A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Patients With EGFR Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Sponsor: Janssen Research & Development, LLC

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Status: Approved, Date: 07 August 2023
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Randomized, Open-label Phase 3 Study of Combination Amivantamab and Carboplatin-
Pemetrexed Therapy, Compared with Carboplatin-Pemetrexed, in Patients with EGFR 
Exon 20ins Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer
PAPILLON
Protocol 61186372NSC3001; Phase 3
Version: Amendment 3
JNJ-61186372 (amivantamab)
*Janssen Research & Development is a global organization that operates through different legal entities in
various countries/territories. Therefore, the legal entity acting as the sponsor for Janssen Research &
Development studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP;
Janssen Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc.; or Janssen Research & Development, LLC. The term
“sponsor” is used throughout the protocol to represent these various legal entities; the sponsor is
identified on the Contact Information page that accompanies the protocol.
United States (US) sites will conduct this study under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s):
IND:
135405
EudraCT NUMBER:
2020-000633-40
EU Trial NUMBER:
2023-506033-29
Status:
Approved
Date:
07 August 2023
Prepared by:
Janssen Research & Development 
EDMS number:
EDMS-ERI-205634813, 5.0
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.
NCT04538664

JNJ-61186372 (amivantamab)
Clinical Protocol 61186372NSC3001 Amendment 3
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Status: Approved, Date: 07 August 2023
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document
Date
Amendment 3
07 Aug 2023
Amendment 2
12 Aug 2022
Amendment 1
20 May 2021
Original Protocol
17 Jul 2020
Amendment 3 (07 August 2023)
Overall Rationale for the Amendment: To continue providing participants access to study treatment and 
collect data of clinical relevance/importance while reducing the burden on participants after the primary 
analysis by adding open-label extension (OLE) and long-term extension (LTE) phases to the study.
In addition, template changes related to the upcoming transition to European Union (EU)/European 
Economic Area (EEA) Clinical Trial Regulations (CTR), and other template-related changes have been 
added to the protocol.
The changes made to the clinical protocol 61186372NSC3001 as part of Protocol Amendment 3 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 10.16 (Appendix 16: Protocol Amendment History).
Section Number
and Name
Description of Change
Brief Rationale
Changes related to adding an OLE Phase and an LTE Phase to the study.
Synopsis (Overall 
Design);
4.1.4 Open-label 
Extension Phase and 
Long-term Extension 
Phase (new subheading)
A description of the new OLE and LTE phases 
was added, with cross-references to the newly 
added appendices.
To add the new OLE and LTE 
phases to the overall study design.
Synopsis (Study 
Treatment Groups and 
Duration);
4.4 End of Study 
Definition
Stated that a final analysis for overall survival 
is planned to occur approximately 48 months 
after the first participant is randomized.
Added an end of study definition.
To keep the final analysis for 
overall survival and the end of 
study distinct.
1.2 Schema, Figure 1 
(Schematic Overview of 
the Study Design)
The schematic was revised to add the new OLE 
and LTE phases.
To add the 2 new phases (OLE 
and LTE) to the study design.
1.3 Schedule of Activities 
(SoA): Table 1, Table 2;
10.11 Appendix 11: 
Optional Crossover After 
Disease Progression to 
Second-Line 
Amivantamab 
Monotherapy (Arm B 
Only): Table 20, Table 21
Added text in parenthesis after each table title 
to indicated that these Schedules of Activities 
were applicable only to the main study.
To distinguish the Schedules of 
Activities in the main study from 
those in the OLE and LTE phases.

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Status: Approved, Date: 07 August 2023
Section Number
and Name
Description of Change
Brief Rationale
7.1 Discontinuation of 
Study Treatment 
(Bullet #5)
Revised text as shown below (bold font denotes 
added text):
Documented radiographic (RECIST v1.1) 
disease progression by BICR (except during 
the OLE and LTE phases, during which 
investigator assessment will be used), unless 
treatment beyond disease progression has been 
approved by the Medical Monitor.
To clarify that disease progression 
will not be determined by blinded 
independent central review 
(BICR) during the OLE and LTE 
phases.
8.1.1 Disease 
Assessments
Added text specifying that, during the 
OLE/LTE Phase, disease assessments, 
treatment decisions, and confirmation of 
disease progression can be made based on 
investigator assessment by RECIST v1.1.
To clarify that these items will not 
be determined by BICR during the 
OLE and LTE phases.
10 (Appendix 1: 
Abbreviations)
New abbreviations used during Amendment 3 
were added.
To provide a comprehensive list 
of abbreviations.
10.7 Appendix 7: Clinical 
Laboratory Tests
Text referring to the Schedule of Activities 
during the OLE Phase was added.
To distinguish clinical laboratory 
tests performed during the OLE 
Phase from those performed in the 
main study.
10.11 Appendix 11: 
Optional Crossover After 
Disease Progression to 
Second-Line 
Amivantamab 
Monotherapy (Arm B 
Only)
Cross-references to study conduct/information 
and study assessments/procedures after 
transition to the OLE Phase were added.
To keep study conduct and 
assessments after transition to the 
OLE Phase distinct from what 
will be done during the optional 
crossover phase of the main study.
10.14 Appendix 14: 
Open-label Extension 
(new appendix)
The study design was changed to include a new 
study phase (an OLE Phase), whose purpose is 
to continue providing participants access to 
study treatment and collect data of clinical 
relevance/importance while reducing the 
burden on participants after the primary 
analysis is complete.
Instructions on eligibility criteria to cross over 
to second-line amivantamab monotherapy 
(Arm B Only), study treatment administration, 
study procedures, and a Schedule of Activities 
for the OLE Phase are provided in the new 
appendix.
During the OLE Phase, patient-reported 
outcomes (PROs) will be collected for 1 year 
after disease progression, reducing the data 
collection frequency from every 3 months to 
every 6 months.
To provide detailed information 
on study conduct during the OLE 
Phase.
10.15 Appendix 15: 
Long-term Extension 
Phase (new appendix)
The study design was changed to include a new 
study phase (an LTE Phase) whose purpose is 
to continue providing participants access to 
study treatment while further reducing the 
burden on participants after the final analysis 
for overall survival is complete.
In this appendix, instructions on eligibility 
criteria to cross over to second-line 
To provide detailed information 
on study conduct during the LTE 
Phase.

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Status: Approved, Date: 07 August 2023
Section Number
and Name
Description of Change
Brief Rationale
amivantamab monotherapy (Arm B Only), 
study treatment administration, study 
procedures, and a Schedule of Activities for the 
LTE Phase are provided in the new appendix.
During the OLE Phase, PROs will not be 
collected.
Changes related to the upcoming EU CTR transition, and other template-specific changes.
Cover page
The EU trial number was added.
To comply with the upcoming EU 
CTR transition.
Synopsis
The IND number, EudraCT Number, and 
EU trial number were added.
To comply with the upcoming EU 
CTR transition.
5.4 Screen Failures
Added the text shown below:
“This study will use IWRS. The investigator 
will generate screening and enrollment logs 
directly from IWRS.”
To comply with the current 
protocol template.
6.1 Study Treatments 
Administered
Additional text related to study treatment was 
added.
To comply with the current 
protocol template.
10.2.4 Data Protection
Minor changes were made to text.
To comply with the current 
protocol template.
Text related to measures by the sponsor to 
mitigate possible adverse effect in the event of 
a data security breach was added.
To comply with the upcoming EU 
CTR transition.
10.2.7 Publication 
Policy/Dissemination of 
Clinical Study Data
Minor changes were made to text.
To comply with the current 
protocol template.
Throughout the protocol
Minor editorial and formatting changes were 
made.
Minor errors, discrepancies, or 
omissions were noted.

JNJ-61186372 (amivantamab)
Clinical Protocol 61186372NSC3001 Amendment 3
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Status: Approved, Date: 07 August 2023
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 5
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1.
PROTOCOL SUMMARY ..................................................................................................................... 9
1.1.
Synopsis........................................................................................................................................... 9
1.2.
Schema .......................................................................................................................................... 12
1.3.
Schedule of Activities (SoA)........................................................................................................... 13
2.
INTRODUCTION................................................................................................................................ 18
2.1.
Background .................................................................................................................................... 18
2.2.
Rationale for Amivantamab Therapy for EGFR EXON 20ins Disease .......................................... 19
2.2.1.
Clinical Studies of Amivantamab................................................................................................ 19
2.2.2.
Rationale for Chemotherapy Comparator...................................................................................21
2.2.3.
Rationale for Amivantamab Chemotherapy Combination .......................................................... 22
2.3.
Benefit-Risk Assessment ............................................................................................................... 23
2.3.1.
Risks for Study Participation....................................................................................................... 23
2.3.2.
Benefits for Study Participation .................................................................................................. 24
2.3.3.
Benefit-Risk Assessment for Study Participation .......................................................................24
3.
OBJECTIVES AND ENDPOINTS ..................................................................................................... 25
4.
STUDY DESIGN ................................................................................................................................ 26
4.1.
Overall Design................................................................................................................................ 26
4.1.1.
Screening Phase ........................................................................................................................ 26
4.1.2.
Treatment Phase ........................................................................................................................ 26
4.1.3.
Follow-up Phase......................................................................................................................... 27
4.1.4.
Open-label Extension Phase and Long-term Extension Phase ................................................. 28
4.2.
Scientific Rationale for Study Design............................................................................................. 28
4.2.1.
Study-Specific Ethical Design Considerations ........................................................................... 29
4.3.
Justification for Dose...................................................................................................................... 30
4.3.1.
Chemotherapy Dose Rationale .................................................................................................. 30
4.3.2.
Amivantamab and Chemotherapy Combination Dose Rationale............................................... 30
4.4.
End of Study Definition................................................................................................................... 31
5.
STUDY POPULATION ...................................................................................................................... 32
5.1.
Inclusion Criteria ............................................................................................................................ 32
5.2.
Exclusion Criteria ........................................................................................................................... 34
5.3.
Lifestyle Considerations................................................................................................................. 38
5.4.
Screen Failures .............................................................................................................................. 38
6.
STUDY MEDICATION AND CONCOMITANT THERAPY................................................................39
6.1.
Study Treatments Administered..................................................................................................... 39
6.2.
Dosage and Administration of Study Treatment............................................................................39
6.2.1.
Scheduled Dosage and Timing .................................................................................................. 39
6.2.2.
Chemotherapy ............................................................................................................................ 41
6.2.3.
Amivantamab.............................................................................................................................. 41
6.3.
Preparation/Handling/Storage/Accountability ................................................................................ 42
6.4.
Measures to Minimize Bias: Randomization and Blinding.............................................................43
6.5.
Study Treatment Compliance ........................................................................................................ 43
6.6.
Concomitant Therapy..................................................................................................................... 44
6.6.1.
Recording Prestudy and Concomitant Therapies....................................................................... 44
6.6.2.
Permitted Medications and Therapies........................................................................................ 44
6.6.2.1.
Pre- and Post-infusion Medications for Chemotherapy........................................................... 44
6.6.2.2.
Pre- and Post-Infusion Medications for Amivantamab ............................................................45

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6.6.3.
Prohibited or Restricted Medications and Therapies..................................................................47
6.7.
Dose Delay Guidance .................................................................................................................... 48
6.8.
Dose Modification........................................................................................................................... 49
6.8.1.
Chemotherapy Dose Modification .............................................................................................. 49
6.8.1.1.
Management of Chemotherapy Toxicities...............................................................................49
6.8.2.
Amivantamab Dose Modification ................................................................................................ 50
6.8.2.1.
Rash-Related Adverse Events ................................................................................................ 51
6.8.2.2.
Infusion-Related Reactions ..................................................................................................... 54
6.8.2.3.
Liver Chemistry Abnormalities................................................................................................. 56
6.8.2.4.
Pulmonary Toxicity .................................................................................................................. 57
6.9.
Treatment of Overdose .................................................................................................................. 57
7.
DISCONTINUATION OF STUDY TREATMENT AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...............................................................................................58
7.1.
Discontinuation of Study Treatment............................................................................................... 58
7.2.
Participant Discontinuation/Withdrawal From the Study................................................................ 58
7.2.1.
Withdrawal From the Use of Research Samples ....................................................................... 59
7.3.
Lost to Follow-up............................................................................................................................ 59
8.
STUDY ASSESSMENTS AND PROCEDURES ...............................................................................60
8.1.
Efficacy Assessments .................................................................................................................... 61
8.1.1.
Disease Assessments ................................................................................................................ 61
8.1.2.
Symptomatic Progression........................................................................................................... 62
8.1.3.
Patient-Reported Outcomes ....................................................................................................... 63
8.2.
Safety Assessments....................................................................................................................... 63
8.2.1.
Physical Examinations................................................................................................................ 63
8.2.2.
Vital Signs................................................................................................................................... 64
8.2.3.
Electrocardiograms..................................................................................................................... 64
8.2.4.
ECOG Performance Status ........................................................................................................ 64
8.2.5.
Clinical Safety Laboratory Assessments .................................................................................... 64
8.3.
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 65
8.3.1.
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event 
Information.................................................................................................................................. 65
8.3.2.
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 66
8.3.3.
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 66
8.3.4.
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 66
8.3.5.
Pregnancy................................................................................................................................... 67
8.3.6.
Disease-Related Events and Disease-Related Outcomes not Qualifying as Adverse 
Events or Serious Adverse Events .............................................................................................67
8.3.7.
Adverse Events of Special Interest............................................................................................. 67
8.4.
Pharmacokinetics........................................................................................................................... 68
8.4.1.
Evaluations ................................................................................................................................. 68
8.4.2.
Analytical Procedures................................................................................................................. 68
8.5.
Biomarkers ..................................................................................................................................... 68
8.6.
Immunogenicity Assessments ....................................................................................................... 69
8.7.
Medical Resource Utilization and Health Economics .................................................................... 70
9.
STATISTICAL CONSIDERATIONS..................................................................................................70
9.1.
Statistical Hypotheses.................................................................................................................... 70
9.2.
Sample Size Determination ........................................................................................................... 70
9.3.
Populations for Analyses Sets ....................................................................................................... 71
9.4.
Statistical Analyses ........................................................................................................................ 71
9.4.1.
General Considerations.............................................................................................................. 71
9.4.2.
Primary Endpoint ........................................................................................................................ 71
9.4.2.1.
Progression-Free Survival by Blinded Independent Central Review ...................................... 71
9.4.3.
Secondary Endpoints.................................................................................................................. 72
9.4.3.1.
Objective Response Rate........................................................................................................ 72
9.4.3.2.
Duration of Response.............................................................................................................. 72

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Status: Approved, Date: 07 August 2023
9.4.3.3.
Overall Survival ....................................................................................................................... 73
9.4.3.4.
Time to Subsequent Therapy .................................................................................................. 73
9.4.3.5.
Progression-free Survival After First Subsequent Therapy..................................................... 73
9.4.3.6.
Time to Symptomatic Progression .......................................................................................... 73
9.4.4.
Exploratory Endpoints................................................................................................................. 74
9.4.5.
Safety Analyses .......................................................................................................................... 74
9.4.6.
Other Analyses ........................................................................................................................... 75
9.5.
Interim Analysis.............................................................................................................................. 77
10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS ............................ 78
10.1.
Appendix 1: Abbreviations ............................................................................................................. 78
10.2.
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations......................................... 81
10.2.1.
Regulatory and Ethical Considerations ...................................................................................... 81
10.2.2.
Financial Disclosure.................................................................................................................... 84
10.2.3.
Informed Consent Process ......................................................................................................... 84
10.2.4.
Data Protection ........................................................................................................................... 85
10.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 86
10.2.6.
Committees Structure................................................................................................................. 86
10.2.7.
Publication Policy/Dissemination of Clinical Study Data ............................................................87
10.2.8.
Data Quality Assurance.............................................................................................................. 88
10.2.9.
Case Report Form Completion................................................................................................... 88
10.2.10.
Source Documents ..................................................................................................................... 89
10.2.11.
Monitoring ................................................................................................................................... 90
10.2.12.
On-Site Audits............................................................................................................................. 90
10.2.13.
Record Retention........................................................................................................................ 91
10.2.14.
Study and Site Start and Closure ............................................................................................... 91
10.3.
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting............................................................................................................... 93
10.3.1.
Adverse Event Definitions and Classifications ........................................................................... 93
10.3.2.
Attribution Definitions.................................................................................................................. 94
10.3.3.
Severity Criteria .......................................................................................................................... 94
10.3.4.
Special Reporting Situations ...................................................................................................... 95
10.3.5.
Procedures ................................................................................................................................. 95
10.3.6.
Contacting Sponsor Regarding Safety ....................................................................................... 96
10.3.7.
Product Quality Complaint Handling........................................................................................... 97
10.4.
Appendix 4: Contraceptive and Barrier Guidance .........................................................................98
10.5.
Appendix 5: Eastern Cooperative Oncology Group (ECOG) Performance Scale....................... 101
10.6.
Appendix 6: New York Heart Association Criteria ....................................................................... 102
10.7.
Appendix 7: Clinical Laboratory Tests ......................................................................................... 103
10.8.
Appendix 8: Anticipated Events ................................................................................................... 104
10.9.
Appendix 9: Dosing Synchronization for Arm A...........................................................................106
10.10.
Appendix 10: Safety Run-in ......................................................................................................... 107
10.11.
Appendix 11: Optional Crossover After Disease Progression to Second-Line 
Amivantamab Monotherapy (Arm B Only) ................................................................................... 108
10.12.
Appendix 12: Paronychia ............................................................................................................. 115
10.13.
Appendix 13: Guidance on Study Conduct During a COVID-19 Pandemic ................................ 116
10.14.
Appendix 14: Open-label Extension Phase .................................................................................120
10.14.1.
Eligibility Criteria to Cross Over to Second-Line Amivantamab Monotherapy (Arm B 
Only) Within the OLE Phase.....................................................................................................120
10.14.2.
Study Treatment Administration ............................................................................................... 122
10.14.3.
Study Procedures ..................................................................................................................... 122
10.15.
Appendix 15: Long-term Extension Phase...................................................................................126
10.15.1.
Eligibility Criteria ....................................................................................................................... 126
10.15.2.
Study Treatment Administration ............................................................................................... 127
10.15.3.
Study Procedures ..................................................................................................................... 127
10.16.
Appendix 16: Protocol Amendment History .................................................................................129
11.
REFERENCES................................................................................................................................. 137
INVESTIGATOR AGREEMENT ............................................................................................................... 139

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LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Schedule of Activities for Study Assessments/Procedures (Main Study Only) ........................ 13
Table 2:
Collection Times for Pharmacokinetics and Immunogenicity Samples Among 
Participants Receiving Amivantamab (Arm A in Main Study Only) .......................................... 17
Table 3:
Comparison of Observed Maximum Exposures Attained After Weekly Induction with 
1,750 mg in the 28-Day Cycle and Expected Steady State Exposure Attained With 
2,100 mg Every 3 Weeks in the 21-day Cycle.......................................................................... 31
Table 4:
Scheduled Dosages and Timing of Study Treatments, by Study Visit (21-Day Cycles) .......... 40
Table 5:
Concomitant Medications for Pemetrexed................................................................................44
Table 6: 
Pre-Infusion Medications for Amivantamab.............................................................................. 45
Table 7: 
Suggested Order of Administration When Amivantamab is Given With Carboplatin and 
Pemetrexed on Day 1 of Cycles 1-4 in Arm A ..........................................................................46
Table 8:
Suggested Order of Administration When Amivantamab is Given Without 
Chemotherapy (eg, on Days 2, 8, and 15 of Cycle 1) in Arm A ............................................... 46
Table 9:
Suggested Order of Administration When Amivantamab is Given With Pemetrexed on 
Day 1 of Cycles 5+ in Arm A..................................................................................................... 47
Table 10: Post-Infusion Medications for Amivantamab ............................................................................47
Table 11:
Guidance for Dose Modifications for Hematologic Chemotherapy Toxicity ............................. 49
Table 12:
Guidance for Dose Modifications for Non-Hematologic Chemotherapy Toxicity...................... 50
Table 13:
Guidance for Amivantamab Dose Delay and Modification for Toxicities Considered 
Related to Amivantamab (Other Than Rash, Paronychia, Infusion-Related Reaction, 
or Pulmonary Toxicity) .............................................................................................................. 50
Table 14:
Guidance for Amivantamab Stepwise Dose Reduction............................................................50
Table 15:
Suggested Algorithm for Management of Rash and Paronychia ............................................. 52
Table 16:
Management of Infusion-Related Reactions ............................................................................ 55
Table 17:
Populations for Analyses Sets .................................................................................................. 71
Table 18:
Preinfusion Medications for Amivantamab .............................................................................109
Table 19: Post-Infusion Medications for Amivantamab ..........................................................................110
Table 20:
Optional Crossover to Second-Line Amivantamab Monotherapy: Schedule of Activities 
for Study Assessments/Procedures (Crossover Section of Main Study Only)....................... 112
Table 21:
Collection Times for Pharmacokinetics and Immunogenicity Samples Among 
Participants Receiving Second-Line Amivantamab Monotherapy (Crossover Section 
of Main Study Only) ................................................................................................................ 114
Table 22:
Schedule of Activities for Study Assessments/Procedures in the Open-label Extension 
Phase...................................................................................................................................... 124
Table 23:
Schedule of Activities for Study Assessments/Procedures in the Long-term Extension 
Phase...................................................................................................................................... 128
FIGURES
Figure 1:
Schematic Overview of the Study Design.................................................................................12
Figure 2:
Waterfall Plot of Best Percentage Change from Baseline in Sum of Diameters (SoD) 
of Target Lesions; Response Evaluable with ≥2 Disease Assessments and 
Measurable Disease at Baseline and Exon 20 Insertion at RP2D Analysis Set in 
Monotherapy (Amivantamab) (Study 61186372EDI1001)........................................................ 20

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Hypothesis
The hypothesis is that amivantamab, when given in combination with standard of care carboplatin-
pemetrexed chemotherapy (Arm A), will prolong PFS compared with standard of care carboplatin-
pemetrexed chemotherapy (Arm B) in patients with locally advanced or metastatic NSCLC characterized 
by EGFR Exon 20ins activating mutations.
OVERALL DESIGN
The study will include a Screening phase, a Treatment phase, and a Follow-up phase. Participants must 
complete screening procedures within 28 days before randomization. Imaging of disease sites will occur at 
regular intervals, as defined in the Schedule of Activities, until objective radiographic disease progression. 
The Treatment phase for each participant will begin on Cycle 1 Day 1 and continue until the End of 
Treatment Visit, approximately 30 days after discontinuation of study treatment. Participants who 
discontinue assigned study treatment for any reason will be followed for subsequent therapy, disease status, 
and survival in the Follow-up phase. This phase starts after the End of Treatment visit and continues until 
the end of study, death, loss to follow-up, or withdrawal of consent, whichever comes first. 
Continuation of study treatment after disease progression may be allowed (see protocol Section 4.1.2). A 
participant in Arm B with disease progression by Response Evaluation Criteria in Solid Tumors (RECIST)
v1.1, as confirmed by blinded independent central review (BICR), may be allowed to cross over to
amivantamab monotherapy (see protocol Section 10.11).
Following the primary analysis for efficacy, the study will transition to an open-label extension (OLE) 
Phase (see details provided in Section 10.14 [Appendix 14]). Participants will be provided the option to 
continue treatment in the OLE Phase until the final analysis for overall survival, after which the study will 
transition to a long-term extension (LTE) Phase.
Participants who continue to benefit from study treatment(s), as determined by their investigator, at the time 
of the OLE Phase may continue to receive access to study treatment(s) within the study by transferring to 
the LTE Phase, where only serious adverse event data and study treatment accountability will be collected.
The LTE Phase (see details provided in Section 10.15 [Appendix 15]) will begin after the final analysis for 
overall survival, and will continue until the discontinuation criteria described in Section 7.1 are met, or until 
2 years after local marketing authorization is obtained for the studied indication, whichever occurs first.
The extension phases will begin after approval of Amendment 3 by health authorities of countries in which 
this study is still being conducted at the time of transition, and by study site ECs/IRBs. In addition, for 
transition to the LTE Phase (after final analysis for overall survival), prior notification from the sponsor 
will be needed.
An Independent Data Monitoring Committee will be commissioned for this study for the periodic review 
of safety and tolerability data, as well as planned efficacy analyses.
NUMBER OF PARTICIPANTS
Approximately 300 eligible participants will be stratified based on Eastern Cooperative Oncology Group 
(ECOG) performance status (0 or 1), history of brain metastases (yes or no), and prior EGFR TKI use (yes 
or no), and assigned randomly in a 1:1 ratio into 1 of 2 treatment arms.
STUDY TREATMENT GROUPS AND DURATION
Study treatment will be administered open-label, without blinding, in 21-day cycles, until disease 
progression or until the participant meets another criterion for discontinuation of study treatment. 

