A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C
Phase: PHASE3
Conditions: KRAS p, G12c Mutated /Advanced Metastatic NSCLC
Sponsor: Amgen

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 1 of 179 
CONFIDENTIAL  
 
 
Title Page 
Protocol Title:  
A Phase 3 Multicenter, Randomized, Open 
Label, Active-controlled, Study of AMG 510 
Versus Docetaxel for the Treatment of Previously 
Treated Locally Advanced and Unresectable or 
Metastatic NSCLC Subjects With Mutated 
KRAS p.G12C 
Short Protocol Title: 
A Phase 3 Study to Compare AMG 510 With 
Docetaxel in NSCLC Subjects With 
KRAS p.G12C Mutation (CodeBreak 200)  
Protocol Number: 
20190009 
Investigational Product: 
AMG 510 
Trade Name: 
Not available 
Sponsor 
Name of Sponsor: 
Amgen Inc. 
Address: 
One Amgen Center Drive 
Thousand Oaks, CA, 91320 
Telephone Number: 
+1 805-447-1000 
Protocol 
Approver 
Name: 
 MD, PhD 
Function: 
Vice President Global Development 
Key 
Sponsor 
Contact 
Name: 
, MD  
Address: 
One Amgen Center Drive 
Thousand Oaks, CA, 91320 
Telephone Number: 
Email Address: 
EudraCT Number: 
2019‐003582‐18 
NCT Number: 
NCT04303780 
Protocol Version Date: 
Document Version 
Date 
Original 
19 November 2019 
Amendment 1 
21 January 2020 
Amendment 2 
03 June 2020 
Superseding 
Amendment 2 
29 June 2020 
Amendment 3 
15 February 2021 
Amendment 4 
06 January 2022 
Data Elements Standards 
Version: 
6.2 
 
This protocol was developed, reviewed, and approved in accordance with Amgen’s 
standard operating procedures.  This format and content of this protocol is aligned with 
Good Clinical Practice:  Consolidated Guidance (ICH E6). 
 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 2 of 179 
CONFIDENTIAL  
 
 
Confidentiality Notice 
 
This document contains confidential information of Amgen Inc. 
This document must not be disclosed to anyone other than the site study staff and 
members of the institutional review board/independent ethics committee/institutional 
scientific review board or equivalent. 
The information in this document cannot be used for any purpose other than the 
evaluation or conduct of the clinical investigation without the prior written consent of 
Amgen Inc. 
If you have questions regarding how this document may be used or shared, call the 
Amgen Medical Information number: US sites 1- 800-77-AMGEN; Canadian sites 
1-866-50-AMGEN. Amgen’s general number in the US: 1-805-447-1000. For all other 
study-related questions, please contact the Key Sponsor Contact. 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 3 of 179 
CONFIDENTIAL  
 
 
Investigator’s Agreement: 
I have read the attached protocol entitled A Phase 3 Multicenter, Randomized, Open 
Label, Active-controlled, Study of AMG 510 Versus Docetaxel for the Treatment of 
Previously Treated Locally Advanced and Unresectable or Metastatic NSCLC Subjects 
With Mutated KRAS p.G12C, dated 06 January 2022, and agree to abide by all 
provisions set forth therein.   
I agree to comply with the International Council for Harmonisation (ICH) Tripartite 
Guideline on Good Clinical Practice (GCP), Declaration of Helsinki, and applicable 
national or regional regulations/guidelines.   
I agree to ensure that Financial Disclosure Statements will be completed by:  me 
(including, if applicable, my spouse [or legal partner] and dependent children) and my 
subinvestigators (including, if applicable, their spouses [or legal partners] and dependent 
children) at the start of the study and for up to 1 year after the study is completed, if 
there are changes that affect my financial disclosure status. 
I agree to ensure that the confidential information contained in this document will not be 
used for any purpose other than the evaluation or conduct of the clinical investigation 
without the prior written consent of Amgen Inc. 
 
