment of antibiotic or antifungal therapy, based upon culture and susceptibility
determination.
 For skin fissures, use of Monsel’s solution (ferric subsulfate solution), silver nitrate, or zinc
oxide cream is recommended.
 For xerosis, fragrance-free moisturizing creams or sprays are recommended.
 For desquamation, emollients and mild soap are recommended.
 After the rash is controlled, consider gradually tapering the antibiotic.
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Amivantamab  JNJ-61186372  
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Status: Approved,  Date:  16 August 2022
A suggested algorithm for stepwise management of rash is provided in Table 7.
Table 7: 
Suggested Algorithm for Management of Rash
Gradea  
Management 
Dose Adjustmentb,c
1 
 Initiate reactive management as above 
 Reassess after 2 weeks 
 Continue current dose of study
treatment
2 
 Initiate reactive management as above 
 Reassess after 2 weeks 
 Continue current dose of study
treatment
3 or 4 
 Initiate reactive management as above 
 Start moderate strength topical corticosteroidsd and 
systemic antibiotics as above, plus systemic prednisone 
(0.5 mg/kg) for 7 days 
 Consider low doses of acitretin or isotretinoin 
(20-30 mg/day) 
 Reassess after 2 weeks 
 Consider dermatology consultation and manage rash per 
recommendation
 Temporarily dose delay of study
treatment until rash improves to
≤Grade 2
 For guidance on dose delay of
study 
treatment 
and 
dose
modification, refer to Table 3 and
Table 4. For additional higher dosing,
refer to Table 5.
Severe 
bullous, 
blistering,
or
exfoliating
skin
conditions
including
toxic
epidermal
necrolysis
(TEN)
 Consult 
dermatologist 
and 
manage 
rash 
per 
recommendation. 
 Permanently 
discontinue
amivantamab
a. Grading per Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
b. If amivantamab must be skipped due to toxicity for 2 consecutive doses, then study treatment cannot be restarted
without consultation from the Medical Monitor. Participants considered by the investigator and sponsor to be
benefiting from treatment may be continued, potentially at a lower dose upon satisfactory resolution of the
toxicity.
c. Resolution defined as: ≤Grade 1 toxicity or back to baseline.
d. For example, hydrocortisone 2.5% cream or fluticasone propionate 0.5% cream.
Scalp Rash
Atypical scalp rash and associated infection may develop over time with the use of EGFR
inhibitors. Treatment options include:
 A topical steroid shampoo (eg, clobetasol 0.05%), or an anti-dandruff shampoo with
anti-inflammatory, antibacterial, and antifungal properties (eg, ketoconazole, selenium sulfide
[Selsun®], zinc pyrithione [Head and Shoulders®], or Ciclopirox). These shampoos should be
used twice/week, massaging into scalp, leaving on for 2 to5 minutes, and then rinsing.
 Application of a steroid lotion may also be effective (eg, betamethasone valerate 0.1% lotion,
mometasone furoate 0.1% lotion, or betamethasone dipropionate 0.05% lotion).
 Initiation of a systemic antibiotic (eg, doxycycline 100 mg twice daily, minocycline 100 mg
twice daily) may also be used to treat acute scalp infection.
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Amivantamab  JNJ-61186372  
Clinical Protocol 61186372GIC2001 Amendment 2
 
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Status: Approved,  Date:  16 August 2022
Of note, while wearing hats to avoid sun damage to the scalp is suggested in a prophylactic setting,
avoiding any headwear for a participant with established scalp rash is strongly recommended to
prevent further spread of the rash.
6.6.3. 
Paronychia
Paronychia is a well-recognized toxicity associated with anti-EGFR therapeutics. As a result, there
are recommendations that should be followed to prevent or minimize participant discomfort
associated with this toxicity.
Prophylaxis Recommendations
 Avoid skin irritants.
 Cushion affected areas.
 Wear gloves and comfortable shoes.
 Apply moisturizer to nails.
Reactive Management Recommendations
Grade 1 paronychia:
 Use antimicrobial soaks once or twice daily: warm bowl of water+5 mL of bleach (sodium
hypochlorite) or vinegar (DO NOT USE BOTH TOGETHER); soak for 5 minutes, rinse, pat
dry, and then apply either emollient or topical treatments below.
 Apply topical antiseptic (povidone-iodine 10% solution) twice daily.
 Apply a topical steroid ointment (eg, betamethasone valerate 0.1% or clobetasol) or topical
calcineurin inhibitor (eg, tacrolimus 0.1%) twice daily. If using topical steroid, once resolved,
switch to topical calcineurin inhibitor daily or decrease to twice per week to maintain.
Grade 2 or 3 paronychia:
 In addition to the guidance for Grade 1 paronychia above:
 
Apply topical antibiotic/antifungal agent (eg, mupirocin, fusidic acid, clotrimazole, or
miconazole) twice daily.
 
Initiate oral antibiotic for at least 14 days (eg, doxycycline 100 mg twice daily,
minocycline 100 mg twice daily, or cephalexin 500 mg twice daily).
 
Consult a dermatologist or podiatrist.
6.6.4. 
Liver Chemistry Abnormalities
Liver chemistry should be monitored according to the Schedule of Activities (Table 1) and study
treatment should be delayed for any liver chemistry abnormality of ≥Grade 3 severity (refer to
Table 3). In addition, if the following criteria are observed, study treatment should be delayed, and
the event should be reported as a serious adverse event (SAE) to the sponsor within 24 hours:
a) ALT or AST ≥3×ULN and bilirubin ≥2×ULN (>35% direct bilirubin) (or ALT ≥3×ULN and
international normalized ratio [INR] >1.5, if INR measured).
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Amivantamab  JNJ-61186372  
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Status: Approved,  Date:  16 August 2022
 
Exception to the bilirubin elevation is made if the participant has Gilbert’s disease and
the elevated bilirubin is predominantly unconjugated.
b) ALT or AST ≥3×ULN (if baseline was normal) with the concurrent appearance of symptoms
suggestive of ongoing severe liver injury, such as fatigue, nausea, vomiting, right upper
quadrant pain or tenderness, fever, rash, and/or new eosinophilia (>5%).
In the event abnormalities of liver function tests require the dose delay of study treatment, liver
chemistry should be repeated within 1-3 days and until abnormal values resolve/return to baseline.
If the liver function test criteria either a) or b) above are met, etiology of the liver chemistry
abnormality should be investigated, as described below. If no alternative etiology of liver toxicity
is identified, study treatment should be permanently discontinued.
Liver Event Follow-up Requirements
The following follow-up assessments should be conducted for any participant meeting liver
chemistry stopping criteria:
 Monitor liver chemistries (ALT, AST, alkaline phosphatase, bilirubin [including bilirubin
fractions], and INR), creatinine phosphokinase, and lactate dehydrogenase, 1 to 2 times per
week until resolution, stabilization, or return to participant’s baseline values
 Monitor clinical condition closely
 Draw blood samples for unscheduled PK analysis at timepoints when liver chemistry is
assessed
 Record use of concomitant medications, acetaminophen, herbal remedies, other
over-the-counter medications, or known hepatotoxins
 Record alcohol use in the eCRF
 Check the viral hepatitis serology as appropriate and include:
 
Hepatitis A IgM antibody
 
Hepatitis B surface antigen and hepatitis B core antibody (IgM)
 
Hepatitis C RNA
 
Hepatitis E IgM antibody
 
Cytomegalovirus IgM antibody
 
Epstein-Barr viral capsid antigen IgM antibody (or equivalent test)
 Assess anti-nuclear antibody, anti-smooth muscle antibody, and type 1 anti-liver kidney
microsomal antibodies
 Conduct liver imaging (ultrasound, magnetic resonance imaging [MRI], or computerized
tomography [CT]) to evaluate liver disease
 Refer to a specialist as appropriate
Rechallenge Criteria
Resumption of study treatment may be considered if all the following criteria are met:
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Status: Approved,  Date:  16 August 2022
 Hy’s Law has been excluded.
 A reversible underlying cause not associated with study treatment (eg, other hepatobiliary
disorder such as cholelithiasis, etc, alcohol use, or concomitant medication) is clearly identified
and agreed upon in consultation with the Medical Monitor.
 Liver chemistry abnormalities have resolved, or values have returned to baseline.
6.6.5. 
Pulmonary Toxicity
The etiology of any clinically significant change in respiratory status and/or non-oncogenic
radiological appearance suggestive of lung inflammation (eg, ground glass opacities) should be
investigated in accordance with local practice/guidelines to rule out early ILD/pneumonitis. The
recommended evaluations include:
 Detailed focused history reviewing respiratory status and exercise tolerance.
 Focused physical exam including full assessment of vital signs (with pulse oximetry).
 Unscheduled radiological assessment, including chest x-ray or CT scan (high-resolution CT is
preferred).
Documentation of ILD/pneumonitis of any grade should prompt withholding study treatment and
contacting the medical monitor. For symptomatic pneumonitis (Grade 2 and above), treatment with
steroids should be initiated in addition to withholding of study treatment. Confirmation of
ILD/pneumonitis of any grade should prompt discontinuation of study treatment and should be
reported as an SAE (see Section 8.3.1). If the ILD/pneumonitis is attributed to prior radiation,
participant can restart after discussion with the sponsor’s medical monitor. Pertinent radiological
images and reports should be submitted to the sponsor.
6.7. 
Treatment of Overdose
There are no data on overdose from studies of amivantamab.
In the event of an overdose, the investigator or treating physician should:
 Contact the medical monitor immediately.
 Closely monitor the participant for AE/SAE and laboratory abnormalities.
 Document the quantity of the excess dose as well as the duration of the overdosing in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in
consultation with the medical monitor based on the clinical evaluation of the participant.
6.8. 
Concomitant Therapy
Concomitant therapies administered up to 28 days before first dose of study treatment must be
recorded at screening and continued until 30 days after the last dose of study treatment or start of
subsequent anticancer therapy, whichever is first. Concomitant therapies should also be recorded
beyond 30 days only in conjunction with SAEs considered related to study treatment. For
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participants with Grade 3 or 4 AEs considered related to study treatment, record concomitant
medications through the end of follow-up of that AE.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special
diets, exercise regimens, or other specific categories of interest) different from the study treatment
must be recorded in the eCRF. Modification of an effective preexisting therapy should not be made
for the explicit purpose of entering a participant into the study.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
6.8.1. 
Amivantamab Pre-infusion and Post-infusion Medications
6.8.1.1. 
Amivantamab Pre-infusion Medications
Required and optional amivantamab pre-infusion medications for IRRs are summarized in Table 8.
Table 8: 
Amivantamab Pre-infusion Medications
Medication 
Dose
Route of
Administration
Recommended Dosing
Window Before
Infusion 
Cycle/Day
Required Pre-infusion Medicationsa,b
Glucocorticoid
Dexamethasone (10 mg) or
Methylprednisolone (40 mg)
IV  
 
45 to 60 minutes
C1D1
C1D2
Antihistamined 
Diphenhydramine (25 to 50 mg)
or equivalent
IV 
15 to 30 minutes
All
Oral 
30 to 60 minutes
Antipyreticd 
Paracetamol (acetaminophen 650 to
1,000 mg) or equivalent
IV  
15 to 30 minutes
All
Oral 
30 to 60 minutes
Optional Pre-infusion Medicationsa
Glucocorticoidc,d 
Dexamethasone (10 mg)
Methylprednisolone (40 mg) 
IV 
45 to 60 minutes 
C1D8
and beyond
Oral 
60 to 90 minutes 
H2 antagonist 
Ranitidine (50 mg) or equivalent 
IV 
15 to 30 minutes 
Any
Antiemetic d
Ondansetron (16 mg) or equivalent 
IV 
15 to 30 minutes
Any
Ondansetron (8 mg) or equivalent 
Oral 
15 to 30 minutes
C Cycle; D Day X; IV intravenous.
a. If a medication noted in this table is not locally available, a similar medication and dose may be substituted and
administered per local guidelines.
b. Participants for whom required medications are contraindicated should explore alternative medications with their study
physician. If alternative medications are not suitable for the intent above, participants are not required to take the
corresponding medication.
c. Beginning with C1D8, optional predose steroids may be administered if clinically indicated for participants who
experienced an infusion related reaction on C1D1 or C1D2.
d. Either IV or oral route is selected for antihistamine, antipyretic, glucocorticoid and antiemetic medications.
6.8.1.2. 
Amivantamab Post-infusion Medications
Optional amivantamab post-infusion medications may be prescribed and continued for up to
48 hours after the infusion if clinically indicated, at the discretion of the investigator as described
in Table 9.
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Table 9: 
Amivantamab Post-infusion Medications
Medication 
Dose
Route of 
Administration 
Administration 
Instructions 
Cycle/
Day
Optional Post-infusion Medicationsa
Glucocorticoid 
Dexamethasone (10 mg) or comparable
corticosteroid 
IV or Oral
As clinically
indicated
Any
Antihistamine 
Diphenhydramine (25-50 mg) or equivalent 
IV or Oral 
As clinically
indicated
Any
Antipyretic 
Paracetamol (acetaminophen) (650-1,000 mg) 
IV or Oral 
As clinically
indicated
Any
Opiates 
Meperidine (25-100 mg) 
IV or Oral 
As clinically
indicated
Any
Antiemeticb 
Ondansetron (8-16 mg) or equivalent;
lon g or short actin  g agents 
IV
As clinically
indicated
Any
Ondansetron (8 mg) or equivalent; 
long or short acting agents
Oral
IV intravenous.
a. Optional medications can be used prophylactically as clinically indicated. If a medication noted in this table is not locally
available, a similar medication and dose may be substituted and administered per local guidelines.
b.  Either IV or oral route is selected for antiemetic medications.
6.8.2. 
Prohibited or Restricted Medications and Therapies
The following concomitant medications and therapies are prohibited during the study. The sponsor
must be notified as soon as possible of any instances in which prohibited therapies were
administered.
 Any chemotherapy, systemic anticancer therapy, or experimental therapy (other than study
treatments). Hormonal treatments as specified in exclusion 5 are allowed.
 Radiotherapy to tumor lesions being assessed for tumor response prior to radiographic
progression
 Use of live or live attenuated vaccines is prohibited. COVID-19 vaccine is not considered as
live or live attenuated vaccines but the administration of COVID-19 vaccine should be avoided
on the same day of study drug administration.
 Due to the potential for hypomagnesemia associated with EGFR inhibitors, concomitant
medications that may decrease serum magnesium should be avoided if possible.
7. 
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Treatment
A participant's study treatment must be discontinued if:
 The participant withdraws consent to receive study treatment
 The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the best
interest of the participant to discontinue study treatment
 The participant becomes pregnant (refer to Section 10.4, Appendix 4: Contraceptive and
Barrier Guidance).
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 Noncompliance with study treatment or procedure requirements
 Documented radiographic (RECIST, Version 1.1) disease progression, unless treatment
beyond disease progression has been approved by the medical monitor
 General or specific changes in the participant’s condition that render the participant
unacceptable for further treatment in the judgement of the investigator
 
The participant receives concurrent (non-protocol) anticancer treatment
If a participant discontinues study treatment for any reason, then the EOT assessments should be
obtained according to the Schedule of Activities and follow-up visits should continue after study
treatment is discontinued. If the initiation of the subsequent anticancer therapy is required prior to
EOT, EOT must be completed prior to the initiation of the subsequent anticancer therapy. Study
treatment assigned to the participant who discontinued study treatment may not be assigned to
another participant. Additional participants will not be entered in the study.
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 Lost to follow-up
 Withdrawal of consent
 The sponsor discontinues the study
When a participant withdraws before study completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. If the reason for withdrawal from the study
is withdrawal of consent, then no additional assessments are allowed.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply (eg, consult with family members, contacting the participant’s other physicians,
medical records, database searches, use of locator agencies at study completion) as local
regulations permit.
7.2.1. 
Withdrawal From the Use of Research Samples
Withdrawal From the Use of Samples in Future Research
The participant may withdraw consent for use of samples for research (refer to Long-term
Retention of Samples for Additional Future Research in Section 10.2, Appendix 2: Regulatory,
Ethical, and Study Oversight Considerations). In such a case, samples will be destroyed after they
are no longer needed for the clinical study. Details of the sample retention for research are
presented in the main ICF.
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7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to first dose of study
treatment, attempts should be made to obtain contact information from each participant, eg, home,
work, and mobile telephone numbers and email addresses for both the participant as well as
appropriate family members.
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 The study site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). These contact attempts should be documented in the participant’s
medical records.
 Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Section 1.3) summarizes the frequency and timing of the
measurements applicable to this study.
The total blood volume collected for the study will be approximately 25 mL (screening), 105 mL
(Cycle 1), 75 mL (Cycle 2), and 30 mL (for each cycle beyond Cycle 3 and EOT).
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.
Refer to the Schedule of Activities (Section 1.3) for the timing and frequency of all sample
collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples
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must be under the specified and where applicable, controlled temperature conditions as indicated
in the laboratory manual.
Study-specific Materials
The investigator will be provided with the following supplies:
 Clinical Protocol
 IB
 IPPI and SIPPM
 Laboratory manual and kits
 NCI-Common Terminology Criteria for Adverse Events (CTCAE) Version 5
 RECIST guidelines Version 1.1
 Electronic data capture (eDC) manual
 Sample ICF
 Wallet cards
 Study treatment
8.1. 
Efficacy Assessments
8.1.1. 
Disease Assessments
Disease assessments will be performed as described in the Schedule of Activities (Table 1)
regardless of any dose modifications. More frequent radiologic assessments are allowed if
clinically indicated.
Computerized tomography scan of the chest (including the supraclavicular region), abdomen,
pelvis, and any other disease location(s), if clinically indicated, should be performed with an IV
contrast agent. Participants not able to undergo CT scans with IV contrast (eg, due to allergy or
renal insufficiency) may have non-contrast CT of the thorax and MRI of the abdomen and pelvis
with IV contrast at baseline and during the study if approved by the sponsor. Contraindications to
the CT scan with IV contrast that develop post-baseline should be discussed with the medical
monitor. Identical methodology should be used for disease assessment at baseline and throughout
the course of the study to characterize each identified and reported lesion to document disease
status. Techniques other than CT or MRI may be used based upon investigator’s judgement, local
standard of care, and RECIST Version 1.1 guidelines for the use of these alternative techniques.
The baseline disease assessments should be performed as close as possible to the start of treatment,
but no more than 28 days prior to the first dose. Subsequent assessments should be performed at
6 weeks (+1 week) after initiation of study treatment administration, then every 6 weeks (±1 week)
for the first 12 months and then every 12 weeks (±1 week) until objective radiographic disease
progression. Timing for each disease assessment is relative to the first dose of study treatment
administration, regardless of dose modifications, and will continue until disease progression. If an
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assessment is performed outside of the scheduled visit and the participant has not progressed, every
attempt should be made to perform the subsequent assessment at their scheduled visit timepoint.
Any other site at which new disease is suspected should also be imaged.
If a participant achieves partial response (PR) or complete response (CR), every effort should be
made to confirm the response after, but as close to, 4 weeks of entering PR or CR instead of
predefined 6 weeks. Response may also be assessed by an Independent Review Committee (IRC)
for the central confirmation.
If the investigator is in doubt as to whether progression has occurred, particularly with response to
nontarget lesions or the appearance of a new lesion, treatment should be continued until the next
scheduled assessment (or sooner if clinically indicated) and reassess the participant’s status. If the
repeated scans confirm progression, then the date of the initial scan should be declared as the date
of progression. To achieve “unequivocal progression” on the basis of nontarget lesions, there must
be an overall substantial worsening in nontarget lesions such that, even in the presence of stable
disease or PR in target lesions, the overall tumor burden has increased sufficiently to merit
discontinuation of therapy. A modest “increase” in size of 1 or more nontarget lesions is usually
not sufficient to qualify for unequivocal progression. If symptomatic deterioration (on the basis of
global deterioration of health status) is recorded as the basis for determining disease progression,
then the clinical findings used to make the determination must be specified in the eCRF and
documented in the source documents. Every effort should be made to document radiographic
progression even after discontinuation of treatment for symptomatic deterioration, but prior to
subsequent therapy, if possible. For participants who discontinue study treatment due to toxicity
or a reason other than objective progressive disease, tumor assessments should be continued per
schedule until radiographic progressive disease is documented.
Participants will have brain MRI scan (CT scan with contrast may also be used to determine the
presence of brain lesions if MRI is contraindicated) at screening to identify any untreated brain
metastases (Exclusion criterion #3). Brain scan is not required with every subsequent disease
assessment, regardless of history of prior brain metastases, and should be performed if clinically
indicated, according to local guidelines and practices.
If a participant is deriving clinical benefit and treatment beyond documented disease progression
is approved by the sponsor’s medical monitor, disease assessments will continue as scheduled and
the investigator and the Medical Monitor will review clinical benefit after each disease assessment.
8.2. 
Safety Assessments
Details regarding the CTMT are provided in Committees Structure in Section 10.2, Appendix 2:
Regulatory, Ethical, and Study Oversight Considerations.
Adverse events will be reported and followed by the investigator as specified in Section 8.3,
Adverse Events, Serious Adverse Events, and Other Safety Reporting, and Section 10.3, Appendix
3: Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other Safety
Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.
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Any clinically relevant changes occurring during the study must be recorded on the AE section of
the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
The study will include the following evaluations of safety and tolerability according to the time
points provided in the Schedule of Activities (see Section 1.3).
8.2.1. 
Physical Examinations
The screening physical examination will include, at a minimum, the participant’s height, weight,
and general appearance and an examination of the skin, ears, nose, throat, lungs, heart, abdomen,
extremities, musculoskeletal system, lymphatic system, and nervous system. On Day 1 of each
cycle, directed physical examinations of involved organs and other body systems, as indicated,
will be performed and participant body weight will be obtained using a scale.
8.2.2. 
Vital Signs
Vital sign measurements will include the following assessments as indicated in the Schedule of
Activities (Table 1):
 