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Arm A (amivantamab plus chemotherapy):
!
Pemetrexed 500 mg/m2 (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination 
with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression
!
Carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) on Day 1 of each 
21-day cycle, for up to 4 cycles
!
Amivantamab 1,400 mg (1,750 mg if body weight is ≥80 kg) by intravenous (IV) infusion once weekly 
up to Cycle 2 Day 1, then 1,750 mg (2,100 mg if body weight is ≥80 kg) on Day 1 of each 21-day 
cycle, starting with Cycle 3
Arm B (chemotherapy):
!
Pemetrexed 500 mg/m2 (with vitamin supplementation) on Day 1 of each 21-day cycle, in combination 
with carboplatin for up to 4 cycles, and then as maintenance monotherapy until disease progression
!
Carboplatin AUC 5 on Day 1 of each 21-day cycle, for up to 4 cycles
A final analysis for overall survival is planned to occur approximately 48 months after the first participant 
is randomized.
End of Study Definition:
The end of study/study completion is considered as the last scheduled study assessment shown in the 
Schedule of Activities for the last participant in the study.
EFFICACY EVALUATIONS
Tumor response will be assessed by BICR according to RECIST v1.1. Baseline disease assessments should 
be performed no more than 28 days prior to randomization. On-study imaging will occur at regular intervals, 
as defined in the Schedule of Activities, until radiographic disease progression is documented.
PHARMACOKINETIC EVALUATIONS
Blood samples will be collected from participants receiving amivantamab for the measurement of serum 
amivantamab.
IMMUNOGENICITY EVALUATIONS
Blood samples will be collected and analyzed for antibodies to amivantamab using a validated 
immunoassay. Other immunogenicity analyses may be performed to further characterize any immune 
responses generated.
BIOMARKER EVALUATIONS
Blood samples and tumor tissue collected at Screening and during the study may be evaluated for 
biomarkers relevant to cancer to understand the molecular biology of the tumor, efficacy observed with 
amivantamab, and mechanisms of acquired resistance to amivantamab. 
SAFETY EVALUATIONS
Safety will be assessed by physical examinations, laboratory tests, vital signs, electrocardiograms, left 
ventricular ejection fraction, monitoring of adverse events, and concomitant medication usage.
STATISTICAL METHODS
The statistical hypothesis is that amivantamab and carboplatin-pemetrexed chemotherapy (Arm A) will 
reduce the risk of either progression or death compared with standard of care carboplatin-pemetrexed
chemotherapy (Arm B). A total of 200 PFS events will provide approximately 90% power to detect a hazard 

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ratio (HR) of 0.625 that corresponds to at least 3-month improvement in the median PFS (5 months for 
chemotherapy and 8 months for the combination of amivantamab with chemotherapy) with a stratified log-
rank test (2-sided alpha = 0.05). The total sample size needed for the study is approximately 
300 participants (150 per group). The sample size calculation takes into consideration an annual dropout 
rate of 5%.
The primary efficacy endpoint of PFS by BICR will be analyzed by stratified log-rank test using the 
Breslow approach for handling ties. The hazard ratio for PFS will be calculated, along with its 95% 
confidence interval, from a stratified Cox model using the same stratification factors as for the log-rank 
test.
To control the overall type I error rate for the hypotheses testing of primary and secondary endpoints at 5%, 
a sequential testing strategy will be used. If the testing for the primary endpoint of PFS is statistically 
significant, key secondary endpoints including ORR and overall survival will be sequentially tested, with 
an overall 2-sided alpha of 0.05.
Safety data will be summarized for all participants who receive at least 1 dose of study treatment. Data for 
PK, immunogenicity, patient-reported outcomes, 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. Details of the hierarchical testing procedure, analyses of other secondary or exploratory 
endpoints and analyses of data after crossover to amivantamab monotherapy will be specified in the 
Statistical Analysis Plan.
1.2.
Schema
Figure 1:
Schematic Overview of the Study Design
AUC=area under the concentration-time curve; ECOG=Eastern Cooperative Oncology Group; EGFR=epidermal growth factor 
receptor; IV=intravenously; LTE=long-term extension; OLE=open-label extension; QW=once weekly; TKI=tyrosine kinase 
inhibitor.
*
Stratification factors: Brain metastases (yes vs no); ECOG performance status (0 vs 1); prior EGFR TKI use (yes or no)
†
Doses shown by body weight (<80 kg/≥80 kg)
‡
Cycle 1: Days 1/2 (split dose), 8, 15; Cycle 2: Day 1

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2.
INTRODUCTION
Amivantamab (JNJ-61186372) is a low fucose, fully human IgG1-based bispecific antibody 
directed against epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition 
(MET) tyrosine kinase receptors that is being developed for the treatment of solid tumors. 
Amivantamab has demonstrated anti-tumor activity in preclinical models of EGFR and 
MET-driven non-small cell lung cancer (NSCLC), through 3 distinct mechanisms of action: 
1) inhibition of ligand binding, 2) receptor degradation, and 3) antibody-dependent cellular 
cytotoxicity (ADCC). Early clinical experience with amivantamab has demonstrated durable 
responses in subjects with various types of EGFR-driven or MET-driven NSCLC that are resistant 
to currently available EGFR-targeted or MET-targeted therapies, including subjects with EGFR 
mutations characterized by one of a group of heterogenous, in-frame base pair insertions in EGFR 
Exon 20 (Exon 20ins). Based on its observed activity in the latter population, amivantamab 
achieved Breakthrough Therapy Designation status by the United States (US) Food and Drug 
Administration (FDA) in March 2020 for the monotherapy treatment of patients with NSCLC 
characterized by EGFR Exon 20ins mutations, after prior treatment with platinum-based doublet 
chemotherapy. This study will explore whether the addition of amivantamab to first-line standard 
of care doublet chemotherapy will further improve disease control and clinical benefit as compared 
to chemotherapy alone.
The term "study treatment" throughout the protocol refers to study drug (amivantamab) or to
carboplatin or pemetrexed. For the most comprehensive nonclinical and clinical information 
regarding amivantamab, refer to the latest version of the Investigator's Brochure (IB) and 
Addenda.12 For further information regarding carboplatin and pemetrexed, refer to the local 
prescribing information for each product.2,5
The term "sponsor" used throughout this document refers to the entities listed in the Contact 
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
Cancer is a leading cause of death worldwide. Lung cancer is one of the most common types of 
cancer and is the most common cause of death from cancer (almost 20% of cancer deaths); NSCLC 
accounts for 80% to 85% of lung cancers.3 Adenocarcinoma is a subset of NSCLC and the most 
common type of lung cancer, comprising 40% of lung cancers.31 Five-year survival rates for 
NSCLC depend on the stage at diagnosis, ranging from 57% for localized cancer to 5% for cancer 
that has spread to distant locations.28 In patients with metastatic NSCLC, clinical guidelines 
recommend testing for activating mutations, which are observed in approximately 50% of 
adenocarcinomas.17,24
The identification of these "driver" activating mutations has provided an opportunity to specifically 
inhibit the constitutively activated pathway using targeted tyrosine kinase inhibitors (TKIs).
Among patients with NSCLC adenocarcinoma, the most prevalent of these driver mutations are 
those that result in the activation of EGFR, which are identified in more than 15% of patients with 

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adenocarcinoma20 and up to 50% of the corresponding Asian population.13 The most commonly 
occurring EGFR mutations, L858R and Exon 19del, are sensitive to approved EGFR TKIs, which 
are associated with high response rates (approximately 60% to 80%), prolonged duration of 
response, and median progression free survival (PFS) of approximately 10-19 months.26 As a 
result, these EGFR TKIs are considered first-line therapy for patients with NSCLC and
EGFR L858R or Exon 19del mutations.
In approximately 10% of EGFR-mutated NSCLC, EGFR is activated through one of a group of 
heterogenous, in-frame base pair insertions in EGFR Exon 20, collectively referred to as EGFR 
Exon 20ins mutations. Although EGFR Exon 20ins-mutated NSCLC is believed to share a similar 
biology with other EGFR-mutated NSCLC, the unique protein structure associated with this group 
of EGFR mutations prevents effective binding by approved EGFR TKIs, by sterically hindering 
access to the receptor active site. Thus, NSCLC arising from Exon 20ins mutations is distinguished 
by de novo resistance to currently approved EGFR TKIs, including third-generation TKIs such as 
osimertinib.29 Correspondingly, recently presented real-world evidence suggests inferior 
therapeutic outcomes with the non-standard use of EGFR TKI in the first-line setting, as compared 
to chemotherapy. 6 As a result, no EGFR TKI or other targeted therapy is approved for the 
treatment of patients with EGFR Exon 20ins NSCLC.
In the absence of effective targeted therapies, platinum-based doublet chemotherapy remains the 
standard of care for first-line therapy in patients with EGFR Exon 20ins-mutated NSCLC. The 
efficacy of combination chemotherapy in patients with advanced NSCLC and EGFR L858R or 
Exon 19del mutations includes an objective response rate (ORR) of approximately 30% and 
median PFS of approximately 5 months.14,16,25 The efficacy of combination chemotherapy, which 
is not dependent on EGFR, is expected to be similar in patients with Exon 20ins mutations.
2.2.
Rationale for Amivantamab Therapy for EGFR EXON 20ins Disease
2.2.1.
Clinical Studies of Amivantamab
Amivantamab is being developed based on the hypothesis that a bispecific antibody, by targeting 
the extracellular domain of each receptor (EGFR and MET), will demonstrate activity against 
tumors resistant to EGFR TKIs, either through primary resistance (EGFR Exon 20ins) or through 
the two most frequent mechanisms of resistance to current EGFR therapies: 1) secondary/tertiary 
mutations in EGFR, and 2) MET amplification or mutation. In the first-in-human Study 
61186372EDI1001, amivantamab has shown clinical proof-of-concept for this approach by 
demonstrating activity in patients with NSCLC disease characterized by activating mutations of 
EGFR and/or MET, including EGFR Exon 20ins mutations. Early clinical experience with 
amivantamab in this patient population suggests that it has activity as a monotherapy that is at least 
equivalent to current standard of care platinum-based doublet chemotherapy, validating the 
approach of targeting these mutations via their extracellular domain, rather than the TKI-resistant 
active site. 
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 
MET-mutated NSCLC, after standard of care therapy). Part 1 of the study includes a chemotherapy 

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The emerging safety profile of amivantamab as a monotherapy suggests it is well tolerated and is 
consistent with that observed with other EGFR and MET-directed therapies. Among the 
252 subjects who received amivantamab, the most commonly reported treatment-emergent 
adverse events (TEAEs) at the data cutoff date were infusion-related reaction (62.7%), rash 
(31.7%) or dermatitis acneiform (28.6%), paronychia (27.8%), and hypoalbuminemia (22.2%), the 
majority of which were Grade 1 or 2. Grade 3 rash was reported for 2.2% of subjects. TEAEs of 
liver enzyme elevations in >10% of subjects included increased alanine aminotransferase (ALT)
in 10.3% of subjects. Treatment-related serious adverse events were reported for 11 subjects 
(4.4%), with infusion-related reaction being the most frequently reported (2 subjects, 0.8%); a
treatment-related serious adverse event of interstitial lung disease (ILD) was reported for 2 subjects
(0.8%). TEAEs led to dose reduction for 6.7% of subjects and discontinuation of amivantamab for 
3.9% of subjects. Updated efficacy and safety data of amivantamab monotherapy in patients with 
EGFR Exon 20ins NSCLC were recently presented at the International Association for the Study 
of Lung Cancer (IASLC) 2021 World Conference.26 Results remain consistent with the previous 
experience with amivantamab. Updated information is also available in the latest version of the
IB.12
2.2.2.
Rationale for Chemotherapy Comparator
National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology 
(ESMO) treatment guidelines for advanced or metastatic NSCLC recommend platinum-based 
combination chemotherapy regimens, including carboplatin-pemetrexed or cisplatin-pemetrexed, 
in the first-line setting treatment of non-squamous NSCLC.17,24 While the activity of cisplatin and 
carboplatin is largely considered to be similar, with no associated difference in overall survival 
(OS),9 the use of cisplatin is typically reserved for therapies with curative intent, such as 
neoadjuvant, adjuvant, or combined chemotherapy-radiation regimens, where a potential slight 
benefit in ORR may outweigh greater toxicity and patient burden in patients who can tolerate it.
Carboplatin-based regimens, with their improved safety profile, are more often used in the 
metastatic NSCLC setting, within clinical regimens with palliative intent. The importance of 
improved toxicity profile and reduced infusion times associated with carboplatin administration, 
and the decreased need for pre-infusion and post-infusion hydration for these patients are reflected 
in recent reviews of real world usage patterns, which demonstrate that carboplatin-pemetrexed is 
the most frequently used platinum-based doublet regimen in the US for the first-line treatment of 
metastatic, nonsquamous NSCLC, and cisplatin-based regimens are used infrequently in this 
setting (<5%).1 In addition, carboplatin and pemetrexed have been combined with the first-
generation EGFR TKI gefitinib, a regimen that is recognized in the ESMO guidelines as a first-
line treatment option for TKI-sensitive EGFR-mutated NSCLC.7
Given the above, the use of carboplatin-pemetrexed combination chemotherapy in this study 
ensures every enrolled subject will receive treatment with the preferred first-line regimen for 
EGFR Exon 20ins NSCLC, and will enable the most robust assessment of amivantamab efficacy 
and safety when administered in combination with carboplatin and pemetrexed in the first-line 
setting.

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2.2.3.
Rationale for Amivantamab Chemotherapy Combination 
As a bispecific antibody capable of engaging the extracellular domains of both EGFR and MET 
receptors, amivantamab has the potential to control EGFR-mutated NSCLC independent of 
activating and resistance mutations within the intracellular domains of the protein, which can 
determine sensitivity or resistance to approved EGFR TKIs. Like the EGFR TKIs already 
approved for the treatment of EGFR-mutated NSCLC, a large contributor of amivantamab activity 
lies in its ability to target the biological driver of tumor growth, halting tumor cell division, and 
ultimately resulting in cell death and tumor response.
With the approval of EGFR TKIs for the treatment of NSCLC, several studies have investigated
the optimal application of these agents, including potential combination with chemotherapy. While 
early studies evaluating the potential of EGFR TKI/chemotherapy failed to demonstrate clinical 
benefit, the failure to use molecular markers to select for populations with EGFR-driven disease 
may have confounded the interpretation of these results. With the significant improvement in 
efficacy observed with second-generation
and third-generation EGFR TKIs
relative to 
chemotherapy, platinum-based chemotherapies were reserved for salvage therapy after TKI 
failure, after tumors had developed mutations that made them resistant to targeted approaches.
More recent studies have suggested a possible benefit with EGFR TKI/chemotherapy combination 
treatment, and that this potential approach deserves re-evaluation. Two studies that combined 
gefitinib (a first-generation EGFR TKI) with carboplatin and pemetrexed demonstrated improved 
outcomes, as compared to gefitinib alone, in terms of ORR, PFS, and OS.11,18 These recent results 
suggest potential benefit of this combined approach when appropriately applied to selected 
populations with EGFR-mutated NSCLC, as the use of concomitant chemotherapy may eliminate 
potential tumor cell populations with inherent TKI resistance, thereby delaying disease recurrence. 
In addition to the suggested benefit of combining chemotherapy with targeted inhibition of the 
EGFR pathway, amivantamab anti-tumor activity is hypothesized to include ADCC-dependent 
mechanisms that are not associated with EGFR TKIs. Thus, there may be additional benefit with
amivantamab/chemotherapy combinations arising from disruption of an inhibitory tumor 
microenvironment8 and targeting of Fc receptor-bearing immune cells to tumor cells. Given the 
demonstrated activity of platinum-based doublet chemotherapy and amivantamab monotherapy in 
patients with EGFR Exon 20ins-mutated NSCLC, it is hypothesized that the combination of these 
2 active regimens will improve patient outcomes over what has been observed with either agent 
alone.
The safety profile for amivantamab, which resembles that of EGFR TKIs or other monoclonal 
antibodies (mAb), is largely distinct from those associated with chemotherapeutic agents. 
Moreover, amivantamab is not a modulator of cytokines that have known effects on metabolizing
enzymes and transporters, and due to the lack of common elimination pathways for amivantamab 
and carboplatin or pemetrexed, no relevant pharmacokinetic (PK) interactions are expected.30
As of 20 October 2020, 16 patients have been dosed with the combination amivantamab and 
chemotherapy (carboplatin and pemetrexed) in the ongoing Phase 1 study CHRYSALIS 
(61186372EDI1001). Preliminary safety analysis of the combination is consistent with the 

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monotherapy experience of amivantamab and chemotherapy alone. Preliminary PK data suggests 
no impact of chemotherapy on amivantamab exposure. Please refer to the latest version of the IB
for additional information.12
This Phase 3 study seeks to demonstrate the tolerability and improved efficacy of combining 
amivantamab with standard of care carboplatin-pemetrexed chemotherapy as first-line treatment 
of patients with EGFR Exon 20ins NSCLC, compared with carboplatin-pemetrexed chemotherapy 
in this setting.
2.3.
Benefit-Risk Assessment
2.3.1.
Risks for Study Participation
As clinical data for the combination of amivantamab plus chemotherapy are limited, unforeseen 
safety risks associated with the study treatments are possible. Previous studies combining 
EGFR TKIs or anti-EGFR mAbs with chemotherapy have shown the combinations were generally 
well tolerated.11,18,21,23 Combining amivantamab with chemotherapy is expected to have a similar 
safety profile to combining an EGFR TKI or mAb with chemotherapy. 
The safety profile for amivantamab is largely distinct from those associated with chemotherapeutic 
agents. However, pemetrexed has been reported to be associated with bullous and exfoliative skin 
toxicity as well as interstitial pneumonitis, which should be considered when evaluating and 
managing potential skin and pulmonary toxicities.
This study protocol includes the following elements to mitigate risks for study participants:
!
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 delay and dose modification guidance is provided to manage toxicities that occur during 
the study (refer to Section 6.7 and Section 6.8), including specific guidance for infusion-
related reactions, ILD/pneumonitis, rash, or liver test abnormalities.
!
The safety of amivantamab in combination with carboplatin and pemetrexed is being 
investigated in a Phase 1 study (61186372EDI1001) and results from this cohort have been 
updated in the IB.12
!
An Independent Data Monitoring Committee (IDMC) will review safety and tolerability data 
periodically (refer to Appendix 2: Regulatory, Ethical, and Study Oversight Considerations).
The IDMC has reviewed safety results for amivantamab in combination with carboplatin and 
pemetrexed in the ongoing Phase 1 study prior to enrollment of participants in this Phase 3 
study. In addition, an early IDMC meeting is planned after approximately 20 participants have 
been randomized and treated for 2 cycles with the protocol treatment for additional review of 
the safety with this combination.
!
If regulatory or health authorities request region specific safety experience for amivantamab 
in combination with carboplatin-pemetrexed, an optional Safety Run-in may be performed to 
collect region/country-specific safety data (refer to Appendix 10: Safety Run-in).

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2.3.2.
Benefits for Study Participation
As described in the previous sections, there are no approved targeted therapies for the treatment of 
NSCLC with EGFR Exon 20ins mutations. Amivantamab has demonstrated significant activity as 
monotherapy in this disease population, and platinum-based combination chemotherapy is the 
accepted standard of care in the first-line setting. It is anticipated that combining these therapeutic 
approaches with non-overlapping mechanisms of action—targeted therapy with amivantamab and 
combination chemotherapy—will be more effective than either approach alone for the treatment 
of NSCLC with EGFR Exon 20ins mutations.
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 combining amivantamab and platinum-based doublet 
chemotherapy are justified by the anticipated benefits that may be afforded to participants with
EGFR Exon 20ins-mutated metastatic NSCLC (refer to Section 2.3.2). More detailed information 
about known and expected benefits and risks of amivantamab can be found in the latest version of
the IB for amivantamab.12

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4.
STUDY DESIGN
4.1.
Overall Design
This is a randomized, open-label, multicenter, Phase 3 study of combination amivantamab and 
carboplatin-pemetrexed therapy, compared with carboplatin-pemetrexed, in patients with 
treatment-naïve, locally advanced or metastatic NSCLC characterized by EGFR Exon 20ins 
activating mutations. A target of 300 participants will be randomly assigned in this study.
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). An IDMC will be commissioned for this study for the periodic 
review of safety and tolerability data, as well as planned efficacy analyses (refer to Appendix 2: 
Regulatory, Ethical, and Study Oversight Considerations). Additional ad-hoc meetings may occur 
as needed. 
A diagram of the study design is provided in Section 1.2, Schema. 
4.1.1.
Screening Phase
The participant must sign an informed consent form (ICF) at the beginning of the Screening phase, 
before the first study-related activity is conducted. Participants will be evaluated for eligibility 
during Screening. Participants must complete all Screening procedures within 28 days of
randomization, including submission of test results for Exon 20ins mutation, submission of a tumor 
biopsy sample, submission of peripheral blood samples for circulating tumor deoxyribonucleic 
acid (ctDNA), baseline imaging of disease sites, and baseline Brain MRI.
4.1.2.
Treatment Phase
The Treatment phase for each participant will begin at Cycle 1 Day 1 and continue in 21-day cycles
until the End of Treatment visit, approximately 30 days after discontinuation of study treatment. 
Study treatment will continue until documented clinical or radiographic (Response Evaluation 
Criteria in Solid Tumors [RECIST] v1.1) disease progression or until the participant meets another 
criterion for discontinuation of study treatment (Section 7.1). Approximately 300 eligible
participants will be stratified based on Eastern Cooperative Oncology Group (ECOG) performance 
status (0 or 1), history of brain metastases (yes or no), and prior EGFR TKI use (yes or no), and
assigned randomly in a 1:1 ratio into 1 of 2 treatment arms as follows:
Arm A (amivantamab plus chemotherapy):
!
Pemetrexed 500 mg/m2 (with vitamin supplementation) on Day 1 of each 21-day cycle, in 
combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until 
disease progression
!
Carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) on Day 1 
of each 21-day cycle, for up to 4 cycles
!
Amivantamab 1,400 mg (1,750 mg if body weight is ≥80 kg) by intravenous (IV) infusion 
once weekly up to Cycle 2 Day 1, then 1,750 mg (2,100 mg if body weight is ≥80 kg) on 
Day 1 of each 21-day cycle, starting with Cycle 3

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Arm B (chemotherapy alone):
!
Pemetrexed 500 mg/m2 (with vitamin supplementation) on Day 1 of each 21-day cycle, in 
combination with carboplatin for up to 4 cycles, and then as maintenance monotherapy until 
disease progression
!
Carboplatin AUC 5 on Day 1 of each 21-day cycle, for up to 4 cycles
Disease assessments will occur as close as possible to the start of treatment (baseline screening 
scans), 6 weeks (+1 week) after randomization, then every 6 weeks (±1 week) for the first 
18 months and then every 12 weeks (±1 week), until objective radiographic disease progression.
At each study visit during the Treatment phase, participants will undergo safety evaluations, 
including physical examinations and assessment of TEAEs, vital signs, concomitant medication 
usage, and clinical laboratory parameters. Participants will complete questionnaires for patient-
reported outcomes (PROs) at selected visits. Participants will also have blood samples drawn for 
assessment of PK and immunogenicity parameters, and for biomarker evaluations, at selected 
visits. Post-progression biopsy will be obtained, if clinically feasible, within 30 days of disease 
progression and before the next anti-cancer therapy.
Continuation of study treatment after disease progression by RECIST v1.1, as confirmed by 
blinded independent central review (BICR) may be allowed after approval from the Medical 
Monitor, if the investigator believes the participant is deriving clinical benefit. Participants 
continuing treatment after documented progression will continue within the Treatment phase of 
the study and comply with all associated visits and procedures, including scheduled disease 
assessments, until the termination of study treatment.
A participant in Arm B with disease progression by RECIST v1.1, as confirmed by BICR, may
cross over to amivantamab monotherapy (refer to Appendix 11: Optional Crossover After Disease 
Progression to Second-Line Amivantamab Monotherapy (Arm B Only)).
4.1.3.
Follow-up Phase
Participants who discontinue assigned study treatment for any reason will be followed for
subsequent therapy, disease status, survival, and symptomatic progression in the Follow-up phase. 
This phase starts from the End of Treatment Visit and continues until the end of study, death, loss 
to follow-up, or withdrawal of consent from participation in the study, whichever comes first. 
Visits (or telephone contact) will occur approximately every 12 weeks during the Follow-up phase. 
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 case report form (CRF) when available. Where 
allowed by local law, public records may be used to document death for obtaining survival status.
Note: For participants who discontinue prior to disease progression by BICR, tumor imaging 
should continue per schedule of activities.