_______________________________ 
Signature 
 
_______________________________ 
____________________________ 
Name of Investigator 
Date (DD Month YYYY) 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 4 of 179 
CONFIDENTIAL  
 
 
Table of Contents 
Table of Contents ................................................................................................... 4 
1. 
Protocol Summary ................................................................................................ 10 
1.1 
Synopsis ................................................................................................... 10 
1.2 
Study Schema ........................................................................................... 23 
1.3 
Schedule of Activities ................................................................................ 24 
2. 
Introduction ........................................................................................................... 35 
2.1 
Study Rationale ......................................................................................... 35 
2.1.1 
Choice of Docetaxel as Comparator .......................................... 36 
2.1.2 
Primary Endpoints ..................................................................... 38 
2.1.3 
Key Secondary Endpoints ......................................................... 38 
2.2 
Background ............................................................................................... 39 
2.2.1 
Disease ..................................................................................... 39 
2.2.1.1 
Oncogenic RAS Driven Tumorigenesis ................... 40 
2.2.1.2 
KRAS p.G12C Mutation and AMG 510 .................... 40 
2.2.1.3 
Current Therapy for Cancers Harboring 
the KRAS p.G12C Mutation ..................................... 41 
2.2.2 
Amgen Investigational Product Background:  
AMG 510 ................................................................................... 43 
2.2.3 
Non-Amgen Investigational Product Background:  
Docetaxel .................................................................................. 45 
2.3 
Benefit/Risk Assessment ........................................................................... 47 
3. 
Objectives and Endpoints ..................................................................................... 48 
4. 
Study Design ........................................................................................................ 51 
4.1 
Overall Design .......................................................................................... 51 
4.2 
Number of Subjects ................................................................................... 55 
4.2.1 
Replacement of Subjects ........................................................... 56 
4.2.2 
Number of Sites ......................................................................... 56 
4.3 
Justification for Investigational Product Dose ............................................ 56 
4.3.1 
Amgen Investigational Product Dose ......................................... 56 
4.3.2 
Non-Amgen Investigational Product Dose ................................. 57 
4.4 
End of Study ............................................................................................. 57 
4.4.1 
End of Study Definition .............................................................. 57 
4.4.2 
Study Duration for Subjects ....................................................... 58 
4.5 
Patient Input on Study Design ................................................................... 58 
5. 
Study Population .................................................................................................. 58 
5.1 
Inclusion Criteria ....................................................................................... 58 
5.2 
Exclusion Criteria ...................................................................................... 60 
5.3 
Subject Enrollment .................................................................................... 63 
5.4 
Screen Failures ......................................................................................... 63 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
6. 
Treatments ........................................................................................................... 64 
6.1 
Treatment(s) Administered ........................................................................ 64 
6.1.1 
Investigational Products ............................................................ 64 
6.1.2 
Non-investigational Products ..................................................... 66 
6.1.3 
Medical Devices ........................................................................ 66 
6.1.4 
Other Protocol-required Therapies ............................................ 66 
6.1.4.1 
Pre- and Post-infusion Medications for 
Docetaxel ................................................................ 66 
6.1.5 
Other Treatment Procedures ..................................................... 66 
6.1.5.1 
Biopsies .................................................................. 66 
6.1.6 
Product Complaints ................................................................... 67 
6.1.7 
Excluded Treatments, Medical Devices, and/or 
Procedures During Study Period ............................................... 67 
6.2 
Dose Modification ...................................................................................... 68 
6.2.1 
Dose-cohort Study Escalation/De-escalation and 
Stopping Rules .......................................................................... 68 
6.2.2 
Dosage Adjustments, Delays, Rules for Withholding or 
Restarting, Permanent  ............................................................. 68 
6.2.2.1 
Amgen Investigational Product:  AMG 510 .............. 68 
6.2.2.2 
Non-Amgen Investigational Product(s):  