Temperature
 
Heart rate
 
Respiratory rate
 
Oxygen saturation
 
Blood pressure
Blood pressure and heart rate measurements will be assessed in a seated position with a completely
automated device. Manual techniques will be used only if an automated device is not available.
Blood pressure and heart rate measurements should be preceded by at least 5 minutes of rest in a
quiet setting without distractions (eg, television, cell phones).
8.2.3. 
Electrocardiograms
Triplicate electrocardiograms (ECGs), performed locally, will be collected at screening to
determine the eligibility. During the collection of ECGs, participants should be in a quiet setting
without distractions (eg, television, cell phones). Participants should rest in a supine position for
at least 5 minutes before ECG collection and should refrain from talking or moving arms or legs.
Three individual ECG tracings should be obtained as closely as possible in succession, but
approximately 2 minutes apart. The clinical investigator will review the ECG, including ECG
morphology, for immediate management. The results, including measurement of heart rate, QRS
axis, and intervals for PR, uncorrected QT interval (QT), QRS, RR, and QTcF will be entered into
the eCRF. Abnormalities at screening should be included in the medical history.
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QTcF is calculated using the Fridericia's formula: QTcF  QT/(RR)^0.33.
8.2.4. 
ECOG Performance Status
Eastern Cooperative Oncology Group performance status score will be evaluated during the
screening phase to determine the eligibility. Any decline in ECOG performance status score should
be reported as an AE.
8.2.5. 
Clinical Safety Laboratory Assessments
Clinical laboratory assessments will be performed locally. Clinical laboratory tests will be
performed as noted in Table 10.
Table 10: 
Clinical laboratory assessments
Laboratory
Assessments 
Parameters
 
Hematology 
Hemoglobin 
Platelet count 
Absolute neutrophil count
White blood cell (WBCs) absolute count
with differential
Clinical 
Chemistry 
Alkaline phosphatase 
Creatinine 
Aspartate aminotransferase 
Alanine aminotransferase 
Gamma-glutamyl transferase  
Bilirubin (total, direct, indirect) 
Lactic acid dehydrogenase 
Albumin
Total protein
Blood urea nitrogen
Magnesium
Phosphorus
Sodium
Potassium
Calcium
Coagulation 
(screening 
only)
Prothrombin time (in seconds) 
Activated partial thromboplastin time
International normalized ratio
Urinalysis 
(screening 
only) 
Dipstick 
Specific gravity 
pH 
Glucose 
Protein 
Blood 
Ketones 
Bilirubin
Urobilinogen
Nitrite
Leukocyte esterase
Sediment (if dipstick result is abnormal)
Red blood cells
WBCs
Epithelial cells
Crystals
Casts
Bacteria
Serology 
Anti- human immunodeficiency virus (anti-HIV) antibody
hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and hepatitis B
core antibody (HBcAb)
(Participants with a history of hepatitis B virus (HBV) are also required to have HBV DNA
quantification.)
Anti- hepatitis C virus (anti-HCV) antibody
(Participants with a histor y of HCV are required to have HCV RNA quantification.)
The investigator must review the laboratory results, document this review, and record any
clinically relevant changes occurring during the study in the AE section of the eCRF. The
laboratory reports must be filed with the source documents.
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More frequent clinical laboratory tests may be performed as indicated by the overall clinical
condition of the participant or abnormalities that warrant more frequent monitoring.
8.2.6. 
Pregnancy Testing
Serum or urine pregnancy testing will be performed at screening (72 hours before the first dose of
study treatment administration) and as clinically indicated, according to local regulation
requirements, or following the local practice of the center during the treatment period for women
of childbearing potential only. At other times, additional serum or urine pregnancy tests may be
performed, at investigator’s decision.
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
and product quality complaint (PQC), from clinical studies are crucial for the protection of
participants, investigators, and the sponsor and are mandated by regulatory agencies worldwide.
The sponsor has established standard operating procedures in conformity with regulatory
requirements worldwide to ensure appropriate reporting of safety information; all clinical studies
conducted by the sponsor or its affiliates will be conducted in accordance with those procedures.
Adverse events will be reported by the participant (or, when appropriate, by a caregiver or
surrogate) for the duration of the study.
Further details on AEs, SAEs, and PQC can be found in Section 10.3, Appendix 3: Adverse Events,
Serious Adverse Events, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-up, and Reporting.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the participant's last study-related
procedure, which may include contact for follow-up of safety.
Serious Adverse Events
All SAEs as well as PQC, occurring during the study must be reported to the appropriate sponsor
contact person by study site personnel within 24 hours of their knowledge of the event.
Serious adverse events, including those spontaneously reported to the investigator within 30 days
after the last dose of study treatment, must be reported. The sponsor will evaluate any safety
information that is spontaneously reported by an investigator beyond the time frame specified in
the protocol.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form and Safety
Report Form of the eCRF, which must be completed and reviewed by a physician from the study
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site and transmitted to the sponsor within 24 hours. The initial and follow-up reports of an SAE
should be transmitted electronically or by facsimile (fax). Telephone reporting should be the
exception and the reporter should be asked to complete the appropriate form(s) first.
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading
verbal questioning of the participant is the preferred method to inquire about AE occurrence.
Solicited Adverse Events
Solicited AEs are predefined local (at the infusion site) and systemic events for which the
participant is specifically questioned.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned.
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the AE, SAE, or
PQC as fully as possible. This may include additional laboratory tests or investigations,
histopathological examinations, or consultation with other health care professionals.
Adverse events, including pregnancy, will be followed by the investigator as specified in
Section  10.3, Appendix 3: Adverse Events, Serious Adverse Events, Product Quality Complaints,
and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all suspected unexpected serious adverse reactions. The investigator (or sponsor where
required) must report suspected unexpected serious adverse reactions to the appropriate IEC/IRB
that approved the protocol unless otherwise required and documented by the IEC/IRB.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor by the study site personnel within 24 hours of their knowledge of the event
using the appropriate pregnancy notification form. Abnormal pregnancy outcomes (eg,
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using an SAE reporting form. Any participant who becomes
pregnant during the study must discontinue further study treatment.
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Because the effect of the study treatment on sperm is unknown, pregnancies in partners of male
participants included in the study will be reported by the study site personnel within 24 hours of
their knowledge of the event using the appropriate pregnancy notification form.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.
8.3.6. 
Disease-related Events and Disease-related Outcomes Not Qualifying
as Adverse Events or Serious Adverse Events
An event such as disease progression, which is part of the natural course of the disease under study,
does not need to be reported as an AE or SAE term. In this circumstance, death due to disease
progression should be recorded on appropriate case report forms (such as the Death or study
treatment disposition eCRF page). However, disease progression must be reported as an SAE term
if the event was accelerated or greater in severity than expected for the participant, or if the
investigator considers there to be a causal relationship between the event and the study treatment,
protocol design, or protocol procedures.
8.3.7. 
Adverse Events of Special Interest
Adverse events of special interest for this study include pneumonitis/ILD, rash, and IRR.
Additional information may be collected to more fully describe these events. Confirmed cases of
pneumonitis/ILD (regardless of grade) should be reported as SAEs (see Section 8.3.1). All Grade 3
or Grade 4 IRRs should be reported within 24 hours to the medical monitor. Events of rash should
follow standard reporting guidelines.
8.4. 
Pharmacokinetics
Blood samples will be used to evaluate the PK of amivantamab. Serum collected for PK may
additionally be used to evaluate safety or efficacy aspects that address concerns arising during or
after the study period. Genetic analyses will not be performed on these serum samples. Participant
confidentiality will be maintained.
8.4.1. 
Evaluations
Blood samples will be collected for measurement of serum amivantamab for PK analyses. The PK
profile of amivantamab will be based on serum concentration data obtained from the timepoints
surrounding the first and fifth dose administrations collected from at least 10 participants in each
cancer type in Phase 2a. Blood samples for sparse PK will also be obtained following all other
dose administrations from participants in Phase 2a and 2b, prior to the start of the infusion and
following the end of the infusion, from all the participants. Additional information about the
collection, handling, and shipment of biological samples can be found in the laboratory manual.
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8.4.2. 
Analytical Procedures
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of amivantamab using a validated,
specific, and sensitive enzyme-linked immunosorbent assay (ELISA) method by or under the
supervision of the sponsor.
In addition, serum PK samples may be stored for future analysis of other co-administered
treatments.
8.4.3. 
Pharmacokinetic Parameters and Evaluations
The primary PK endpoints include, but are not limited to maximum serum concentration (Cmax),
Tmax, AUC(t1-t2) (eg, AUCDay1-8), AUCtau, plasma/serum concentration immediately prior the next
study treatment administration (Ctrough), t1/2, CL, steady state volume of distribution (VSS), and
accumulation ratio. Population PK modeling may be performed to assess the potential effect of
intrinsic factors and extrinsic on the PK of amivanatamab.
8.5. 
Pharmacogenomics
Pharmacogenomics are not evaluated in this study.
8.6. 
Biomarkers
Collected tumor tissue samples will be used to evaluate the tumor surface levels of EGFR and
cMET protein expression by centrally performed IHC assay to determine the patient eligibility,
although documentation of previously performed local IHC results may be submitted for the
purposes of demonstrating eligibility for study conduct. All statistical and biomarker analysis,
however, will utilize the results of the centrally performed IHC results, based on the statistical
analysis plan. Tumor tissue collected at screening may also be analyzed by tumor next-generation
sequencing to evaluate molecular alterations and track response to treatment. Tumor samples
collected post-treatment and post-progression may also be evaluated by IHC and next-generation
sequencing to track response to amivantamab. Tissues may also be used to determine biomarkers
relevant to GC/EC and/or analyzed to confirm ctDNA results.
Screening blood samples from all participants will undergo ctDNA analysis to evaluate
pre-treatment mutational status of EGFR, cMet, and other key oncogenes to characterize the tumor.
Additional blood samples will be collected during the study and may be evaluated for ctDNA to
assess changes in the levels or types of genetic alterations observed over time and to monitor for
the emergence of potential markers of resistance to amivantamab.
Blood samples will also be collected at time points specified in the Schedule of Activities (Table 2)
and may be analyzed for circulating factors relevant to disease biology (eg, hepatocyte growth
factor).
Blood samples will also be collected from at least 10 participants in each cancer type at selected
time points to analyze PD markers (eg, soluble EGFR and cMet) in samples taken prior to and
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after exposure to amivantamab, to explore whether the complete soluble target saturation
throughout the dosing was attained.
For the provision of biopsy tissue samples, fresh or formalin-fixed, paraffin-embedded (FFPE)
tissue samples are requested and will be evaluated for biomarkers (DNA, RNA, and/or protein)
relevant to cancer.
Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the
end of the study, it becomes clear that the analysis will not have sufficient scientific value for
biomarker evaluation, or if there are not enough samples or responders to allow for adequate
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.
Additional Collections
If it is determined at any time before study completion that additional material is needed from a
formalin-fixed, paraffin-embedded tumor sample for the successful completion of the
protocol-specified analyses, the sponsor may request that additional material be retrieved from
existing samples. Also, based on emerging scientific evidence, the sponsor may request additional
material from previously collected tumor samples during or after study completion for a
retrospective analysis. In this case, such analyses would be specific to research related to the study
treatment(s) or diseases being investigated.
8.7. 
Immunogenicity Assessments
Serum samples will be collected for immunogenicity assessments of amivantamab (anti-drug
antibodies to amivantamab). The detection and characterization of antibodies to amivantamab will
be performed using a validated immunoassay method by or under the supervision of the sponsor.
Serum samples will be screened for antibodies binding to amivantamab and serum titer will be
determined from positive samples. Antibodies may be further characterized and/or evaluated for
their ability to neutralize the activity of the study treatment. All samples collected for immune
response analysis will also be evaluated for amivantamab serum concentration to ensure
appropriate interpretation of immunogenicity data. Other immunogenicity analyses may be
performed to further characterize any immune responses generated.
8.8. 
Medical Resource Utilization and Health Economics
Health Economics/Medical Resource Utilization and Health Economics parameters are not
evaluated in this study.
9. 
STATISTICAL CONSIDERATIONS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general
description of the statistical methods to be used to analyze the efficacy and safety data is outlined
below. Specific details will be provided in the statistical analysis plan (SAP).
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9.1. 
Statistical Hypotheses
No hypothesis is planned to be tested in Phase 2a.
The statistical hypothesis in Phase 2b is that amivantamab monotherapy will lead to objective
response rate (ORR) higher than 15% (ie, H0 ≤15% vs Ha >15%) in patients with GC or EC,
selected on the basis of expression of EGFR, cMET, or both. This threshold is based on historical
studies for approved 3L regimens for GC (11.2%-13.6%) and reported efficacy of approved 2L
regimens for EC (approximately 15%).
9.2. 
Sample Size Determination
In Phase 2a, approximately 30 response evaluable participants with tumors expressing either
EGFR, cMet, or both, as determined by central IHC, will be enrolled in GC and EC cohorts.
Twenty participants will be enrolled for IHC 2+/3+ that will provide approximately 90%
probability to observe the posterior probability of (ORR >22.5%) ≥40% (which is similar with
ORR ≥20%) assuming ORR is 30% for the subpopulation. By enrolling 10 participants with IHC
1+, the probability to observe the posterior probability (ORR >22.5%) ≥40% is 80%.
Upon agreement with CTMT, a maximum of 11 participants may be enrolled in each Phase 2a
extension cohort. Enrollment will halt if no response or stable disease of 6 weeks or more is
observed among the first 6 participants for futility in each of the Phase 2a extension cohorts. If 2
or more responses are observed in each of Phase 2a extension cohorts, CTMT will assess the data
and may recommend additional participants to be enrolled for further characterization.
In each dose cohort of phase 2a, approximately 20 response evaluable participants will be
additionally enrolled if the CTMT recommends exploration of higher doses. The probability to
observe 4 or more response (ORR >  20%) is 89% assuming ORR of 30%.
In Phase 2b cohorts, approximately 100 participants will be enrolled in each of GC and EC
expansion cohort. The eligible participants will be decided based on the results in Phase 2a part.
Assuming an overall ORR of 30% for amivantamab, 100 participants in Phase 2b part will provide
approximately 90% power to reject the null hypothesis, 15% ORR, using 2-side z test at
alpha 0.05.
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Population 
Description
All Enrolled 
All participants who are assigned with stud y treatment.
All Treated 
All participants who take at least 1 dose of stud y treatment
Response  
evaluable 
All participants who satisfy the following criteria:
• Receive at least 1 dose of study treatment
• Met all eligibility criteria for the study
• Had a baseline and at least 1 post-baseline efficacy disease assessments, or have disease
progression/death due to disease progression prior to the first post-baseline disease
assessment
Safety 
All participants who take at least 1 dose of stud y treatment
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Population 
Description
Pharmacokinetics 
All participants who receive at least 1 dose of study treatment and have at least 1 evaluable
post-baseline measurement
Immunogenicity 
All participants who receive at least 1 dose of study treatment and have at least 1 evaluable
post-baseline measurement
Biomarker 
All participants who receive at least 1 dose of study treatment and have at least 1 biomarker
measurement
9.4. 
Statistical Analyses
The statistical analysis plan will be finalized prior to the database lock and it will include a more
technical and detailed description of the statistical analyses described in this section. This section
is a summary of the planned statistical analyses of the most important endpoints including primary
and key secondary endpoints.
9.4.1. 
General Considerations
All continuous variables will be summarized using number of participants (n), mean, standard
deviation (SD), median, minimum, and maximum. Discrete variables will be summarized with
number and percent. The Kaplan-Meier product limit method will be used to estimate the
time-to-event variables including median survival time. Unless otherwise specified, the phases,
arm and dose regimen will be analyzed separately.
Analyses of ORR and disease control rate (DCR) will be performed on the response evaluable
population. The other efficacy analyses will be performed on all treated population. The central
IHC data will be used for the statistical analysis purposes.
At the end of Phase 2a part, CTMT will review the result and determine which subpopulations and
dose to be included in the Phase 2b part (see Appendix 2, Section 10.2.6: Committees Structure).
9.4.2. 
Primary Endpoint
9.4.2.1. 
Objective Response Rate
Primary Estimand
 
Population: participants with GC or EC expressing EGFR and/or MET
 
Variable: overall response; CR or PR
 
Study drug: amivantamab monotherapy
 
Intercurrent event: subsequent anticancer therapy. The while-on-treatment policy: Response
after this intercurrent event will not be included.
 