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4.1.4.
Open-label Extension Phase and Long-term Extension Phase
Following the primary analysis for efficacy, the study will transition to an open-label extension 
(OLE) Phase (see details provided in Section 10.14 [Appendix 14]). Participants will be provided 
the option to continue treatment in the OLE Phase until the final analysis for overall survival, after 
which the study will transition to a long-term extension (LTE) Phase.
Participants who continue to benefit from study treatment(s), as determined by their investigator, 
at the time of the OLE Phase may continue to receive access to study treatment(s) within the study 
by transferring to the LTE Phase, where only serious adverse event data and study treatment 
accountability will be collected.
The LTE Phase (see details provided in Section 10.15 [Appendix 15]) will begin after the final 
analysis for overall survival, and will continue until the discontinuation criteria described in 
Section 7.1 are met, or until 2 years after local marketing authorization is obtained for the studied 
indication, whichever occurs first.
The extension phases will begin after approval of Amendment 3 by health authorities of countries 
in which this study is still being conducted at the time of transition, and by study site ECs/IRBs. 
In addition, for transition to the LTE Phase (after final analysis for overall survival), prior 
notification from the sponsor will be needed.
4.2.
Scientific Rationale for Study Design
Blinding, Control, Study Phase/Periods, Study Treatment Groups
Randomization will be used to minimize bias in the assignment of participants to study treatment
groups, to increase the likelihood that known and unknown participant attributes (eg, demographic 
and baseline characteristics) are evenly balanced across study treatment groups, and to enhance 
the validity of statistical comparisons across study treatment groups. Due to differences in safety 
profile, safety monitoring, premedication requirements, and administration, blinded study 
treatment and a placebo control will not be used.
Clinical Pharmacology Assessments
Blood samples will be analyzed for amivantamab serum concentrations and estimation of PK 
parameters. Immunogenicity (antibodies to amivantamab) will be evaluated for impact on PK, 
safety and efficacy. A population PK model will be developed as a means to derive the individual 
participant’s exposure, for determination of participant covariates that influence the PK of 
amivantamab, and for exposure-response analysis to support regulatory submission.
ctDNA and Biomarker Collection
Tumor biopsy samples will be collected to evaluate pretreatment mutational status of EGFR
(Exon 20ins and co-occurring EGFR mutations), MET, and other key oncogenes to characterize 
the tumor or help to explain interindividual variability in clinical outcomes or may help to identify 
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The ctDNA and serum biomarker samples may be used to better understand dynamics of tumor 
response and/or resistance to therapy and to enable the development of safer, more effective, and 
ultimately individualized therapies.
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 adverse events of the study, and provide their consent voluntarily will be 
enrolled.
Thorough scientific evaluation of any treatment before market authorization is an ethical 
requirement. As the benefits and risks of the combination of amivantamab and chemotherapy in 
this study population are not fully known, this study will evaluate the safety and clinical activity 
of this combination. Participants will be closely monitored throughout the study, as discussed 
throughout this protocol, for both safety and clinical benefit. The IDMC will review evolving 
safety data from this study, as well as efficacy data as appropriate. Based on the mechanism of 
action of both study treatments, there is adequate justification, including significant unmet clinical 
need, for evaluating these drugs in combination for the treatment of NSCLC in participants who 
are eligible for this study.
All participants will undergo regular disease assessments to monitor the underlying disease. In 
general, these procedures are routinely performed during a participant’s diagnostic workup and 
follow-up care; therefore, archival tumor material collected at the time of locally advanced or
metastatic diagnosis may be submitted in lieu of pre-treatment biopsies. A post-progression biopsy 
should be performed within 30 days of the last dose of study treatment and before the start of next 
anticancer treatment, if clinically feasible. Although biopsy collection is associated with risk, the 
complication rate for these procedures is low. The data obtained from this procedure will generate 
valuable scientific data on the pharmacodynamic effect of the combination of these study 
treatments in this study population. 
As with all clinical and pharmacology studies, there are risks associated with venipuncture and 
multiple blood sample collection. The blood sample collection scheme was designed to collect the 
minimum number of blood samples that accurately and completely describe the pharmacology of 
the study treatment. This minimizes the number of venipunctures and the total volume of blood 
collected from each participant during the study. The total blood volume to be collected (see 
Section 8) 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 American Red Cross.4

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4.3.
Justification for Dose
4.3.1.
Chemotherapy Dose Rationale
Participants in this study will receive chemotherapy with clinically approved doses of pemetrexed 
500 mg/m2 and carboplatin AUC 5 on the first day of every 21-day cycle. Platinum-based 
combination chemotherapy is a commonly used regimen for all patients with NSCLC, either alone 
or in approved combinations with anti-PD-1 agents, anti-PD-L1 agents, or bevacizumab, as well 
as investigational approaches such as in combination with an EGFR TKI. Although targeted 
EGFR TKIs are now standard of care for the first-line treatment of the majority of EGFR-mutated 
NSCLC (eg L858R, Exon19del), no targeted therapies are approved for the treatment of EGFR 
Exon 20ins NSCLC. Platinum-based doublet chemotherapy is therefore considered the standard 
of care for first-line treatment of newly diagnosed patients with advanced or metastatic EGFR 
Exon 20ins NSCLC and will be used as the control arm in this study. Among patients with 
metastatic adenocarcinoma, the combination of carboplatin and pemetrexed has become a 
preferred regimen based upon the superior tolerability and the ability to continue pemetrexed as a 
maintenance therapy in patients continuing to derive benefit after completion of combination 
therapy.
4.3.2.
Amivantamab and Chemotherapy Combination Dose Rationale 
Combination of amivantamab with standard of care carboplatin and pemetrexed chemotherapy 
may provide improved treatment outcomes than either regimen alone. The safety of chemotherapy 
combinations with EGFR-targeted monoclonal antibody therapy has been previously 
demonstrated in randomized, Phase 3 studies.21,23 To optimize treatment with this potential 
combination, the amivantamab dosing schedule in this study allows dosing on the same 21-day 
chemotherapy regimen schedule.
In the ongoing Phase 1 Study 61186372EDI1001, amivantamab has been generally well tolerated 
up to the dose of 1,750 mg administered weekly for the first cycle, and every 2 weeks thereafter, 
on a 28-day cycle. No dose-limiting toxicity (DLTs) were reported during dose escalation and no 
maximum tolerated dose identified. Moreover, amivantamab had no apparent dose dependent
TEAEs in the dose range of 350 to 1,400 mg. While the RP2D of amivantamab has been 
established as 1,050 mg for body weight <80 kg or 1,400 mg for body weight ≥80 kg when 
administered weekly for the first cycle and every 2 weeks thereafter, tolerability has been 
demonstrated up to a dose of 1,750 mg: of the first 5 subjects enrolled in the Phase 1 study at 
1,750 mg, 3 subjects achieved treatment durations of at least 9 cycles. Of the 5 subjects enrolled 
at 1,750 mg, all had baseline body weight <80 kg (mean [range] body weight of 66 kg [58.0-79.4]), 
and 3 of these subjects were treated with 1,750 mg biweekly dosing beyond the anticipated 4 cycles 
planned to be administered in combination with chemotherapy (6, 8, and 9 cycles, respectively).
The mean (%CV) maximum concentration and maximum exposure (AUC2week) achieved after the 
weekly induction dosing of 1,750 mg on the 28-day cycle were 1,355 (21%) ∀g/mL and 10,932 
(25%) μg×day/mL respectively.
Amivantamab has therefore been demonstrated to have an adequate therapeutic window using the 
28-day cycle (every 2 weeks) dosing regimen. The planned amivantamab dosing according to the 

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21-day cycle is 1,400 mg for body weight <80 kg and 1,750 mg for body weight ≥80 kg once 
weekly up to Cycle 2 Day 1 (induction period), then 1,750 mg for body weight <80 kg and 
2,100 mg for body weight ≥80 kg on Day 1 of each 21-day cycle, starting with Cycle 3
(maintenance period). This dosing regimen is intended to achieve equivalent exposures to every 
2-week dosing regimen using the 28-day cycle. 
During the induction period, the anticipated maximum serum concentration (Cmax) achieved with 
21-day cycles (4 weekly doses) will be lower than that observed for 1,750 mg with 28-day cycles
(5 weekly doses) in the Phase 1 study. During the maintenance period, at the proposed dose of 
2,100 mg for body weight ≥80 kg every 3 weeks, the anticipated exposures will be lower or within 
the already safely explored exposure range. Population PK simulation suggests that the maximum 
median predicted drug concentration at the proposed dose of 2,100 mg is 703 (95% confidence 
interval [CI]: 358, 1,372) μg/mL, which is within the observed concentration in the amivantamab 
monotherapy 1,750 mg cohort (Table 3). Moreover, the simulated exposure (AUC3weeks) of 5,883 
(95% CI: 3,004, 12,138) μg×day/mL achieved with 2,100 mg every 3 weeks is less than the 
observed maximum exposure after the weekly induction dosing of 1,750 mg on the 28-day cycle
(Table 3). Thus, the population PK simulations demonstrate that the anticipated exposures in the
21-day cycle dosing will be within the exposures already demonstrated to be safe and tolerable in 
the amivantamab monotherapy cohort of the ongoing Phase 1 Study. Further, dosing of 
amivantamab in combination with chemotherapy is also being explored in the ongoing Phase 1
Study.
In the ongoing Phase 1 Study 61186372EDI1001, Cycle 1 PK data suggest no impact of 
chemotherapy on amivantamab exposure. Preliminary trough concentration comparisons suggest 
that higher doses of amivantamab given every 3 weeks (Q3W; 21-day cycle), are similar to the 
recommended dose for monotherapy given every 2 weeks (28-day cycle). Please refer to the latest 
version of the IB for further information.12
Table 3:
Comparison of Observed Maximum Exposures Attained After Weekly Induction with 
1,750 mg in the 28-Day Cycle and Expected Steady State Exposure Attained With 
2,100 mg Every 3 Weeks in the 21-day Cycle
Dose (mg)
Regimen
Data
Cmax, ∀g/mL
AUC, ∀g×day/mL
1,750a
After induction (28-day cycle)
Observed mean (CV%)
1,355 (21%)
10,932 (25%)
2,100b
Every 3 weeks (21-day cycle)
Simulated median (95%CI)
703 (358, 1372)
5,883 (3004, 12138)
a.
Mean [range] body weight = 66 [58.0-79.4] kg.
b.
Simulation for body weight ≥80 kg.
4.4.
End of Study Definition
End of Study Definition
A final analysis for overall survival is planned to occur approximately 48 months after the first 
participant is randomized. The end of study/study completion is considered as the last scheduled 
study assessment shown in the Schedule of Activities for the last participant in the study. The final 
data from the study site will be sent to the sponsor (or designee) after completion of the final 
participant assessment at that study site, in the time frame specified in the Clinical Trial 
Agreement. The sponsor will establish a clinical data cutoff date for clinical study report (CSR) 

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analysis reporting. The data cutoff will be communicated to the sites. Subjects who continue to 
receive study drug or who are in Follow-up after the data cutoff will continue to be monitored.
These data will be reported to the appropriate health authorities in a CSR addendum.
Study Completion Definition
A participant will be considered to have completed the study if he or she has died before the end 
of the study or has not prematurely discontinued the study for another reason.
5.
STUDY POPULATION
Screening for eligible participants will be performed within 28 days prior to randomization. Refer 
to Section 5.4 for conditions under which the repeat of any screening procedures is allowed.
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.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2.
5.1.
Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1.
Participant must be ≥18 years of age (or the legal age of consent in the jurisdiction in 
which the study is taking place).
2.
Participant must have histologically or cytologically confirmed, locally advanced or 
metastatic, nonsquamous NSCLC with documented primary EGFR Exon 20ins
activating mutation (a copy of the mutation analysis must be submitted during 
screening) performed by a Clinical Laboratory Improvement Amendments (CLIA)-
certified (US sites) or an accredited (outside of the US) local laboratory.
3.
Participant must have measurable disease according to RECIST v1.1. If only one 
measurable lesion exists, it may be used for the screening biopsy (if required for 
submission of tumor tissue) if the baseline tumor assessment scans are performed 
≥14 days after the biopsy.
4.
Participant must have ECOG performance status 0 or 1.
5.
Participant must agree to genetic characterization of tumor status through the required 
pretreatment tumor biopsy (or submission of equivalent archival material), as well as 
baseline and periodic blood samples for analysis of tumor mutations in the bloodstream.

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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.
!
Hemoglobin ≥10 g/dL
!
Absolute neutrophil count ≥1.5#109/L, without use of granulocyte colony-
stimulating factor (G-CSF) within 10 days prior to the date of the test
!
Platelets ≥100#109/L
!
ALT and aspartate aminotransferase (AST) ≤3×upper limit of normal (ULN)
!
Total bilirubin ≤1.5#ULN (participants with Gilbert’s syndrome can enroll if 
conjugated bilirubin is within normal limits)
!
Creatinine clearance >50 mL/min as measured or calculated by Cockcroft-Gault
formula
7.
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.
8.
A female participant of childbearing potential must have a negative serum or urine test 
at screening and within 72 hours of the first dose of study treatment and must agree to 
further serum or urine pregnancy tests during the study.
9.
Criterion modified per Amendment 1:
9.1. A female participant must be (as defined in Appendix 4: Contraceptive and Barrier 
Guidance) either of the following:
a.
Not of childbearing potential
b. Of childbearing potential and practicing 2 methods of contraception, 
including 1 highly effective, user independent method. Examples of highly 
effective methods of contraception are located in Appendix 4: Contraceptive 
and Barrier Guidance.
Participant must agree to continue contraception throughout the study and through 
6 months after the last dose of study treatment.
Note: If the childbearing potential changes after start of the study (eg, woman who is 
not heterosexually active becomes active, premenarchal woman experiences menarche) 
the woman must begin 2 methods of birth control, as described above.
10.
A female participant must agree not to donate eggs (ova, oocytes) for the purposes of 
assisted reproduction during the study and for 6 months after receiving the last dose of 
study treatment.
11.
A male participant must wear a condom when engaging in any activity that allows for 
passage of ejaculate to another person during the study and for a minimum of 6 months 
after receiving the last dose of study treatment. If the participant is vasectomized, he 

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must still use a condom (with or without spermicide) for prevention of passage of 
exposure through ejaculation, but his female partner is not required to use contraception.
A male participant who is sexually active with a woman of childbearing potential must 
agree to use a condom with spermicidal foam/gel/film/cream/suppository and his 
partner must also be practicing a highly effective method of contraception 
(ie, established use of oral, injected, or implanted hormonal methods of contraception;
placement of an intrauterine device [IUD] or intrauterine hormone-releasing system
[IUS]).
12.
A male participant must agree not to donate sperm for the purpose of reproduction 
during the study and for a minimum of 6 months after receiving the last dose of study 
treatment.
13.
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.
Criterion modified per Amendment 1:
1.1. Participant has received any prior systemic treatment for locally advanced or 
metastatic disease, with the following exceptions:
!
Prior adjuvant or neoadjuvant platinum-based doublet chemotherapy is allowed, 
if completed at least 12 months prior to signing the study ICF.
!
Localized radiotherapy to the lung must be completed at least 6 months prior to 
randomization. Palliative radiation to other sites must be completed at least 
7 days prior to randomization.
!
Prior monotherapy with an approved EGFR TKI (ie, gefitinib, erlotinib, afatinib, 
dacomitinib, or osimertinib) as non-standard first-line therapy for the treatment 
of locally advanced or metastatic disease is allowed, if: 1) treatment duration 
did not exceed 8 weeks; 2) lack of disease response was documented 
(radiographically) by an increase in tumor burden (a copy of the computerized 
tomography [CT] report showing increase in tumor burden from baseline should 
be submitted); 3) associated toxicities have resolved to baseline; and 4) the 
EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to 
randomization, whichever is longer. Prior therapy with investigational EGFR 
TKI agents targeting Exon 20ins mutations, including TAK788 or poziotinib, is 
not allowed.

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2.
Criterion modified per Amendment 1:
2.1. Participant has evidence of synchronous NSCLC disease (as suggested by genetic 
characterization or radiographic appearance).
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 randomization is eligible). If brain metastases are diagnosed on 
Screening imaging, the participant may be rescreened for eligibility after definitive 
treatment.
4.
Participant has a history of leptomeningeal disease.
5.
Participant has history of spinal cord compression that has not been treated definitively 
with surgery or radiation.
6.
Participant has uncontrolled tumor-related pain (symptomatic lesions amenable to 
palliative radiotherapy [eg, bone metastases or metastases causing nerve impingement]
should be treated prior to Screening).
7.
Participant has a medical history of ILD, including drug-induced ILD, or radiation 
pneumonitis.
8.
Criterion modified per Amendment 1:
8.1. Participant has an active malignancy (ie, ongoing, progressing or requiring 
treatment change in the last 24 months) other than the disease being treated under study. 
The only allowed exceptions are: 
a.
Non-muscle invasive bladder cancer (NMIBC) 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):
!
with a Gleason score of 6, treated within the last 24 months or untreated and 
under surveillance,
!
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,
!
or history of localized prostate cancer and receiving androgen deprivation 
therapy and considered to have a very low risk of recurrence. 
e.
Breast cancer:

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!
adequately treated lobular carcinoma in situ or ductal carcinoma in situ,
!
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
9.
Participant has a history of clinically significant cardiovascular disease including, but 
not limited to:
!
Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior 
to randomization or any of the following within 6 months prior to randomization: 
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.
!
Prolonged corrected QT interval by Fridericia’s (QTcF) >480 msec, clinically 
significant cardiac arrhythmia, or electrophysiologic disease (eg, placement of 
implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate)
!
Uncontrolled (persistent) hypertension: systolic blood pressure >160 mm Hg; 
diastolic blood pressure >100 mm Hg
!
Congestive heart failure defined as New York Heart Association (NYHA) Class 
III-IV or hospitalization for congestive heart failure (any NYHA class) within 6 
months of study Day 1 (refer to Appendix 6: New York Heart Association Criteria)
!
Pericarditis/clinically significant pericardial effusion
!
Myocarditis
!
Baseline left ventricular ejection fraction below the lower limit of normal as 
assessed by screening echocardiogram (ECHO) or multigated acquisition scan.
10.
Participant has at Screening: 
!
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) 
an HBV deoxyribonucleic acid (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.
!
Positive hepatitis C (hepatitis C virus [HCV]) antibody (anti-HCV)
Note: Participants with a prior history of HCV who have completed antiviral 
treatment and have subsequently documented HCV ribonucleic acid (RNA) below 
the lower limit of quantification per local testing are eligible.
!
Other clinically active infectious liver disease.

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11.
Criterion modified per Amendment 1:
11.1. Participant is known to be positive for human immunodeficiency virus (HIV) and 
meets one of the following criteria:
!
Not receiving highly active antiretroviral therapy (ART)
!
Had a change in antiretroviral therapy within 6 months of the start of screening
!
Receiving antiretroviral therapy that may interfere with study treatment (consult 
Sponsor for review of medication prior to enrollment)
!
CD4 count <350 at screening
!
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 an uncontrolled illness, including but not limited to the following:
!
Diabetes
!
Ongoing or active bacterial infection (includes infection requiring treatment with 
antimicrobial therapy [participants will be required to complete antibiotics 1 week 
before randomization]), symptomatic viral infection, or any other clinically 
significant infection
!
Active bleeding diathesis
!
Impaired oxygenation requiring supplemental oxygen
!
Psychiatric illness/social situation that would limit compliance with study 
requirements
13.
Participant had major surgery (eg, requiring general anesthesia) or significant traumatic 
injury within 4 weeks of randomization, will not have fully recovered from surgery, or 
has surgery planned during the time the participant is expected to participate in the 
study.
Note: Participants with planned surgical procedures to be conducted under local 
anesthesia may participate.
14.
Participant has a contraindication to the use of carboplatin or pemetrexed (refer to local 
prescribing information for each agent2,5). Participant has a history of hypersensitivity 
to, or cannot take, vitamin B12 or folic acid.
15.
Participant has a history of hypersensitivity to the excipients of amivantamab (refer to 
the IB12).

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NOTE: Investigators must ensure that all study enrollment procedures have been completed 
during the screening period and the subject continues to meet eligibility at the time of 
randomization, is clinically stable and is expected to initiate therapy within 72 hours of 
randomization. The required source documentation to support meeting the enrollment criteria are 
noted in Appendix 2: Regulatory, Ethical, and Study Oversight Considerations.
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 6.6.3 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).
3.
Agree to use sun protective measures (such as a hat, sunglasses, and protective 
clothing), limit prolonged exposure to natural sunlight, and avoid artificial sunlight 
(tanning beds or phototherapy) from baseline until the last dose of study treatment. 
Avoid unnecessary exposure to sunlight. Use broad-spectrum sunscreen (containing 
titanium dioxide or zinc oxide) with a skin protection factor (SPF) ≥30 (refer to 
Section 6.8.2.1).
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 
16.
Participant has received a live or live attenuated vaccine within 3 months before 
randomization.
17.
Participant has received an investigational intervention (including investigational 
vaccines) within 6 weeks before randomization. 
18.
Participant is pregnant, breast-feeding, or planning to become pregnant while enrolled 
in this study or within 6 months after the last dose of study treatment.
19.
Participant plans to father a child while enrolled in this study or within 6 months after 
the last dose of study treatment.
20.
Participant has 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.

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the sponsor study-site contact for completeness. This study will use IWRS. The investigator will
generate screening and enrollment logs directly from IWRS.
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 randomized 
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 once if their condition changes. Rescreening must be discussed with and approved by 
the sponsor on a case-by-case basis. Participants who are determined to be eligible for the study 
after their condition changes must sign a new ICF.
6.
STUDY MEDICATION 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 Treatments Administered
For this study, “study treatment” refers to JNJ-61186372 (amivantamab), carboplatin, and 
pemetrexed. 
Study treatment administration must be captured in the source documents and the CRF. Study-site 
personnel will instruct participants on how to store and administer required premedications at
home as required for this protocol.
Amivantamab will be manufactured and provided under the responsibility of the sponsor. Refer to 
the latest version of the IB for a list of excipients.
For information related to study treatment overdose, refer to Section 6.9, Treatment of Overdose.
6.2.
Dosage and Administration of Study Treatment
6.2.1.
Scheduled Dosage and Timing
Administration of study treatment should begin within 3 days of randomization. The scheduled 
dosage and timing of each study treatment are outlined in Table 4. On Day 1 of each cycle in which 
combination therapy is administered, they should occur in the following order: 1) pemetrexed,
2) carboplatin, and 3) amivantamab.
The proposed timing for carboplatin and pemetrexed should be according to the local guidelines 
and regulatory labeling (eg, pemetrexed can be given over approximately 10 to 15 minutes and 
carboplatin can be given over approximately 30 to 60 minutes). Refer to IPPI for detailed 
information on amivantamab administration. Due to the multiple infusions in Arm A, dosing
should be scheduled to begin with sufficient time to accommodate all infusions on Cycle 1 Day 1. 