Docetaxel ................................................................ 70 
6.2.3 
Hepatotoxicity Stopping and Re-Challenge Rules ..................... 72 
6.3 
Preparation/Handling/Storage/Accountability ............................................ 74 
6.4 
Measures to Minimize Bias:  Randomization and Blinding ......................... 74 
6.4.1 
Method of Treatment Assignment .............................................. 74 
6.4.2 
Blinding ..................................................................................... 74 
6.5 
Treatment Compliance .............................................................................. 74 
6.6 
Treatment of Overdose ............................................................................. 75 
6.6.1 
AMG 510 Overdose ................................................................... 75 
6.6.2 
Docetaxel Overdose .................................................................. 75 
6.7 
Prior and Concomitant Treatment ............................................................. 75 
6.7.1 
Prior Treatment ......................................................................... 75 
6.7.2 
Concomitant Treatment ............................................................. 76 
7. 
Discontinuation Criteria ......................................................................................... 76 
7.1 
Discontinuation of Study Treatment........................................................... 76 
7.2 
Discontinuation From the Study ................................................................ 77 
7.2.1 
Reasons for Removal From Washout Period, Run-in 
Period, or Invasive Procedures ................................................. 78 
7.2.2 
Reasons for Removal From Study ............................................. 78 
7.3 
Lost to Follow-up ....................................................................................... 78 
8. 
Study Assessments and Procedures .................................................................... 78 
8.1 
General Study Periods .............................................................................. 79 
8.1.1 
Screening, Enrollment and/or Randomization ............................ 79 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
8.1.2 
Treatment Period ....................................................................... 80 
8.1.3 
Safety Follow-up ........................................................................ 80 
8.1.4 
Long-term Follow-up .................................................................. 80 
8.1.5 
End of Study .............................................................................. 81 
8.1.6 
Continuation on AMG 510 Treatment After 
Independent Central Confirmation of Progression at 
the time of First PD ................................................................... 81 
8.1.7 
Continuation on Docetaxel Treatment After 
Independent Central Confirmation of Progression at 
the Time of First PD .................................................................. 82 
8.1.8 
Crossover .................................................................................. 83 
8.2 
Description of General Study Assessments and Procedures ..................... 85 
8.2.1 
General Assessments ............................................................... 85 
8.2.1.1 
Informed Consent .................................................... 85 
8.2.1.2 
Demographics ......................................................... 85 
8.2.1.3 
Medical History ........................................................ 85 
8.2.1.4 
Physical Examination .............................................. 86 
8.2.1.5 
Physical Measurements .......................................... 86 
8.2.1.6 
Substance Abuse History ........................................ 86 
8.2.1.7 
Performance Status................................................. 86 
8.2.2 
Efficacy Assessments ................................................................ 86 
8.2.2.1 
Disease Assessments ............................................. 86 
8.2.3 
Safety Assessments .................................................................. 91 
8.2.3.1 
Vital Signs ............................................................... 91 
8.2.3.2 
Electrocardiograms ................................................. 92 
8.2.3.3 
Vital Status .............................................................. 92 
8.2.3.4 
Other Safety ............................................................ 92 
8.2.4 
Adverse Events and Serious Adverse Events ............................ 92 
8.2.4.1 
Time Period and Frequency for Collecting 
and Reporting Safety Event Information .................. 92 
8.2.4.2 
Reporting a Safety Endpoint as a Study 
Endpoint .................................................................. 93 
8.2.4.3 
Method of Detecting Adverse Events and 
Serious Adverse Events .......................................... 94 
8.2.4.4 
Follow-up of Adverse Events and Serious 
Adverse Events ....................................................... 94 
8.2.4.5 
Regulatory Reporting Requirements for 
Serious Adverse Events .......................................... 94 
8.2.4.6 
Safety Monitoring Plan ............................................ 95 
8.2.4.7 
Pregnancy and Lactation ......................................... 95 
8.2.5 
Clinical Laboratory Assessments ............................................... 95 
8.2.6 
Pregnancy Testing..................................................................... 96 
8.2.7 
Pharmacokinetic Assessments .................................................. 96 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
8.2.7.1 
Biomarker Assessment to Determine 
Eligibility (KRAS G12C):  Tumor Tissue .................. 96 
8.2.7.2 
Central KRAS p.G12C Laboratory 
Methods Summary .................................................. 98 
 