Summary: ORR
The primary efficacy measure is ORR. Objective response rate is defined as the proportion of
participants who achieve either CR or PR, determined by investigator assessment using RECIST
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Version 1.1. Confirmation of investigator-assessed ORR may be performed through IRC in the
Phase 2b.
For Phase 2a part, there will be no formal hypothesis testing. ORR will be calculated for response
evaluable population descriptively.
For Phase 2b part, a z test with normal approximation will be used to compare the ORR with 15%.
Multiplicity caused by subpopulation selection at the interim analysis (see section 9.5) will be
controlled by closed testing procedure and weighted statistics. More detail will be described in
SAP. The ORR and its 95% confidence interval (CI) will also be calculated.
9.4.3. 
Secondary Endpoints
9.4.3.1. 
Disease Control Rate
Disease control rate is defined as the percentage of participants achieving complete or partial
response or stable disease for at least 6 weeks as defined by RECIST Version1.1. The DCR and
its 95% CI with Clopper-Pearson method will also be calculated.
9.4.3.2. 
Duration of Response
Duration of Response (DoR) is defined as the time from the date of first documented response (CR
or PR) until the date of documented progression or death, whichever comes first. The end of
response should coincide with the date of progression or death from any cause used for the PFS
endpoint. If a participant does not progress following a response, then his/her duration of response
will use the PFS censoring time. A Kaplan-Meier plot and median DoR with 95% confidence
interval (calculated from the Kaplan-Meier estimate) will be presented. Confirmation of
investigator-assessed DoR may be performed through IRC in the Phase 2b.
9.4.3.3. 
Time to Response
Time to Response (TTR) is defined as the time from the date of first amivantamab administration
to the date of achieving objective response (CR or PR) by investigator assessment using RECIST
Version 1.1 among patients who achieve objective response.  TTR will be analyzed using the same
methodology as for the analysis of DoR.
9.4.3.4. 
Progression-free Survival
Progression-free survival is defined as the time from first dose until the date of objective disease
progression or death (by any cause in the absence of progression), whichever comes first, based
on investigator assessment using RECIST Version 1.1. Participants who have not progressed or
have not died at the time of analysis will be censored at the time of the latest date of assessment
from their last evaluable RECIST Version 1.1 assessment. PFS will be analyzed using the same
methodology as for the analysis of DoR.
9.4.3.5. 
Overall Survival
Overall survival is defined as the time from the date of first dose until the date of death due to any
cause. Any participant not known to have died at the time of analysis will be censored based on
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the last recorded date on which the participant was known to be alive. OS will be analyzed using
the same methodology as for the analysis of DoR.
9.4.4. 
Safety Analyses
All safety analyses will be made on the safety population. Baseline for all laboratory evaluations,
and vital signs will be defined as the last evaluation done before the first study treatment
administration.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the initial
administration of study treatment through the day of last dose plus 30 days or until the start of
subsequent anticancer therapy, if earlier, is considered to be treatment-emergent. All reported
treatment-emergent AEs will be included in the analysis. For each AE, the percentage of
participants who experience at least 1 occurrence of the given event will be summarized by
treatment group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those
participants who die, who discontinue treatment due to an AE or who experience a severe or an
SAE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Descriptive statistics will be
calculated for each laboratory analyte at baseline and for observed values and changes from
baseline at each scheduled time point. Frequency tabulations of the changes from baseline will be
presented in pre- versus post-treatment cross-tabulations (with classes for below, within, and above
normal ranges). Frequency tabulations of the laboratory abnormalities will be made. A listing of
participants with any laboratory results outside the reference ranges will be provided. A listing of
participants with any markedly abnormal laboratory results will also be provided.
Parameters with predefined NCI-CTCAE toxicity grades will be summarized. Change from
baseline to the worst AE grade experienced by the participant during the study will be provided as
shift tables.
Vital Signs
Vital signs including temperature, heart rate, respiratory rate, and blood pressure (systolic and
diastolic) and oxygen saturation will be summarized over time, using descriptive statistics and/or
graphically. The percentage of participants with values beyond clinically important limits will be
summarized.
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9.4.5. 
Other Analyses
Pharmacokinetic Analyses
The PK analyses will use the PK population. Serum amivantamab concentrations will be
summarized for each cancer type and overall population in tables of mean, SD, median, and range
over time, as appropriate. PK parameters will be estimated for individuals and descriptive statistics
will be calculated for each cancer type and overall population.
Participants will be excluded from the PK analysis if their data do not allow for accurate
assessment of the PK (eg, incomplete administration of the study treatment; missing information
of dosing and sampling times; concentration data not sufficient for PK parameter calculation).
All concentrations below the lowest quantifiable concentration or missing data will be labeled as
such in the concentration database. All participants and samples excluded from the analysis will
be clearly documented in the study report.
Pharmacokinetic/Pharmacodynamic Analyses
The exposure-response relationship between amivantamab exposure and key efficacy and safety
parameters may be explored if the data allow. In addition, the relationship may be characterized
using an exposure-response model. Details will be provided in an analysis plan and detailed results
may be reported separately from the CSR.
Immunogenicity Analyses
The incidence of anti-amivantamab antibodies will be summarized for immunogenicity population.
Serum samples will be screened for antibodies binding to amivantamab and the number of
confirmed positive samples will be reported. Other analyses may be performed to further
characterize the immunogenicity of amivantamab.
Pharmacodynamic and Biomarker Analyses
The biomarker analyses will use the biomarker population. Analyses are planned to explore PD
and other biomarkers that may be indicative of the mechanisms of action of the drug or predictive
of efficacy as well as the potential mechanisms of resistance to amivantamab.
The association of biomarker-positivity with clinical response or time-to-event endpoints will be
assessed using statistical methods appropriate for each endpoint (eg, analysis of variance,
categorical, or survival models). Correlation of baseline biomarker expression levels with clinical
response or relevant time to-event endpoints will be performed to identify responsive (or resistant)
subgroups.
Additional biomarkers (DNA, RNA, and/or protein) relevant to GC/EC may also be assessed in
blood and tissue samples collected during the study to better understand the disease and
mechanisms of response or resistance to amivantamab.
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9.5. 
Interim Analysis
If the CTMT recommends exploration of higher doses in each cohort of phase 2a, an interim futility
analysis is planned for the participants receiving the higher dose, when 10 response evaluable
participants have radiographic assessment. The enrollment may halt if the number of participants
with objective response (ie, CR or PR) is 1 or less. CTMT will make a decision considering all
other aspects of study data such as safety, PK and other efficacy endpoints.
In Phase 2b, an interim futility analysis is planned in each of GC and EC arm approximately
12 weeks after 50 participants receive the first infusion. The interim futility analyses will be based
on the best response rate for each subpopulation (for example, IHC 2+/3+ and IHC 1+) selected at
the end of Phase 2a and prespecified before initiating Phase 2b). The enrollment of each
subpopulation may be terminated for futility if the posterior probability (ORR >22.5%) is <40%.
Specific details will be provided in the data review committee Charter and interim analysis plan.
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1. 
Appendix 1: Abbreviations
2L 
secon d line
3L 
thir d line
AEs 
adverse events
ALT 
alanine aminotransferase
AUC 
area under the curve
ART 
antiretroviral therapy 
AST 
aspartate aminotransferase
CI 
confidence interval
cMet 
tyrosine-protein kinase mesenchymal-epithelial transition
COVID-19 
Coronovirus disease 2019
CR 
complete response
CSR 
clinica l stud y report
CT 
computerized tomography 
CTCAE 
Common Terminology Criteria for Adverse Events
CTMT 
clinical trial management team
ctDNA 
circulatin  g tumor deoxyribonucleic acid
C 
Cycle
D 
Day 
DCR 
disease control rate
DoR 
duration of response
EC 
esophageal cancer
ECG 
Electrocardiogram
ECOG 
Eastern Cooperative Oncology Group
eCRF 
electronic case report form
eDC 
electronic data capture
EGF 
Epidermal growth factor
EGFR 
epidermal growth factor receptor
EOT 
end-of-treatment
FSH 
follicle stimulatin  g hormone
GC 
gastric cancer
GCP 
Good Clinical Practice
GEJ 
gastroesophageal junction
HA 
Health authority 
HBsAg 
hepatitis B surface antigen
HBV 
hepatitis B virus
HCV 
hepatitis C virus
HER 
human epidermal growth factor receptor
HGF 
hepatocyte growth factor
HIV 
human immunodeficienc y virus
HRT 
hormonal replacement therapy 
IB 
investigator’s brochure
ICF 
informed consent form
ICH 
International Council for Harmonisation of Technical Requirements for Pharmaceuticals for
Human Use
IEC 
Independent Ethics Committee
IgG1 
immunoglobulin G1
IHC 
Immunohistochemistry 
ILD 
interstitial lun  g disease
INR 
international normalized ratio
IPPI 
Investigational Product Preparation Instructions
IRB 
Institutional Review Board
IRC 
Independent Review Committee
IRR 
infusion-related reaction
IV 
intravenous
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mPFS 
median progression-free survival
MRI 
magnetic resonance imaging
NCCN 
National Comprehensive Cancer Network
NCI-CTCAE 
National Cancer Institute - Common Terminology Criteria for Adverse Events
NSCLC 
non-small cell lun  g cancer
NYHA 
New York Heart Association
ORR 
objective response rate
OS 
overall survival
PD 
Pharmacodynamic
PFS 
progression-free survival
PK 
pharmacokinetic(s)
PQC 
product qualit y complaint
PR 
partial response
RTK 
Receptor tyrosine kinases
RECIST 
Response Evaluation Criteria in Solid Tumors
SAE 
serious adverse event
SAP 
Statistical analysis plan
Scr 
Screening
SD 
standard deviation
SIPPM 
Site Investigational Product and Procedures Manual
SPF 
Skin protection factor
SUSAR 
suspected unexpected serious adverse reaction
TEAE 
treatment-emergent adverse event
TEN 
Toxic epidermal necrolysis
TKI 
tyrosine kinase inhibitor
Tmax  
time to reach the maximum plasma/serum concentration
TTR 
Time to Response
ULN 
upper limit of normal
US 
Unite d States
WBC 
White blood cells
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10.2. 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations
10.2.1. 
Regulatory and Ethical Considerations
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the
protocol, current International Council for Harmonisation of Technical Requirements for
Pharmaceuticals for Human Use (ICH) guidelines on Good Clinical Practice (GCP), and applicable
regulatory and country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing,
conducting, recording, and reporting studies that involve the participation of human participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment by
the sponsor. All protocol amendments must be issued by the sponsor and signed and dated by the
investigator. Protocol amendments must not be implemented without prior IEC/IRB approval, or
when the relevant competent authority has raised any grounds for non-acceptance, except when
necessary to eliminate immediate hazards to the participants, in which case the amendment must
be promptly submitted to the IEC/IRB and relevant competent authority. Documentation of
amendment approval by the investigator and IEC/IRB must be provided to the sponsor. When the
change(s) involve only logistic or administrative aspects of the study, the IEC/IRB (where
required) only needs to be notified.
During the course of the study, in situations where a departure from the protocol is unavoidable,
the investigator or other physician in attendance will contact the appropriate sponsor representative
listed in the Protocol Supplementary Information page(s), which will be provided as a separate
document. Except in emergency situations, this contact should be made before implementing any
departure from the protocol. In all cases, contact with the sponsor must be made as soon as possible
to discuss the situation and agree on an appropriate course of action. The data recorded in the eCRF
and source documents will reflect any departure from the protocol, and the source documents will
describe this departure and the circumstances requiring it.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities
in each respective country, if applicable. A study may not be initiated until all local regulatory
requirements are met.
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Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study treatment to
the study site:
 Protocol and amendment(s), if any, signed and dated by the principal investigator
 A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if applicable,
participant compensation programs. This approval must clearly identify the specific protocol
by title and number and must be signed (or sealed, where appropriate per local regulations) by
the chairman or authorized designee.
 Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their
function, with a statement that it is organized and operates according to GCP and the applicable
laws and regulations. If accompanied by a letter of explanation, or equivalent, from the
IEC/IRB, a general statement may be substituted for this list. If an investigator or a member of
the study site personnel is a member of the IEC/IRB, documentation must be obtained to state
that this person did not participate in the deliberations or in the vote/opinion of the study.
 Regulatory authority approval or notification, if applicable
 Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
 Documentation of investigator qualifications (eg, curriculum vitae)
 Completed investigator financial disclosure form from the principal investigator, where
required
 Signed and dated clinical trial agreement, which includes the financial agreement
 Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 Completed investigator financial disclosure forms from all subinvestigators
 Documentation of subinvestigator qualifications (eg, curriculum vitae)
 Name and address of any local laboratory conducting tests for the study, and a dated copy
of current laboratory normal ranges for these tests, if applicable
 Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB
with current and complete copies of the following documents (as required by local regulations):
 Final protocol and, if applicable, amendments
 Sponsor-approved ICF (and any other written materials to be provided to the participants)
 IB (or equivalent information) and amendments/addenda
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 Sponsor-approved participant recruiting materials
 Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 Investigator's curriculum vitae or equivalent information (unless not required, as
documented by the IEC/IRB)
 Information regarding funding, name of the sponsor, institutional affiliations, other
potential conflicts of interest, and incentives for participants
 Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final protocol,
amendments (if any, excluding the ones that are purely administrative, with no consequences for
participants, data or study conduct, unless required locally), the ICF, applicable recruiting materials,
and participant compensation programs, and the sponsor has received a copy of this approval. This
approval letter must be dated and must clearly identify the IEC/IRB and the documents being
approved.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 Protocol amendments (excluding the ones that are purely administrative, with no consequences
for participants, data or study conduct)
 Revision(s) to ICF and any other written materials to be provided to participants
 If applicable, new or revised participant recruiting materials approved by the sponsor
 Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 New edition(s) of the IB and amendments/addenda
 Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
 Reports of AEs that are serious, unlisted/unexpected, and associated with the study treatment
 New information that may adversely affect the safety of the participants or the conduct of the
study
 Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 Report of deaths of participants under the investigator's care
 Notification if a new investigator is responsible for the study at the site
 Development Safety Update Report and Line Listings, where applicable
 Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct), the amendment and applicable ICF revisions
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must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise help
ensure access to the developed product if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section 4.2.1, Study-specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.1.
10.2.2. 
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.2.3. 
Informed Consent Process
Each participant must give written consent according to local requirements after the nature of the
study has been fully explained. The ICF(s) must be signed before performance of any study-related
activity. The ICF(s) that is/are used must be approved by both the sponsor and by the reviewing
IEC/IRB and be in a language that the participant can read and understand. The informed consent
should be in accordance with principles that originated in the Declaration of Helsinki, current ICH
and GCP guidelines, applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study site personnel
must explain to potential participants the aims, methods, reasonably anticipated benefits, and
potential hazards of the study, and any discomfort participation in the study may entail. Participants
will be informed that their participation is voluntary and that they may withdraw consent to
participate at any time. They will be informed that choosing not to participate will not affect the
care the participant will receive for the treatment of his or her disease. Participants will be told that
alternative treatments are available if they refuse to take part and that such refusal will not
prejudice future treatment. Finally, they will be told that the investigator will maintain a participant
identification register for the purposes of long-term follow up if needed and that their records may
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be accessed by HA and authorized sponsor personnel without violating the confidentiality of the
participant, to the extent permitted by the applicable law(s) or regulations. By signing the ICF the
participant is authorizing such access, which includes permission to obtain information about his
or her survival status. It also denotes that the participant agrees to allow his or her study physician
to recontact the participant for the purpose of obtaining consent for additional safety evaluations,
and subsequent disease-related treatments, if needed.
The participant will be given sufficient time to read the ICF and the opportunity to ask questions.
After this explanation and before entry into the study, consent should be appropriately recorded by
means of the participant's personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
If the participant is unable to read or write, an impartial witness should be present for the entire
informed consent process (which includes reading and explaining all written information) and
should personally date and sign the ICF after the oral consent of the participant is obtained.
When prior consent of the participant is not possible, enrollment procedures should be described
in the protocol with documented approval/favorable opinion by the IEC/IRB to protect the rights,
safety, and well-being of the participant and to ensure compliance with applicable regulatory
requirements. The participant must be informed about the study as soon as possible and give
consent to continue.
10.2.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants enrolled in this study will be
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality
and compliance with applicable data privacy protection laws and regulations. Appropriate
technical and organizational measures to protect the personal data against unauthorized disclosures
or access, accidental or unlawful destruction, or accidental loss or alteration must be put in place.
Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant includes explicit consent for the processing of
personal data and for the investigator/institution to allow direct access to his or her original medical
records (source data/documents) for study-related monitoring, audit, IEC/IRB review, and
regulatory inspection. This consent also addresses the transfer of the data to other entities and to
other countries.
The participant has the right to request through the investigator access to his or her personal data
and the right to request rectification of any data that are not correct or complete. Reasonable steps
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will be taken to respond to such a request, taking into consideration the nature of the request, the
conditions of the study, and the applicable laws and regulations.
Exploratory research is not conducted under standards appropriate for the return of data to
participants. In addition, the sponsor cannot make decisions as to the significance of any findings
resulting from exploratory research. Therefore, exploratory research data will not be returned to
participants or investigators, unless required by law or local regulations. Privacy and
confidentiality of data generated in the future on stored samples will be protected by the same
standards applicable to all other clinical data.
10.2.5. 
Long-term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand amivantamab, to understand
disease under investigation, to understand differential treatment responders, and to develop
tests/assays related to amivantamab and GC/EC. The research may begin at any time during the
study or the post-study storage period.
Stored samples will be coded throughout the sample storage and analysis process and will not be
labeled with personal identifiers. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.2.6. 
Committees Structure
Clinical Trial Management Team
The safety and conduct of the study will be monitored by the CTMT established by the sponsor in
conjunction with the coordinating investigator. The CTMT will consist of coordinating
investigator(s) or their designee(s), the sponsor’s medical monitor, the Safety Management Team
Chair, one of the sponsor’s clinical pharmacologists or their designees, and additional sponsor staff
as appropriate. The sponsor’s statistician or biomarker scientist will be consulted when the CTMT
determines it is necessary. In general, the CTMT will monitor the conduct of the study and review
study data in an ongoing basis. The CTMT may recommend and decide on modifications in the
study conduct which may include, but are not restricted to, changes in (1) study treatment
administration dose/schedule, (2) participant population based on the emerging biomarker data,
(3) allowing further enrollment of or terminate enrollment of a specific subpopulation to better
characterize the specific population (eg, enrollment of IHC 2+/3+ or EGFR and cMET double
positive population), (4) opening of Phase 2a extension cohorts, and (5) PK or biomarker sampling
times. All decisions made by the CTMT will be documented in a CTMT decision document. The
IRB/IEC will be notified for all CTMT decisions, if required. The recommendations may be
instituted by the CTMT, pending protocol amendment, as long as they are consistent with the
benefit-risk and populations already reviewed and approved by the HA and local IRBs. All the
CTMT documentation will be maintained in the sponsor’s study master file and, as appropriate, in
the investigator’s study files. If unexpected safety findings are identified, the CTMT will assess
the safety data in a prompt manner.
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At the end of Phase 2a part, CTMT will review the results and determine which subpopulations
and dose to be included in the Phase 2b part. In general, Phase 2b will be initiated if a Phase 2a
population (or subset of Phase 2a populations) achieves posterior probability (ORR >22.5%) ≥40%
(which is similar with ORR ≥20%). All available data (eg, efficacy, safety, and biomarker data)
will be assessed to determine whether enrollment in a given subpopulation should continue. More
details will be described in the CTMT charter.
10.2.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding amivantamab or the sponsor's
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior
clinical data, formulation information) supplied by the sponsor to the investigator and not
previously published, and any data, including biomarker research data, generated as a result of this
study, are considered confidential and remain the sole property of the sponsor. The investigator
agrees to maintain this information in confidence and use this information only to accomplish this
study and will not use it for other purposes without the sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the
sponsor in connection with the continued development of amivantamab, and thus may be disclosed
as required to other clinical investigators or regulatory agencies. To permit the information derived
from the clinical studies to be used, the investigator is obligated to provide the sponsor with all
data obtained in the study.
The results of the study will be reported in a CSR generated by the sponsor and will contain data
from all study sites that participated in the study as per protocol. Recruitment performance or
specific expertise related to the nature and the key assessment parameters of the study will be used
to determine a coordinating investigator for the study. Results of any analyses performed after the
CSR has been issued will be reported in a separate report and will not require a revision of the
CSR.
Study participant identifiers will not be used in publication of results. Any work created in
connection with performance of the study and contained in the data that can benefit from copyright
protection (except any publication by the investigator as provided for below) shall be the property
of the sponsor as author and owner of copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal
Editors guidelines, the sponsor shall have the right to publish such primary (multicenter) data and
information without approval from the investigator. The investigator has the right to publish study
site-specific data after the primary data are published. If an investigator wishes to publish
information from the study, a copy of the manuscript must be provided to the sponsor for review
at least 60 days before submission for publication or presentation. Expedited reviews will be
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in
writing, the investigator will withhold such publication for up to an additional 60 days to allow for
filing of a patent application. In the event that issues arise regarding scientific integrity or
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor will
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not mandate modifications to scientific content and does not have the right to suppress information.
For multicenter study designs and sub-study approaches, secondary results generally should not
be published before the primary endpoints of a study have been published. Similarly, investigators
will recognize the integrity of a multicenter study by not submitting for publication data derived
from the individual study site until the combined results from the completed study have been
submitted for publication, within 18 months after the study end date, or the sponsor confirms there
will be no multicenter study publication. Authorship of publications resulting from this study will
be based on the guidelines on authorship, such as those described in the International Committee
of Medical Journal Editors Recommendations for the Conduct, Reporting, Editing and Publication
of Scholarly Work in Medical Journals, which state that the named authors must have made a
significant contribution to the conception or design of the work; or the acquisition, analysis, or
interpretation of the data for the work; and drafted the work or revised it critically for important
intellectual content; and given final approval of the version to be published; and agreed to be
accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity
of any part of the work are appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.2.8. 
Data Quality Assurance
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified
investigators and appropriate study sites, review of protocol procedures with the investigator and
study site personnel before the study, and periodic monitoring visits by the sponsor, and direct
transmission of clinical laboratory data from a central laboratory into the sponsor's data base.
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study site personnel before
the start of the study. The sponsor will review eCRF for accuracy and completeness during on-site
monitoring visits and after transmission to the sponsor; any discrepancies will be resolved with the
investigator or designee, as appropriate. After upload of the data into the study database they will
be verified for accuracy and consistency with the data sources.
10.2.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and
alterations must be made by the investigator or authorized study site personnel. The investigator
must verify that all data entries in the eCRF are accurate and correct.
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The study data will be transcribed by study site personnel from the source documents onto an
electronic eCRF, if applicable.  Study-specific data will be transmitted in a secure manner to the
sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
eCRF in English. The eCRF must be completed as soon as possible after a participant visit and the
forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed after
the initial entry into the eCRF, this can be done in either of the following ways:
 Investigator and study site personnel can make corrections in the eDC tool at their own
initiative or as a response to an auto query (generated by the eDC tool).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study
site personnel.
10.2.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; study discussion and date of signed
informed consent; dates of visits; results of safety and efficacy parameters as required by the
protocol; record of all AEs and follow-up of AEs; concomitant medication; treatment
receipt/dispensing/return records; study treatment administration information; and date of study
completion and reason for early discontinuation of study treatment or withdrawal from the study,
if applicable.
The author of an entry in the source documents should be identifiable.
Specific details required as source data for the study and source data collection methods will be
reviewed with the investigator before the study and will be described in the monitoring guidelines
(or other equivalent document).
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.2, Exclusion Criteria that specify a need for documented medical history are as follows:
 Referral letter from treating physician or
 Complete history of medical notes at the site
 Discharge summaries
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Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol-required assessment (eg, physical examination,
laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF.
10.2.11. 
Monitoring
The sponsor will use a combination of monitoring techniques: central, remote, or on-site
monitoring to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the
monitor will compare the data entered into the eCRF with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source
documents will be identified to ensure that all sources of original data required to complete the
eCRF are known to the sponsor and study site personnel and are accessible for verification by the
sponsor study site contact. If electronic records are maintained at the study site, the method of
verification must be discussed with the study site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review will
be discussed with the study site personnel. The sponsor expects that, during monitoring visits, the
relevant study site personnel will be available, the source documents will be accessible, and a
suitable environment will be provided for review of study-related documents. The monitor will
meet with the investigator on a regular basis during the study to provide feedback on the study
conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these
remote contacts, study site personnel will be available to provide an update on the progress of the
study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.2.12. 
On-site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at
any time during or after completion of the study to conduct an audit of the study in compliance
with regulatory guidelines and company policy. These audits will require access to all study
records, including source documents, for inspection. Participant privacy must, however, be
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respected. The investigator and study site personnel are responsible for being present and available
for consultation during routinely scheduled study site audit visits conducted by the sponsor or its
designees.
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part
of a national GCP compliance program or to review the results of this study in support of a
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
10.2.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.2.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study/Site Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been collected
and a study site closure visit has been performed.
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The investigator may initiate study site closure at any time, provided there is reasonable cause and
sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are not
limited to:
 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or
local HA, the sponsor's procedures, or GCP guidelines
 Inadequate recruitment of participants by the investigator
 Discontinuation of further study treatment development
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10.3. 
Appendix 3: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
10.3.1. 
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant administered a
pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have
a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a
medicinal (investigational or non-investigational) product, whether or not related to that medicinal
(investigational or non-investigational) product. (Definition per ICH).
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to All Adverse Events
under Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information, for time of last AE recording).
Serious Adverse Event
An SAE based on ICH and Europeon Union (EU) Guidelines on Pharmacovigilance for Medicinal
Products for Human Use is any untoward medical occurrence that at any dose:
 Results in death
 Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 Requires inpatient hospitalization or prolongation of existing hospitalization
 Results in persistent or significant disability/incapacity
 Is a congenital anomaly/birth defect
 Is a suspected transmission of any infectious agent via a medicinal product
 Is medically important*
*Medical and scientific judgement should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
life-threatening or result in death or hospitalization but may jeopardize the participant or may
require treatment to prevent one of the other outcomes listed in the definition above. These should
usually be considered serious.
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If a serious and unexpected AE occurs for which there is evidence suggesting a causal relationship
between the study treatment and the event (eg, death from anaphylaxis), the event must be reported
as a serious and unexpected suspected adverse reaction even if it is a component of the study
endpoint (eg, all-cause mortality).
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable product
reference safety information. For amivantamab, the expectedness of an AE will be determined by
whether or not it is listed in the IB.
10.3.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study treatment is determined by the Investigator. The following
selection should be used to assess all AEs.
Related
There is a reasonable causal relationship between study treatment administration and the AE.
Not Related
There is not a reasonable causal relationship between study treatment administration and the AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.3.3. 
Severity Criteria
Adverse event severity is a clinical determination of the intensity of an AE. The severity
assessment for an AE or serious AE should be completed using the NCI-CTCAE, Version 5. Any
AE or SAE not listed in the NCI-CTCAE, Version 5 will be graded according to the investigator
clinical judgment by using the standard grades as follows:
 Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only;
intervention not indicated.
 Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age
appropriate instrumental activities of daily living.
 Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization
or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily
living.
 Grade 4: Life-threatening consequences; urgent intervention indicated.
 Grade 5: Death related to AE.
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10.3.4. 
Special Reporting Situations
Safety events of interest on a sponsor study treatment in an interventional study that may require
expedited reporting or safety evaluation include, but are not limited to:
 Overdose of a sponsor study treatment
 Suspected abuse/misuse of a sponsor study treatment
 Accidental or occupational exposure to a sponsor study treatment
 Medication error, intercepted medication error, or potential medication error involving a
Johnson & Johnson medicinal product (with or without participant exposure to the Johnson &
Johnson medicinal product, eg, product name confusion, product label confusion, intercepted
prescribing or dispensing errors)
 Exposure to a sponsor study treatment from breast-feeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
10.3.5. 
Procedures
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study treatment, must be
recorded using medical terminology in the source document and the eCRF. Whenever possible,
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough,
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory
infection"). Investigators must record in the eCRF their opinion concerning the relationship of the
AE to study therapy. All measures required for AE management must be recorded in the source
document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant must be
provided with a "wallet (study) card" and instructed to carry this card with them for the duration
of the study indicating the following:
 Study number
 Statement, in the local language(s), that the participant is participating in a clinical study
 Investigator's name and 24-hour contact telephone number
 Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
 Site number
 Participant number
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Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon the
participant's discontinuation from the study, must be followed until any of the following occurs:
 The event resolves
 The event stabilizes
 The event returns to baseline, if a baseline value/status is available
 The event can be attributed to agents other than the study treatment or to factors unrelated to
study conduct
 It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE.
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the study must be reported as an SAE, except hospitalizations for the following:
 Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending
placement in long-term care facility or Phase 2a participants during C1D1 until C1D8)
 Surgery or procedure planned before entry into the study (must be documented in the eCRF).
Note: Hospitalizations that were planned before the signing of the ICF and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any AE that results in a prolongation of the originally planned
hospitalization is to be reported as a new SAE.
 For convenience the investigator may choose to hospitalize the participant for the duration of
the treatment period.
Disease progression does not need to be reported as an adverse event or serious adverse event term;
instead, signs and symptoms of clinical sequelae resulting from disease progression/lack of
efficacy will be reported if they fulfill the serious adverse event definition (refer to Adverse Event
Definitions and Classifications in Section 10.3, Appendix 3: Adverse Events, Serious Adverse
Events, Product Quality Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting). Information regarding SAEs will be
transmitted to the sponsor using an SAE reporting form and safety report form of the eCRF, which
must be completed and reviewed by a physician from the study site, and transmitted in a secure
manner to the sponsor within 24 hours. The initial and follow-up reports of an SAE should be
transmitted in a secure manner electronically or by facsimile (fax). Telephone reporting should be
the exception and the reporter should be asked to complete the appropriate form(s) first.
10.3.6. 
Product Quality Complaint Handling
Definition
A PQC is defined as any suspicion of a product defect related to manufacturing, labeling, or
packaging, ie, any dissatisfaction relative to the identity, quality, durability, reliability, or
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performance of a distributed product, including its labeling, drug delivery system, or package
integrity. A PQC may have an impact on the safety and efficacy of the product. In addition, it
includes any technical complaints, defined as any complaint that indicates a potential quality issue
during manufacturing, packaging, release testing, stability monitoring, dose preparation, storage
or distribution of the product or the drug delivery system.
Procedures
All initial PQCs must be reported to the sponsor by the study site personnel within 24 hours after
being made aware of the event.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.3.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safety issues, PQC, or questions regarding the study are listed in the Protocol
Supplementary Information page(s), which will be provided as a separate document.
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10.4. 
Appendix 4: Contraceptive and Barrier Guidance
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Section 10.3, Appendix 3: Adverse Events, Serious Adverse Events, Product Quality Complaints,
and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting.
Definitions
Woman of Childbearing Potential
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
 premenarchal: state in which menarche has not yet occurred.
 postmenopausal: defined as no menses for 12 months without an alternative medical cause. A
high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the postmenopausal
range may be used to confirm a postmenopausal state in women not using hormonal
contraception or hormonal replacement therapy (HRT), however in the absence of 12 months
of amenorrhea, a single FSH measurement is insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
 permanently sterile: permanent sterilization methods include hysterectomy, bilateral
salpingectomy, bilateral tubal occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study or the risk of pregnancy changes,
a female participant must begin a highly effective method of contraception, as described
throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
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Examples of Contraceptives
1. HIGHLY EFFECTIVE METHODS (Failure rate of <1% per year when used consistently and
correctly.)
1.1. USER INDEPENDENT - Highly Effective Methods.
 Implantable progestogen-only hormone contraception associated with inhibition of ovulation b,d
 Intrauterine device (IUD)
 Intrauterine hormone-releasing system (IUS)
 Bilateral tubal ligation/occlusion
 Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not, additional
highly effective method(s) of contraception should be used. Spermatogenesis cycle is approximately 74 days.)
1.2. USER DEPENDENT - Highly Effective Methods
 Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition
of ovulation b
 oral
 intravaginald
 transdermald
 injectabled
 Progestogen-only hormone contraception associated with inhibition of ovulation b, d
 oral
 injectable
 Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle of
the participant.)
2. NOT HIGHLY EFFECTIVE METHODS (Failure rate of >1% per year)
 USER DEPENDENT and NOT considered to be (highly) effective methods. Progestogen-only oral
hormonal contraception where inhibition of ovulation is not the primary mode of action.
 Male or femaled condom with or without spermicide c, d
 Capd, diaphragm, or sponged with spermicide
 A combination of male condom with either capd, diaphragm, or sponged with spermicide (double-
barrier methods) c
 Periodic abstinence (calendar, symptothermal, post-ovulation methods)
 Withdrawal (coitus-interruptus)
 Spermicides alone
 Lactational amenorrhea method (LAM)
a Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent with
local regulations regarding the use of contraceptive methods for participants in clinical studies.
b The study treatment may interact with hormonal contraception, which may reduce the efficacy of the contraceptive
method. In addition, consider if the hormonal contraception may interact with the study treatment.
c Male condom and female condom should not be used together (due to risk of failure with friction).
d Not approved in Japan.
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10.5. 
Appendix 5: Eastern Cooperative Oncology Group (ECOG) Performance
Status
Grade  Eastern Cooperative Oncology Group Performance Status
0 
Full y active, able to carr y on all predisease performance without restriction
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or
sedentar y nature (eg, light housework, office work)
2 
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more
than 50% of wakin  g hours
3 
Capable of onl y limited self-care, confined to bed or chair more than 50% of wakin  g hours
4 
Completel y disabled. Cannot carr y on an  y self-care. Totall y confined to bed or chair
5 
Dead
Eastern Cooperative Oncology Group, Robert Comis M.D, Group Chair (Oken 1982).
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10.6. 
Appendix 6: New York Heart Association Criteria
The following table presents the NYHA classification of cardiac disease:
Functional Capacity  
Objective Assessment
Class I. Patients with cardiac disease but without resulting limitation of physical 
activity. Ordinary physical activity does not cause undue fatigue, palpitation, 
dyspnea, or anginal pain.
A. No objective evidence of
cardiovascular disease.
Class II. Patients with cardiac disease resulting in slight limitation of physical 
activity. They are comfortable at rest. Ordinary physical activity results in fatigue, 
palpitation, dyspnea, or anginal pain. 
B. Objective evidence of
minimal cardiovascular
disease.
Class III. Patients with cardiac disease resulting in marked limitation of physical 
activity. They are comfortable at rest. Less than ordinary activity causes fatigue, 
palpitation, dyspnea, or anginal pain. 
C. Objective evidence of
moderately severe
cardiovascular disease.
Class IV. Patients with cardiac disease resulting in inability to carry on any 
physical activity without discomfort. Symptoms of heart failure or the anginal 
syndrome may be present even at rest. If any physical activity is undertaken,
discomfort is increased.
D. Objective evidence of
severe cardiovascular disease.
 