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If, however, delays in initiation of therapy leave insufficient time on Cycle 1 Day 1 for full 
amivantamab dosing, the initial split dose of amivantamab (Cycle 1 Days 1 and 2) may be delayed 
(until Cycle 1 Days 2 and 3), with corresponding changes to scheduled activities (PK and vital 
signs), and should be reported in the electronic case report form (eCRF) as a dose delay. If 
amivantamab treatment is delayed from Cycle 1 Day 1 to Day 2 and Cycle 1 Day 2 to Day 3, 
appropriate premedications should be administered before amivantamab infusion. Please refer to 
Table 6 for premedications required with amivantamab.
Table 4:
Scheduled Dosages and Timing of Study Treatments, by Study Visit (21-Day Cycles)
Study Visit
Study Treatment (Study Arm)
Study Treatment Dosage
Cycle 1 Day 1
Pemetrexed (Arm A + Arm B)
500 mg/m2
Carboplatin (Arm A + Arm B)
AUC 5; maximum of 750 mg
Amivantamab (Arm A only)
350 mg
Cycle 1 Day 2
Amivantamab (Arm A only)
1,050 mg (if <80 kg)
1,400 mg (if ≥80 kg)
Cycle 1 Day 8
Amivantamab (Arm A only)
1,400 mg (if <80 kg)
1,750 mg (if ≥80 kg)
Cycle 1 Day 15
Amivantamab (Arm A only)
1,400 mg (if <80 kg)
1,750 mg (if ≥80 kg)
Cycle 2 Day 1
Pemetrexed (Arm A + Arm B)
500 mg/m2
Carboplatin (Arm A + Arm B)
AUC 5; maximum of 750 mg
Amivantamab (Arm A only)
1,400 mg (if <80 kg)
1,750 mg (if ≥80 kg)
Cycles 3-4 Day 1
Pemetrexed (Arm A + Arm B)
500 mg/m2
Carboplatin (Arm A + Arm B)
AUC 5; maximum of 750 mg
Amivantamab (Arm A only)
1,750 mg (if <80 kg)
2,100 mg (if ≥80 kg)
Cycles 5+ Day 1
Pemetrexed (Arm A + Arm B)
500 mg/m2
Amivantamab (Arm A only)
1,750 mg (if <80 kg)
2,100 mg (if ≥80 kg)
AUC=area under the concentration-time curve 5 mg/mL per minute.
Amivantamab should typically be administered Q3W but if amivantamab dosing needs to align 
with a delayed dose of chemotherapy then it can be administered at an interval between 2 and 
4 weeks (see Appendix 9: Dosing Synchronization for Arm A). Any missed scheduled doses 
should be discussed with the Medical Monitor prior to redosing. If a dose is delayed on Cycle 1
Day 8 and/or Cycle 1 Day 15 it will not be made up. If a dose is delayed in Cycle 2 or beyond, 
then the dates of the subsequent doses will be scheduled based on the timing of the previous dose 

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of amivantamab. If amivantamab is delayed for ≥6 weeks from the last dose, a discussion should 
occur with the Medical Monitor prior to redosing.
6.2.2.
Chemotherapy
Chemotherapy will be supplied as carboplatin (600 mg/vial, with concentration 10 mg/mL in a 
60 mL vial) and pemetrexed (500 mg/vial powder for concentration for solution for infusion).
Refer to the local prescribing information for each agent for a list of excipients.2,5
6.2.3.
Amivantamab
Amivantamab is supplied for this study in a glass vial containing 350 mg/vial with concentration 
50 mg/mL, 7 mL per vial. Amivantamab will be manufactured and provided under the 
responsibility of the sponsor. Refer to the latest version of the IB for a list of excipients.12
The dosage of amivantamab will be based on the participant's body weight at Screening. Qualified 
site personnel will administer amivantamab as an intravenous (IV) infusion in 21-day cycles as 
follows:
!
Once weekly (with the first dose split over Days 1-2) up to Cycle 2 Day 1: 1,400 mg (1,750 mg 
if body weight is ≥80 kg)
!
Cycles 3+: 1,750 mg (2,100 mg if body weight is ≥80 kg) on Day 1 of each 21-day cycle
Amivantamab will be administered by IV using the escalating infusion rate regimen as 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 Cycle 2 Day 1 dose. In cases where 
peripheral access may be limiting to treatment administration, earlier use of a central line for 
amivantamab infusion in Cycle 1 starting after Cycle 1 Day 8 may be considered, only after prior 
approval with the Medical Monitor.
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:
!
Do not mix or dilute amivantamab with other drugs.
!
Amivantamab must not be administered as an IV push or bolus.
!
Due to the risk of infusion-related reactions, equipment and agents for treating anaphylaxis
(eg, epinephrine, corticosteroids, IV antihistamines, bronchodilators, oxygen, resuscitation
equipment) must be available during amivantamab administration. Trained personnel
(eg, resuscitation team) must also be available.
After 12 cycles of amivantamab (1 year), participants receiving the full dosage of amivantamab 
can skip up to 3 doses in a year and participants on a reduced dose of amivantamab (refer to 

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Section 6.8.2) can skip up to 2 doses in a year, as needed for life events. The skipped doses should 
be at least 3 months apart.
6.3.
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
The instructions below on study treatment preparation, handling, and storage apply only to 
amivantamab and/or centrally sourced chemotherapy. For locally sourced chemotherapy, please 
follow the instructions on the local package insert.
All study treatment must be stored at controlled temperatures according to the requirements on the
label and protected from light prior to use. Refer to the pharmacy manual/SIPPM for additional 
guidance on study treatment preparation, handling, and storage.
Accountability
The instructions below on study treatment apply only to amivantamab and/or centrally sourced 
chemotherapy. For locally sourced chemotherapy, please follow the instructions on the local 
package insert.
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 study 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, and study treatment returned by the participant, 
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, or used returned study treatment for 
destruction, 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 study 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. 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.

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6.4.
Measures to Minimize Bias: Randomization and Blinding
Study Treatment Allocation
Procedures for Randomization 
Central randomization will be implemented in this study. Participants will be randomly assigned 
to 1 of 2 study treatment groups based on a computer-generated randomization schedule prepared 
before the study by or under the supervision of the sponsor. The randomization will be balanced 
by using randomly permuted blocks and will be stratified by ECOG performance status (0 or 1),
history of brain metastases (yes or no), and prior EGFR TKI use (yes or no). The interactive web 
response system (IWRS) will assign a unique study treatment code, which will dictate the study 
treatment assignment and matching study treatment kit for the participant. The requestor must use 
his or her own user identification and personal identification number when contacting the IWRS 
and will then give the relevant participant details to uniquely identify the participant.
Blinding
As this is an open study, blinding procedures are not applicable.
6.5.
Study Treatment Compliance
The instructions below on study treatment compliance apply only to amivantamab and/or centrally 
sourced chemotherapy. For locally sourced chemotherapy, please follow the instructions on the 
local package insert.
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 sub-investigator 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.
Pemetrexed and carboplatin 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. 

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6.6.
Concomitant Therapy
6.6.1.
Recording Prestudy and Concomitant Therapies
Prestudy therapies administered up to 28 days before randomization must be recorded at 
Screening. Concomitant therapies must be recorded throughout the study beginning when the ICF 
is signed and continuing until 30 days after the last dose of study treatment or start of new 
anticancer therapy, whichever is first. Concomitant therapies used in conjunction with new or 
worsening adverse events considered related to study treatment should be recorded through the 
end of follow-up of that adverse event.
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 CRF. 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.
6.6.2.
Permitted Medications and Therapies 
6.6.2.1.
Pre- and Post-infusion Medications for Chemotherapy
Corticosteroids, folic acid, and vitamin B12 will be administered concomitantly with pemetrexed
according to local prescribing information (Table 5) or per standard local practice.
Table 5:
Concomitant Medications for Pemetrexed
Medication
Dose
Timing
Corticosteroid
Dexamethasone 4 mg 
orally twice daily or 
equivalent
1 day before, the day of, and 1 day after each dose of pemetrexeda
Folic Acidb
350-1,000 μg orally
Daily beginning 7 days prior to first infusion and continuing until 21 days 
after the last dose of pemetrexed
Vitamin B12
1,000 μg intramuscularly
1 dose within 7 days of Cycle 1 Day 1, then every 3 cycles afterwards. 
Vitamin B12 may be administered on the same day as pemetrexed
a.
Dexamethasone 4 mg orally twice daily dose can be skipped on Cycle 1 Day 1, if patient is administered 20 mg IV dose of 
dexamethasone with amivantamab 
b.
Folic acid may be given either as a separate preparation or as a component of a multivitamin.
Participants may receive other pre-treatment or concomitant treatment for pemetrexed or 
carboplatin as recommended by local prescribing information,2,5 local practice guidelines, or as 
clinically indicated. Permitted prophylactic medications may include the following: 
!
Appropriate prophylactic antiemetic regimens for high risk of emesis associated with 
carboplatin (eg, ondansetron, aprepitant, dexamethasone), in accordance with institutional 
practice or current NCCN and/or ESMO guidelines.
!
Leukocyte-depleted blood transfusions are allowed at any time after randomization.

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!
G-CSFs should not be used prophylactically during Screening. Use of prophylactic colony 
stimulating factors may be considered after randomization as per local guidelines or 
prescribing information.2,5
Concomitant medications for the symptomatic treatment of related toxicities (Grade 1-4) may be 
administered according to the standard of care at the site and at the treating physician’s discretion, 
as clinically indicated. Supportive care and other medications that are considered necessary for the 
participant’s well-being may be given at the discretion of the investigator.
Localized, limited radiotherapy of short duration for palliative purposes may be permitted but only 
after discussion with and approval by the Medical Monitor.
6.6.2.2.
Pre- and Post-Infusion Medications for Amivantamab
Pre-Infusion Medications
Required pre-infusion medications and optional pre-infusion medications for amivantamab are 
summarized in Table 6.
Table 6: 
Pre-Infusion Medications for Amivantamab
Cycle/Day
Medication
Dose
Route of
Administration
Recommended Dosing
Window Before
Amivantamab Infusion
Required Pre-Infusion Medicationsa,b
Cycle 1 Day 1
Glucocorticoid
Dexamethasone 20 mg
IV
45 to 60 minutes
Cycle 1 Day 2
Glucocorticoid
Dexamethasone 10 mg or 
Methylprednisolone 40 mg
IV
45 to 60 minutes
All
Antihistamine
Diphenhydramine 25 to 50 mg
(or equivalent)
IV
15 to 30 minutes
Oral
30 to 60 minutes
All
Antipyretic
Paracetamol (acetaminophen)
650 to 1,000 mg (or equivalent)
IV 
15 to 30 minutes
Oral
30 to 60 minutes
Optional Pre-Infusion Medicationsa
Cycle 1 Day 8
and beyond
Glucocorticoidc
Dexamethasone 10 mg or
methylprednisolone 40 mg
IV
45 to 60 minutes
Oral
60 to 90 minutes
Any
Histamine H2-
antagonist
Ranitidine 50 mg (or equivalent)
IV
15 to 30 minutes
Any
Antiemetic
Ondansetron 8-16 mg (or equivalent)
Oral or IV
15 to 30 minutes
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 
doctor. If alternative medications are not suitable for the intent above, participants are not required to take the corresponding 
medication.
c.
Beginning with Cycle 1 Day 8, optional pre-dose steroids may be administered prior to amivantamab if clinically indicated 
for participants who experienced an infusion-related reaction on Cycle 1 Day 1 or Cycle 1 Day 2.

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Examples of specific schedules for administration of study treatments and concomitant therapies 
in Arm A are shown in the following tables:
!
Table 7: When amivantamab is given with carboplatin and pemetrexed (Day 1 of Cycles 1 
to 4)
!
Table 8: When amivantamab is given without chemotherapy (eg, Days 2, 8, and 15 of Cycle 1)
!
Table 9: When amivantamab is given with pemetrexed (Day 1 of Cycles 5+)
Table 7: 
Suggested Order of Administration When Amivantamab is Given With Carboplatin and 
Pemetrexed on Day 1 of Cycles 1-4 in Arm A
Medication
Dose
Route of
Administration
Recommended
Dosing
Window
Antiemetic for 
chemotherapy
Ondansetron 8 to 16 mg or equivalenta
IV
Start 60-90 minutes 
before amivantamab
infusion; administer in 
the order indicated
Fosprepitant/Aprepitant a
IV
Antihistamine for 
chemotherapy
Diphenhydramine 25 mg or equivalenta
Oral
Antipyretic for 
chemotherapy
Paracetamol (acetaminophen) 325 to 500 mg
(or equivalent)a
Oral
Glucocorticoid
Day 1 of Cycle 1: Dexamethasone 20 mgb
Day 1 of Cycles 2, 3, 4: Dexamethasone 10 to 12 mg as 
per local practice and guidelines for chemotherapya
IV
Chemotherapy
Pemetrexed
IV
-
Chemotherapy
Carboplatin
IV
-
Antipyretic for 
amivantamab
Paracetamol (acetaminophen) 325 to 500 mg
(or equivalent)b
IV or oral
Start 15-30 minutes
before amivantamab
infusion
Antihistamine for 
amivantamab
Diphenhydramine 25 mg or equivalentb
IV
Study treatment
Amivantamab
IV
-
IV=intravenous.
a.
Other agents/dosing can be considered/substituted as per local guidelines for chemotherapy prophylaxis.
b.
Required premedications for amivantamab.
Table 8:
Suggested Order of Administration When Amivantamab is Given Without Chemotherapy (eg,
on Days 2, 8, and 15 of Cycle 1) in Arm A
Medication
Dose
Route of
Administration
Recommended
Dosing Window
Glucocorticoida
Dexamethasone 10 mg or Methylprednisolone 40 mg
IV
Start 15-30 minutes
before amivantamab 
infusion
Antipyretic
Paracetamol (acetaminophen) 650 to 1,000 mg
(or equivalent)
IV or oral
Antihistamine
Diphenhydramine 25 to 50 mg (or equivalent)
IV
Study Treatment
Amivantamab
IV
-
IV=intravenous.
a.
Pre-dose steroids are mandatory for Cycle 1 Day 2 and optional for Cycle 1 Day 8 and Cycle 1 Day 15. Beginning with 
Cycle 1 Day 8, optional pre-dose steroids may be administered prior to amivantamab if clinically indicated for participants 
who experienced an infusion-related reaction on Cycle 1 Day 1 or Cycle 1 Day 2.

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Table 9:
Suggested Order of Administration When Amivantamab is Given With Pemetrexed on Day 1 
of Cycles 5+ in Arm A
Medication
Dose
Route of
Administration
Recommended Dosing
Window
Antiemetic for 
chemotherapya
Ondansetron 8 to 16 mg or equivalent
IV/oral
Start 30-45 minutes
before amivantamab infusion; 
administer in the order indicated
Glucocorticoidb
Dexamethasone 10 mg or 
methylprednisolone 40 mg (optional) 
IV
Antipyreticc
Paracetamol (acetaminophen) 650 to 
1,000 mg (or equivalent)
IV/oral
Antihistaminec
Diphenhydramine 25 to 50 mg 
(or equivalent)
IV
Chemotherapy
Pemetrexed
IV
-
Study Treatment
Amivantamab
IV
-
IV=intravenous.
a.
Other agents/dosing can be considered/substituted as per local guidelines for chemotherapy prophylaxis.
b.
Pre dose steroids for pemetrexed can be used as per local practice and guidelines. Beginning with Cycle 1 Day 8, optional 
pre-dose steroids may be administered prior to amivantamab if clinically indicated for participants who experienced an 
infusion-related reaction on Cycle 1 Day 1 or Cycle 1 Day 2.
c.
Required pre-infusion medications for amivantamab.
Post-Infusion Medications
Optional post-infusion medications may be prescribed and continued for up to 48 hours after any
infusion if clinically indicated, at the discretion of the investigator (Table 10).
Table 10: 
Post-Infusion Medications for Amivantamab
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 to 50 mg or equivalent
IV or Oral
As clinically indicated
Any
Antipyretic
Paracetamol (acetaminophen) 650 to 1,000 mg
IV or Oral
As clinically indicated
Any
Opiates
Meperidine 25 to 100 mg
IV or Oral
As clinically indicated
Any
Antiemetic
Ondansetron 8 to 16 mg or equivalent
IV
As clinically indicated
Any
Ondansetron 8 mg or equivalent
Oral 
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. 
6.6.3.
Prohibited or Restricted Medications and Therapies
The following concomitant medications and therapies are prohibited or restricted during the study. 
The sponsor must be notified in advance, or as soon as possible thereafter, of any instances in 
which prohibited therapies were administered.
!
Any chemotherapy, anti-cancer therapy, or experimental therapy (other than study treatments)
is prohibited.
!
Radiotherapy to tumor lesions being assessed for tumor response prior to radiographic 
progression is prohibited.
!
Use of live or live attenuated vaccines is prohibited.

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!
Use of phenytoin, or fosphenytoin with carboplatin is prohibited.
!
Nephrotoxic or ototoxic agents should be used cautiously with carboplatin. Concomitant 
administration of aminoglycosides should be avoided with carboplatin.
!
Caution should be exercised when administering pemetrexed concurrently with a nonsteroidal 
anti-inflammatory drug to a participant whose creatinine clearance is <80 mL/min (exception: 
low-dose aspirin once daily is permitted during the study).
!
Avoid using ibuprofen 2 days before, the day of, and 2 days after administration of 
pemetrexed, as ibuprofen increases exposure of pemetrexed in patients with creatinine 
clearance of 45 to 79 mL/min.
!
Due to the potential for hypomagnesemia associated with EGFR inhibitors, concomitant 
medications that may decrease serum magnesium should be avoided if possible.
6.7.
Dose Delay Guidance
In instances where treatment delay is indicated, treatment with chemotherapy and/or 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.
Participants must meet retreatment criteria for chemotherapy (as per Section 6.8.1 based on 
product labeling and as per local regulations and guidelines) or amivantamab (as per 
Section 6.8.2), in accordance with protocol, prior to redosing with the respective agents. 
!
Combination Chemotherapy (pemetrexed ± carboplatin): If retreatment criteria are not met 
for carboplatin and/or pemetrexed, then treatment should be delayed by 1 week at a time. If 
chemotherapy cannot be administered on the scheduled day, dosing with amivantamab should 
proceed as planned, if retreatment criteria are met. If chemotherapy is delayed by a week 
(eg, administered on Day 8 of the cycle) subsequent cycle dosing of amivantamab may be 
delayed by 1 week to align with the chemotherapy dosing schedule. Alternatively, if 
chemotherapy is delayed twice (eg, administered on Day 15 of the cycle), then the subsequent 
cycle dosing of amivantamab can be accelerated by 1 week to align with chemotherapy (see
Appendix 9: Dosing Synchronization for Arm A). While some flexibility in the amivantamab
dosing schedule is allowed as described above, combination chemotherapy must be dosed at 
a minimum interval of 21 days (carboplatin administration cannot exceed for more than a total 
of 4 cycles). In the event chemotherapy administration is delayed beyond 42 days (±3 days)
from the last treatment, chemotherapy will be discontinued unless approved by the sponsor.
!
Amivantamab: In the event amivantamab dosing on Day 1 of the cycle is delayed, but 
retreatment criteria for chemotherapy are met, dosing with chemotherapy should continue as 
planned and subjects should be evaluated weekly for retreatment. If amivantamab is delayed 
for ≥6 weeks from the last dose, a discussion should occur with the Medical Monitor prior to 
redosing. All study treatments will be interrupted in an event of Grade 3 or higher toxicity 
(exception: for hematologic toxicities, amivantamab will be interrupted only if there is 
Grade 4 toxicity lasting for >7 days and/or Grade 4 thrombocytopenia associated with 
bleeding or hospitalization or Grade 4 febrile neutropenia). In the event all treatments must 
be delayed, subjects should be re-evaluated weekly for retreatment. Redosing with 
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the cycle. The dosing of both chemotherapy and amivantamab may resume on the subsequent 
cycle once retreatment criteria for pemetrexed ± carboplatin are met, as described above. 
Discussion with the Medical Monitor should occur prior to restarting protocol treatment.
6.8.
Dose Modification
Any dose/dosage adjustment should be overseen by medically qualified study-site personnel 
(principal or subinvestigator unless an immediate safety risk appears to be present).
6.8.1.
Chemotherapy Dose Modification
For chemotherapy dose modification, final treatment decisions should depend on clinical 
judgment, based on local regulations and labeling. For subjects receiving amivantamab in 
combination with chemotherapy, decisions on study treatment dose modification should be guided 
by the safety profile of each drug and the likelihood of causality. 
Dose modifications of chemotherapy will be based on the maximum toxicity experienced during 
a cycle. Treatment should be delayed until the toxicity resolves to Grade ≤1 or the baseline status 
of the participant.
Participants may have a maximum of 2 dose modifications to each treatment throughout the course 
of the study for toxicities before the agent should be discontinued. Dose reduction should be based
upon the most severe toxicity if multiple toxicities are experienced concurrently.
6.8.1.1.
Management of Chemotherapy Toxicities
Given the prevalent use of platinum-based doublet chemotherapy in the treatment of NSCLC, the 
safety profiles of both carboplatin and pemetrexed are well described. Safety monitoring and dose 
modifications should therefore follow local regulations and labeling. 
In general, participants should undergo laboratory assessments including a complete blood count 
with platelet counts, as well as an evaluation of liver and kidney function, per the respective 
approved prescribing information.2,5 Chemotherapy should be delayed if absolute neutrophil count
is <1,500/μL, platelet count is <100,000/μL, or the participant is experiencing non-hematologic 
toxicity of Grade >2 severity. Table 11 and Table 12 provide additional guidance for dose 
modification to manage hematologic and non-hematologic toxicities related to chemotherapy 
based on product labeling. Refer to local labeling for complete information regarding dose 
adjustment for carboplatin and pemetrexed.2,5
Table 11:
Guidance for Dose Modifications for Hematologic Chemotherapy Toxicity
Platelets
Absolute Neutrophil Count
Pemetrexed Dosage
Carboplatin Dosage
≥50,000/μL
≥500/μL
100% of previous 
dose
100% of previous dose
≥50,000/μL
<500/μL
75% of previous dose
75% of previous dose
<50,000/μL
without bleeding
(Any)
75% of previous dose
75% of previous dose
<50,000/μL
with Grade ≥ 2 bleeding
(Any)
50% of previous dose
50% of previous dose
≥50,000/μL
<1,000/μL + fever ≥38.5°C (101°F)
75% of previous dose
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The safety profile of amivantamab is largely distinct from that associated with chemotherapeutic 
agents. However, overlapping toxicity should be considered in the evaluation of all adverse events. 
Refer to the local prescribing information for carboplatin and pemetrexed for additional details.2,5
If dose reduction of amivantamab is required during dosing with combination chemotherapy, 
re-escalation of amivantamab to planned dose may be considered in the maintenance setting (when 
dosed with pemetrexed or as monotherapy). Starting at Cycle 5 Day 1, the dose of amivantamab 
can be re-escalated to a target dose of 1,750 mg (2,100 mg in participants weighing ≥80 kg) in 
increments of 350 mg per cycle with pemetrexed, based on tolerability.
The following sections provide additional guidance for the prevention, monitoring, and 
management of toxicities that have been reported with amivantamab.
6.8.2.1.
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 Protocol 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. UVA 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. 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 
and appropriate management. 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%

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!
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 reactive management of pruritic lesions, the use of cool compresses and oral antihistamine 
agents may be helpful.
!
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.
!
For paronychia, antiseptic soaks and topical potent corticosteroids in addition to oral 
antibiotics are recommended and, if no improvement is seen, a dermatology or surgery 
consultation is recommended. Refer to Appendix 12: Paronychia.
!
After the rash is controlled, consider gradually tapering the antibiotic.
!
In case of a Grade 4 rash including severe bullous, blistering, or exfoliating skin condition 
such as toxic epidermal necrolysis (TEN), study treatment should be discontinued 
permanently.
A suggested algorithm for stepwise management of rash and paronychia associated with 
amivantamab is provided in Table 15. Refer to Table 13 and Table 14 for recommended dose 
adjustment.
Table 15:
Suggested Algorithm for Management of Rash and Paronychia
Step
Gradea
Management
Amivantamab Dose 
Adjustmentb,c
1
1
!
Initiate reactive management as above
!
Reassess after 2 weeks
!
Continue current dose of 
study treatment
2
2
!
Initiate reactive management as above
!
Reassess after 2 weeks
!
Continue current dose of 
study treatment
3
3
!
Initiate reactive management as above
!
Start moderate strength topical corticosteroidd and 
systemic antibiotic 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 withhold 
study treatment until 
rash improves to 
≤Grade 2
!
For guidance on 
withholding study 
treatment and dose 
reduction, refer to 
Table 13 and Table 14

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Table 15:
Suggested Algorithm for Management of Rash and Paronychia
Step
Gradea
Management
Amivantamab Dose 
Adjustmentb,c
3
4
!
Initiate reactive management as above
!
Start moderate strength topical corticosteroidd and 
systemic antibiotic 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
!
Permanently discontinue
amivantamab for 
Grade 4 events
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 National Cancer Institute - Common Terminology Criteria for Adverse Events (Version 5.0).
b.
If amivantamab must be withheld 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 non-hematologic 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 2-5 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. 
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.

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6.8.2.2.
Infusion-Related Reactions
General Guidelines for Infusion-Related Reactions
Infusion-related reactions have been observed during treatment with amivantamab, predominantly 
with the first exposure on Cycle 1 Day 1. The severity of infusion-related reactions has been 
variable. Refer to Summary of Data and Guidance for Investigators in the latest version of the IB 
for amivantamab.12
During the amivantamab infusion, participants should be clinically monitored at regular intervals 
as specified in Table 1 (including an assessment prior to the start of infusion). The monitoring 
should include heart rate, blood pressure, temperature, respiratory rate, and oxygen saturation 
measurements.
Particularly with the initial dose (Cycle 1, Days 1 and 2), participants should be closely monitored 
for early signs and symptoms indicative of an acute infusion-related reaction or anaphylaxis. If 
clinically indicated, even with mild symptoms, the study treatment infusion should be interrupted
immediately, as described in the tables below. Trained clinical personnel should be prepared to 
intervene in the event of infusion-related reactions. 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) should be readily available.
Prevention of Infusion-Related Reactions
Required prophylaxis for infusion-related reactions is described in Section 6.6.2.2.
Treatment of Infusion-Related Reactions 
Participants who experience early symptoms of infusion-related reactions, manifesting as fever, 
chills, rigors, bronchospasm, headache, rash, pruritus, arthralgia, hypotension or hypertension or 
other symptoms, should have their amivantamab infusion interrupted, if indicated, and the 
symptoms managed according to the recommendations provided in Table 16. With the initial dose 
of amivantamab (Cycle 1, Days 1 and 2), interruption of the infusion should be considered even 
with mild symptoms to prevent more severe manifestations of infusion-related reaction. All 
Grade 3 or 4 infusion-related reactions should be reported within 24 hours to the Medical Monitor.