*The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases
of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.
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10.7. 
Appendix 7: MDRD formula for eGFR
Modified Diet in Renal Disease Formula
For standardized serum creatinine (SCr) in mg/dL, the estimated glomerular filtration rate (eGFR) is:
eGFR (MDRD) mL/min per 1.73 m2 = 175 x [standardized SCr (mg∕dL)]-1.154 x age-0.203 x 1.212if black x
0.742if female
Creatinine levels in µmol/L can be converted to mg/dL by dividing them by 88.4.
creatinine (mg∕dL) =
creatinine (µmol)∕L
88.4
Alternatively, for standardized serum creatinine (SCr) in µmol/L, the estimated glomerular filtration rate
(eGFR) is:
eGFR (MDRD) mL/min per 1.73 m2  30,849 x [standardized SCr (µmol)/L)]-1.154) x age -0.203 x
1.212if black x 0.742if female
Sources: (Levey 2006)
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10.8. 
Appendix 8: Study Conduct During a Natural Disaster
GUIDANCE ON STUDY CONDUCT DURING CORONOVIRUS DISEASE 2019
(COVID-19) PANDEMIC
It is recognized that the COVID-19 pandemic may have an impact on the conduct of this clinical
study due to, for example, self-isolation/quarantine by participants and study site personnel; travel
restrictions/limited-access to public places, including hospitals; study site personnel being
reassigned to critical tasks.
In alignment with recent HA guidance, the sponsor is providing options for study-related
participant management in the event of disruption to the conduct of the study. This guidance does
not supersede any local or government requirements or the clinical judgement of the investigator
to protect the health and well-being of participants and site staff. If, at any time, a participant’s
safety is considered to be at risk, study treatment will be discontinued, and study follow-up will
be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments
should be performed if required and as feasible. Participants will also be questioned regarding
general health status to fulfill any physical examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
treatment, including follow-up. Modifications to protocol-required assessments may be permitted
via COVID-19 pandemic Appendix after consultation with the participant, investigator, and the
sponsor. Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations. Discontinuations of study treatments and withdrawal from the study should
be documented with the prefix “COVID-19-related” in the eCRF.
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the HA according to local guidance. If a
participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for study treatment and follow-up. Modifications made
to the study conduct as a result of the COVID-19 pandemic should be summarized in the CSR.
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10.9. 
Appendix 9: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 1 (10 November 2021)
Overall Rationale for the Amendment: The overall reason for the amendment is addition of time to
response (TTR) as a secondary endpoint, update to require skin protection factor (SPF) ≥30 for participants
with sun exposure as part of the rash prophylaxis guidance, correction of PK, clarification of dose delay
criteria, Additionally, some changes for the clarification and some corrections were made.
Section Number 
and Name
Description of Change 
Brief Rationale
3. Objectives and
Endpoints
 
9.4.3.3. Time to
Response
Time to response (TTR) was added. 
Section added.
To add a secondary endpoint.
5.3.1 Activity
6.6.2. Rash related
Adverse Events -
Prophylaxis
Recommendations
Following update was made:
Use broad-spectrum sunscreen (containing titanium
dioxide or zinc oxide) with a skin protection factor
(SPF) ≥15 30.
 
Use broad-spectrum sunscreen with an SPF of ≥15
30 and reapply as necessary.
To align the updated management
guideline in protocol within the
amivantamab program.
1.3. Schedule of
Activities (SoA) –
Table 2
Updated the collection window as below:
C1D15 EOI: ±2 hr +5 min
C2D1 EOI: ±2 hr +5 min
C2D8 EOI+168 hours:< 2 hr ± 4 hr
C4D1 EOI: ±2 hr +5 min
The error was corrected.
1.3. Schedule of
Activities (SoA) –
Table 1
Footnote d was updated:
d. Any missed doses should be discussed with the
medical monitor prior to redosing. A dose in Cycle
1 other than Day 1 and 2 in Cycle 1 can be
delayed for 1 day and in Cycle 2 and beyond a
dose delay is allowed 7 days. A planned dose
must be skipped if amivantamab is not
administered beyond 7-day. If a dose is delayed
in Cycle 2 or beyond, then the dates of all
subsequent doses must be maintained as originally
scheduled based on first dose (ie. C1D1).
Clarified the dose delay window
and actions to be taken if out of the
window.
6.5. Dose Delay
Guidance
The text ‘withhold dosing’ was changed to ‘dose
delay’.
To clarify the definition.
Throughout 6.6.
Dose Modification
Guidance
The text ‘interruption’ was changed to ‘dose
delay’.
 
The text ‘withhold’ or ‘hold’ was changed to
‘delay’ or ‘dose delay’.
 
The text ‘reduction’ was changed to ‘modification’.
To clarify the definition.
1.3. Schedule of
Activities (SoA) –
Table 1
Updated the pre-screening window from ‘-28 of
C1D1’ to ‘before full-screening’.
The description was corrected
because pre-screening may be
performed over 28 days prior to
C1D1.
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Section Number 
and Name
Description of Change 
Brief Rationale
1.3. Schedule of 
Activities (SoA) – 
Table 1
Updated the EOT window from ‘30D After Last 
Dose’ to ‘Up to 30D After Last Dose’.
The description was clarified.
1.3. Schedule of 
Activities (SoA) – 
Table 1 
Note was added in the tumor biopsy as below: 
If the differential diagnosis between recurrence and 
fibrotic on the irradicated lesion makes possible,
the biopsy may be conducted on the irradicated
lesion.
To clarify biopsy from irradiated
lesion.
1.3. Schedule of 
Activities (SoA) – 
Table 1 
Note was added in the ctDNA and biomarker as 
below: 
Blood sample for ctDNA and biomarker at EOT 
will be collected from participants with disease
progression within 30 days of disease progression
and before the next anticancer therapy in case the
next anticancer therap y is planned.
To clarify the timing of blood
sample for ctDNA and biomarker at
EOT.
1.3. Schedule of 
Activities (SoA) – 
Table 1 
Footnote j was added: 
j. If the initiation of the subsequent anticancer 
therapy is required prior to EOT, EOT must be 
completed prior to the initiation of the subsequent 
anticancer therapy.
Considered the possibility of
starting the next anticancer therapy
immediately after treatment
discontinuation.
1.3. Schedule of 
Activities (SoA) – 
Table 1 
Footnote k was added: 
k. If the imaging data is obtained within 28 days 
prior to the initiation of study treatment (C1D1), it 
is not necessar y to repeat the imagin  g tests.
It was considered that an imaging
test would be available within 28
days prior to C1D1.
1.3. Schedule of 
Activities (SoA) – 
Table 1 
Footnote l was added: 
l. If performed within 72 hours of the first
Amivantamab dose, the assessment does not have
to be repeated for C1D1.
The description was clarified.
4.1. Overall Design 
Section updated as below: 
This is an open-label, multicenter, multi-arm Phase 
2 interventional study in participants with 
previously treated advanced or unresectable GC or
EC who are 20 years or older (or the legal age of
consent in the jurisdiction in which the study is
taking place). Japanese The participants with
gastric/GEJ or EC who express varying degrees of
EGFR, cMet, or both as determined by IHC locally
or centrally will be enrolled in the GC cohort or EC
cohort.
To update in consideration of the
possibility of expansion of
countries.
4.1.1. Screening 
Phase (Pre- and Full 
Screening) 
Section updated as below: 
The participant must sign an informed consent 
form (ICF) at the beginning of the full screening 
phase, before the first study-related activity is 
conducted. During the full screening period, 
participants will be evaluated for eligibility for
study participation. Participants must complete all
screening procedures within 28 days of C1D1. Pre
treatment biopsy will be collected for all
participants in Phase 2a and Phase 2b. The tumor
IHC result regardless of the local or central
must be obtained and confirmed for the
eligibility prior to C1D1. If the central tumor
IHC is used for the eligibility prior to the
initiation of the study treatment and the central
results are not completed during the screening
To clarify that IHC result (EGFR or
cMet) will be confirmed positive
during the screening period
regardless of local or central
pathology results.
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Section Number 
and Name
Description of Change 
Brief Rationale
period, the screening period can be extended by
14 days. The screening period can be extended by
14 days if reporting of central tumor IHC results
are not completed within the 28 day screening
period. However, all other assessments must still
meet timing criteria relative to C1D1 or must be
repeated.
4.1.1. Screening 
Phase (Pre- and Full 
Screening) 
Following description was added: 
If an assessment was performed as part of the 
participant’s routine clinical evaluation and not 
specifically for this study, it needs not be repeated
after signed ICF has been obtained provided the
assessments fulfill the study requirements and are
performed within the specified timeframe prior to
C1D1.
To clarify that an assessment, if had
be performed routinely, do not need
to be repeated in screening.
4.1.1. Screening 
Phase (Pre- and Full 
Screening) 
 
Following description was added: 
If IHC assay is performed locally, enrollment 
should be considered with reference to the scoring
criteria used in the central IHC assay.
To clarify the IHC scoring criteria
for local IHC assay.
4.1.1. Screening 
Phase (Pre- and Full 
Screening) 
Following description was added: 
If there is a discrepancy between the local and 
central IHC assay, the study treatment may be 
continued at the investigator discretion. 
To clarify that subjects enrolled
with a positive local result can
continue the study even if the
central pathology results are
different from the local results.
4.1.2. Treatment 
Phase 
Addition of the text in bold: 
The treatment phase for a participant will begin on 
C1D1 and continue as 28 day cycles until the EOT 
visit, approximately 30 days after the last dose of 
study treatment. If the initiation of the
subsequent anticancer therapy is required prior
to EOT, EOT must be completed prior to the
initiation of the subsequent anticancer therapy.
Considered the possibility of
starting the next anticancer therapy
immediately after treatment
discontinuation.
4.1.2. Treatment 
Phase 
Post-treatment biopsy, circulating tumor DNA 
(ctDNA), and biomarker at C2D15 as well as per 
the Schedule of Activities (Section 1.3) will be
collected on C2D15 (+1 week ±1 day) from all
participants in Phase 2a.
To align the visit window with
other blood drawing on C2D15.
4.4. End of Study 
Definition
Study completion definition was added. 
To clarify the definition.
5.1. Inclusion 
Criteria 
Inclusion criterion 2. Addition of the following 
text: 
Participant tumor must express either EGFR, cMet, 
or both as determined by either local or central IHC
assay (IHC 1+ or above). A copy of the de-
identified pathology report, or equivalent
information, for IHC analysis must be submitted
during the screening period if local IHC test was
used for the eligibility determination.
 
Phase 2a extension cohorts: Participant tumor must
lack expression of EGFR and MET as determined
by either local or central IHC assessment. A copy
of the de-identified pathology report, or equivalent
information, for IHC analysis must be submitted
durin  g the screenin  g period if local IHC test was
Added text because IHC results
may not be included in pathology
reports.
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Section Number 
and Name
Description of Change 
Brief Rationale
used for the eligibilit y determination.
5.4. Screen Failures 
Following change was made: 
Rescreened participants should be assigned the
same a new participant number as for that is
different from the initial screening.
Correction was made.
6.6.4. Liver 
Chemistry 
Abnormalities 
Following change was made: 
In the event abnormalities of liver function tests
require the dose delay of study treatment, liver
chemistry should be repeated within 1-3 days and
until abnormal values resolve/return to baseline.
EtiologyIf the liver function test criteria either
a) or b) above are met, etiology of the liver
chemistry abnormality should be investigated, as
described below. If no alternative etiology of liver
toxicity is identified, study treatment should be
permanentl y discontinued.
To clarify the definition.
6.8.1.1. 
Amivantamab Pre- 
infusion 
Medications – Table 
7
6.8.1.2. 
Amivantamab Post- 
infusion 
Medications – Table
8
Footnote d was added: 
d. Either IV or oral route is selected for
antihistamine, antipyretic, glucocorticoid and
antiemetic medications.
 
Footnote b was added:
b. Either IV or oral route is selected for antiemetic
medications.
To clarify the description.
6.8.2. Prohibited or 
Restricted 
Medications and 
Therapies 
Addition of the text in bold: 
• Use of live or live attenuated vaccines is
prohibited. COVID-19 vaccine is not considered
as live or live attenuated vaccines but the
administration of COVID-19 vaccine should be
avoided on the same day of study drug
administration.
To clarify COVID-19 vaccination.
7.1. Discontinuation 
of Study Treatment 
Addition of the text in bold: 
If a participant discontinues study treatment for any 
reason, then the EOT assessments should be 
obtained according to the Schedule of Activities 
and follow-up visits should continue after study
treatment is discontinued. If the initiation of the
subsequent anticancer therapy is required prior
to EOT, EOT must be completed prior to the
initiation of  the subsequent anticancer therapy.
Study treatment assigned to the participant who
discontinued study treatment may not be assigned
to another participant. Additional participants will
not be entered in the study.
Considered the possibility of
starting the next anticancer therapy
immediately after treatment
discontinuation.
8.2.3. 
Electrocardiograms 
Following description was deleted: 
If blood sampling or vital sign measurement is 
scheduled for the same time point as ECG
recording, the procedures should be performed in
the following order: ECG(s), vital signs, blood
draw.
To clarify the order of procedures
are not specified.
9.3. Populations for 
Analysis Sets 
‘All enrolled’ population was added. 
 
Followin  g change was made in ‘Response
To clarify and correct the
definition.
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Section Number 
and Name
Description of Change 
Brief Rationale
evaluable’ population:
All participants who satisfy the following criteria:
• Receive at least 1 dose of study treatment
• AtMet all eligibility criteria for the study
• Had a baseline and at least 2 1 post-baseline
efficacy disease assessments, or discontinued
treatment for any reason, or have disease
progression/death due to disease progression prior
to the secondfirst post-baseline disease assessment
10.4. Appendix 4: 
Contraceptive and 
Barrier Guidance
Addition of the text in bold: 
Woman Not of Childbearing Potential
 permanently 
sterile: 
permanent
sterilization 
methods 
include
hysterectomy, bilateral salpingectomy,
bilateral 
tubal 
occlusion/ligation
procedures, 
and 
bilateral
oophorectomy.
To align with other programs of
Amivantamab.
Throughout the
protocol
Minor grammatical, formatting, or spelling changes
were made.
Minor errors were noted.
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11. 
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Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced
gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013;14(6):490-499.
Muro K (2004), Hamaguchi T, Ohtsu A, et al. A phase II study of single-agent docetaxel in patients with metastatic
esophageal cancer. Ann Oncol. 2004;15(6):955-959.
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Version 3.2020. https://www.nccn.org.
Ohtsu A (2011), Shah MA, Van Cutsem E, et al. Bevacizumab in combination with chemotherapy as first-line
therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol.
2011;29(30):3968-3976.
Olayioye MA (2000), Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in
development and cancer. EMBO J. 2000;19(13):3159-3167.
Ozawa Y (2015), Nakamura Y, Fujishima F, et al. c-Met in esophageal squamous cell carcinoma: an independent
prognostic factor and potential therapeutic target. BMC Cancer. 2015;15:451.
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Satoh T (2015), Lee KH, Rha SY, et al. Randomized phase II trial of nimotuzumab plus irinotecan versus irinotecan
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Sattler M (2011), Reddy MM, Hasina R, Gangadhar T, Salgia R. The role of the c-Met pathway in lung cancer and
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January 2021
Vijayaraghavan S (2020), Lipfert L, Chevalier K, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet
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Trogocytosis. Mol Cancer Ther. 2020;19(10):2044-2056.
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panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised,
open-label phase 3 trial. Lancet Oncol. 2013;14(6):481-489.
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esophagogastric junction adenocarcinomas: association with poor outcome. Cancer. 2007;109(4):658-667.
Wilke H (2014), Muro K, Van Cutsem E, et al; RAINBOW Study Group. Ramucirumab plus paclitaxel versus
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Xu YP (2016), Lin G, Sun XJ, et al. C-Met as a Molecular Marker for Esophageal Squamous Cell Carcinoma and Its
Association with Clinical Outcome. J Cancer. 2016;7(5):587-594.
Yamada Y (2015), Higuchi K, Nishikawa K, et al. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus
S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015;26(1):141-148.
Yano S (2003), Kondo K, Yamaguchi M, et al. Distribution and function of EGFR in human tissue and the effect of
EGFR tyrosine kinase inhibition. Anticancer Res. 2003;23(5A):3639-3650.
Yoon HH (2016), Bendell JC, Braiteh FS, et al. Ramucirumab combined with FOLFOX as front-line therapy for
advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: a randomized, double-blind,
multicenter Phase II trial. Ann Oncol. 2016;27(12):2196-2203. 
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Status: Approved,  Date:  16 August 2022
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study treatment, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
 
Date:
  
 
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
 
Date:
  
 
(Day Month Year)
 
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Pharmaceutical K.K
Signature: 
electronic signature appended at the end of the protocol 
Date:
  
 
(Day Month Year)
 
Note: If the address or telephone number of the investigator changes during the course of the study, written
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
NCT04945733
PPD


Signature
User 
Date 
Reason
16-Aug-2022
06:06:55
(GMT)
Document Approval
NCT04945733
PPD

SAP_001.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
1 
Status: Approved,  Date: 11 August 2023 
Janssen Pharmaceutical K.K.* 
Statistical Analysis Plan 
A Phase 2, Open-label Study of Amivantamab in Subjects With Previously Treated 
Advanced or Metastatic Gastric or Esophageal Cancer 
Protocol 61186372GIC2001; Phase 2 
 JNJ-61186372  (Amivantamab)  
*This study is being conducted by Janssen Pharmaceutical K.K. in Japan. The term “sponsor” is used
throughout the protocol to represent Janssen Pharmaceutical K.K.
Status: 
Approved 
Date: 
11 August 2023 
Prepared by: 
Janssen Pharmaceutical K.K. 
Document No.: EDMS-RIM-589988 
Compliance:  The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement 
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
2 
Status: Approved,  Date: 11 August 2023 
TABLE OF CONTENTS 
TABLE OF CONTENTS .......................................................................................................................... 2 
VERSION HISTORY................................................................................................................................ 4 
1. 
INTRODUCTION ............................................................................................................................ 5 
1.1. 
Objectives and Endpoints ............................................................................................................ 5 
1.2. 
Study Design .............................................................................................................................. 5 
2. 
STATISTICAL HYPOTHESES........................................................................................................ 8 
3. 
SAMPLE SIZE DETERMINATION .................................................................................................. 8 
4. 
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS .................................................................... 9 
5. 
STATISTICAL ANALYSES ............................................................................................................ 9 
5.1. 
General Considerations............................................................................................................... 9 
5.1.1. 
Visit Windows .......................................................................................................................... 9 
5.1.2. 
Pooling Algorithm for Analysis Centers..................................................................................... 9 
5.1.3. 
Study Day/Relative Day ........................................................................................................... 9 
5.1.4. 
Baseline Measurement .......................................................................................................... 10 
5.2. 
Participant Dispositions ............................................................................................................. 10 
5.3. 
Primary Endpoint(s) Analysis .................................................................................................... 10 
5.3.1. 
Definition of Endpoint(s) ......................................................................................................... 10 
5.3.2. 
Estimand ............................................................................................................................... 11 
5.3.3. 
Analysis Methods ................................................................................................................... 11 
5.3.4. 
Sensitivity Analysis ................................................................................................................ 13 
5.3.5. 
Supplementary Analysis......................................................................................................... 13 
5.3.5.1. 
ORR for All Treated Population ........................................................................................... 13 
5.3.5.2. 
ORR determined by Independent Review Committee IRC (Phase 2b only) ......................... 13 
5.4. 
Secondary Endpoints Analysis .................................................................................................. 13 
5.4.1. 
Disease Control Rate ............................................................................................................. 13 
5.4.1.1. 
Definition ............................................................................................................................ 13 
5.4.1.2. 
Estimand(s) ........................................................................................................................ 13 
5.4.1.3. 
Analysis Methods ................................................................................................................ 14 
5.4.2. 
Duration of Response ............................................................................................................ 14 
5.4.2.1. 
Definition ............................................................................................................................ 14 
5.4.2.2. 
Estimand(s) ........................................................................................................................ 15 
5.4.2.3. 
Analysis Methods ................................................................................................................ 15 
5.4.3. 
Time to Response .................................................................................................................. 15 
5.4.3.1. 
Definition ............................................................................................................................ 15 
5.4.3.2. 
Estimand(s) ........................................................................................................................ 15 
5.4.3.3. 
Analysis Methods ................................................................................................................ 16 
5.4.4. 
Progression-free Survival ....................................................................................................... 16 
5.4.4.1. 
Definition ............................................................................................................................ 16 
5.4.4.2. 
Estimand(s) ........................................................................................................................ 17 
5.4.4.3. 
Analysis Methods ................................................................................................................ 17 
5.4.5. 
Overall Survival (Phase 2b only) ............................................................................................ 17 
5.4.5.1. 
Definition ............................................................................................................................ 17 
5.4.5.2. 
Estimand(s) ........................................................................................................................ 17 
5.4.5.3. 
Analysis Methods ................................................................................................................ 18 
5.5. 
Tertiary/Exploratory Endpoint(s) Analysis .................................................................................. 18 
5.5.1. 
ORR by IHC result at pre-screening ....................................................................................... 18 
5.5.2. 
ORR by local IHC result ......................................................................................................... 18 
5.6. 
Safety Analyses ........................................................................................................................ 18 
5.6.1. 
Extent of Exposure ................................................................................................................ 18 
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JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
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3 
Status: Approved,  Date: 11 August 2023 
5.6.2. 
Compliance of Disease Evaluation ......................................................................................... 19 
5.6.3. 
Adverse Events ..................................................................................................................... 19 
5.6.3.1. 
Treatment Emergent Adverse Events .................................................................................. 19 
5.6.3.1.1. 
All TEAEs ........................................................................................................................ 20 
5.6.3.1.2. 
Toxicity Grade 3 or higher TEAEs .................................................................................... 20 
5.6.3.1.3. 
Study Drug-Related TEAEs ............................................................................................. 20 
5.6.3.1.4. 
Serious TEAEs ................................................................................................................ 20 
5.6.3.1.5. 
TEAEs Leading to Study Drug Interruption/Dose Reduction/Dose Delay .......................... 20 
5.6.3.1.6. 
TEAEs Leading to Discontinuation of Study drug ............................................................. 20 
5.6.3.2. 
Adverse Events of Special Interest ...................................................................................... 20 
5.6.3.3. 
Deaths ................................................................................................................................ 22 
5.6.3.3.1. 
Death Due to TEAEs ....................................................................................................... 22 
5.6.3.3.2. 
All Deaths ........................................................................................................................ 22 
5.6.4. 
Additional Safety Assessments (if applicable)......................................................................... 22 
5.6.4.1. 
Clinical Laboratory Tests ..................................................................................................... 22 
5.6.4.2. 
Vital Signs and Physical Examination Findings .................................................................... 23 
5.6.4.3. 
Electrocardiogram ............................................................................................................... 23 
5.6.5. 
ECOG Performance Status .................................................................................................... 23 
5.7. 
Other Analyses ......................................................................................................................... 23 
5.7.1. 
Pharmacokinetics .................................................................................................................. 23 
5.7.2. 
Immunogenicity ..................................................................................................................... 24 
5.7.3. 
Pharmacodynamics (PD)/Biomarkers ..................................................................................... 24 
5.7.4. 
Pharmacokinetic/Pharmacodynamic Relationships ................................................................. 25 
5.7.5. 
Health Economics .................................................................................................................. 25 
5.7.6. 
Definition of Subgroups .......................................................................................................... 25 
5.8. 
Interim Analyses ....................................................................................................................... 26 
5.8.1. 
Clinical Trial Management Team ............................................................................................ 26 
6. 
SUPPORTING DOCUMENTATION .............................................................................................. 28 
6.1. 
Appendix 1 List of Abbreviations ............................................................................................... 28 
6.2. 
Appendix 2 Demographics and Baseline Characteristics ........................................................... 29 
6.3. 
Appendix 3 Protocol Deviations ................................................................................................. 31 
6.4. 
Appendix 4 Prior and Concomitant Medications ......................................................................... 32 
6.5. 
Appendix 5 Medical History ....................................................................................................... 33 
6.6. 
Appendix 6 Adverse Events of Special Interest .......................................................................... 34 
6.7. 
Appendix 7 Laboratory Toxicity Grading .................................................................................... 35 
7. 
REFERENCES ............................................................................................................................. 42 
 
 
 
 
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JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
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Status: Approved,  Date: 11 August 2023 
VERSION HISTORY 
Table 1: 
SAP Version History Summary 
SAP Version 
Approval Date 
Change 
Rationale 
1 
25 Nov 2021 
Not Applicable 
Initial release 
2 
11 Aug 2023 
Refer to the Table below 
Refer to the Table below 
 
Amendments below are listed. 
Amendment 1 (11 Aug 2023) 
Summary of key changes: Protocol Amendment 3 was performed to allow higher dose if CTMT 
recommended. The SAP has been updated to align with protocol language and analyze per dose group. 
Sections 
Description of Changes 
Rationale 
Section 1.2 
Update description for potential new dose if 
recommended by CTMT, eligibility criteria 
and EOT assessment. 
Per changes in Protocol Amend 3. 
Section 3. Sample Size 
Determination 
Added the target sample size for higher 
dose if CTMT recommended. 
Per changes in Protocol Amend 3 
to allow higher dose if CTMT 
recommend. 
Section 4. Populations 
(Analysis sets) for analysis 
Add Enrolled sets. 
To analyze number of subjects 
included in each analysis sets. 
Section 5.3.3 Analysis 
Methods 
Add best response analysis and the 
minimum duration of SD. 
To understand the activity of 
amivantamab for this population, 
the best response analysis is added. 
Section 5.6.1 Extent of 
Exposure 
Add sentence to clarify to summarize both 
prior and during infusion. 
To summarize exposure related 
events both prior and during 
infusion. 
Section 5.6.2 Compliance 
of Disease evaluation 
Add analysis for missing assessment due to 
COVID. 
To assess the impact of COVID to 
the study result. 
Section 5.7.6 Definition of 
subgroups 
Add new subgroup for EGFR, cMET 
(0+/1+, ≥2+), prior ramucirumab use and 
prior anti HER2 therapy use. 
To investigate the relationship 
between biomarker expression and 
efficacy as well as prior therapy 
used. 
Section 5.8.1 Clinical trial 
management team. 
Add interim futility analysis for higher 
dose. 
To align with Protocol Amend 3.  
Section 6.1 Appendix 2. 
Demographics and baseline 
Characteristics. 
Add analysis for prior fluoropyrimidine 
agent use, prior platinum agent use, prior 
ramucirumab use, prior anti HER2 therapy 
use. 
To summarize distribution of prior 
therapy more detail. 
 