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Table 16:
Management of Infusion-Related Reactions
Toxicity Gradea
Treatment / Study Treatment
Premedication at 
Subsequent Dosing
Grade 1
Mild reaction;
Monitor participant as medically indicated until 
recovery from symptoms. If occurring with initial dose 
(ie, Cycle 1 Day 1 or 2), consider early infusion 
interruption to prevent more severe symptoms.
Antihistamine, antipyretic, 
and glucocorticoid, as per 
Table 6.
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 CRF. 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 6.
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, 
epinephrine 0.2 to 1 mg of a 1:1,000 solution for 
subcutaneous administration or 0.1 to 0.25 mg of a 
1:10,000 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. 
Grade 3: Based on severity 
of symptoms, consider 
permanent discontinuation of 
amivantamab. Discussion 
with Medical Monitor
required before continuing 
with subsequent dosing.
Grade 4: Discontinue further 
treatment with amivantamab.
General
Prophylactic medications (after initial event) may be 
used as described in Table 6 and Table 10. Appropriate 
personnel and appropriate resuscitation equipment 
should be available in or near the infusion room and a 
physician should be readily available during the 
infusion of study treatment
CRF=case report form; IV=intravenous.
a.
Per National Cancer Institute - Common Terminology Criteria for Adverse Events Version 5.0

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6.8.2.3.
Liver Chemistry Abnormalities
Liver chemistry should be monitored according to the Schedule of Activities (Table 1) and study 
treatment should be withheld for any liver chemistry abnormality of ≥Grade 3 severity (refer to 
Section 6.7). In addition, if the following criteria are observed, the event should be reported as a 
serious adverse event 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).
!
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 (beyond what is 
anticipated from chemotherapy), right upper quadrant pain or tenderness, fever, rash, and/or 
new eosinophilia (>5%).
In the event abnormalities of liver function tests require withholding 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 a) above (ALT or AST ≥3×ULN and bilirubin ≥2×ULN [>35% 
direct bilirubin] [or ALT ≥3×ULN and INR >1.5, if INR measured]) is concurrently 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 CRF
!
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

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∃
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 [MRI], or CT) to evaluate liver 
disease
!
Refer to a specialist as appropriate
Rechallenge Criteria
Resumption of study treatment(s) may be considered if all the following criteria are met:
!
Hy’s Law has been excluded.
!
A reversible underlying cause not associated with study treatment(s) (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.
6.8.2.4.
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, to rule out 
pneumonitis and to investigate other causes such as pneumonia, pulmonary embolus, or 
worsening pulmonary disease.
Documentation of ILD/pneumonitis of any grade should prompt withholding study treatments 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 all study treatment and should be 
reported as a serious adverse event (see Section 8.3.1). Pertinent radiological images and reports 
should be submitted to the Sponsor.
6.9.
Treatment of Overdose
There are no data on overdose from studies of amivantamab.
In the event of an overdose of a study treatment, the investigator or treating physician should:
!
Contact the Medical Monitor immediately.
!
Closely monitor the participant for adverse event/serious adverse event and laboratory 
abnormalities.

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!
Document the quantity of the excess dose as well as the duration of the overdosing in the CRF.
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.
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, adverse event) it 
is in the best interest of the participant to discontinue study treatment
!
The participant becomes pregnant (refer to Appendix 4: Contraceptive and Barrier Guidance).
!
Noncompliance with study treatment administration
!
Documented radiographic (RECIST v1.1) disease progression by BICR (except during the 
OLE and LTE phases, during which investigator assessment will be used), unless treatment 
beyond disease progression has been approved by the Medical Monitor. Discontinuation for 
disease progression based on local assessment prior to BICR confirmation should be discussed 
with the Medical Monitor.
!
General or specific changes in the participant’s condition that render the participant
unacceptable for further treatment in the judgment of the investigator
!
The participant receives concurrent (nonprotocol) anticancer treatment
If a participant discontinues study treatment for any reason before the end of the treatment period,
then the end of treatment assessments should be obtained and Follow-up Visits should continue 
after study treatment is discontinued. Study treatment assigned to the participant who discontinued 
study treatment may not be assigned to another participant. Additional participants will not be 
entered.
Continuation of study treatment after BICR confirmed disease progression may be allowed in
accordance with local practice, after approval from the Medical Monitor, if the investigator 
believes the participant is deriving clinical benefit.
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

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When a participant withdraws before study completion, the reason for withdrawal is to be 
documented in the CRF 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 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 ICF.
7.3.
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization 
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.

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8.
STUDY ASSESSMENTS AND PROCEDURES
Overview
The Schedule of Activities (Table 1) summarizes the frequency and timing of measurements 
applicable to this study.
The total blood volume to be collected from each participant will be approximately 300 mL for a 
participant in Arm A who receives study treatment for 11 cycles in the main study, and 
approximately 350 mL for a participant in Arm B who receives study treatment for 7 cycles in the 
main study and amivantamab monotherapy for 6 cycles after crossover.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF and laboratory 
requisition form.
Refer to the Schedule of Activities (Table 1) 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. 
Study-Specific Materials
The investigator will be provided with the following supplies:
!
Clinical Protocol
!
IB for amivantamab
!
IPPI and SIPPM
!
Laboratory manual and kits
!
Electronic data capture (eDC) Manual
!
IWRS manual
!
Imaging Manual
!
National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE)
Version 5.0
!
RECIST guidelines, Version 1.1
!
Sample master ICF
!
Wallet cards
!
Study treatment (amivantamab will be supplied centrally; depending on region, chemotherapy 
may be either centrally or locally sourced)
!
Ancillary supplies (as needed)
!
Tablets (for PRO collection)

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8.1.
Efficacy Assessments
8.1.1.
Disease Assessments
Disease assessments will be performed as scheduled according to the Schedule of Activities 
(Table 1), regardless of any dose modifications. More frequent radiologic assessments are allowed 
if clinically indicated. 
CT scan of the chest (including the supraclavicular region), abdomen, pelvis, and any other disease 
location(s) 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. 
The baseline disease assessments should be performed as close as possible to the start of treatment, 
but no more than 28 days prior to randomization. Subsequent assessments should be performed at 
6 weeks (+1 week) after randomization, then every 6 weeks (±1 week) for the first 18 months and 
then every 12 weeks (±1 week), until objective radiographic disease progression by BICR. In the 
OLE/LTE Phase, disease assessments should continue until objective radiographic disease 
progression by investigator assessment by RECIST v1.1. If an 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 the Investigator is in doubt as to whether progression has occurred, particularly with response 
to nontarget lesions or the appearance of a new lesion, continue treatment 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.
In the event an Investigator suspects progression, they should submit scans with a request for 
confirmation of progression to the BICR. The BICR will confirm if radiographic progression is 
observed at the suspected imaging assessment. Investigators should consider BICR non-PD 
assessments when making discontinuation decisions and can continue with study treatment until 
BICR confirmed disease progression. However, Investigators may use discretion, based on clinical 
benefit and other factors, to retain a participant on study despite BICR confirmation. In the 
OLE/LTE Phase, treatment decisions will be made based on investigator assessment by
RECIST v1.1.
MRI can be used to evaluate sites of disease that cannot be adequately imaged using CT. Identical 
methodology (CT scan with contrast agent or MRI) should be used for disease assessment at 

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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 judgment, local standard of care, and RECIST v1.1 guidelines for the use of these 
alternative techniques. For example, bone scintigraphy may be used to identify bone lesions at 
screening or new bone lesions during treatment, but bone lesions will not be considered target 
lesions. Sites will be required to retain digital copies of radiologic images (eg, x-ray, CT, MRI) 
used for disease assessments for potential independent review.
Participants will have MRI of the brain at screening, with subsequent definitive treatment of 
identified active lesions before starting study treatment (see Section 5.1). For patients who are 
intolerant to brain MRI, alternative imaging modality can be considered for screening after 
discussion with the Medical Monitor. Brain MRI is not required with every subsequent disease 
assessment and should be performed according to local guidelines and practice.
All imaging assessments including unscheduled visit scans should be collected on an ongoing basis 
and sent to a Janssen-appointed Clinical Research Organization for independent central analyses. 
RECIST v1.1 criteria will be used to assess participant response to treatment: complete response, 
partial response, stable disease, progressive disease, or unevaluable.
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 CRF 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 by BICR, tumor assessments should be continued per schedule until 
radiographic progressive disease is documented and confirmed by BICR. In the OLE/LTE Phase, 
radiographic disease progression will be by investigator assessment by RECIST v1.1). Following
disease progression, these participants should continue to be followed up for survival every 
12 weeks as outlined in the Schedule of Activities (Table 1). Additional follow-up calls may be 
made in the 2 weeks (14 days) before data cutoff to assess participant survival less than 12 weeks
after the previous assessment.
If a participant is treated beyond documented disease progression, disease assessments will 
continue as scheduled and the investigator and the Medical Monitor will review clinical benefit 
after each disease assessment.
8.1.2.
Symptomatic Progression
Symptoms, attribution, and related interventions will be recorded in the eCRF at the times 
specified in the Schedule of Activities. If symptomatic progression is not reported prior to 
treatment discontinuation, continued assessment of the symptoms is required during the follow up 
period even after subsequent therapy is initiated.

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8.1.3.
Patient-Reported Outcomes 
PRO measures will be collected at the times specified in the Schedule of Activities (Table 1). All 
PROs should be administered prior to other assessments. The PRO instrument will be provided in 
the local language in accordance with local guidelines. The PRO instrument must be available for 
regulators and for IRB/IRC submissions, therefore the PRO instrument or screen shots need to be 
attached to the protocol or provided in a companion manual with the instruments that will be 
submitted with the protocol. The PRO and adverse event data will not be reconciled with one 
another.
The PRO instruments in this study are:
!
The EuroQol five dimensional descriptive system (5 level version) (EQ-5D-5L) is a validated 
tool to measure health status and health utility, including mobility, self-care, usual activities, 
pain, discomfort, and anxiety/depression.10
!
The European Organization of Research and Treatment of Cancer Quality of Life 
Questionnaire Core 30 (EORTC-QLQ-C30) assesses functioning domains and common 
cancer symptoms with recall in the past week.15
!
Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function 
(short-form) is used to characterize and better understand overall health, level of physical 
disability, and general well-being. Physical function is a foundation for commonly used 
general and cancer-specific PRO measures.
8.2.
Safety Assessments 
Details regarding the Data Monitoring Committee are provided in Committees Structure in 
Appendix 2: Regulatory, Ethical, and Study Oversight Considerations.
Adverse events will be reported and followed by the investigator as specified in Section 8.3 and 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting.
Any clinically relevant changes occurring during the study must be recorded on the Adverse Event 
section of the CRF. 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.
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 calibrated scale.

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8.2.2.
Vital Signs
Vital sign measurements will include the following assessments and be obtained as indicated in 
the Schedule of Activities (Table 1). 
!
Temperature
!
Heart rate 
!
Respiratory rate
!
Oxygen saturation
!
Blood pressure
Blood pressure and pulse/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 pulse/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
During the collection of electrocardiograms (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. 
Collection of ECGs will be obtained as indicated in the Schedule of Activities (Table 1). At each 
time point at which triplicate ECGs are required, 3 individual ECG tracings should be obtained as 
closely as possible in succession, but approximately 2 minutes apart. A copy of triplicate ECGs on 
Cycle 1 Day 1 and Cycle 3 Day 1 will be sent to a central reader. If the Screening ECG is
performed in triplicate within 72 hours before the first dose of study treatment, the assessment 
does not need to be repeated at Cycle 1 Day 1 (and a copy of these triplicate ECGs can be sent to 
a central reader in lieu of Cycle 1 Day 1). Refer to the ECG Manual for additional details.
The clinical investigator will review the printout, including ECG morphology, for immediate 
management, and will enter the results in the eCRF. Clinically significant abnormalities noted at 
Screening should be included in the medical history.
8.2.4.
ECOG Performance Status
ECOG performance status score will be determined during the Screening Phase and at time points 
listed in the Schedule of Activities (Table 1). Any decline in ECOG performance status score 
should be reported as an adverse event.
8.2.5.
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry, hematology, coagulation, and a urine sample for urinalysis 
will be collected as noted in Appendix 7: Clinical Laboratory Tests at the times listed in the 
Schedule of Activities (Table 1). The investigator must review the laboratory results, document 

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this review, and record any clinically relevant changes occurring during the study in the adverse 
event section of the CRF. The laboratory reports must be filed with the source documents. At the 
start of each new cycle, the investigator must confirm that participants meet treatment criteria.
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.
8.3.
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
including adverse events, serious adverse events, and product quality complaints (PQC) 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, surrogate, 
or the participant's legally acceptable representative) for the duration of the study.
Further details on adverse events, serious adverse events, and PQC can be found in Appendix 3: 
Adverse Events: 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 adverse events 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 scheduled
study-related procedure, which may include contact for follow-up of safety. Please refer to Table 1
for more details.
Serious Adverse Events
All serious adverse events, 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 using the serious adverse event 
form. A serious adverse event spontaneously reported to the investigator more than 30 days after 
the last dose of study treatment must also be reported using a serious adverse event form, if the 
investigator considers the event to be related to study treatment. The sponsor will evaluate any 
safety information that is spontaneously reported by an investigator beyond the time frame 
specified in the protocol.
Information regarding serious adverse events will be transmitted to the sponsor using the Serious 
Adverse Event Form and Safety Report Form of the CRF, which must be completed and reviewed 
by a physician from the study site, and transmitted to the sponsor within 24 hours. The initial and 

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follow-up reports of a serious adverse event 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 adverse events or serious adverse events. 
Open-ended and nonleading verbal questioning of the participant is the preferred method to inquire 
about adverse event occurrence. 
Solicited Adverse Events
Solicited adverse events are predefined local (at the infusion site) and systemic events for which 
the participant is specifically questioned.
Unsolicited Adverse Events
Unsolicited adverse events are all adverse events 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 adverse event, 
serious adverse event, 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 
Appendix 3: Adverse Events: 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 adverse events 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 (SUSARs). The 
investigator (or sponsor where required) must report SUSARs to the appropriate Independent 
Ethics Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless 
otherwise required and documented by the IEC/IRB. A SUSAR will be reported to regulatory 
authorities unblinded. Participating investigators and IEC/IRB will receive a blinded SUSAR 
summary, unless otherwise specified.
An anticipated event is an adverse event that commonly occurs in the study population independent 
of exposure to the drug under investigation. For the purposes of this study, the serious adverse 
events listed in Appendix 8: Anticipated Events will be considered anticipated events. 
These anticipated events will be periodically analyzed in aggregate by the sponsor during study 
conduct. The sponsor will prepare a safety report in narrative format if the aggregate analysis 

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indicates that the anticipated event occurs more frequently in the treatment group than in the 
control group and the sponsor concludes there is a reasonable possibility that the drug under 
investigation caused the anticipated event.
The plan for monitoring and analyzing the anticipated events is specified in a separate Anticipated 
Events Safety Monitoring Plan. The assessment of causality will be made by the sponsor’s 
unblinded safety assessment committee.
The sponsor assumes responsibility for appropriate reporting of the listed anticipated events 
according to the requirements of the countries in which the studies are conducted.
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 serious adverse events and must be reported using the serious adverse event reporting
form. Any participant who becomes pregnant during the study must discontinue further study 
treatment. 
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
All events that meet the definition of a serious adverse event will be reported as serious adverse 
events, regardless of whether they are protocol-specific assessments.
Progression of disease should not be considered nor should be reported as an adverse event 
(or serious adverse event). However, signs and symptoms of disease progression or clinical 
sequelae resulting from disease progression/lack of efficacy that are determined by the investigator 
to be of clinical significance should be reported per the usual reporting requirements (refer to 
Adverse Event Definitions and Classifications in Appendix 3: Adverse Events: Definitions and 
Procedures for Recording, Evaluating, Follow-up, and Reporting).
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 serious adverse events (see 
Section 8.3.1). All Grade 3 or 4 IRRs should be reported within 24 hours to the Medical Monitor. 
Events of rash should follow standard reporting guidelines.

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8.4.
Pharmacokinetics
Blood samples will be used to evaluate the PK of amivantamab in Arm A. Serum collected for PK 
may additionally be used to evaluate exposure-response relationships for safety or efficacy 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 from participants in Arm A for the evaluation of PK of 
amivantamab at the designated time points according to the Schedule of Activities (Table 2). The 
exact dates and times of blood sampling must be recorded on the laboratory requisition form. Refer 
to the Laboratory Manual for sample collection requirements. Blood collected for PK may 
additionally be used to identify circulating metabolites and/or evaluate safety or efficacy aspects 
that address concerns arising during or after the study period.
Pharmacokinetic analysis of serum concentration data for amivantamab will be performed. Serum 
concentrations and PK parameters will be listed and summarized by sampling interval. 
Pharmacokinetic serum concentration-time data from this study will be analyzed using a 
population PK approach. The data collected from this study may also 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.
8.4.2.
Analytical Procedures
Pharmacokinetics
Serum samples will be analyzed to determine concentrations of amivantamab using a validated, 
specific, and sensitive 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, protein binding,
and the metabolite profile.
8.5.
Biomarkers
To be eligible for the study, each participant must have a documented EGFR Exon 20ins activating 
mutation, as assessed before screening by local testing of tissue or ctDNA, as per standard of care. 
Provision of an unstained, tumor tissue sample (archival or recently collected) is required for each 
participant before randomization. If possible, the tissue provided for central analysis should be 
from the same biopsy utilized for local testing and identification of Exon 20ins. A minimum of 
10 slides (up to 15 when available) or equivalent material from formalin-fixed and paraffin-
embedded (FFPE) tissue block must be provided. Slides cut from FFPE blocks of resections or 
biopsies are recommended not be older than 27 months; FFPE blocks are not recommended to
exceed 5 years of age and FNA cell blocks are not recommended be older than 4 months. If the 
tissue sample is archival, it must have been obtained at or after diagnosis of locally advanced or
metastatic NSCLC. Please refer to the laboratory manual.

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Screening blood samples collected from all participants will undergo ctDNA analysis by the 
sponsor to evaluate pre-treatment mutational status of EGFR, MET, and other key oncogenes to 
characterize the tumor. Tumor tissue will undergo genetic analysis to provide additional 
characterization of 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 the study therapy.
Blood samples will also be collected at time points specified in Table 1 for potential analysis of 
circulating biomarkers (eg, cytokines, growth factors) in samples taken prior to and after exposure 
to study treatment(s). Changes in circulating markers may be assessed in pre- and post-treatment 
samples and levels correlated with response to study treatments.
Additional biomarkers (eg, DNA, RNA, and protein) relevant to cancer and/or metabolism of study 
treatments 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 study therapy.
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, 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.
8.6.
Immunogenicity Assessments
Serum samples will be collected for immunogenicity assessments of amivantamab (anti-drug 
antibodies to amivantamab) from all participants in Arm A at the time points outlined in Table 2. 
The detection and characterization of antibodies to amivantamab will be performed using a 
validated assay method by or under the supervision of the sponsor. All serum samples collected 
for detection of antibodies to amivantamab will also be evaluated for amivantamab serum 
concentration to enable interpretation of the immunogenicity data. Other analyses may be 
performed to characterize immunogenicity.
Serum samples will be screened for antibodies binding to amivantamab and the titer of confirmed 
positive samples will be reported. Other analyses may be performed to verify the stability of 

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antibodies to amivantamab and/or further characterize the immunogenicity of amivantamab.
Additionally, serum samples should also be collected at the final visit from participants who 
discontinued study treatment or were withdrawn from the study. These samples will be tested by 
the sponsor or sponsor's designee.
Samples collected for immunogenicity analyses 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.
Analytical Procedures 
The detection and characterization of antibodies to amivantamab will be performed using a 
validated assay method by or under the supervision of the sponsor. All samples collected for 
detection of antibodies to amivantamab will also be evaluated for amivantamab serum 
concentration to enable interpretation of the antibody data. Antibodies may be further 
characterized and/or evaluated for their ability to neutralize the activity of the study treatment(s). 
Samples may be stored up to 15 years (or according to local regulations) following the last 
participant’s last visit for the study at a facility selected by the sponsor to enable further analysis 
of immune responses to amivantamab.
8.7.
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.
9.1.
Statistical Hypotheses
The statistical hypothesis is that amivantamab and chemotherapy combination therapy will reduce 
the risk of either progression or death compared with standard of care combination chemotherapy
in patients with locally advanced or metastatic NSCLC characterized by Exon 20ins mutations.
9.2.
Sample Size Determination
A total of 200 PFS events will provide approximately 90% power to detect a hazard ratio (HR) of 
0.625 that corresponds to at least 3-month improvement in the median PFS (5 months for 
chemotherapy and 8 months for the combination of amivantamab with chemotherapy) with a log-
rank test (two-sided alpha=0.05). The total sample size needed for the study is approximately 
300 participants (150 per group). The sample size calculation has taken into consideration an 
annual dropout rate of 5%. 
Assuming a 15-month recruitment period, 200 PFS events are expected to occur approximately 
18 months after the first participant is randomized in the study.

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9.3.
Populations for Analyses Sets
For purposes of analysis, the following populations are defined:
Table 17:
Populations for Analyses Sets
Population
Description
Full Analysis Set
All randomized participants, classified according to their assigned treatment arm regardless of the 
actual treatment received.
Safety
Randomized participants who receive at least 1 dose of study treatment.
Pharmacokinetics
Randomized participants who receive at least 1 dose of study treatment and have at least 
1 evaluable post-baseline concentration measurement.a
Patient-Reported 
Outcomes
Randomized participants who receive at least 1 dose of study treatment and have at least 
1 evaluable post-baseline patient-reported outcome measurement.
Biomarkers
Randomized participants who receive at least 1 dose of study treatment, have at least 1 disease 
assessment, and have at least 1 biomarker measurement.
a.
Participants may be removed from the estimation of certain PK parameters on an individual basis due to, for example, 
missing PK samples such that the PK parameters cannot be appropriately derived. These participants will be identified at the 
time of the analyses along with their reason for removal.
The Full Analysis Set will be used to summarize the study population and characteristics, as well 
as efficacy data; the Safety Population will be used to summarize the safety data, unless otherwise 
specified.
9.4.
Statistical Analyses
The Statistical Analysis Plan, which will be finalized prior to database lock for the primary 
analysis, 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 tests will be conducted at a 2-sided alpha level of 0.05, and 95% CI will be provided, unless 
stated otherwise. All efficacy endpoints will be analyzed using the Full Analysis Set. The Kaplan-
Meier product limit method and a stratified Cox model will be used to estimate the time-to-event 
variables and to obtain the HR along with the associated confidence intervals. Unless otherwise 
specified, a log-rank test stratified by ECOG performance status (0 or 1), history of brain 
metastases (yes or no), and prior EGFR TKI use (yes or no) will be used to test the treatment effect 
for time-to-event variables; response rate variables will be evaluated using Cochran Mantel 
Haenszel test stratified by the randomization stratification factors; Continuous variables will be 
analyzed using an analysis of covariate (ANCOVA) model, with treatment group and 
randomization stratification factors as fixed effects and baseline value as a covariate.
9.4.2.
Primary Endpoint
9.4.2.1.
Progression-Free Survival by Blinded Independent Central Review
The primary efficacy endpoint is PFS, defined as the time from randomization until the date of 
objective disease progression based on BICR using RECIST v1.1 or death (by any cause) in the 
absence of progression, whichever comes first. Participants who have not progressed or have not 

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died at the time of analysis will be censored at the time of the latest date of their last evaluable 
RECIST v1.1 assessment. If the participant progresses or dies after 2 or more consecutive missed 
disease assessments, the participant will be censored at the time of the last evaluable RECIST v1.1 
assessment. If the participant has no evaluable visits or does not have baseline data, they will be
censored at Day 1 unless they die within 2 visits of baseline.
The primary efficacy endpoint will be analyzed in the Full Analysis Set based on randomized 
treatment group and strata at randomization. A log rank test will be stratified by ECOG 
performance status (0 or 1), history of brain metastases (yes or no), and prior EGFR TKI use (yes 
or no) using the Breslow approach for handling ties. The hazard ratio for PFS will be calculated, 
along with its 95% confidence intervals, from a stratified Cox model using the same stratification 
factors as for the log-rank test.
9.4.3.
Secondary Endpoints
9.4.3.1.
Objective Response Rate
Objective response rate (ORR) is defined as the percentage of participants with best response of
complete response or partial response, as defined by RECIST v1.1. Complete response is defined 
as disappearance of all target lesions and non-target lesions present at baseline (with the exception 
of lymph nodes, which must be <10 mm to be considered non-pathological) and new lesions since 
baseline. Partial response is defined as a decrease of 30% or more from baseline in the sum of 
diameters of the target lesions, with no evidence of progression, and non-target lesions are at least 
stable with no evidence of new lesions.
Participants who do not have a tumor response assessment for any reason will be considered non-
responders and will be included in the denominator when calculating the response rate. Data 
obtained up until progression, or last evaluable assessment in the absence of progression, will be 
included in the assessment of ORR. However, any complete response or partial response which 
occurred after a further anticancer therapy was received will not be included in numerator of the 
ORR calculation (where the Full Analysis Set will be the denominator).
Objective response will be analyzed using a logistic regression model stratified by ECOG 
performance status (0 or 1) and history of brain metastases (yes or no), and prior EGFR TKI use 
(yes or no). The results of the analysis will be presented in terms of an odds ratio together with its 
associated 95% profile likelihood confidence intervals.
9.4.3.2.
Duration of Response
Duration of response (DoR) is defined as the time from the date of first documented response 
(complete response or partial response) 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. The analysis of DoR will be 
stratified by the same covariates as the primary analysis. DoR in responding participants will be 
summarized and the number of responding participants with a duration of response (>6, >9, >12, 
and >15 months) will be presented by treatment group. A Kaplan-Meier plot and median DoR with 

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95% confidence interval (calculated from the Kaplan-Meier estimate) will be presented by 
treatment group.
9.4.3.3.
Overall Survival
Overall survival (OS) is defined as the time from the date of randomization 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. OS will be analyzed 
using the same methodology and model as for the analysis of PFS provided there are sufficient 
events available for a meaningful analysis.
The analysis of OS will be conducted at 2 time points:
!
At the time of the primary analysis of PFS, when approximately 85 deaths overall are 
anticipated. Based on the O’Brien Fleming alpha spending approach, a 2-sided alpha of 0.0008
will be allocated to the interim analysis.
!
Approximately 48 months after the first participant is randomized, when approximately 
210 deaths overall are anticipated. The final analysis will be conducted at a 2-sided alpha of 
0.0498.
To control the overall type I error rate for the hypotheses testing of primary and secondary 
endpoints strongly at 5%, a sequential testing strategy will be used. If the testing for the primary 
endpoint of PFS is statistically significant, key secondary endpoints including ORR and OS will 
be sequentially tested, each with an overall 2-sided alpha of 0.05. Details of the hierarchical testing 
procedure will be specified in the Statistical Analysis Plan.
9.4.3.4.
Time to Subsequent Therapy
Time to subsequent therapy (TST) is defined as the time from the date of randomization to the start 
date of the subsequent anti-cancer therapy following study treatment discontinuation, or death. 
Participants not starting subsequent therapy and still alive will be censored at last time known to 
be alive. The TST will be analyzed using the same method as the analysis of PFS. Summary 
statistics will be produced for time on first subsequent anti-cancer treatment, by treatment group.
9.4.3.5.
Progression-free Survival After First Subsequent Therapy
Progression-free survival after first subsequent therapy (PFS2) is defined as the time from the date 
of randomization to the earliest of the progression event subsequent to that used for the primary 
variable PFS or death after starting the next line of treatment. Patients alive and for whom a second 
disease progression has not been observed should be censored at the last time known to be alive 
and without a second disease progression (ie, censored at the last progression assessment date if 
the patient has not had a second progression or death). PFS2 will be analyzed using the same 
method as the analysis of PFS.
9.4.3.6.
Time to Symptomatic Progression
Time to symptomatic progression (TTSP) is defined as the time from randomization to 
documentation in the eCRF of any of the following (whichever occurs earlier): onset of new 

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symptoms or symptom worsening that is considered by the investigator to be related to lung cancer
and requires either a change in anticancer treatment and/or clinical intervention to manage 
symptoms. The TTSP for a participant who does not experience any of these events will be 
censored on the date on which the participant was last known to be event-free. The TTSP will be 
analyzed using the similar methods as the analysis of PFS.
9.4.4.
Exploratory Endpoints
Analyses of exploratory (clinical) endpoints will be described in the Statistical Analysis Plan.
9.4.5.
Safety Analyses
All safety analyses will be made on the Safety Population. Baseline for all laboratory evaluations, 
vital signs, and ECG measurements will be defined as the last evaluation done before the first 
study treatment administration.
An IDMC will be established as noted in Appendix 2: Regulatory, Ethical, and Study Oversight 
Considerations. The frequency of IDMC meetings will be described in the charter.
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 adverse event 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 adverse events will be included in the analysis. For each adverse 
event, the percentage of participants who experience at least 1 occurrence of the given event will 
be summarized by study treatment group.
Summaries, listings, datasets, or participant narratives may be provided, as appropriate, for those 
participants who die, who discontinue study treatment due to an adverse event, or who experience 
a severe or a serious adverse event.
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. Changes from baseline results will be presented in pre-
versus post-study 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 adverse event grade experienced by the participant during the study will be 
provided as shift tables.