 
 
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JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
5 
Status: Approved,  Date: 11 August 2023 
1. 
INTRODUCTION 
This statistical analysis plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical methods for the Phase 2 study of amivantamab in subjects with previously treated 
advanced or metastatic gastric cancer (GC) or esophageal cancer (EC). The SAP is to be interpreted 
in conjunction with the protocol. This SAP covers the planned analysis for the clinical study report 
(CSR). 
1.1. 
Objectives and Endpoints 
Following objectives and end points are defined as per the protocol v3.0 (16 August 2022): 
Objectives 
Endpoints 
Primary 
 
To investigate the activity of amivantamab in 
gastric cancer (GC) and esophageal cancer 
(EC) participants (Phase 2a) 
 
To characterize the preliminary antitumor 
activity of amivantamab in selected GC and EC 
population (Phase 2b) 
 
Objective 
response 
rate, 
as 
determined 
by 
investigator, according to the Response Criteria in 
Solid Tumors (RECIST) Version 1.1.  
Secondary 
 
To assess additional measures of clinical 
benefits with amivantamab 
 
Disease control rate (DCR), duration of response 
(DoR), time to response (TTR), progression-free 
survival (PFS), and overall survival (OS; Phase 2b 
only). 
 
To confirm the safety of amivantamab in 
participants with gastric or esophageal cancers 
(ECs) 
 
Adverse events defined by the National Cancer 
Institute Common Terminology Criteria for Adverse 
Events (NCI-CTCAE) Version 5.0 in participants 
treated with amivantamab 
 
To assess the pharmacokinetics (PK) and 
immunogenicity of amivantamab following 
multiple intravenous dose administrations 
 
Serum PK parameters including but not limited to 
maximum serum concentration (Cmax), time to reach 
the maximum serum concentration (Tmax), area under 
the 
curve 
(AUC)(t1-t2), 
AUCtau, 
plasma/serum 
concentration immediately prior the next study 
treatment administration (Ctrough), and accumulation 
ratio; incidence of anti-amivantamab antibodies 
Exploratory 
 
Explore biomarkers predictive of clinical response and resistance to amivantamab in blood and tumor tissue 
 
Explore the relationship between serum PK and pharmacodynamic (PD) markers (eg, soluble EGFR and 
cMet) 
 
Determine whether amivantamab can impact the anti-tumor immune response or microenvironment 
1.2. 
Study Design 
This is an open-label, multicenter, multi-arm Phase 2 interventional study in participants with 
previously treated advanced or unresectable GC or EC who are 20 years or older (or the legal age 
of consent in the jurisdiction in which the study is taking place). The participants with gastric/GEJ 
or EC who express varying degrees of EGFR, cMet, or both as determined by IHC locally or 
centrally will be enrolled in the GC cohort or EC cohort. If activity is demonstrated in the Phase 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
6 
Status: Approved,  Date: 11 August 2023 
2a cohorts, Phase 2a extension cohorts investigating participants without expression of EGFR and 
cMet, may open for enrollment upon agreement with the CTMT. If activity is observed within the 
Phase 2a cohorts, the corresponding Phase 2b GC or EC expansion cohorts will be initiated to 
evaluate the antitumor activity of amivantamab in selected GC and EC participants based upon the 
prospective assessment of IHC during Phase 2a. 
A maximum of approximately 302 participants will be enrolled in the combined Phase 2a and 
Phase 2b populations, in the event the efficacy observed in both Phase 2a cohorts warrants full 
enrollment in their respective Phase 2b cohorts. Approximately, 30 response evaluable participants 
will be enrolled in each of Phase 2a GC and EC arm. However, based on the prior experiences 
investigating anti-EGFR and anti-cMet antibodies in gastroesophageal cancers, at least 20 
participants expressing IHC 2+ or higher (defined as participants expressing EGFR IHC 2+ or 
above or cMet IHC 2+ or above) will be enrolled. Moreover, at least 10 participants expressing 
any level of cMet protein (IHC1+ or above) will be enrolled in each Phase 2a cohort to better 
characterize the contribution of cMet in amivantamab activity. The CTMT may allow additional 
enrollment in the Phase 2a cohorts to achieve this minimal enrollment, if these criteria aren’t met 
in the initial 30 evaluable subjects. If activity is demonstrated in the Phase 2a cohorts, Phase 2a 
expansion cohorts investigating a maximum of 11 participants without any expression of EGFR 
and cMet, may open for enrollment upon agreement with the CTMT. The CTMT will assess the 
data and may recommend additional participants to be enrolled for further characterization if 2 or 
more responses are observed in each of Phase 2a GC or EC extension cohorts. Based on emerging 
data, the CTMT may also recommend exploration of higher doses of amivantamab. The Phase 2b 
GC expansion or EC expansion cohorts will evaluate the antitumor activity of amivantamab in GC 
and EC patients, using biomarker selection based upon Phase 2a results. If activated, 
approximately 100 participants will be enrolled in each of the Phase 2b cohorts. Details of CTMT 
are described in Section 5.8.1. 
The study will include a Screening phase, a Treatment phase, and a Follow-up phase (Phase 2b 
only). During the full screening period, participants will be evaluated for eligibility for study 
participation. Participants must complete all screening procedures within 28 days of C1D1. 
Pretreatment biopsy will be collected for all participants in Phase 2a and Phase 2b.  The tumor 
IHC result regardless of the local or central must be obtained and confirmed for the eligibility prior 
to C1D1. If the central tumor IHC is used for the eligibility prior to the initiation of the study 
treatment and the central results are not completed during the screening period, the screening 
period can be extended by 14 days. However, all other assessments must still meet timing criteria 
relative to C1D1 or must be repeated. 
The treatment phase for a participant will begin on C1D1 and continue as 28-day cycles until the 
end-of-treatment (EOT) visit, approximately 30 days after the last dose of study treatment. If the 
initiation of the subsequent anticancer therapy is required prior to EOT, EOT must be completed 
prior to the initiation of the subsequent anticancer therapy. This study will be conducted in an 
outpatient setting. However, in-hospital observation, from C1D1 until C1D8 is permitted in the 
Phase 2a (including Phase 2a extension cohorts) to allow close monitoring at the discretion of the 
investigator. Study treatment will continue until documented clinical or radiographic (RECIST 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
7 
Status: Approved,  Date: 11 August 2023 
Version 1.1) disease progression or until the participant meets another criterion for discontinuation 
of study treatment. Disease assessments will occur as close as possible to the start of treatment 
(baseline screening scans), 6 weeks (+1 week) after the first dose of study treatment, then every 
6 weeks (±1 week) for the first 12 months and then every 12 weeks (±1 week) until objective 
radiographic disease progression or withdrawal of consent. 
The follow up Phase is scheduled only in Phase 2b. Participants who discontinue study treatment 
will be followed for subsequent therapy, disease status (applicable only if participants 
discontinuing treatment due to reasons other than progressive disease, to confirm disease 
progression date), and survival in the follow-up phase. This phase starts from the EOT visit 
assessment will be done every 12 weeks (±14 days) after the last dose of study treatment or disease 
progression (whichever occurs first) and continues until the end of study, death, lost to follow-up, 
or withdrawal of consent from participation in the study, whichever comes first. 
The primary efficacy endpoint is objective response rate (ORR). Objective response rate is defined 
as the proportion of participants who achieve either complete response (CR) or partial response 
(PR), determined by investigator assessment using RECIST Version 1.1. Confirmation of 
investigator-assessed ORR may be performed through IRC in the Phase 2b. 
Safety will be assessed by physical examinations, laboratory tests, vital signs, electrocardiograms, 
Eastern Cooperative Oncology Group (ECOG) performance status, monitoring of adverse events, 
and concomitant medication usage. 
A diagram of the study design is provided in Figure 1, as follows: 
Figure 1: 
Schematic Overview of the Study 
 
*At least 20 participants with IHC2+ or higher and at least 10 participants with cMet expression will be enrolled.  
†Participants without expression of EGFR and cMet 
If the CTMT recommends exploration of higher dose levels, approximately 20 response evaluable participants with 
expression of EGFR and/or cMet will be enrolled in each dose cohort. 
 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
8 
Status: Approved,  Date: 11 August 2023 
Blinding 
This is an open-label study. 
2. 
STATISTICAL HYPOTHESES 
No hypothesis is planned to be tested in Phase 2a. 
The statistical hypothesis in Phase 2b is that amivantamab monotherapy will lead to objective 
response rate (ORR) higher than 15% (ie, H0 ≤15% vs Ha >15%) in patients with GC or EC, 
selected on the basis of expression of EGFR, cMET, or both. This threshold is based on historical 
studies for approved 3L regimens for GC (11.2%-13.6%) and reported efficacy of approved 2L 
regimens for EC (approximately 15%). The interim analysis with subpopulation selection is 
planned in Phase 2b, so multiplicity caused by subpopulation selection will be controlled by closed 
testing procedure and weighted statistics. 
3. 
SAMPLE SIZE DETERMINATION 
In Phase 2a, approximately 30 response evaluable participants with tumors expressing either 
EGFR, cMet, or both, as determined by central IHC, will be enrolled in GC and EC cohorts. 
Twenty participants will be enrolled for IHC 2+/3+ that will provide approximately 90% 
probability to observe the posterior probability of (ORR >22.5%) ≥40% (which is similar with 
ORR ≥20%) assuming ORR is 30% for the subpopulation. By enrolling 10 participants with IHC 
1+, the probability to observe the posterior probability (ORR >22.5%) ≥40% is 80%. Upon 
agreement with CTMT, a maximum of 11 participants may be enrolled in each Phase 2a extension 
cohort. Enrollment will halt if no response or stable disease of 6 weeks or more is observed among 
the first 6 participants for futility in each of the Phase 2a extension cohorts. If 2 or more responses 
are observed in each of Phase 2a extension cohorts, CTMT will assess the data and may 
recommend additional participants to be enrolled for further characterization. 
In each dose cohort of Phase 2a, approximately 20 response evaluable participants will be 
additionally enrolled if the CTMT recommends exploration of higher doses. The probability to 
observe 4 or more response (ORR >= 20%) is 89% assuming ORR of 30%. 
In Phase 2b cohorts, approximately 100 participants will be enrolled in each of GC and EC 
expansion cohort. The eligible participants will be decided based on the results in Phase 2a part. 
Assuming an overall ORR of 30% for amivantamab, 100 participants in Phase 2b part will provide 
approximately 90% power to reject the null hypothesis, 15% ORR, using 2-side z test at 
alpha=0.05.  
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
9 
Status: Approved,  Date: 11 August 2023 
4. 
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS 
For purposes of analysis, the following populations are defined: 
Population 
Description 
All Enrolled 
All participants who are assigned with study treatment. 
All Treated 
All participants who take at least 1 dose of study treatment 
Response  
Evaluable 
All participants who satisfy the following criteria: 
• Receive at least 1 dose of study treatment 
• Met all eligibility criteria for the study 
• Had a baseline and at least 1 post-baseline efficacy disease assessments, or have 
disease progression/death due to disease progression prior to the first post-baseline 
disease assessment 
Safety 
All participants who take at least 1 dose of study treatment 
Pharmacokinetics 
All participants who receive at least 1 dose of study treatment and have at least 
1 evaluable post-baseline measurement 
Immunogenicity 
All participants who receive at least 1 dose of study treatment and have at least 
1 evaluable post-baseline measurement 
Biomarker 
All participants who receive at least 1 dose of study treatment and have at least 
1 biomarker measurement 
Analyses of ORR and disease control rate (DCR) will be performed on the Response Evaluable 
Population. The other efficacy analyses will be performed on All Treated Population. 
5. 
STATISTICAL ANALYSES 
5.1. 
General Considerations 
Unless otherwise specified, the phases (Phase 2a or 2b), cohort (GC or EC) and dose regimen (if 
applicable) will be analyzed separately. The efficacy analysis will be performed by IHC subgroups 
(≥2+, 1+, 0+, not available). 
5.1.1. 
Visit Windows 
The study will consist of 3 phases: a Screening Phase, a Treatment Phase, and a Follow-up Phase. 
The Screening Phase will start up to 28 days before randomization. The Treatment Phase will 
extend from Cycle 1 Day 1 to until the end-of-treatment (EOT) visit, approximately 30 days after 
discontinuation of study treatment. Scheduled visits within each cycle will have a window up to 
±1 day as per SoA in study protocol (except C1D1 and C1D2 with no window and C3 and after 
with ±3 day window). 
Visit windowing will be based on cycles. Unless otherwise specified, data to be analyzed or 
presented over time will be presented by cycle, day and time point (as appropriate) that are 
recorded in CRF. 
5.1.2. 
Pooling Algorithm for Analysis Centers 
There will be no pooling of centers for analyses. 
5.1.3. 
Study Day/Relative Day 
Study day or relative day is defined as: 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
10 
Status: Approved,  Date: 11 August 2023 
 
Reference date (Day 1) = first dose date of amivantamab. 
 
Study Day = assessment date – reference date + 1 for assessment performed on or after the 
reference date; assessment date – reference date for assessment performed before the reference 
date. 
There is no 'Day 0'. First dose date will be the date of starting amivantamab. 
5.1.4. 
Baseline Measurement 
Baseline measurement is defined as the closest non-missing measurement taken on or prior to the 
first study drug administration (including time if time is available). If the first administration date 
is missing or the administration is not done, then the baseline measurement is the closest non-
missing measurement taken on or prior to the corresponding visit date. 
For IHC, EGFR and cMET, the data by centrally performed IHC assay will be used. The tissue 
samples obtained at full screening visit will be used as baseline, if available. 
5.2. 
Participant Dispositions 
Screened participants and reason for screen failures will be summarized overall. 
The number of participants in the following disposition categories will be summarized throughout 
the study by intervention group and overall: 
 
Participants who received study intervention 
 
Participants who terminated study prematurely 
 
Participants who completed the study 
 
Reason for termination of study 
 
Participants who discontinued study intervention 
 
Reasons for discontinuation of study intervention 
The number of participants who discontinued treatment by cycle with reported reasons will also 
be provide. 
Listings of participants will be provided for the following categories: 
 
Participants who discontinued study intervention 
 
Participants who terminated study prematurely 
5.3. 
Primary Endpoint(s) Analysis 
Overall response rate (ORR) as per RECIST v.1.1 as evaluated by the investigator.  
5.3.1. 
Definition of Endpoint(s) 
ORR is defined as the proportion of subjects achieved either a confirmed CR or PR based on 
RECIST v. 1.1. among Response Evaluable Population. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
11 
Status: Approved,  Date: 11 August 2023 
5.3.2. 
Estimand 
Estimand Scientific Question of Interest: What is the overall response rate under receiving 
amivantamab monotherapy in patients with EGFR mutation or cMET expressed GC or EC? 
Study intervention: amivantamab monotherapy 
Population: participants with previously treated advanced or metastatic GC or EC expressing 
EGFR and/or MET  
Variable: overall response; a confirmed CR or PR, determined by investigator assessment using 
RECIST Version 1.1  
Summary Measure (Population-level summary): ORR  
Intercurrent event: 
Intercurrent Events 
Name of Strategy for Addressing Intercurrent Events and 
Its Description 
Study treatment discontinuation due to 
any reason 
Treatment Policy strategy: use response, regardless of 
whether or not study treatment discontinuation had occurred 
Subsequent anticancer therapy 
While-on-treatment policy strategy: Response after this 
intercurrent event will not be included 
5.3.3. 
Analysis Methods 
Phase 2a 
There will be no formal hypothesis testing. ORR will be calculated for response evaluable 
population descriptively. The 95% confidence interval will also be calculated by Clopper-Pearson 
method. 
The posterior probability of ORR >22.5% will also be evaluated based on beta distribution. Let ߠ 
be the distribution of ORR following beta distribution and the non-informative beta distribution 
ߠ଴ will be used as a prior.  
ߠ଴~ܤ݁ݐܽሺ1, 1ሻ 
When n1 of responder and n2 of non-responder are observed, the posterior distribution follows beta 
distribution 
ߠ~ܤ݁ݐܽሺ1 + ݊ଵ, 1 + ݊ଶሻ 
The Pr (ORR >22.5%) will be derived from following formula. 
න
݌ሺߠ|݊ଵ, ݊ଶሻ݀ߠ
ଵ
଴.ଶଶହ
 
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JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
12 
Status: Approved,  Date: 11 August 2023 
The ORR, 95% confidence interval and Pr (ORR >22.5%) will be calculated for IHC subgroup 
variant 2 defined in Section 5.7.6. 
The best overall response (BOR) will also be summarized. The minimum duration for BOR of SD 
is 6 weeks from the baseline. 
 