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Electrocardiogram
The effects of study treatment on cardiovascular variables will be evaluated by descriptive 
statistics and frequency tabulations. These tables will include observed values and changes from 
baseline values at each scheduled timepoint (the predose ECG at Cycle 1 Day 1 will be used as 
baseline) in ECG parameters including heart rate, QRS axis, and intervals for PR, QT, QRS, RR, 
and QTcF. Frequency tabulations of the abnormalities will be made. Moreover, the data collected 
from this study may also be combined with similar data from other studies to perform exposure-
QTcF analysis.
Vital Signs
Vital signs including weight, temperature, pulse/heart rate, respiratory rate, 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.
9.4.6.
Other Analyses
Pharmacokinetic Analyses
Participants with at least one measurable PK and relevant date and time of the sample will be 
included in the analysis set. For participants randomized to the combination of amivantamab and 
chemotherapy, all serum concentrations below the lowest quantifiable concentration or missing 
data will be labeled as such in the concentration data presentations or Statistical Analysis Software 
(SAS) dataset. Concentrations below the lower quantifiable concentration will be treated as zero 
in the summary statistics. All participants and samples excluded from the analysis will be clearly 
documented in the CSR.
Individual PK parameters will be estimated by inspection of the concentration-time profiles. Based 
on the individual serum concentration-time data, using the actual sampling times, the following 
PK parameters of amivantamab will be determined.
!
Ceoi: end of infusion serum concentration
!
Ceoi,ss: end of infusion serum concentration at steady state
!
Ctrough: serum concentration immediately prior the next study treatment administration
!
Ctrough,ss: serum concentration immediately prior the next study treatment administration at 
steady state
In addition, population PK analysis of serum concentration-time data of amivantamab will be
performed using nonlinear mixed-effects modeling (NONMEM) and may be combined with 
similar data from other studies, with the aim of providing estimates of PK parameters or metrics 
of systemic exposure. Model-derived plasma concentrations or metrics of exposure parameters 
(eg, Cmax or AUC) may be subjected to further analyses to explore PK correlation between 
exposure and relevant safety and efficacy endpoints or biomarkers.

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Biomarkers Analyses
Each baseline tumor status will be evaluated by both tumor and ctDNA NGS to characterize 
potential mechanisms of resistance to amivantamab in combination with chemotherapy. 
The association of biomarker-positivity (eg, EGFR mutation status, circulating biomarkers) 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. 
Assessment of additional genes or biomarkers (DNA, RNA, or protein) relevant to lung or other 
cancers and assessment of the mechanism of action or metabolism of study treatments may also 
be performed in blood and tissue samples collected on study to better understand mechanisms of 
response or resistance to study treatments. Alterations in blood characteristics may be evaluated 
for correlation with response to study treatments, tumor burden, and disease progression as data 
warrant.
Immunogenicity Analyses
The incidence of antibodies to amivantamab will be summarized for all participants who receive 
at least 1 dose of amivantamab 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.
Exposure-Response Analyses
The exposure-response relationship between amivantamab (eg, derived AUC or trough 
concentrations) and key efficacy (eg, PFS and OS) and safety parameters (eg, skin rash), will be 
explored graphically, as data allow. In addition, the relationship may be characterized using an 
exposure-response or logistic regression model. Details will be provided in an analysis plan and 
detailed results may be reported separately from the CSR.
Patient-Reported Outcomes Analyses
Results for EORTC-QLQ-C30 and Patient Reported Outcomes Measurement Information System 
– Physical Function (PROMIS-PF) will be summarized for randomized participants who receive 
at least 1 dose of study treatment and have at least 1 evaluable post-baseline measurement 
(Table 17).

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Time to worsening in EORTC-QLQ-C30 total score and individual scales will be analyzed using 
a Kaplan-Meier method and stratified Cox proportional-hazard model. Additional analysis may be 
done, if appropriate. Analysis details will be included in the Statistical Analysis Plan. 
The PROMIS-PF data will be summarized descriptively by treatment group and study visit. Each 
multi-item scale and individual item will be summarized using count and percent.
9.5.
Interim Analysis
Not applicable.

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10.
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
10.1.
Appendix 1: Abbreviations
ADCC
antibody-dependent cellular cytotoxicity
ALT
alanine aminotransferase
Anti-HCV
hepatitis C virus antibody
ART
anti-retroviral therapy
AST
aspartate aminotransferase
AUC
area under the concentration-time curve
AUC 5
area under the concentration-time curve 5 mg/mL per minute
AxMP
auxiliary medicinal product
BICR
blinded independent central review
CI
confidence interval
Cmax
maximum serum concentration
CRF
case report form
CSR
clinical study report
CT
computerized tomography
CTR
Clinical Trial Regulations
ctDNA
circulating tumor deoxyribonucleic acid
Ctrough
serum concentration immediately prior the next study treatment administration
DBL
database lock
DLT
dose-limiting toxicity
DNA
deoxyribonucleic acid
DoR
duration of response
ECG
electrocardiogram
ECHO
echocardiogram
ECOG
Eastern Cooperative Oncology Group
eCRF
electronic case report form
eDC
electronic data capture
EEA
European Economic Area
EGFR
epidermal growth factor receptor
EORTC-QLQ-C30
European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire
EQ-5D-5L
EuroQol five-dimensional descriptive system (5-level version)
ESMO
European Society for Medical Oncology
EU
European Union
Exon 20ins
Exon 20 insertion
FDA
Food and Drug Administration
FFPE
formalin-fixed and paraffin-embedded
G-CSF
granulocyte colony-stimulating factor
GCP
Good Clinical Practice
HBcAb
hepatitis B core antibody
HBsAb
hepatitis B surface antibody
HBsAg
hepatitis B surface antigen
HBV
hepatitis B virus
HCV
hepatitis C virus

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HIV
human immunodeficiency virus
HR
hazard ratio
HRT
hormonal replacement therapy
IASLC
International Association for the Study of Lung Cancer 
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Council for Harmonization
IDMC
Independent Data Monitoring Committee
IEC
Independent Ethics Committee
ILD
interstitial lung disease
IMP
investigational medicinal product
INR
international normalized ratio
IPPI
Investigational Product Preparation Instructions
IRB
Institutional Review Board
IUD
intrauterine device
IUS
intrauterine hormone-releasing system
IV
intravenous
IWRS
interactive web response system
LTE
long-term extension
mAb
monoclonal antibody
MET
mesenchymal-epithelial transition
MRI
magnetic resonance imaging
NCI-CTCAE
National Cancer Institute - Common Terminology Criteria for Adverse Events
NGS
Next Generation Sequencing
NIMP
non-investigational medicinal product
NSCLC
non-small cell lung cancer
NYHA
New York Heart Association 
OLE
open-label extension
ORR
objective response rate
OS
overall survival
PFS
progression-free survival
PK
pharmacokinetic(s)
PQC
product quality complaint
PRO
patient reported outcomes
PROMIS-PF
Patient-Reported Outcomes Measurement Information System – Physical Function
Q3W
every 3 weeks
QTcF
corrected QT interval by Fridericia
RECIST
Response Evaluation Criteria in Solid Tumors
RNA
ribonucleic acid
RP2D
recommended Phase 2 dose
RR
RR interval
SAC
Safety Assessment Committee
SIPPM
Site Investigational Product and Procedures Manual
SMT
safety management team 
SPF
skin protection factor

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SUSAR
suspected unexpected serious adverse reaction
TEAE
treatment-emergent adverse event
TKI
tyrosine kinase inhibitor
TTSP
time to symptomatic progression
ULN
upper limit of normal
US
United States
Definitions of Terms 
Electronic source 
system
Contains data traditionally maintained in a hospital or clinic record to document medical care or data 
recorded in a CRF as determined by the protocol. Data in this system may be considered source 
documentation.

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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 Harmonization (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 Contact 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 CRF 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.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study treatment to 
the study site:

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!
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
!
Sponsor-approved participant recruiting materials
!
Information on compensation for study-related injuries or payment to participants for 
participation in the study, if applicable

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!
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 adverse events 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 
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.

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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 or their legally acceptable representatives 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 be accessed by health authorities 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 or legally acceptable 
representative 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 

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physician to recontact the participant for the purpose of obtaining consent for additional safety 
evaluations, and subsequent disease-related treatments, if needed.
The participant or legally acceptable representative 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 either the participant's or his or her legally 
acceptable representative'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 or legally acceptable representative 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 or legally acceptable representative is obtained.
When prior consent of the participant is not possible and the participant's legally acceptable 
representative is not available, 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 or legally acceptable representative 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 (or his or her legally acceptable representative) 
includes information about, and where required per applicable regulations, 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. The informed consent also provides information to address the 
lawful transfer of the data to other entities and to other countries/territories.
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, or make requests 

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concerning his or her personal data in accordance with applicable data protection law. Reasonable 
steps 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.
In the event of a data security breach, the sponsor will apply measures to adequately manage and 
mitigate possible adverse effects taking into consideration the nature of the data security breach as 
necessary to address other obligations such as notifying appropriate authorities in accordance with 
applicable data protection law.
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 the 
disease under investigation, to understand differential study treatment responders, and to develop 
tests/assays related to amivantamab and NSCLC. 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
Independent Data Monitoring Committee (IDMC)
An IDMC will be established to monitor data on an ongoing basis. This committee will consist of 
at least one medical expert in the relevant therapeutic area and at least one statistician; committee 
membership responsibilities, authorities, and procedures will be documented in its charter. The 
committee will meet periodically to review interim data, at intervals that will be described in the 
charter. After the review, the IDMC will make recommendations regarding the continuation of the 
study.
Safety Evaluation Team (SET)
If a Safety Run-in phase is conducted, the SET will oversee safety evaluation during this part of 
the study. The SET will monitor all available treatment-emergent data from the Safety Run-in on 
an ongoing basis to ensure the continued safety of participants. The SET will be responsible for 
making a formal determination of whether the study will proceed to the randomization, based on 
the DLT rules. The Sponsor's study-responsible physician will chair the SET. Other Sponsor 
membership will include a clinical scientist, statistician, clinical pharmacologist, and additional 

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staff, as appropriate. Investigators who have enrolled participants in the Safety Run-in phase will 
also participate in the SET. The SET will meet approximately monthly during the Safety Run-in 
phase and as necessary during the remainder of the study. Documentation of meeting outcomes 
will be maintained by the Sponsor in the Trial Master File. Decisions with the potential to affect 
participant safety (eg, unfavorable change in benefit/risk assessment) will be promptly 
communicated to investigators and regulatory authorities as appropriate.
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 the 
goals of 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 Clinical Study Report 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 biomarker 
analyses performed after the Clinical Study Report has been issued will be reported in a separate 
report and will not require a revision of the Clinical Study Report. 
Study participant identifiers will not be used in the 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 (ICMJE) 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 
not mandate modifications to scientific content and does not have the right to suppress information. 

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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 ICMJE 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 interim results of clinical studies as required by law. The 
disclosure of the 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. Written 
instructions will be provided for collection, handling, storage, and shipment of samples. 
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review CRF 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. All CRF 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 CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the 
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Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the participant's source documents. Data must be entered into 
CRF in English. The CRF 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 a CRF are needed after 
the initial entry into the CRF, 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 adverse events and follow-up of adverse events; concomitant medication; 
study 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 another 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
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 

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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 CRF in the protocol include the 
eSource system, but information collected through eSource may not be limited to that found in the 
CRF.
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 CRF 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 
CRF 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 
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 

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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 CRF 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 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.
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:

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!
Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, 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: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting
10.3.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study participant administered 
a medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the study treatment. An adverse event 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 
International Council for Harmonization [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 adverse events starting with the signing of the ICF (refer to All Adverse 
Events under Section 8.3.1, Time Period and Frequency for Collecting Adverse Events and Serious 
Adverse Events Information, for time of last adverse event recording).
Serious Adverse Event
A serious adverse event based on ICH and European Union 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 except for the 
following
∃
Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons 
such as pending placement in long-term care facility)
∃
Surgery or procedure planned before entry into the study (must be documented in the 
CRF). 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 serious adverse events. Any adverse event that results in a prolongation 
of the originally planned hospitalization is to be reported as a new serious adverse event.
∃
For convenience the investigator may choose to hospitalize the participant for the 
duration of the study treatment period.
!
Results in persistent or significant disability/incapacity
!
Is a congenital anomaly/birth defect

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!
Is a suspected transmission of any infectious agent via a medicinal product
!
Is Medically Important*
*Medical and scientific judgment 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 intervention to prevent one of the other outcomes listed in the definition above. These 
should usually be considered serious.
If a serious and unexpected adverse event 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 adverse event is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For amivantamab, expectedness of an adverse event 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 adverse events.
Related
There is a reasonable causal relationship between study treatment administration and the adverse 
event. Related events would include probably and possibly related events.
Not Related
There is not a reasonable causal relationship between study treatment administration and the 
adverse event. Not related events would include doubtfully related events.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.3.3.
Severity Criteria
An assessment of severity grade will be made by the investigator according to the National Cancer 
Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0 using the 
following categorical descriptors:
!
Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.
!
Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental activities of daily living.

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!
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 adverse event.
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 patient 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 breastfeeding
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the CRF.
10.3.5.
Procedures
All Adverse Events
All adverse events, regardless of seriousness, severity, or presumed relationship to study treatment, 
must be recorded using medical terminology in the source document and the CRF. 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 CRF their opinion concerning the 
relationship of the adverse event to study therapy. All measures required for adverse event 
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

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!
Local sponsor's name and 24-hour contact telephone number (for medical personnel only)
!
Site number
!
Participant number
Serious Adverse Events
All serious adverse events that have not resolved by the end of the study, or that have not resolved 
upon discontinuation of the participant's participation in 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 a serious 
adverse event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs 
during the course of a participant's participation in a study must be reported as a serious adverse 
event, except hospitalizations for the following:
!
Hospitalizations not intended to treat an acute illness or adverse event (eg, social reasons such 
as pending placement in long-term care facility)
!
Surgery or procedure planned before entry into the study (must be documented in the CRF). 
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 serious adverse events. Any adverse event that results in a prolongation of the 
originally planned hospitalization is to be reported as a new serious adverse event.
!
For convenience the investigator may choose to hospitalize the participant for the duration of 
the study treatment period.
Progression of disease should not be recorded as an adverse event (or serious adverse event). 
However, signs and symptoms of disease progression or of clinical sequelae resulting from disease 
progression/lack of efficacy that are determined by the investigator to be of clinical significance 
should be reported per the usual reporting requirements.
10.3.6.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed in the Contact Information 
page(s), which will be provided as a separate document.

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10.3.7.
Product Quality Complaint Handling
A product quality complaint (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, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of participants, 
investigators, and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor 
has established procedures in conformity with regulatory requirements worldwide to ensure 
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates will 
be conducted in accordance with those procedures.
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.
If the defect is combined with a serious adverse event, the study-site personnel must report the 
PQC to the sponsor according to the serious adverse event reporting timelines (refer to 
Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious Adverse 
Event Information). A sample of the suspected product should be maintained for further 
investigation if requested by the sponsor.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact 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 
Appendix 3: Adverse Events: Definitions and Procedures for Recording, Evaluating, Follow-up, 
and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless 
permanently sterile (see below).
Woman Not of Childbearing Potential
!
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
!
postmenopausal
A postmenopausal state is 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 (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually 
active becomes active), 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.
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.

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Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used 
consistently and correctly.
!
Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
!
Intrauterine device (IUD)
!
Intrauterine hormone-releasing system (IUS)
!
Bilateral tubal 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.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used 
consistently and correctly.
!
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb
∃oral
∃intravaginal
∃transdermal
injectable
!
Progestogen-only hormone contraception associated with inhibition of ovulationb
∃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.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not 
considered to be highly effective - failure rate of %1% per year)
!
Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary 
mode of action
!
Male or female condom with or without spermicidec
!
Cap, diaphragm, or sponge with spermicide
!
A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-
barrier methods)c
!
Periodic abstinence (calendar, symptothermal, post-ovulation methods)
!
Withdrawal (coitus-interruptus)
!
Spermicides alone
!
Lactational amenorrhea method (LAM)

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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).
Pregnancy During the Study
Female participants who become pregnant during the study will be withdrawn from the study 
treatment and followed for safety (Section 8.3.5).

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10.5.
Appendix 5: Eastern Cooperative Oncology Group (ECOG) Performance 
Scale
Grade
Eastern Cooperative Oncology Group Performance Status
0
Fully active, able to carry on all predisease performance without restriction
1
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature 
(eg, light housework, office work)
2
Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of 
waking hours
3
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
4
Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5
Dead
Eastern Cooperative Oncology Group, Robert Comis M.D, Group Chair (Oken, 1982).19

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10.6.
Appendix 6: New York Heart Association Criteria
The following table presents the New York Heart Association classification of cardiac disease:
Class
Functional Capacity
Objective Assessment
I
Patients with cardiac disease but without resulting limitations of 
physical activity. Ordinary physical activity does not cause undue 
fatigue, palpitation, dyspnea, or anginal pain.
No objective evidence of cardiovascular 
disease.
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.
Objective evidence of minimal cardiovascular 
disease.
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.
Objective evidence of moderately severe 
cardiovascular disease.
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.
Objective evidence of severe cardiovascular 
disease.
Classification of Functional Capacity and Objective Assessment. Available at 
http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-
Failure_UCM_306328_Article.jsp Accessed 18 March 2019.

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10.8.
Appendix 8: Anticipated Events
An anticipated event is an adverse event (serious or nonserious) that commonly occurs as a 
consequence of the underlying disease or condition under investigation (disease-related) or 
background regimen. For the purposes of this study, the following events will be considered 
anticipated events:
Assessment of anticipated events will be stopped after the OLE Phase has started.
Constitutional
Cardiovascular
Dehydration
Superior vena cava syndrome
Sepsis
Pericardial effusion
Weakness/asthenia
Cardiac tamponade (associated with pericardial metastasis)
Fatigue
Myocardial infarction
Fever/pyrexia
Stroke
Weight loss
Failure to thrive
Gastrointestinal
Decreased appetite/Anorexia
Dysphagia
General physical health deterioration 
(decline in ECOG status to 3 or 4)
Esophageal obstruction
Intestinal obstruction
Bleeding ulcers
Respiratory
Diverticulitis
Pneumonia
Upper respiratory infection
Musculoskeletal (associated with metastatic or advanced disease)
Lower lung infection
Pain
Hypoxia
Fracture (pathologic fracture)
Dyspnea
Bronchitis
Hematologic
Emphysema
Thromboembolic events – deep vein thromboses, pulmonary emboli
COPD exacerbation
Anemia
Malignant pleural effusion
Cough
Neurologic (associated with metastatic or advanced disease)
Empyema
Cranial nerve palsies
Pulmonary emboli
Weakness of upper, lower extremities
Respiratory failure
Confusion
Pneumothorax
Mental status changes
Hemoptysis
Seizures
Radiation pneumonitis
Unstable gait
Reporting of Anticipated Events
All adverse events will be recorded in the eCRF regardless of whether considered to be anticipated 
events and will be reported to the sponsor as described in Section 10.3.1. Any anticipated event 
that meets serious criteria will be reported to the sponsor as described in Section 10.3.1. Each 
anticipated event will be assessed by the investigator at the individual case level and if considered 
to be drug-related will undergo expedited reporting (if appropriate) per applicable clinical trial 
legislation to Health Authorities and IRB/IECs (Note: Japan will not identify anticipated events 
for the Health Authorities). If an anticipated event is considered disease-related or not related to 
study drug the event will be exempt from expedited reporting.
To meet US regulatory clinical trial legislation, the sponsor will perform aggregate review of 
anticipated events as outlined below, and if determined to be drug-related will implement 
expedited reporting of these events to Health Authorities and IRBs/IECs. If an interim analysis of 

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trial results leads to an unblinded, aggregate review of safety data by the study team, the sponsor 
may terminate the review of pre-specified anticipated events outlined above.
Safety Assessment Committee (SAC)
A Safety Assessment Committee (SAC) will be established to perform reviews of pre-specified 
anticipated events at an aggregate level. The SAC is a safety committee within the sponsor’s 
organization that is independent of the sponsor’s study team. The SAC will meet to aid in the 
recommendation to the sponsor’s study team as to whether there is a reasonable possibility that an 
anticipated event is related to the study treatment based on a review of the aggregate data by arm.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and threshold 
to trigger an aggregate analysis of anticipated events will be provided in a separate Anticipated 
Events Safety Monitoring Plan.

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10.9.
Appendix 9: Dosing Synchronization for Arm A
One week delay of chemotherapy, retreatment
on Day 8, then delay amivantamab by 1 week to
align with chemotherapy in subsequent cycles
Two week delay of chemotherapy, retreatment
on Day 15, then administer amivantamab
1 week prior to scheduled dose in subsequent
cycles to align with chemotherapy dosing
Scheduled administration
of study intervention
(21-day cycles)
One cycle delay of chemotherapy (3 weeks),
then dosing of chemotherapy and amivantamab
would occur on Day 1 of the subsequent cycle
Amivantamab
Chemotherapy
Cycles
Amivantamab
Chemotherapy
Cycles
Amivantamab
Chemotherapy
Cycles
Amivantamab
Chemotherapy
Cycles
D1
D8
D15

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10.10. Appendix 10: Safety Run-in
The safety of amivantamab in combination with carboplatin and pemetrexed is being investigated 
in the ongoing Phase 1 Study (61186372EDI1001), in parallel to Phase 3 study development, and 
will be confirmed prior to enrollment of participants in this Phase 3 study. If regulatory or health 
authorities request region-specific safety experience for amivantamab in combination with 
carboplatin-pemetrexed, an optional Safety Run-in may be performed prior to enrollment of 
participants in the randomized Phase 3 portion of the study in that region/country.
In the Safety Run-in, approximately 6-12 participants of the target population will be dosed with 
the carboplatin-pemetrexed-amivantamab combination, and safety experience will be summarized 
using descriptive statistics. These participants will be in addition to the approximately 
300 participants in the main study.
The Safety Run-in will use the study inclusion (Section 5.1) and exclusion (Section 5.2) criteria 
from the main study, with the following exceptions: 
1) The Safety Run-in will not be limited to participants with an Exon 20ins activating mutation. 
Participants in the Safety Run-in can have histologically or cytologically confirmed, locally 
advanced or metastatic, NSCLC with any previously documented primary EGFR or MET 
activating mutation.
2) Participants in the Safety Run-in may have received prior systemic therapy. Participants who 
have received prior EGFR TKI or MET therapy must have a washout period of 2 weeks or 5 
half-lives, whichever is longer, before the first administration of study treatment. For agents 
with long half-lives, the maximum required time since last dose is 4 weeks. Toxicities from 
previous TKI therapies should have resolved to baseline levels or to Grade 1 or less.
Pemetrexed, carboplatin, and amivantamab for the Safety Run-in will be dosed and administered 
as described in Section 6.
Collection times for PK and immunogenicity samples in the Safety Run-in are shown in Table 2. 
Tumor biopsies are not required for participants in the Safety Run-in; other activities in the Safety 
Run-in will be conducted as listed in the Schedule of Activities (Table 1).

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10.11. Appendix 11: Optional Crossover After Disease Progression to Second-
Line Amivantamab Monotherapy (Arm B Only)
A participant who was randomized into the Arm B (platinum-based doublet chemotherapy) may 
cross over to amivantamab monotherapy after disease progression, as confirmed by blinded 
independent central review (BICR) (see Figure 1). A participant crossing over to second-line 
amivantamab monotherapy will be re-screened to ensure eligibility is met to receive amivantamab.
For study conduct/information after the study has transitioned to the OLE Phase, please refer to 
Section 10.14.
STUDY DESIGN
This phase of the study will not be randomized or controlled. All participants in the Crossover
Phase will receive amivantamab in 21-day cycles as follows:
!
Amivantamab 1,400 mg (1,750 mg if body weight is ≥80 kg) by intravenous (IV) infusion 
once weekly up to Cycle 2 Day 1, then 1,750 mg (2,100 mg if body weight is ≥80 kg) on Day 
1 of each 21-day cycle, starting with Cycle 3
Crossover participants must not initiate treatment with amivantamab earlier than 21 days or later 
than 90 days after their last dose of chemotherapy, regardless of the time of progression.
Other treatment related procedures are described in Table 20.
STUDY POPULATION
Crossover Eligibility Criteria
Each potential participant must satisfy all the following criteria to be enrolled in the crossover:
1.
Prior study randomization to Arm B, with subsequent disease progression after treatment 
with carboplatin-pemetrexed, and confirmation of disease progression by BICR.
2.
No intervening systemic anti-cancer therapy or investigational therapy following 
discontinuation of assigned Arm B study treatment.
3.
Any unresolved toxicities from prior therapy should have resolved to NCI-CTCAE ≤Grade 1 
severity (except for alopecia, which may be Grade 2) at the time of starting amivantamab 
monotherapy.
4.
Participant must have signed ICF for crossover section of the study.
5.
Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 0 
or 1.
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 test.
∃
Hemoglobin ≥10 g/dL
∃
Absolute neutrophil count (ANC) ≥1.5#109/L, without any prior use of G-CSF
∃
Platelets ≥100#109/L

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CROSSOVER ASSESSMENTS AND PROCEDURES
Participants receiving crossover amivantamab monotherapy will follow the assessments and 
procedures described in the main study protocol, with the modifications described in this appendix.
For assessments/procedures after the study has transitioned to the OLE Phase, please refer to 
Section 10.14.
!
Screening procedures need to be completed within 28 days of the first dose of amivantamab.
!
All procedures and assessments completed at the time of withdrawal from the main study may 
be used as appropriate for the start of the Crossover Phase of the study, if done within 28 days. 
!
Baseline tumor imaging must be performed within 28 days before the first dose of 
amivantamab monotherapy. The tumor image that was used to determine progressive disease 
in the main study can be used as the baseline image for the Crossover phase if:
∃
The tumor image was collected within 28 days before the first dose of amivantamab 
monotherapy.
∃
No study treatment was administered between the imaging and the first dose of 
amivantamab monotherapy. 
As summarized in Table 20, follow the guidance in Section 8 for study assessments and 
procedures, with the following modifications:
!
Efficacy assessments (Section 8.1): conduct disease assessments at 6 weeks (+1 week) relative 
to Cycle 1 Day 1 of amivantamab monotherapy, every 6 weeks (±1 week) for the first 
18 months, then every 12 weeks (±1 week), with brain MRI as clinically indicated.
!
Patient-reported outcomes (Section 8.1.3): assess PROs every 12 weeks for 1 year, starting 
from the date of first disease progression. 
!
Safety assessments (Section 8.2) and adverse events (Section 8.3): see Table 20.
!
Pharmacokinetics (Section 8.4) and immunogenicity (Section 8.6): collect blood samples for 
PK and immunogenicity as summarized in Table 21.
!
Biomarkers (Section 8.5): ctDNA and tumor biopsy (if clinically feasible) will be collected at 
the End of Treatment Visit.
STATISTICAL CONSIDERATIONS
Data from the crossover Phase will be summarized descriptively. Endpoints to be analyzed include 
overall response rate, duration of response, and safety. Other statistical considerations for this 
phase of the study will be specified in the Statistical Analysis Plan.

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10.12. Appendix 12: 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 patient 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.
For dose modifications in the event of paronychia, please refer to Table 15.

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10.13. Appendix 13: Guidance on Study Conduct During a COVID-19 Pandemic
It is recognized that a Coronavirus Disease 2019 (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; and 
changes in hospital or clinic procedures required to address the COVID-19 challenge, including 
study site personnel being reassigned to critical tasks. The guidance herein is applicable until the 
clinical site returns to pre-pandemic operational capacity and practices.
In alignment with recent health authority 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 at risk, study intervention will be discontinued, and study follow-up will be 
conducted as outlined in the protocol.
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted via COVID-19 Appendix after consultation with the participant, investigator, and the 
sponsor. Study drug interruptions, discontinuations of study interventions, changes in study visit 
schedules, missed visits/assessments, and/or participant discontinuations may lead to missing data, 
including data related to protocol-specified procedures, and will be captured in the clinical trial 
management system for protocol deviations and documented with the prefix “COVID-19-related” 
in the case report form (CRF). 
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 health authorities 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 intervention and follow-up. Modifications 
made to the study conduct as a result of a COVID-19 pandemic will be summarized in the clinical 
study report.
Consent/Screening
!
Consenting of subjects for study screening including the crossover portion of the study can 
be performed remotely by telephone or video conferencing. Re-consenting of active 
subjects due to new safety information or updated study design should also be assessed for 
its feasibility to be conducted remotely.
!
All screening procedures and assessments must be conducted per protocol at the 
investigative site. 
!
During screening of participants, the investigator should evaluate the feasibility of 
participants returning for scheduled dosing visits per protocol based on history of potential 
COVID-19 exposure and local travel restrictions. If the situation suggests that this is not 
possible, the participant may be screen failed and re-screened when conditions improve.

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!
COVID-19 screening procedures that may be mandated by local healthcare systems do not 
need to be reported as an amendment to the protocol even if done during clinical study 
visits.
!
As SARS-CoV-2 represents a new infectious agent, and COVID-19 a new clinical 
syndrome, it is unclear how infection with this virus will impact the benefit/risk assessment 
with regards to JNJ-61186372 and/or chemotherapy treatment, particularly given its 
association with the risk of severe viral pneumonia. As per the study exclusion criteria, 
participants with active infection, including viral illnesses such as COVID-19, should be 
excluded from study participation.
Study Treatment 
Study treatment with amivantamab and/or chemotherapy (carboplatin and/or pemetrexed), should 
continue to be administered at the investigative site in accordance with the protocol. Potential 
interruptions to therapy should be assessed on a case by case basis and include consideration of 
potential impact on participant’s safety. If doses are missed or delayed due to COVID-19 related 
circumstances, these deviations should be noted in the appropriate CRF page, as “missed or 
delayed due to COVID-19”. The sponsor’s Medical Monitor should be alerted to any anticipated 
interruption in Amivantamab, carboplatin, and/or pemetrexed.
Study treatment should be held for all participants with suspected (symptomatic) or documented 
SARS-CoV-2 positive disease, until recovery from all infection-related symptoms, and 
documented to be negative for SARS-CoV-2. Given the unmet medical need of this study 
population, and the unknown impact of prior COVID-19 infection on the risk of study treatment, 
re-initiation of study treatments should be evaluated with the Medical Monitor on a case-by-case 
basis, taking into account the severity of the COVID-19 related symptoms, and the observed 
clinical benefit from study treatment. Please report the event to the sponsor, following usual 
Adverse Event reporting requirements.
COVID-19 vaccination
The amivantamab safety management team (SMT) evaluated available COVID-19 vaccines for 
study participants. The study excludes subjects who have received live or live attenuated vaccines 
in the past 3 months and such vaccines are also prohibited while on study treatment. Based on this 
evaluation, the SMT has concluded that the administration of any COVID-19 vaccine that is not 
live or live attenuated is permitted in accordance with local guidelines and practice.
Treatment and Follow-up Visits
All study visits and assessments specified in the Schedule of Activities including key efficacy 
endpoint assessments should be followed in accordance to the protocol, unless COVID-19 related 
staffing shortages, site policies, or travel restrictions render these infeasible. In such cases, the 
following modifications may be implemented:
!
If study imaging procedures cannot be performed at the active clinical study site, 
participants will be permitted to use other local imaging facilities (eg, at hospitals that are 

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not the active study site). In these cases, digital copies should be made available to the 
investigator for submission to the central imaging vendor. 
Safety evaluations (eg, laboratory assessments) may be conducted at certified testing and 
triage facilities or at other local hospitals. Records for these evaluations must be available 
for the investigator to review prior to dosing and copies of the results should be included 
in the participant’s study chart as a source document.
Telemedicine/ Teleconferencing/Videoconferencing:
If the subject is doing well and has no safety concerns, scheduled visits that cannot be conducted 
in person at the study site will be performed to the extent possible remotely/virtually (eg, conducted 
via phone or computer), where feasible, or delayed until such time which access is determined to 
be appropriate by the Investigator and Sponsor. At each telephone or telemedicine contact:
!
Review of new, and follow-up of existing, adverse events and concomitant medications 
between regularly scheduled on-site visits (eg, weekly assessments of adverse events 
leading to treatment delay, as described in Section 6.7).
!
The subject can complete any scheduled patient-reported outcome (PRO) assessments.
!
Review of body systems and collection of general health status (to be followed up with in-
person examination if indicated) prior to dosing days, if consistent with site’s typical 
practice.
!
Study assessments requiring investigator judgement should be conducted by the 
investigator. 
Home Health Care
Blood sample collection may be done at the participant’s home by mobile study personnel (ie, 
nurse or mobile phlebotomist) or at a commercial laboratory (eg, LabCorp). Other programs may 
be implemented with approval from the sponsor, such as Home Health Care Visits for study 
assessments and procedures (eg, physical exam), where feasible and permissible by local policy 
and regulations. Study treatment with Amivantamab and/ or chemotherapy will only be 
administered at the study site and will not be administered at Home Health Care Visits.
Flexibility for all protocol-required assessments will be provided on a case-by-case basis, and with 
agreement between the Sponsor and Investigator. However, every effort should be made to adhere 
to protocol-specified assessments, including follow-up, if it is in the best interest of the subject. 
For regions significantly impacted by a COVID-19 pandemic, the investigator and sponsor may 
explore the possibility of transferring participants to nearby, less impacted, study sites (if 
warranted) on either a temporary or permanent basis. The sponsor should be informed of any 
decisions related to the transfer of participants to other study sites prior to their transfer

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Monitoring Visits
When on-site monitoring by the sponsor is not feasible due to changes in hospital or clinic’s 
visitation policies, the sponsor’s site monitor will contact the study site to schedule remote visits. 
In such cases, on-site monitoring visits will resume when feasible, with increased frequency to 
address the source data verification backlog.
Even with staffing limitations during this COVID-19 pandemic, all routine operations related to 
clinical trials should be well-documented and archived as part of standard process. When 
conditions permit, all parties involved in this clinical trial should communicate relevant 
information in a timely manner so that all relevant parties remain sufficiently informed to take any 
necessary measures in a timely manner.

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10.14. Appendix 14: Open-label Extension Phase
The purpose of the OLE Phase is to continue providing participants access to study treatment and 
collect data of clinical relevance/importance while reducing the burden on participants after the 
primary analysis. Data collected during this phase will be limited to those procedures and 
assessments specified in Table 22.
The OLE Phase will begin after approval of Amendment 3 by health authorities of countries in 
which this study is still being conducted at the time of transition, and by study site ECs/IRBs.
During the OLE Phase:
!
Participants in Arm A (amivantamab plus chemotherapy) will continue to receive the study 
treatment they are currently receiving at the time of transition to the OLE Phase and until the 
discontinuation criteria described in Section 7.1 are met, or until the end of the OLE Phase
and/or transition to the LTE Phase.
!
Participants in Arm B (chemotherapy) will continue to receive the study treatment they are 
currently receiving at the time of transition to the OLE Phase and until the discontinuation 
criteria described in Section 7.1 are met, or until the end of the OLE Phase and/or transition 
to the LTE Phase. Participants who discontinue chemotherapy in Arm B for any reason, 
including investigator-assessed disease progression, have not started subsequent therapy, and 
satisfy the eligibility criteria described in Section 10.14.1 will be allowed to cross over to start 
receiving amivantamab monotherapy. If a participant in Arm B does not meet these eligibility
criteria, the participant will enter the Follow-up phase.
!
Participants in the optional crossover to second-line amivantamab monotherapy will continue 
to receive amivantamab monotherapy until the discontinuation criteria described in 
Section 7.1 are met, or until the end of the OLE Phase and/or transition to the LTE Phase.
!
Participants who have already ended study treatment altogether and are in the Follow-up 
Phase in the main study will continue to be in Follow-up as specified in the Schedule of 
Activities for the OLE Phase (Table 22).
10.14.1.
Eligibility Criteria to Cross Over to Second-Line Amivantamab 
Monotherapy (Arm B Only) Within the OLE Phase
Each participant in Arm B who is identified as a candidate for crossover to amivantamab 
monotherapy must satisfy all of the following eligibility criteria below within 28 days prior to 
initiating amivantamab monotherapy.
1. Prior study randomization to Arm B, with subsequent disease progression after treatment with 
carboplatin-pemetrexed, and confirmation of disease progression by investigator assessment
by RECIST v1.1.
2.
No intervening systemic anti-cancer therapy or investigational therapy following 
discontinuation of assigned Arm B study treatment.
3.
Any unresolved toxicities from prior therapy should have resolved to NCI-CTCAE ≤Grade 1 
severity (except for alopecia, which may be Grade 2) at the time of starting amivantamab 
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4.
Participant must have signed an ICF for the crossover.
5.
Participant must have Eastern Cooperative Oncology Group (ECOG) performance status 
0 or 1.
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 test.
∃
Hemoglobin ≥10 g/dL
∃
Absolute neutrophil count (ANC) ≥1.5#109/L, without any prior use of G-CSF
∃
Platelets ≥100#109/L
∃
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3×ULN
∃
Total bilirubin ≤1.5#ULN (participants with Gilbert’s syndrome can enroll if conjugated 
bilirubin is within normal limits)
∃
Creatinine clearance >50 mL/min as measured or calculated by Cockcroft-Gault formula
7.
Participant must have no untreated CNS metastases (a participant with definitively, locally 
treated metastasis who is clinically stable and asymptomatic for at least 2 weeks off 
corticosteroid treatment before enrollment will be eligible).
8.
Participant must have no ongoing or active bacterial infection (includes infection requiring 
treatment with antimicrobial therapy [participants will be required to complete antibiotics 
1 week before the first dose of amivantamab]), symptomatic viral infection, or any other 
clinically significant infection.
9.
Participants must not have a medical history of ILD/pneumonitis.
10.
A female participant of childbearing potential must have a negative serum or urine test at 
screening and within 72 hours of the first dose of study treatment and must agree to further 
serum or urine pregnancy tests during the study.
11.
A female participant must be (as defined in Appendix 4: Contraceptive and Barrier 
Guidance) either of the following:
c.
Not of childbearing potential
d. Of childbearing potential and practicing 2 methods of contraception, including 1 highly 
effective, user independent method. Examples of highly effective methods of 
contraception are located in Appendix 4: Contraceptive and Barrier Guidance.
Participant must agree to continue contraception throughout the study and through 6 months 
after the last dose of study treatment.
Note: If the childbearing potential changes after start of the study (eg, woman who is not 
heterosexually active becomes active, premenarchal woman experiences menarche) the 
woman must begin 2 methods of birth control, as described above.
12.
A female participant must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for 6 months after receiving the last dose of study 
treatment.
13.
A male participant must wear a condom when engaging in any activity that allows for passage 
of ejaculate to another person during the study and for a minimum of 6 months after receiving 

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the last dose of study treatment. If the participant is vasectomized, he must still use a condom 
(with or without spermicide) for prevention of passage of exposure through ejaculation, but 
his female partner is not required to use contraception. 
A male participant who is sexually active with a woman of childbearing potential must agree 
to use a condom with spermicidal foam/gel/film/cream/suppository and his partner must also 
be practicing a highly effective method of contraception (ie, established use of oral, injected, 
or implanted hormonal methods of contraception; placement of an intrauterine device [IUD] 
or intrauterine hormone-releasing system [IUS]).
14.
A male participant must agree not to donate sperm for the purpose of reproduction during the 
study and for a minimum of 6 months after receiving the last dose of study treatment.
15.
Participant is pregnant, breast-feeding, or planning to become pregnant while enrolled in this 
study or within 6 months after the last dose of study treatment.
16.
Participant plans to father a child while enrolled in this study or within 6 months after the 
last dose of study treatment.
Participants who satisfy the eligibility criteria above will receive amivantamab monotherapy, with 
treatment beginning with Cycle X+1, where X is the last cycle that the participant completed 
during the OLE Phase.
10.14.2.
Study Treatment Administration
Study treatment should be continued as specified in Section 6. Participants in Arm B who cross 
over to amivantamab monotherapy should follow study treatment as specified in Section 10.11
(Appendix 11).
10.14.3.
Study Procedures
All participants in the OLE Phase should follow the Schedule of Activities for the OLE Phase
(Table 22).
Laboratory tests should be conducted by a local laboratory as specified in the Schedule of 
Activities for the OLE Phase (Table 22). The investigator should review the laboratory report, 
document this review, and record only clinically relevant changes in the adverse event eCRF. 
Additional follow-up monitoring as specified in the Schedule of Activities in Table 22 should be 
performed. Pregnancy reporting should continue as described in Section 8.3.5. A positive 
pregnancy test should be reported via the adverse event/serious adverse event process (see 
Section 8.3.5 and Appendix 3: Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting).
After notification from the sponsor to the site that final analysis for overall survival is complete, 
participants on study treatment in the OLE Phase will be provided the option to transfer to the LTE 
Phase (see Section 10.15 [Appendix 15]).
During the OLE Phase, data for the following study assessments will be collected.
•
Dosing, including pre-infusion and post-infusion medications
•
Investigator-assessed disease assessment by RECIST v1.1
•
Survival data

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•
TTSP (until final OS analysis)
•
TTST
•
PROs (predose on dosing days): EQ-5D-5L, EORT-QLQ-C30, PROMIS-PF (for 1 year after 
disease progression, reducing the data collection frequency from every 3 months to every 
6 months)
•
All adverse events (including serious adverse events and adverse events of special interest)
•
Concomitant medications (for safety), clinical laboratory assessments (for safety), 
subsequent treatment

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Table 22:
Schedule of Activities for Study Assessments/Procedures in the Open-label Extension Phase
Study Phase
Screening
(Arm B 
crossover 
only)
Treatment (21 Days/Cycle)
End of
Treatment
Follow-up
(Visit/Call)
Notes
Cycle
Cycle 1
Cycles 2+
30 Days After
Last Dose*
Q12W
Cycle Day
1
2
8
15
1
Visit Window (Days)
-28 to -1
-
-
±1
±1
±3
+7
±14
STUDY PROCEDURES
Treatment cycles are 21 days in duration. In Cycle 1, amivantamab is administered on Days 1, 2, 8, and 15. In all subsequent cycles, amivantamab is administered once every 3 weeks on Day 1 of each 21-day
cycle. Assessments during in-clinic dosing days should be performed prior to administration of study treatment unless otherwise stated. Investigator must confirm that the participant meets treatment criteria 
before administration of study treatment. *End of Treatment visit should occur 30 days after the last dose or before starting the next anti-cancer treatment, whichever occurs first.
In Follow-up phase, collect data until the end of study unless the participant has died, is lost to follow-up, or has withdrawn consent.
Screening Assessments
Informed consent
X
(all 
participants)
Must be signed before the first study-related procedure in the OLE Phase.
Inclusion/exclusion 
criteria
X
Confirm all criteria are met before participant enters crossover in the OLE 
Phase (see Section 10.14.1).
ECOG performance status
X
Pregnancy test (serum or 
urine)
X
As clinically indicated, according to local regulation 
requirements, or following the local practice of the center.
Women of child-bearing potential only. Required at Screening and within 
72 hours before the first dose of amivantamab. If local regulations mandate 
pregnancy testing before administration of amivantamab, the test should be 
completed within 72 hours before Day 1 of each cycle or monthly, whichever 
is more frequent.
Pregnancy reporting should continue as described in Section 8.3.5. A positive 
pregnancy test should be reported via the AE/SAE process (see Section 8.3 5
and Appendix 3).
Coagulation
X
Urinalysis
X
12-lead ECG
X
At Screening, then as clinically indicated (triplicate if clinically significant).
Hematology/chemistry 
(up to 72 hours predose)
X
X
X
X
X
X
Laboratory assessments are listed in Appendix 7. Laboratory assessments must 
be reviewed by the Investigator prior to the infusion of amivantamab.  Report 
only clinically significant abnormalities as an adverse event in the eCRF.
Efficacy Assessments
CT/MRI tumor imaging
X
6 weeks (+1 week) from first dose of amivantamab monotherapy, then every 
6 weeks (±1 week) for the first 18 months, then every 12 weeks (±1 week)
afterward
Use same method throughout study (Section 8.1). Continue until disease 
progression per investigator assessment by RECIST v1.1. If a participant is 
treated beyond documented disease progression, continue disease assessments 
as scheduled and review clinical benefit with the Medical Monitor after each 
disease assessment.
Brain MRI
X
As clinically indicated
Symptomatic progression 
events
X
Collect continuously from randomization (including during the
Follow-up Phase)
Survival/disease status
X
Subsequent anticancer 
therapy
X
Collect information on type of therapy, treatment start date, and treatment stop 
date.
Safety Assessments (predose, except as noted) – vital signs and physical exam must be conducted as specified; however, they will be recorded in the eCRF only if associated with an Adverse Event
Vital signs
X
X
X
X
X
X
X
Heart rate, BP, respiratory rate, temperature, and O2 saturation 

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Table 22:
Schedule of Activities for Study Assessments/Procedures in the Open-label Extension Phase
Study Phase
Screening
(Arm B 
crossover 
only)
Treatment (21 Days/Cycle)
End of
Treatment
Follow-up
(Visit/Call)
Notes
Cycle
Cycle 1
Cycles 2+
30 Days After
Last Dose*
Q12W
Cycle Day
1
2
8
15
1
Visit Window (Days)
-28 to -1
-
-
±1
±1
±3
+7
±14
Physical examination
X
X
X
X
Screening will include, at a minimum, weight, general appearance, and an 
examination of the skin, ears, nose, throat, lungs, heart, abdomen, extremities, 
musculoskeletal system, lymphatic system, and nervous system.
Adverse events
Continuous from the time ICF is signed through 30 days after the last dose of study treatment 
(or >30 days, if considered related to study treatment)
Prior and concomitant 
medications
X
Record all prescription and over-the-counter treatments administered through 
30 days after the last dose of study treatment (or the start of a subsequent 
systemic anti-cancer therapy, if earlier). For participants with Grade 3 or 4 
adverse events considered related to amivantamab, or adverse events 
considered related to amivantamab occurring after 30 days following the last 
dose, record concomitant medications through the end of follow-up.
Patient-Reported Outcomes (predose on dosing days)
EQ-5D-5L, EORTC-
QLQ-C30, PROMIS-PF
X
C3, 5, 7, 9, etc
X
Every 
6 months
On C1D1, the Patient-Reported Outcomes data can be collected 24 hours 
before the first dose.
Continue in Follow-up phase for 1 year, regardless of whether subsequent 
therapy has been started.
Study Treatment
Amivantamab (Arm A 
and crossover)
X
X
X
X
X
If amivantamab is delayed for ≥6 weeks from the last dose, a discussion 
should occur with the Medical Monitor prior to redosing. If the first dose in 
Cycle 2 or beyond is delayed, then the next dose of amivantamab will be based 
on the previous dose of amivantamab .
Pemetrexed 
administration (Arm A/B)
X
X
Preinfusion Medications
Preinfusion medications
X
X
X
X
X
See Table 18. Record all preinfusion medications.
AE=adverse event; BP=blood pressure; CT=computerized tomography; ECOG=Eastern Cooperative Oncology Group; ICF=informed consent form; MRI=magnetic resonance imaging; O2=oxygen; OLE=open-
label extension; Q12W=every 12 weeks.