Phase 2b 
A z test with normal approximation (i.e, continuous correction) will be used to compare the ORR 
with 15%. An interim futility analysis is planned in each of GC and EC arm approximately 
12 weeks after 50 participants receive the first infusion. If both IHC 2+/3+ and IHC 1+ populations 
are included in Phase 2b, based on posterior probability, IDMC will make a recommendation 
whether both populations, only IHC 2+/3+ subpopulation or neither of them should continue the 
study. To control multiplicity caused by this subpopulation selection at the interim analysis, closed 
testing procedure and weighted statistics proposed by Jenkins (2011) et al will be applied. 
Let ݌ଵ
ଵ and ݌ଵ
ଶ be 1 sided p-value for overall population and IHC 2+/3+ subpopulation from 
participants at IA (i.e, first ݊ଵ= 50 participants) and  ݌ଵ
ଵ,ଶ be p-value for intersection hypothesis 
corresponding with ݌ଵ
ଵ and ݌ଵ
ଶ,which is adjusted by Simes test as 
pଵ
ଵ,ଶ= min ሾ2minሼpଵ
ଵ, pଵ
ଶሽ, maxሼpଵ
ଵ, pଵ
ଶሽሿ 
Let ݌ଶ be p-value from participants only after IA (i.e, later ݊ଶ= 50 participants) in selected 
population at IA (either overall or IHC 2+/3+ subpopulation). The weighted test statistics will be 
applied to calculate p value. If overall population is selected at IA and both of p value derived from 
test statistics below are less than 0.025, the null hypothesis will be rejected.  
√݊ଵ
√݊ଵ+ ݊ଶ
ߔିଵሺ1 −݌ଵ
ଵሻ+
√݊ଶ
√݊ଵ+ ݊ଶ
ߔିଵሺ1 −݌ଶሻ 
√݊ଵ
√݊ଵ+ ݊ଶ
ߔିଵ൫1 −݌ଵ
ଵ, ଶ൯+
√݊ଶ
√݊ଵ+ ݊ଶ
ߔିଵሺ1 −݌ଶሻ 
If 2+/3+ subpopulation is selected at IA and both of p value derived from test statistics below are 
less than 0.025, the null hypothesis will be rejected. 
√݊ଵ
√݊ଵ+ ݊ଶ
ߔିଵሺ1 −݌ଵ
ଶሻ+
√݊ଶ
√݊ଵ+ ݊ଶ
ߔିଵሺ1 −݌ଶሻ 
√݊ଵ
√݊ଵ+ ݊ଶ
ߔିଵ൫1 −݌ଵ
ଵ, ଶ൯+
√݊ଶ
√݊ଵ+ ݊ଶ
ߔିଵሺ1 −݌ଶሻ 
In the preceding formulas, Φ is the cumulative distribution function of the standard normal 
distribution. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
13 
Status: Approved,  Date: 11 August 2023 
The ORR and its 95% confidence interval (CI) will also be calculated. The 95% CI will be derived 
by grid search of threshold when 2 sided p-value is 0.05. 
The best overall response (BOR) will also be summarized. The minimum duration for BOR of SD 
is 6 weeks from the baseline. 
5.3.4. 
Sensitivity Analysis 
No sensitivity analysis is planned. 
5.3.5. 
Supplementary Analysis 
5.3.5.1. 
ORR for All Treated Population 
The supplementary analysis will be performed for All Treated Population in the same manner with 
primary estimand. 
5.3.5.2. 
ORR determined by Independent Review Committee IRC (Phase 2b 
only) 
If tumor response is assessed by independent review committee (IRC) in Phase 2b, the 
supplementary analysis will be performed using the ORR determined by IRC in the same manner 
with the primary estimand. 
5.4. 
Secondary Endpoints Analysis 
Following secondary endpoints analysis is planned to be performed.  
For disease control rate (DCR), duration of response (DoR) and progression free survival (PFS), 
if tumor response is assessed by IRC in Phase 2b, the analysis will also be performed using the 
response determined by IRC. The estimands is the same as the one using response determined by 
investigator described below with only the variable changing to the one determined by IRC. 
5.4.1. 
Disease Control Rate 
5.4.1.1. 
Definition 
Disease control rate is defined as the percentage of participants achieving CR, PR or stable disease 
for at least 6 weeks determined by investigator assessment using RECIST Version 1.1.  
5.4.1.2. 
Estimand(s) 
Estimand Scientific Question of Interest: What is the DCR under receiving amivantamab 
monotherapy in patients with EGFR mutation or cMET expressed GC or EC? 
Study intervention: amivantamab monotherapy 
Population: participants with previously treated advanced or metastatic GC or EC expressing 
EGFR and/or MET  
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
14 
Status: Approved,  Date: 11 August 2023 
Variable: disease control; CR, PR or stable disease for at least 6 weeks, determined by investigator 
assessment using RECIST Version 1.1  
Summary Measure (Population-level summary): DCR  
Intercurrent event:  
Intercurrent Events 
Name of Strategy for Addressing Intercurrent Events and Its 
Description 
Study treatment discontinuation due to 
any reason 
Treatment Policy strategy: use response, regardless of whether 
or not study treatment discontinuation had occurred 
Subsequent anticancer therapy 
While-on-treatment policy strategy: Response after this 
intercurrent event will not be included 
5.4.1.3. 
Analysis Methods 
The DCR and its 95% CI with Clopper-Pearson method will also be calculated. 
5.4.2. 
Duration of Response 
5.4.2.1. 
Definition 
Duration of Response (DoR) is defined as the time from the date of first documented response (CR 
or PR) until the date of documented progression or death, whichever comes first. The end of 
response should coincide with the date of progression or death from any cause used for the PFS 
endpoint. If a participant does not progress following a response, then his/her duration of response 
will use the PFS censoring time. This analysis only includes participants who achieve CR or PR. 
Key censoring rules for DoR are summarized below. 
Situation 
Date of Censoring 
No evaluable baseline or postbaseline 
disease assessment 
Censored at the date of initial amivantamab administration 
No documented disease progression or 
death 
Censored at the date of last evaluable disease assessment using 
RECIST Version 1.1 
Receive subsequent therapy 
Censored at the date of last evaluable disease assessment using 
RECIST Version 1.1 before the start of subsequent therapy 
Documented disease progression or death 
after 
2 
or 
more 
consecutive 
missed/unevaluable disease assessments* 
Censored at the date of last evaluable disease assessment before 
the missed/unevaluable visits. However, if an adequate image-
based response assigned as CR, PR, or stable disease is obtained 
after 2 or more consecutive missed/unevaluable disease 
assessments, then the tumor response assessment will not be 
excluded from the analysis as long as no other censoring events 
have occurred. 
*If no evaluable disease assessment before the consecutive missed/unevaluable visits, participants will be censored 
at the date of initial amivantamab administration. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
15 
Status: Approved,  Date: 11 August 2023 
5.4.2.2. 
Estimand(s) 
Estimand Scientific Question of Interest: How long the response will be kept under receiving 
amivantamab monotherapy after CR or PR is observed in patients with EGFR mutation or MET 
expressed GC or EC? 
Study intervention: amivantamab monotherapy 
Population: participants with previously treated advanced or metastatic GC or EC expressing 
EGFR and/or MET who achieve CR or PR during amivantamab administration before receiving 
subsequent anticancer therapy 
Variable: DoR  
Summary Measure (Population-level summary):  Median DoR 
Intercurrent event:  
Intercurrent Events 
Name of Strategy for Addressing Intercurrent Events and 
Its Description 
Study treatment discontinuation due to 
any reason 
Treatment Policy strategy: use response, regardless of 
whether or not study treatment discontinuation had occurred 
Subsequent anticancer therapy 
Hypothetical strategy: Response after this intercurrent event 
will not be included 
Death 
Composite strategy: death being a component of the variable 
5.4.2.3. 
Analysis Methods 
A Kaplan-Meier plot and median DoR with 95% confidence interval (calculated from the Kaplan-
Meier estimate) will be presented. A swim lane plot for responders will also be presented. 
5.4.3. 
Time to Response 
5.4.3.1. 
Definition 
Time to response is defined as the time from the date of first amivantamab administration to the 
date of achieving objective response (CR or PR) by investigator assessment using RECIST Version 
1.1 among patients who achieve objective response. This analysis only includes participants who 
achieve CR or PR. 
5.4.3.2. 
Estimand(s) 
Estimand Scientific Question of Interest: How long it will take to achieve CR or PR under 
receiving amivantamab monotherapy in patients with EGFR mutation or cMET expressed GC or 
EC? 
Study intervention: amivantamab monotherapy 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
16 
Status: Approved,  Date: 11 August 2023 
Population: participants with previously treated advanced or metastatic GC or EC expressing 
EGFR and/or MET achieve CR or PR during amivantamab administration before receiving 
subsequent anticancer therapy  
Variable: Time to Response  
Summary Measure (Population-level summary): Median time to response 
Intercurrent event:  
Intercurrent Events 
Name of Strategy for Addressing Intercurrent Events and 
Its Description 
Study treatment discontinuation due to
any reason 
Treatment Policy strategy: use response, regardless of 
whether or not study treatment discontinuation had occurred 
5.4.3.3. 
Analysis Methods 
A Kaplan-Meier plot and median time to response with 95% confidence interval (calculated from 
the Kaplan-Meier estimate) will be presented. 
5.4.4. 
Progression-free Survival  
5.4.4.1. 
Definition 
Progression-free survival is defined as the time from first dose until the date of objective disease 
progression or death (by any cause in the absence of progression), whichever comes first, based 
on investigator assessment using RECIST Version 1.1. Participants who have not progressed or 
have not died at the time of analysis will be censored at the time of the latest date of assessment 
from their last evaluable RECIST Version 1.1 assessment.  
Key censoring rules for PFS are summarized below. 
Situation 
Date of Censoring 
No evaluable baseline or postbaseline disease 
assessment 
Censored at the date of initial amivantamab administration 
No documented disease progression or death Censored at the date of last evaluable disease assessment using RECIST 
Version 1.1 
Receive subsequent therapy 
Censored at the date of last evaluable disease assessment using RECIST 
Version 1.1 before the start of subsequent therapy 
Documented disease progression or death 
after 
2 
or 
more 
consecutive 
missed/unevaluable disease assessments* 
Censored at the date of last evaluable disease assessment before the 
missed/unevaluable visits. However, if an adequate image-based 
response assigned as CR, PR, or stable disease is obtained after 2 or 
more consecutive missed/unevaluable disease assessments, then the 
tumor response assessment will not be excluded from the analysis as 
long as no other censoring events have occurred. 
*If no evaluable disease assessment before the consecutive missed/unevaluable visits, participants will be censored 
at the date of initial amivantamab administration. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
17 
Status: Approved,  Date: 11 August 2023 
5.4.4.2. 
Estimand(s) 
Estimand Scientific Question of Interest: How long amivantamab monotherapy can prevent 
disease progression in patients with EGFR mutation or MET expressed GC or EC? 
Study intervention: amivantamab monotherapy 
Population: participants with previously treated advanced or metastatic GC or EC expressing 
EGFR and/or MET  
Variable: PFS 
Summary Measure (Population-level summary):  Median PFS 
Intercurrent event:  
Intercurrent Events 
Name of Strategy for Addressing Intercurrent Events and 
Its Description 
Study treatment discontinuation due to
any reason 
Treatment Policy strategy: use response, regardless of whether 
or not study treatment discontinuation had occurred 
Subsequent anticancer therapy 
Hypothetical strategy: Observation after this intercurrent event 
will not be included 
Death 
Composite strategy: death being a component of the variable 
5.4.4.3. 
Analysis Methods 
A Kaplan-Meier plot and median PFS with 95% confidence interval (calculated from the Kaplan-
Meier estimate) will be presented. 
5.4.5. 
Overall Survival (Phase 2b only) 
5.4.5.1. 
Definition 
Overall survival is defined as the time from the date of first dose until the date of death due to any 
cause. Any participant not known to have died at the time of analysis will be censored based on 
the last recorded date on which the participant was known to be alive. 
Key censoring rules for OS are summarized below. 
Situation 
Date of Censoring 
No documented death 
Censored at the date of last recorded date on which the participant 
was known to be alive 
5.4.5.2. 
Estimand(s) 
Estimand Scientific Question of Interest: How long participants with EGFR mutation or MET 
expressed GC or EC can survive by receiving amivantamab monotherapy  
Study intervention: amivantamab monotherapy 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
18 
Status: Approved,  Date: 11 August 2023 
Population: participants with previously treated advanced or metastatic GC or EC expressing 
EGFR and/or MET  
Variable: OS 
Summary Measure (Population-level summary):  Median survival time 
Intercurrent Events 
Name of Strategy for Addressing Intercurrent Events and 
Its Description 
Study treatment discontinuation due to
any reason 
Treatment Policy strategy: use time to death, regardless of 
whether or not study treatment discontinuation had occurred  
Subsequent anticancer therapy 
Treatment Policy strategy:  use time to death, regardless of 
whether or not started subsequent anticancer therapies 
5.4.5.3. 
Analysis Methods 
A Kaplan-Meier plot and median OS with 95% confidence interval (calculated from the Kaplan-
Meier estimate) will be presented. 
5.5. 
Tertiary/Exploratory Endpoint(s) Analysis 
5.5.1. 
ORR by IHC result at pre-screening 
The exploratory analysis will be performed by using central IHC result at pre-screening in the 
same manner with primary estimand. The concordance of IHC result between pre-screening and 
screening will also be summarized. 
5.5.2. 
ORR by local IHC result 
The exploratory analysis will be performed by using local IHC result at screening in the same 
manner with primary estimand. The concordance between central and local IHC result will also be 
summarized. 
5.6. 
Safety Analyses 
All safety analyses will be based on the safety analysis set. 
For all continuous safety variables, descriptive statistics will include the N, mean, standard 
deviation, median, minimum, and maximum. Categorical variables will be summarized using 
frequency counts and percentages. 
5.6.1. 
Extent of Exposure 
All the exposure information will be summarized based on safety analysis set. Study treatment 
duration is defined as (date of last dose of study intervention – date of first dose of intervention) 
+1. Descriptive statistics for duration of study intervention will be presented in months. 
The total number of administration cycles of amivantamab received for each participant will be 
summarized by descriptive statistics. Cumulative duration of amivantamab will be provided by 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
19 
Status: Approved,  Date: 11 August 2023 
cycle (≥1 cycle, ≥2 cycles, …). Total number of amivantamab infusion and the total dose of 
amivantamab for each participant will be summarized by descriptive statistics. 
The relative dose intensity (%) defined as the ratio of total received dose versus total prescribed 
dose will be summarized by descriptive statistics.  
The number (%) of participants with a dose modification prior to infusion (such as dose reduction, 
dose not administrated and cycle delay) and its reason will be summarized. A dose modification 
during infusion (such as infusion abort, infusion interruption and infusion rate decrease) will also 
be summarized. 
5.6.2. 
Compliance of Disease Evaluation 
Tumor assessment will occur at regular intervals, as defined per SoA in study protocol. Descriptive 
statistics will be provided for imaging assessments separately for the All Treated Population for: 
 
Number of participants missed at least 1 scheduled disease evaluation 
 
Number of participants missed 2 or more consecutive scheduled disease evaluation 
 
Number of missed scheduled disease evaluation per participant 
The missing assessments due to COVID-19 will also be summarized. 
5.6.3. 
Adverse Events 
The verbatim terms used in the CRF by investigators to identify adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after the 
initial administration of study intervention through the day of last dose plus 30 days or until the 
start of subsequent anticancer therapy, if earlier, is considered to be treatment emergent. If the 
event occurs on the day of the initial administration of study intervention, and either event time or 
time of administration are missing, then the event will be assumed to be treatment emergent. If the 
event date is recorded as partial or completely missing, then the event will be considered to be 
treatment emergent unless it is known to be prior to the first administration of study intervention 
based on partial onset date or resolution date. All reported treatment-emergent adverse events will 
be included in the analysis.  For each adverse event, the number and percentage of participants 
who experience at least 1 occurrence of the given event will be summarized by the phases (Phase 
2a or 2b) and cohort (GC or EC). 
The incidence (%) of TEAEs will be summarized overall, by MedDRA system organ class (SOC) 
and preferred term (PT), by toxicity grade, and by relationship to study drug administration. 
5.6.3.1. 
Treatment Emergent Adverse Events 
An overview of TEAEs reported through the study will be provided. The overview will include 
summaries of participants with TEAEs, with TEAEs related to study intervention, with TEAEs of 
maximum toxicity grade of 1 to 5, Serious TEAEs, TEAEs leading to discontinuation of study 
intervention, and deaths due to TEAE. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
20 
Status: Approved,  Date: 11 August 2023 
5.6.3.1.1. 
All TEAEs 
 
Incidence (%) of TEAEs by SOC and PT 
5.6.3.1.2. 
Toxicity Grade 3 or higher TEAEs 
 
Incidence (%) of toxicity grade 3 or higher TEAEs by SOC and PT 
5.6.3.1.3. 
 Study Drug-Related TEAEs 
 
Incidence (%) of TEAEs by relationship to study treatment, and by SOC and PT 
 
Incidence (%) of TEAEs with toxicity grade 3 or higher by relationship to study treatment, 
and by SOC and PT 
 
Incidence (%) of TEAEs leading to study treatment interruption/dose reduction by 
relationship to study treatment, and by SOC and PT 
 
Incidence (%) of TEAEs leading to study treatment discontinuation by relationship to study 
treatment, and by SOC and PT 
5.6.3.1.4. 
 Serious TEAEs 
 
Incidence (%) of serious TEAEs by SOC and PT 
 
Incidence (%) of serious TEAEs by toxicity grade, and by SOC and PT 
 
Incidence (%) of serious TEAEs by relationship to study treatment, and by SOC and PT 
 
Listing of participants with any serious TEAEs 
5.6.3.1.5. 
TEAEs Leading to Study Drug Interruption/Dose Reduction/Dose 
Delay 
Incidence (%) of TEAEs leading to study treatment reduction and dose delay will be summarized 
respectively by SOC and PT. The summaries will be presented for all toxicity grades and for 
toxicity grade 3 or higher. In addition, the summary by relationship will be presented. 
5.6.3.1.6. 
TEAEs Leading to Discontinuation of Study drug 
Incidence (%) of TEAEs leading to study treatment discontinuation will be summarized by SOC 
and PT. The summaries will be presented by all toxicity grades and toxicity grade 3 or higher. In 
addition, the summary by relationship will be presented. The AEs leading to discontinuation of 
study treatment are based on AEs recorded in the AE CRF page with an action taken of drug 
withdrawal for any study drug. 
5.6.3.2. 
Adverse Events of Special Interest 
Adverse events of special interest are pneumonitis/interstitial lung disease (ILD), rash, and 
infusion-related-reaction (IRR). The MedDRA preferred terms associated with each of these 
categories are identified in Appendix 6 Adverse Events of Special Interest. Additional information 
will be collected for these events. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
21 
Status: Approved,  Date: 11 August 2023 
Treatment-emergent adverse events of special interest will be included for analysis. Incidence (%) 
for the following AEs will be provided for each AE of special interest as appropriate: 
 
TEAEs by PT 
 
TEAEs by toxicity grade 
 
TEAEs of toxicity grade 3 or higher by PT 
 
Serious TEAEs by PT 
 
TEAEs by relationship to study intervention 
 
Serious TEAEs by PT 
 
Serious TEAEs by relationship to study intervention 
 
TEAEs leading to study intervention discontinuation by PT 
 
TEAEs leading to study intervention discontinuation by relationship to study intervention 
 
TEAEs leading to death by PT 
Additional analyses will be provided based on information collected in CRF. 
Pneumonitis/ILD 
For participants with pneumonitis/ILD, frequency tabulation will be provided for: 
 
Symptom (fever, dry cough, productive cough, dyspnea, chest pain, other) 
 
Pleural effusion present at the time of the pneumonitis/ILD (yes/no) 
Relative onset day (since Day 1) of pneumonitis/ILD will be summarized by descriptive statistics 
(N, mean, standard deviation, median, and range). 
All information related to pneumonitis/ILD collected in CRF page will be presented in listing. 
Rash 
Relative onset day (since Day 1), duration, and time between onset and the preceding infusion 
administration will be summarized for rash by descriptive statistics (N, mean, standard deviation, 
median, and range) in days. 
IRR 
Incidence (%) of IRR leading to infusion modification (infusion interrupted, infusion rate 
decreased, and infusion aborted) will be presented. 
Relative onset day (since Day 1), and duration will be summarized for IRR by descriptive statistics 
(N, mean, standard deviation, median, and range) in days. 
NCT04945733


JNJ-61186372  (Amivantamab)  
 
 
 
Statistical Analysis Plan 61186372GIC2001  
 
CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
22 
Status: Approved,  Date: 11 August 2023 
5.6.3.3. 
Deaths 
5.6.3.3.1. 
Death Due to TEAEs 
The number of participants who died due to TEAEs will be summarized by preferred term and 
relationship to study treatment. The TEAEs included in this table are AEs with outcome of death 
or toxicity grade of 5 recorded in the AE CRF page within 30 days of the last dose or until the start 
of subsequent anticancer therapy (if earlier). 
A listing of participants who died due to TEAE will be provided. 
5.6.3.3.2. 
All Deaths 
A summary of all death and cause of death will be tabulated. Specifically, the number of 
participants who died during the study will be summarized. The primary cause of death collected 
on the death information CRF page will be reported.  
The similar summaries will be presented for participants who died within 30 days of last study 
drug dose. 
5.6.4. 
Additional Safety Assessments (if applicable) 
5.6.4.1. 
Clinical Laboratory Tests 
Clinical laboratory tests will be displayed for the participants included in the safety analysis set. 
Descriptive statistics will be presented for all chemistry and hematology laboratory tests at 
scheduled time points. Change from baseline over time will be summarized and displayed. Plots 
for selected laboratory tests change over time may be provided. 
NCI-CTCAE version 5.0 will be used to derive toxicity grades for clinical laboratory tests when 
applicable. Shift tables from baseline to worst value on treatment (from treatment start to 30 days 
after last dose date or until the start of subsequent anti-cancer therapy, whichever is later) will be 
provided. The worst toxicity grade during the treatment will be tabulated.  
An eDISH plot of peak ALT/ AST versus peak BILI will be provided along with a listing of 
participants who had ALT/ AST values > 3xULN (Upper Limit of Normal) or BILI values > 
2xULN. 
Laboratory criteria for potential Hy's Law cases are defined as: 
 
Peak aminotransaminases (AT, either ALT or AST) of >3xULN; 
 
Total bilirubin ≥2xULN; 
 
Alkaline phosphatase (ALK-P) <2xULN prior to or on the same date of the first occurrence 
of total bilirubin ≥2x ULN; 
Note: data from all the on-treatment (postbaseline) visits are combined to check the above 
laboratory criteria. 
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 
All potential Hy’s Law cases based on the laboratory criteria will be presented. 
5.6.4.2. 
Vital Signs and Physical Examination Findings 
Continuous vital sign parameters including temperature, respiratory rate, oxygen saturation, 
pulse/heart rate, blood pressure (systolic and diastolic), as well as weight from physical 
examination will be summarized at each scheduled timepoint. Change from baseline will be 
summarized over time. Descriptive statistics (mean, standard deviation, median, minimum and 
maximum) will be presented. 
Post baseline physical examination findings were collected as AEs, and therefore will not be 
summarized.  
For criteria that do not include an increase or decrease from baseline: 
 
 Treatment-Emargent will be concluded if the postbaseline value is above the upper limit and 
the baseline value is below the upper limit (eg, Normal or Low). The same applies to the 
postbaseline value being below the lower limit with the baseline value being above the lower 
limit (eg, Normal or High). 
 