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10.15. Appendix 15: Long-term Extension Phase
The purpose of the LTE Phase is to continue providing participants access to study treatment while 
further reducing the burden on participants after the final analysis for overall survival is complete.
Investigators should monitor and assess the participants for disease status (response, progression, 
survival) and safety according to routine standard practice and local label requirements. The 
LTE Phase will begin after the final analysis for overall survival and will continue until the 
discontinuation criteria described in Section 7.1 are met, or until 2 years after local marketing 
authorization is obtained for the studied indication, whichever occurs first. After prior notification 
from the sponsor. participants still in the study after the OLE Phase will be provided the option to 
transfer to the LTE Phase.
Data collection will be limited to serious adverse events, which will be reported on the appropriate 
serious adverse event form and recorded by the sponsor in the Global Medical Safety database.
Pregnancy reporting should continue as described in Section 8.2.5. Other safety and efficacy data 
will not be collected during the LTE Phase. No analyses other than routine periodic safety reviews
encompassing reported serious adverse events are planned for the LTE Phase.
Participants who had discontinued study treatment and are in the Follow-up Phase, or participants 
who elect not to enter the LTE Phase will be discontinued from the study upon the start of the 
LTE Phase.
Participants entering the LTE Phase will continue to receive the study treatment they were 
receiving at the time of transfer to the LTE Phase. The sponsor will continue to provide study 
drugs until the discontinuation criteria described in Section 7.1 are met, or until 2 years after local 
marketing authorization is obtained for the studied indication, whichever occurs first. Study 
treatment dispensation and accountability will be performed via IWRS.
10.15.1.
Eligibility Criteria
All participants still in the OLE Phase are eligible to transfer to the LTE Phase.
Participants who discontinue chemotherapy in Arm B for any reason, including investigator-
assessed disease progression, have not started subsequent therapy, and satisfy the eligibility criteria 
described in Section 10.14.1 will be allowed to cross over to start receiving amivantamab 
monotherapy.
Each participant in Arm B who is identified as a candidate for crossover to amivantamab 
monotherapy must satisfy all of the eligibility criteria in Section 10.14.1 within 28 days prior to 
initiating amivantamab monotherapy. If a participant in Arm B does not meet these eligibility 
criteria, the participant will enter the Follow-up phase.
Participants who satisfy the eligibility criteria will receive amivantamab monotherapy, with 
treatment beginning with Cycle X+1, where X is the last cycle that the participant completed 
during the LTE Phase.

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10.15.2.
Study Treatment Administration
Study treatment should be continued as specified in Section 6. Participants in Arm B who cross 
over to amivantamab monotherapy should follow study treatment as specified in Section 10.11
(Appendix 11).
10.15.3.
Study Procedures
All participants in the LTE Phase should follow the Schedule of Activities for the LTE Phase 
(Table 23).
Participants in the LTE Phase should be followed up for disease assessment and safety per the 
local practice and following the local label(s). No efficacy data will be collected; only serious 
adverse events will be collected via the serious adverse event form per the serious adverse event
process. Pregnancy reporting should continue as described in Section 8.2.5. A positive pregnancy 
test should be documented in the subject file/source notes. Other procedures and safety
assessments may be performed per local practice.
No data will be collected in the eCRF during the LTE Phase. However, assessments performed 
should continue to be documented in the subject file/source notes.

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10.16. Appendix 16: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located directly 
before the Table of Contents.
Amendment 2 (12 August 2022)
Overall Rationale for Amendment: To clarify that tumor imaging assessments should continue until 
objective disease progression by blinded central independent review (BICR) has been documented, and to 
add appropriate action in the event of toxic epidermal necrolysis (TEN) occurrence, as requested by Health 
Authority.
When changes are provided verbatim, deleted text is shown as strikethrough, and added text is shown as 
bold font.
Section 
Number and 
Name
Description of Change(s)
Brief Rationale
Section 1.3: 
Schedule of 
Activities
CT/MRI tumor imaging row; notes section, text added to say: Use same 
method throughout study (Section 8.1). Continue until disease 
progression by BICR.
Added text to Subsequent anticancer therapy, Notes, column: Collect 
information on type of therapy, treatment start date, and treatment stop 
date, objective disease response and progression
Added the full term for BICR in Table 1 footnote.
To clarify imaging 
assessments.
To clarify 
assessments in the 
follow up phase
To define the full 
term of 
abbreviation 
mentioned in 
Table 1.
Section 4.1.3 
Follow up Phase
Added Note: Note: For participants who discontinue prior to disease 
progression by BICR, tumor imaging should continue per schedule of 
activities.
To clarify 
assessments in the 
follow up phase
Section 6.8.2.1: 
Rash-Related 
Adverse Events
Bullet point added: •
In case of a Grade 4 rash including severe 
bullous, blistering, or exfoliating skin condition such as toxic epidermal 
necrolysis (TEN), study treatment should be discontinued permanently.
Text was added for Grade 4 event management and for management of 
severe bullous, blistering, or exfoliating skin conditions including toxic 
epidermal necrolysis (TEN) in Table 15: Suggested Algorithm for 
Management of Rash and Paronychia.
Cross reference to Table 13 and Table 14 added for recommended dose 
adjustment.
Description of 
action in the event 
of TEN required by 
Health Authority.
Section 7.1: 
Discontinuation 
of Study 
Treatment
Added text: Documented radiographic (RECIST, Version 1.1) disease 
progression by BICR, unless treatment beyond disease progression has 
been approved by the Medical Monitor. Discontinuation for disease 
progression based on local assessment prior to BICR confirmation 
should be discussed with the Medical Monitor 
Continuation of study treatment after BICR confirmed disease 
progression may be allowed in accordance with local practice, after 
approval from the Medical Monitor, if the investigator believes the 
participant is deriving clinical benefit.
To clarify steps 
beyond disease 
progression.

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Section 8.1.1: 
Disease 
Assessments
Text added: Subsequent assessments should be performed at 6 weeks 
(+1 week) after randomization, then every 6 weeks (±1 week) for the 
first 18 months and then every 12 weeks (±1 week), until objective 
radiographic disease progression by BICR. 
Also added: Investigators should consider BICR non-PD assessments 
when making discontinuation decisions and can continue with study 
treatment until BICR confirmed disease progression.
Also added: For participants who discontinue study treatment due to 
toxicity or a reason other than objective progressive disease by BICR, 
tumor assessments should be continued per schedule until radiographic 
progressive disease is documented and confirmed by BICR
To clarify imaging 
assessments. 
Section 8.1.2 
Symptomatic 
Progression
Text added: Symptoms, attribution, and related interventions will be 
recorded in the eCRF at the times specified in the Schedule of Activities. 
If symptomatic progression is not reported prior to treatment 
discontinuation, continued assessment of the symptoms is required 
during the follow up period even after subsequent therapy is 
initiated.
To clarify 
assessments for 
symptomatic 
progression. 
Section 8.3.1 
Time Period and 
Frequency for 
Collecting 
Adverse Event 
and Serious 
Adverse Event 
Information
Cross-reference to Table 1 added.
To provide cross-
reference to extra 
detail.
10.7:.Appendix 
7: Clinical 
Laboratory 
Tests
Text added: Leukocyte esterase (if available)
To allow flexibility 
at site.
Appendix 11: 
Optional 
Crossover After 
Disease 
Progression to 
Second-Line 
Amivantamab 
Monotherapy 
(Arm B Only)
Table 18: Preinfusion Medications for Amivantamab: Timing of 
preinfusion medications has been updated. Route of administration of 
antihistamines has also been updated.
Text added to Discontinuation Of Study Treatment And Participant 
Discontinuation/Withdrawal subsection: Follow the guidance in 
Section 7 for discontinuation of study treatment and participant 
discontinuation or withdrawal. Additionally, study treatment must be 
discontinued for documented radiographic disease progression as 
per RECIST v1.1 unless treatment beyond disease progression is 
approved by the Medical Monitor.
To be consistent 
with pre-infusion 
medication 
guidelines 
throughout the 
study.
To clarify 
discontinuation of 
crossover subjects.

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Amendment 1 (20 May 2021)
Overall Rationale for the Amendment: To provide clarifications to the current protocol and to 
provide the latest combination therapy data from the Phase 1 Study 61186372EDI1001. When 
changes are provided verbatim, deleted text is shown as strikethrough, and added text is shown as 
bold font.
Section Number 
and Name
Description of Changes(s)a
Brief Rationale
1.1 Synopsis 
Addition of the text in bold
The combination of amivantamab with chemotherapy in participants with 
EGFR mutated NSCLC is also being evaluated in this study. As of 
20 October 2020, 16 patients have been dosed with the combination 
amivantamab and chemotherapy (carboplatin and pemetrexed). 
Preliminary safety analysis of the combination is consistent with the 
monotherapy experience of amivantamab and chemotherapy alone. 
Preliminary pharmacokinetic (PK) data suggests no impact of 
chemotherapy on amivantamab exposure.
Presentation of the 
latest combination 
therapy data from 
Phase 1 Study 
61186372EDI1001.
Figure 1: Schematic 
Overview of the 
Study Design
Corrected to show that the crossover dosing is from Cycle 3 Day 1 onwards
Clarification.
Table 1: Schedule 
of Activities for 
Study Assessments/
Procedures
Serology note updated:
HIV antibody, HBV, HCV, HBsAg, HBsAb, HBcAb, anti-HCV antibody, 
HBV viral load (if needed) and HCV viral load (if needed).
Hematology/chemistry note updated: 
Hematology/chemistry schedule on C1D8 and C1D15 applies to both 
Arm A and Arm B.
Vital signs note updated: 
Vital signs on C1D2 are not required for Arm B as no C1D2 visit is 
required.
Amivantamab administration (Arm A only) note updated:
Any missed scheduled doses should be discussed with the Medical Monitor 
prior to redosing. 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 of Cycle 1.
See Section 6.2.1 for guidance if changes are required to scheduled doses of 
amivantamab.
Patient-Reported Outcomes note updated:
On C1D1, the Patient-Reported Outcomes data can be collected 24 hours 
before the first dose.
Clarification.
2.2.1. Clinical 
Studies of 
Amivantamab
Addition of the text in bold
Updated efficacy and safety data of amivantamab monotherapy in patients 
with EGFR Exon 20ins NSCLC were recently presented at the 
International Association for the Study of Lung Cancer (IASLC) 2021 
World Conference.26 Results remain consistent with the previous 
experience with amivantamab. These updated data are also available in IB 
Version 5.0.12
Addition of the 
latest monotherapy 
data and reference.
2.2.3 Rationale for 
Amivantamab 
Chemotherapy 
Combination
Addition of the text in bold
As of 20 October 2020, 16 patients have been dosed with the combination 
amivantamab and chemotherapy (carboplatin and pemetrexed) in the 
ongoing Phase 1 study CHRYSALIS (61186372EDI1001). Preliminary 
safety analysis of the combination is consistent with the monotherapy 
experience of amivantamab and chemotherapy alone. Preliminary PK data 
suggests no impact of chemotherapy on amivantamab exposure. Please 
refer to the IB (Version 5.0) for additional information.12
Presentation of the 
latest combination 
therapy data from 
Phase 1 Study 
61186372EDI1001.

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2.3.1. Risks for 
Study Participation
Addition of the text in bold
The safety of amivantamab in combination with carboplatin and pemetrexed is 
being investigated in a Phase 1 study (61186372EDI1001) and results from 
this cohort have been updated in the IB.12
An Independent Data Monitoring Committee (IDMC) will review safety and 
tolerability data periodically (refer to Appendix 2: Regulatory, Ethical, and 
Study Oversight Considerations). The IDMC will has reviewed safety results 
for amivantamab in combination with carboplatin and pemetrexed in the 
ongoing Phase 1 study prior to enrollment of participants in this Phase 3 study. 
In addition, an early IDMC meeting is plannedmay occur after approximately 
20 participants have been randomized and treated for 2 cycles with the protocol 
treatment for additional review of the safety with this combination.
Presentation of the 
latest combination 
therapy data from 
Phase 1 Study 
61186372EDI1001.
4.3.2. 
Amivantamab and 
Chemotherapy 
Combination Dose 
Rationale
Addition of the text in bold:
In the ongoing Phase 1 Study 61186372EDI1001, Cycle 1 PK data suggest 
no impact of chemotherapy on amivantamab exposure. Preliminary 
trough concentration comparisons suggest that higher doses of 
amivantamab given every 3 weeks (Q3W; 21-day cycle), are similar to the 
recommended dose for monotherapy given every 2 weeks (28-day cycle). 
Please refer to IB Version 5.0 for further information.12
Presentation of the 
latest combination 
therapy data from 
Phase 1 Study 
61186372EDI1001.
5.1.Inclusion 
Criteria
Updates to inclusion criterion 9: 
Criterion modified per Amendment 1:
9.1. A female participant must be (as defined in Appendix 4: Contraceptive and 
Barrier Guidance) either of the following:
a.
Not of childbearing potential
Of childbearing potential and
!
practicing true abstinence during the entire period of the study, 
including up to 6 months after the last dose of study treatment is 
given;
!
have a sole partner who is vasectomized;
or practicing 2 highly effective methods of contraception, including 1 
highly effective, user independent method. Examples of highly effective 
methods of contraception are located in Appendix 4: Contraceptive and 
Barrier Guidance.
Participant must agree to continue contraception throughout the study and 
through 6 months after the last dose of study treatment.
Note: If the childbearing potential changes after start of the study (eg, woman 
who is not heterosexually active becomes active, premenarchal woman 
experiences menarche) the woman must begin 2 highly effective methods of 
birth control, as described above.
To comply with the 
requirements of the 
2020 Clinical Trials 
Facilitation Group 
Contraception 
Guidance.

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5.2.Exclusion 
Criteria 
Exclusion criterion 1, addition of the text in bold:
Criterion modified per Amendment 1:
1.1. Participant has received any prior systemic treatment for locally advanced 
or metastatic disease, with the following exceptions:
!
Prior adjuvant or neoadjuvant platinum-based doublet chemotherapy 
is allowed, if completed at least 12 months prior to signing the study 
ICF.
!
Localized radiotherapy to the lung must be completed at least 6 months 
prior to randomization. Palliative radiation to other sites must be 
completed at least 7 days prior to randomization. See Section 8.1 for 
information regarding irradiated target lesions.
!
Prior monotherapy with an approved EGFR TKI (ie gefitinib, erlotinib, 
afatinib, dacomitinib, or osimertinib) as non-standard first-line 
therapy for the treatment of locally advanced or metastatic disease is 
allowed, if: 1) treatment duration did not exceed 8 weeks; 2) lack of 
disease response was documented (radiographically) by an increase in 
tumor burden (a copy of the computerized tomography [CT] report 
showing increase in tumor burden from baseline should be 
submitted); 
Exclusion criterion 2, addition of the text in bold:
Criterion modified per Amendment 1:
2.1. Participant has evidence of synchronous NSCLC disease (as suggested by 
genetic characterization or radiographic appearance). with an EGFR 
mutation other than EGFR Exon 20ins.
Exclusion criterion 8, addition of the text in bold:
Criterion modified per Amendment 1:
8.1. Participant has an active malignancy (ie, ongoing, progressing or requiring 
treatment change in the last 24 months) other than the disease being treated 
under study.
Exclusion criterion 11, addition of the text in bold: 
Criterion modified per Amendment 1:
11.1. Participant is known to be positive for human immunodeficiency virus 
(HIV) and meets one of the following criteria:
Note updated, addition of the text in bold:
NOTE: Investigators should must ensure that all study enrollment criteria
procedures have been met at screening completed during the screening 
period and the subject continues to meet eligibility at the time of 
randomization, is clinically stable and is expected to initiate therapy within 
72 hours of randomization. If a participant’s clinical status changes (including 
any available 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, then the participant should be 
excluded from participation in the study. Section 5.4 describes options for 
retesting.
Clarification.

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6.2.1 Scheduled 
Dosage and Timing
Addition of the text in bold:
If amivantamab treatment is delayed from Cycle 1 Day 1 to Day 2 and 
Cycle 1 Day 2 to Day 3, appropriate premedications should be 
administered before amivantamab infusion. Please refer to Table 6 for 
premedications required with amivantamab.
[…]
Amivantamab should typically be administered Q3W but if amivantamab 
dosing needs to align with a delayed dose of chemotherapy then it can be 
administered at an interval between 2 and 4 weeks (see Appendix 9: 
Dosing Synchronization for Arm A). Any missed scheduled doses should 
be discussed with the Medical Monitor prior to redosing. If a dose is 
delayed on Cycle 1 Day 8 and/or Cycle 1 Day 15 it will not be made up. If a 
dose is delayed in Cycle 2 or beyond, then the dates of the subsequent 
doses will be scheduled based on the timing of the previous dose of 
amivantamab. If amivantamab is delayed for ≥6 weeks from the last dose, 
a discussion should occur with the Medical Monitor prior to redosing.
Clarification.
6.2.3 Amivantamab
Deletion of the following text:
The minimum infusion time will be 120 minutes.
To ensure that 
investigators refer 
to the IPPI for 
information 
describing the 
stability and 
administration of 
amivantamab.
6.3 
Preparation/Handli
ng/ Storage/ 
Accountability
Addition of the text in bold: 
Preparation/Handling/Storage
The instructions below on study treatment preparation, handling, and 
storage apply only to amivantamab and/or centrally sourced 
chemotherapy. For locally sourced chemotherapy, please follow the 
instructions on the local package insert.
Accountability
The instructions below on study treatment apply only to amivantamab 
and/or centrally sourced chemotherapy. For locally sourced 
chemotherapy, please follow the instructions on the local package insert.
Clarification.
6.5 Study 
Treatment 
Compliance
Addition of the text in bold: 
The instructions below on study treatment compliance apply only to 
amivantamab and/or centrally sourced chemotherapy. For locally sourced 
chemotherapy, please follow the instructions on the local package insert.
Clarification.
6.6.2.2. Pre- and
Post-Infusion 
Medications for 
Amivantamab
Table 7 updated:
Fosprepitant/Aprepitant 150 mg
Clarification.
6.7. Dose Delay 
Guidance
Addition of the text in bold:
Combination Chemotherapy (pemetrexed ± carboplatin): […]While some 
flexibility in the amivantamab dosing schedule is allowed as described above, 
combination chemotherapy must be dosed at a minimum interval of 21 days 
(carboplatin administration cannot exceed for more than a total of 
4 cycles)for a total of 4 cycles.
Amivantamab: In the event amivantamab dosing on Day 1 of the cycle is 
delayed, but retreatment criteria for chemotherapy are met, dosing with 
chemotherapy should continue as planned and subjects should be evaluated 
weekly for retreatment. If amivantamab is delayed for ≥6 weeks from the 
last dose, a discussion should occur with the Medical Monitor prior to 
redosing. In the event chemotherapy dosing on Day 1 of the cycle is delayed, 
but retreatment criteria for amivantamab are met, dosing with amivantamab 
should continue as planned. As discussed above, if chemotherapy dosing 
subsequently occurs on Day 8 or Day 15 of the cycle, the next dose of 
amivantamab can be aligned with chemotherapy dosing in the subsequent cycle.
Clarification.

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6.8.2. 
Amivantamab Dose 
Modification
Addition of the text in bold:
Table 13: Guidance for Amivantamab Dose Delay and Modification for 
Toxicities Considered Related to Amivantamab (Other Than Rash, 
Paronychia, Infusion-Related Reaction, Liver Toxicity, or Pulmonary 
Toxicity).
Footnote c edited:
Resolution defined as: Grade ≤1 non hematologic toxicity or back to baseline. 
For hypoalbuminemia, the dose can be resumed without resolution of the 
event to Grade ≤1 or baseline and based on the Investigator’s clinical 
judgement. For liver enzyme abnormalities requiring interruption of 
treatment, a discussion should occur with the Medical Monitor before 
restarting amivantamab.
Table 15: Suggested Algorithm for Management of Rash and Paronychia.
Clarification.
6.8.2.3. Liver 
Chemistry 
Abnormalities
Clarification added in bold:
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 (beyond what is anticipated from 
chemotherapy), right upper quadrant pain or tenderness, fever, rash, 
and/or new eosinophilia (>5%).
In the event abnormalities of liver function tests require withholding 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 a) above 
(ALT or AST ≥3×ULN and bilirubin ≥2×ULN [>35% direct bilirubin] [or 
ALT ≥3×ULN and INR >1.5, if INR measured]) is concurrently 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.
Clarification.
8. STUDY 
ASSESSMENTS 
AND 
PROCEDURES
Clarification added in bold:
Study treatment (amivantamab will be supplied centrally; depending on 
region, chemotherapy may be either centrally or locally sourced)
Clarification.
8.1.1. Disease 
Assessments
Addition of the text in bold
Participants will have MRI of the brain at screening, with subsequent definitive 
treatment of identified active lesions before starting study treatment (see 
Section 5.1). For patients who are intolerant to brain MRI, alternative 
imaging modality can be considered for screening after discussion with the 
Medical Monitor.
Clarification.
8.2.3. 
Electrocardiograms
Section updated:
During the collection of electrocardiograms (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. 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.
Collection of ECGs will be obtained as indicated in the Schedule of Activities 
(Table 1). At each time point at which triplicate ECGs are required, 
3 individual ECG tracings should be obtained as closely as possible in 
succession, but approximately 2 minutes apart. A copy of triplicate ECGs on 
Cycle 1 Day 1 and Cycle 3 Day 1 will be sent to a central reader. If the 
Screening ECG is performed in triplicate within 72 hours before the first 
dose of study treatment, the assessment does not need to be repeated at 
Cycle 1 Day 1 (and a copy of these triplicate ECGs can be sent to a central 
reader in lieu of Cycle 1 Day 1).
Clarification.

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Appendix 3: 
Adverse Events: 
Definitions and 
Procedures for 
Recording, 
Evaluating, Follow-
up, and Reporting; 
Section 10.3.2
Addition of the text in bold
Related
There is a reasonable causal relationship between study treatment 
administration and the AE. Related events would include probably and 
possibly related events.
Not Related
There is not a reasonable causal relationship between study treatment 
administration and the AE. Not related events would include doubtfully 
related events.
Clarification.
Appendix 7: 
Clinical Laboratory 
Tests, Protocol-
Required Safety 
Laboratory 
Assessments
Protocol-required safety laboratory assessments updated to include the 
following clinical chemistry at each assessment (not just at Screening): 
magnesium, phosphorus, sodium, potassium, calcium.
Blood glucose added as an additional test at Screening only
Clarification.
Appendix 11: 
Optional Crossover 
After Disease 
Progression to 
Second Line 
Amivantamab 
Monotherapy (Arm 
B Only)
Crossover 
Eligibility Criteria
Addition of the text in bold
9. Criterion added per Amendment 1:
Patients must not have a medical history of ILD/pneumonitis.
Study treatment clarified:
If amivantamab is delayed for ≥6 weeks from the last dose, a discussion 
should occur with the Medical Monitor prior to redosing.
Table 20:
Updated to reflect the updates made to Table 1 (Schedule of Assessments).
Addition of the 
crossover eligibility 
criterion and study 
treatment clarified.
Appendix 12: 
Paronychia, 
Reactive 
Management 
Recommendations
Addition of the text in bold
For dose modifications in the event of paronychia, please refer to Table 15.
Clarification.
Appendix 13: 
Guidance on Study 
Conduct During a 
COVID-19 
Pandemic
Addition of the text in bold
COVID-19 vaccination
The amivantamab safety management team (SMT) evaluated available 
COVID-19 vaccines for study participants. The study excludes subjects 
who have received live or live attenuated vaccines in the past 3 months and 
such vaccines are also prohibited while on study treatment. Based on this 
evaluation, the SMT has concluded that the administration of any COVID-
19 vaccine that is not live or live attenuated is permitted in accordance 
with local guidelines and practice.
Instructional text 
was updated for 
clarification.
Appendix 14: 
Protocol 
Amendment 
History
The Protocol Amendment Summary of Changes Table for the current 
amendment is located directly before the Table of Contents.
Updated to include
Protocol 
Amendment 1. 
References
Addition of the following references:
Investigator’s Brochure: JNJ-61186372 Edition 5. Janssen Research & 
Development, LLC (08 March 2021).
Park et al, 2020.
Sabari, J. et al. 2021.
To align with 
changes made in the 
Protocol 
Amendment 1.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.
Minor errors were 
noted.
a Text added during Amendment 1 is shown in bold font, text removed since the original protocol is shown in strikethrough. 

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