If the baseline value is missing, a postbaseline abnormality will always be considered as TE. 
5.6.4.3. 
Electrocardiogram 
Triplicate electrocardiograms (ECG) will be performed at Screening to determine the eligibility. 
Post baseline measurement may be collected as clinically indicated. Since there is no scheduled 
timepoint for ECG, ECG will not be summarized. 
A listing of clinically relevant ECG abnormalities will be provided. 
5.6.5. 
ECOG Performance Status 
Eastern Cooperative Oncology Group performance status score will be evaluated during the 
screening phase to determine the eligibility. Post baseline measurement may be collected as 
clinically indicated. Baseline ECOG performance status will be summarized (see Appendix 2). 
5.7. 
Other Analyses 
5.7.1. 
Pharmacokinetics 
Serum samples will be collected for PK and immunogenicity assessments of amivantamab. 
Sampling timepoints are outlined in Table 2 of study protocol.  
PK analyses will be performed on the PK Population, defined as participants who received at least 
1 dose of a study treatment and have at least 1 evaluable postbaseline concentration measurement. 
Participants or samples will be excluded from the PK analysis if their data do not allow for accurate 
assessment of the PK (eg, incomplete administration of the study treatment; missing information 
of dosing and sampling times; concentration data not sufficient for PK parameter calculation). 
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Concentrations below the lowest quantifiable concentration or missing data will be labeled as such 
in the concentration data presentations. Concentrations below the lower quantifiable concentration 
will be treated as zero in the summary statistics.  
Descriptive statistics (N, mean, SD, median, range, CV (%) and IQ range) will be used to 
summarize amivantamab concentrations at each sampling time point and for each PK parameter 
of amivantamab. PK data may be displayed graphically, such as mean +/- SD PK concentrations 
over time by study intervention. 
Amivantamab concentrations will be presented based on the following baseline body weight 
categories at each time point: 
 
<80 kg 
 
≥ 80 kg 
All participants and samples excluded from the analysis will be clearly documented. 
The pharmacokinetic serum/plasma concentration-time data collected from this study will be 
combined with similar data from other studies to perform population PK and assess the relationship 
between PK or immunogenicity and selected safety and efficacy endpoints. Details will be 
provided in a population PK and exposure-response analysis plan and results of the analysis will 
be presented in a separate report. 
5.7.2. 
Immunogenicity 
The incidence (%) of antibodies to Amivantamab will be summarized based on Immunogenicity 
Population, defined as all participants who receive at least 1 dose of study intervention and have 
appropriate samples for detection of antibodies to Amivantamab (ie, participants with at least 1 
sample obtained after their first dose of Amivantamab). 
A listing of participants who are positive for antibodies to Amivantamab will be provided. The 
maximum titers of antibodies to Amivantamab will be summarized for participants who are 
positive for antibodies to Amivantamab. 
Other immunogenicity analyses may be performed to further characterize the immune responses 
that are generated. 
5.7.3. 
Pharmacodynamics (PD)/Biomarkers 
Analyses are planned to explore PD and other biomarkers that may be indicative of the 
mechanisms of action of the study intervention or predictive of efficacy. Correlation of baseline 
expression levels or changes in expression levels with response or time-to-event endpoints could 
identify responsive (or resistant) subgroups. Any PD or other biomarker measures will be listed, 
tabulated, and plotted, as appropriate. 
Serum soluble-free EGFR and MET concentrations versus time by treatment cohort will be 
summarized using plots. 
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Assessment of additional genes or biomarkers (DNA, RNA, or protein) relevant to gastric, 
esophageal or other cancers or the mechanism of action of study interventions, may also be 
performed in blood samples collected during study to better understand mechanisms of response 
or resistance to study interventions. 
Alterations in blood may be evaluated for correlation with response to study interventions, tumor 
burden, and disease progression as data warrant. 
Plasma mutation data derived from ctDNA and tumor tissue NGS analyses collected from this 
study will be used to perform mutational analysis and assess the relationship of individual 
mutations, and classes of mutations, to efficacy endpoints.  IHC analyses (may include H score) 
on tissue specimens collected from this study will be used to assess the relationship of exploratory 
endpoints to efficacy endpoints.  Additional exploratory endpoints may be explored from serum 
samples collected from this study and may be used to understand the relationship of these 
endpoints to efficacy endpoints.  Results of these analyses will be presented in a separate report. 
Stopping Analysis 
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and 
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the 
end of the study, it becomes clear that the analysis will not have sufficient scientific value for 
biomarker evaluation, or if there are not enough samples or responders to allow for adequate 
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy, 
completion of biomarker assessments is based on justification and intended utility of the data. 
5.7.4. 
Pharmacokinetic/Pharmacodynamic Relationships 
The relationship between PK and PD measures may be evaluated by PK/PD modeling. Participants 
may be grouped by dose schedule or clinical response. Results of PD and exploratory biomarker 
analyses will be presented in separate reports. 
5.7.5. 
Health Economics 
Not Applicable 
5.7.6. 
Definition of Subgroups 
The following pre-specified subgroup analyses are to be performed for the selected efficacy and/or 
safety endpoints. Additional subgroup analyses may be planned if deemed necessary. 
Definition of Subgroups 
Subgroup 
Variant 
Definition 
IHCc 
1 
0+, 1+, 2+, 3+ 
2 
≥0+, ≥1+, ≥2+, ≥3+ 
EGFRc 
1 
0+, 1+, 2+, 3+ 
 
2 
0+/1+, ≥2+ 
cMETc 
1 
0+, 1+, 2+, 3+ 
 
2 
0+/1+, ≥2+ 
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Subgroup 
Variant 
Definition 
Combination of EGFR and cMETc 
 
0+/0+, 1+/0+, 2+/0+, 3+/0+,  
0+/1+, 1+/1+, 2+/1+, 3+/1+,  
0+/2+, 1+/2+, 2+/2+, 3+/2+,  
0+/3+, 1+/3+, 2+/3+, 3+/3+ 
HER2 status 
 
Negative, Positive 
Age Group 
 
<65 years, ≥65 years; <75 years, ≥75 years 
 
Sex 
 
Male, Female 
Race 
 
Asian, Non-Asian 
Weight 
 
<80 kg, ≥80 kg 
ECOG performance status score 
 
0,  1 
Diagnosis subtype 
 
Adenocarcinoma, Squamous Cell Carcinoma, Other 
Number of location of metastasis at 
screeningc 
 
1-2, ≥3 
Number of prior lines of systemic 
therapyc 
1a 
2, 3, ≥4 
2b 
1, 2, ≥3 
Prior immuno-check inhibitor use c 
 
Yes, No 
Prior taxane usec 
 
Yes, No 
Prior irinotecan usea, c 
 
Yes, No 
Prior trifluridine/tipiracil usea, c 
 
Yes, No 
Prior ramucirumab use 
 
Yes, No 
Prior anti HER2 therapy use 
 
Yes, No 
aOnly for gastric cancer 
bOnly for esophageal cancer 
cOnly for efficacy endpoints 
5.8. 
Interim Analyses 
In Phase 2b, an interim futility analysis is planned in each of GC and EC arm approximately 
12 weeks after 50 participants receive the first infusion. The interim futility analyses will be based 
on the best response rate for each subpopulation (for example, IHC 2+/3+ and IHC 1+) selected at 
the end of Phase 2a and prespecified before initiating Phase 2b. The enrollment of each 
subpopulation may be terminated for futility if the posterior probability (ORR >22.5%) is <40%. 
The posterior probability will be calculated the method in Section 5.3.3. 
5.8.1. 
Clinical Trial Management Team 
The safety and conduct of the study will be monitored by the CTMT established by the sponsor in 
conjunction with the coordinating investigator. The CTMT will consist of participating principal 
investigators, the sponsor’s medical monitor, the Safety Management Team Chair, one of the 
sponsor’s clinical pharmacologists or their designees, and additional sponsor staff as appropriate. 
The sponsor’s statistician or biomarker scientist will be consulted when the CTMT determines it 
is necessary. In general, the CTMT will monitor the conduct of the study and review study data in 
an ongoing basis. The CTMT may recommend and decide on modifications in the study conduct 
which may include, but are not restricted to, changes in (1) study treatment administration 
dose/schedule, (2) participant population based on the emerging biomarker data, (3) allowing 
further enrollment of or terminate enrollment of a specific subpopulation to better characterize the 
specific population (eg, enrollment of IHC 2+/3+ or EGFR and cMET double positive population), 
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(4) opening of Phase 2a extension cohorts, and (5) PK or biomarker sampling times. All decisions 
made by the CTMT will be documented in a CTMT decision document. The IRB/IEC will be 
notified for all CTMT decisions, if required. The recommendations may be instituted by the CTMT, 
pending protocol amendment, as long as they are consistent with the benefit-risk and populations 
already reviewed and approved by the HA and local IRBs. All the CTMT documentation will be 
maintained in the sponsor’s study master file and, as appropriate, in the investigator’s study files. 
If unexpected safety findings are identified, the CTMT will assess the safety data in a prompt 
manner.  
If the CTMT recommends exploration of higher doses in each cohort of Phase 2a, an interim 
futility analysis is planned for the participants receiving the higher dose, when 10 response 
evaluable participants have radiographic assessment. The enrollment may halt if the number of 
participants with objective response (ie, CR or PR) is 1 or less. CTMT will make a decision 
considering all other aspects of study data such as safety, PK and other efficacy endpoints.  
At the end of Phase 2a part, CTMT will review the results and determine which subpopulations to 
be included in the Phase 2b part. In general, Phase 2b will be initiated if a Phase 2a population (or 
subset of Phase 2a populations) achieves posterior probability (ORR >22.5%) ≥40% (which is 
similar with ORR ≥20%). All available data (eg, efficacy, safety, and biomarker data) will be 
assessed to determine whether enrollment in a given subpopulation should continue. 
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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 List of Abbreviations 
AE 
adverse event 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
ATC 
anatomic and therapeutic class 
AUC 
area under the curve 
BMI 
body mass index 
CI 
confidence interval 
Cmax 
maximum serum concentration 
cMet 
tyrosine-protein kinase mesenchymal-epithelial transition 
CR 
complete response 
CRF 
case report form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
circulating tumor deoxyribonucleic acid 
CTMT 
clinical trial management team 
Ctrough 
plasma/serum concentration immediately prior the next study treatment administration 
CV 
coefficient of variation 
DCR 
disease control rate 
DoR 
duration of response 
EC 
esophageal cancer 
ECOG 
Eastern Cooperative Oncology Group 
ECG 
electrocardiogram 
EGFR 
epidermal growth factor receptor 
EOT 
end-of-treatment 
GC 
gastric cancer 
IDMC 
independent data monitoring committee 
IEC 
Independent Ethics Committee 
IHC 
immunohistochemistry 
ILD 
interstitial lung disease 
IQ 
interquartile 
IRB 
Institutional Review Board 
IRC 
independent review committee 
IRR 
infusion-related-reaction 
MedDRA 
Medical Dictionary for Regulatory Activities 
NCI 
National Cancer Institute 
ORR 
objective response rate 
OS 
overall survival 
PD 
pharmacodynamic(s) 
PFS 
progression-free survival 
PK 
pharmacokinetic(s) 
PR 
partial response 
PT 
preferred term 
RECIST 
Response Criteria in Solid Tumors 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
Tmax 
time to reach the maximum serum concentration 
ULN 
Upper Limit of Normal 
WHO-DD 
World Health Organization Drug Dictionary 
 
 
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6.2. 
Appendix 2 Demographics and Baseline Characteristics 
The number of participants in each analysis set will be summarized and listed by IHC and overall. 
In addition, the distribution of participants by country and site ID will be presented unless 
otherwise noted. 
Table below presents a list of the demographic variables that will be summarized by IHC group 
and overall for the All Treated Population.   
Continuous Variables 
Summary Type 
Age (years) 
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum]. 
Weight (kg) 
Height (cm) 
Body Mass Index (BMI) (kg/m2) 
Categorical Variables 
 
Age (<65 years, ≥65 years; <75 years, ≥75 years) 
Frequency distribution with the 
number and percentage of 
participants in each category. 
Sex (male, female, unknown, undifferentiated) 
Weight (<80 kg, ≥80 kg) 
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Multiple) 
Race (Asian, non-Asian) 
Ethnicity (Hispanic or Latino, not Hispanic or Latino, Not reported, 
Unknown) 
Baseline ECOG performance status (0, 1) 
Prior fluoropyrimidine agent use (Yes, No) 
Prior platinum agent use (Yes, No) 
Prior immunocheck inhibitor use (Yes, No) 
Prior taxane use (Yes, No) 
Prior irinotecan use (Yes, No)b 
Prior trifluridine/tipiracil use (Yes, No)b  
Prior ramucirumab use (Yes, No) 
Prior anti HER2 therapy use (Yes, No) 
Prior Cancer-Related Surgery / Procedure(Yes, No) 
Prior Chemoradiation Therapy (Yes, No) 
aIf multiple race categories are indicated, the Race is recorded as 'Multiple' 
bOnly for gastric cancer 
 
The following table presents a list of the baseline characteristics variables that will be summarized 
by IHC group and overall for the All Treated Population.  
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Gastric Cancer 
Continuous Variables 
Summary Type 
Time since initial gastric cancer diagnosis (months) 
Descriptive statistics 
(N, mean, standard 
deviation [SD], 
median and range 
[minimum and 
maximum]. 
Number of prior lines of systemic therapy 
Number of location of metastasis at screening  
Categorical Variables 
 
GC initial diagnosis (gastric cancer, gastroesophageal junction 
cancer) 
Frequency distribution 
with the number and 
percentage of 
participants in each 
category. 
GC subtype at initial diagnosis (adenocarcinoma, squamous cell 
carcinoma, other) 
Histology grade at initial diagnosis (well differentiated, 
moderately differentiated, poorly differentiated, other) 
Lauren classification (intestinal, diffuse, mixed, unclassified) 
Location of metastasis at screening (bone, liver, brain, lymph 
node, adrenal gland, lung, peritoneum, other) 
Number of prior lines of systemic therapy (2, 3, ≥4) 
Number of location of metastasis at screening (1-2, ≥3) 
HER2 status (Positive, Negative) 
Result by IHC (Central) (0, 1+, 2+, 3+, unknown) 
Result by EGFR (Central) (0, 1+, 2+, 3+, unknown) 
Result by cMET (Central) (0, 1+, 2+, 3+, unknown) 
Result by combination of EGFR and cMET (Central) 
Esophageal 
Cancer 
Continuous Variables 
 
Time since initial esophageal cancer diagnosis (months) 
Descriptive statistics 
(N, mean, standard 
deviation [SD], 
median and range 
[minimum and 
maximum]. 
Number of prior lines of systemic therapy 
Number of location of metastasis at screening 
Categorical Variables 
 
EC subtype at initial diagnosis (adenocarcinoma, squamous cell 
carcinoma, other) 
Frequency distribution 
with the number and 
percentage of 
participants in each 
category. 
Histology grade at initial diagnosis (well differentiated, 
moderately differentiated, poorly differentiated, other) 
Location of metastasis at screening (bone, liver, brain, lymph 
node, adrenal gland, lung, peritoneum, other) 
Number of prior lines of systemic therapy taken (1, 2, ≥3) 
Number of location of metastasis at screening (1-2, ≥3) 
Result by IHC (Central) (0, 1+, 2+, 3+, unknown) 
Result by EGFR (Central) (0, 1+, 2+, 3+, unknown) 
Result by cMET (Central) (0, 1+, 2+, 3+, unknown) 
Result by combination of EGFR and cMET (Central) 
 
 
 
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6.3. 
Appendix 3 Protocol Deviations 
In general, the following list of major protocol deviations may have the potential to impact 
participants’ rights, safety or well-being, or the integrity and/or result of the clinical study. 
Participants with major protocol deviations will be identified prior to database lock in each phase 
and the participants with major protocol deviations will be summarized by category in the All 
Treated Population. 
 
 
Developed withdrawal criteria but not withdrawn 
 
Entered but did not satisfy criteria 
 
Received a disallowed concomitant treatment 
 
Received wrong treatment or incorrect dose 
 
Any major protocol deviation due to COVID 
 
Other 
A listing of all major protocol deviations including participant ID, type of deviation, and reason 
will be provided. 
 
 
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6.4. 
Appendix 4 Prior and Concomitant Medications 
Prior and Concomitant medications collected in the CRF page will be coded using the World 
Health Organization Drug Dictionary (WHO-DD) and summarized by IHC and overall for the All 
Treated Population. 
Prior medications will be summarized by ATC level/preferred terms and treatment. The number 
and percentage of participants who received prior systemic therapy will be summarized.  
Summaries of concomitant medications will be presented by ATC level/preferred terms. The 
proportion of participants who receive each concomitant medication will be summarized as well 
as the proportion of participants who receive at least 1 concomitant medication.  
The incidence (%) of pre-infusion and post-infusion medication will be presented by ATC 
level/preferred terms. 
 
 
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6.5. 
Appendix 5 Medical History 
Medical history collected at baseline or screening visit will be summarized by system-organ 
class and preferred term by IHC and overall for the All Treated Population. 
 
 
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6.6. 
Appendix 6 Adverse Events of Special Interest 
Adverse events of special interest are defined as follows: 
AE of Special Interest Category 
Preferred Term 
Infusion Related Reaction 
INFUSION RELATED REACTION 
 
 
Rash 
ACNE 
ACNE CONGLOBATA 
ACNE CYSTIC 
ACNE FULMINANS 
ACNE PUSTULAR 
ACNE VARIOLIFORMIS 
ACUTE GENERALISED EXANTHEMATOUS PUSTULOSIS 
DERMATITIS 
DERMATITIS ACNEIFORM 
DERMATITIS EXFOLIATIVE 
DERMATITIS INFECTED 
DRUG ERUPTION 
EPIDERMOLYSIS 
ERYTHEMA 
ERYTHEMA MULTIFORME 
EXFOLIATIVE RASH 
FOLLICULITIS 
HERPES GESTATIONIS 
IMPETIGO HERPETIFORMIS 
MACULE 
MUCOCUTANEOUS RASH 
NODULAR RASH 
PALMAR ERYTHEMA 
PAPULE 
PERINEAL RASH 
PRIDE SYNDROME 
PUSTULE 
RASH 
RASH ERYTHEMATOUS 
RASH FOLLICULAR 
RASH MACULAR 
RASH MACULO-PAPULAR 
RASH MACULOVESICULAR 
RASH MORBILLIFORM 
RASH PAPULAR 
RASH PRURITIC 
RASH PUSTULAR 
RASH VESICULAR 
SJS-TEN OVERLAP 
SKIN EXFOLIATION 
SKIN LESION 
STEVENS-JOHNSON SYNDROME 
TOXIC EPIDERMAL NECROLYSIS 
TOXIC SKIN ERUPTION 
 
 
Interstitial Lung Disease 
ACUTE INTERSTITIAL PNEUMONITIS 
INTERSTITIAL LUNG DISEASE 
PNEUMONITIS 
 
 
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6.7. 
Appendix 7 Laboratory Toxicity Grading 
The grading scale use for lab assessments is based on ‘Common Terminology Criteria for Adverse 
Events (CTCAE) v5.0’. 
Pre-baseline measurements will use the same grading ranges as applied to baseline measurements. 
In case a test has two sets of ranges – one for baseline normal and one for baseline abnormal, the 
one for baseline normal will be applied for all measurements taken pre-baseline and on baseline. 
Text in gray italic in the table is present in the grading scale, but is not applied by Janssen when 
grading lab data. 
 
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7. 
REFERENCES 
Jenkins M, et al. An adaptive seamless phase II/III design for oncology trials with subpopulation selection using 
correlated survival endpoints. Pharmaceutical statistics. 2011;10(4):347-356. 
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