 
 98 
 
 99 
 
 99 
8.2.8 
Medical Resource Utilization and Health Economics ............... 100 
9. 
Statistical Considerations .................................................................................... 100 
9.1 
Statistical Hypotheses ............................................................................. 100 
9.2 
Sample Size Determination ..................................................................... 103 
9.3 
Analysis Sets, Subgroups, and Covariates .............................................. 104 
9.3.1 
Analysis Sets ........................................................................... 104 
9.3.1.1 
Full Analysis Set .................................................... 104 
9.3.1.2 
Safety Analysis Set ............................................... 104 
9.3.1.3 
Per Protocol Analysis Set ...................................... 105 
9.3.2 
Covariates ............................................................................... 105 
9.3.3 
Subgroups ............................................................................... 105 
9.3.4 
Handling of Missing and Incomplete Data ................................ 106 
9.4 
Statistical Analyses ................................................................................. 107 
9.4.1 
Planned Analyses .................................................................... 107 
9.4.1.1 
Interim Analysis and Early Stopping 
Guidelines ............................................................. 107 
9.4.1.2 
Primary Analysis ................................................... 108 
9.4.1.3 
Final Analysis ........................................................ 108 
9.4.2 
Methods of Analyses ............................................................... 108 
9.4.2.1 
General Considerations ......................................... 108 
9.4.2.2 
Efficacy Analyses .................................................. 109 
9.4.2.3 
Safety Analyses .................................................... 114 
10. 
References ......................................................................................................... 116 
11. 
Appendices ......................................................................................................... 120 
11.1 
Appendix 1.  List of Abbreviations and Definitions of Terms .................... 121 
11.2 
Appendix 2.  Clinical Laboratory Tests .................................................... 125 
11.3 
Appendix 3.  Study Governance Considerations ..................................... 128 
Data Monitoring Committee ..................................................................... 128 
Blinded Independent Central Review Committee (BICR) ......................... 128 
Regulatory and Ethical Considerations .................................................... 129 
Recruitment Procedures .......................................................................... 129 
Informed Consent Process ...................................................................... 130 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
Data Protection/Subject Confidentiality ................................................... 131 
Publication Policy .................................................................................... 132 
Investigator Signatory Obligations ........................................................... 133 
Data Quality Assurance ........................................................................... 133 
Source Documents .................................................................................. 135 
Remote Source Data Review and Verification ......................................... 136 
Study and Site Closure............................................................................ 136 
Compensation ......................................................................................... 136 
11.4 
Appendix 4.  Safety Events:  Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting ..................................... 137 
Definition of Adverse Event ..................................................................... 137 
Definition of Serious Adverse Event ........................................................ 138 
Recording Adverse Events and Serious Adverse Events ........................ 139 
Evaluating Adverse Events and Serious Adverse Events ........................ 140 
Reporting of Serious Adverse Event ........................................................ 141 
11.5 
Appendix 5.  Contraceptive Guidance and Collection of 
Pregnancy and Lactation Information ...................................................... 147 
Definition of Females of Childbearing Potential ....................................... 147 
Collection of Pregnancy Information ........................................................ 149 
Collection of Lactation Information .......................................................... 150 
11.6 
Appendix 6.  Sample Storage and Destruction ........................................ 153 
11.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions 
and Follow-up Assessments and Study Treatment Rechallenge 
Guidelines ............................................................................................... 155 
Criteria for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other 
Protocol-required Therapies Due to Potential 
Hepatotoxicity.......................................................................... 155 
Criteria for Re-challenge of Amgen Investigational Product and 
Other Protocol-required Therapies After Potential 
Hepatotoxicity.......................................................................... 156 
11.8 
Appendix 8.  Response Evaluation Criteria in Solid Tumors 
Version 1.1 (RECIST v1.1) ...................................................................... 159 
11.9 
Appendix 9.  QLQ-C30 ............................................................................ 167 
11.10 Appendix 10.  EQ-5D-5L ......................................................................... 169 
11.11 Appendix 11.  QLQ-LC13 ........................................................................ 171 
11.12 Appendix 12.  PGIS ................................................................................. 172 
11.13 Appendix 13.  PGIC ................................................................................ 173 
11.14 Appendix 14.  PRO-CTCAE .................................................................... 174 
11.15 Appendix 15.  GP5 of the FACT-G .......................................................... 177 
11.16 Appendix 16.  Pain (BPI short form) ........................................................ 178 
 
List of Tables 
Table 1-1.  Schedule of Activities:  AMG 510 ................................................................. 24 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 9 of 179 
CONFIDENTIAL  
 
 
Table 1-2.  Schedule of Activities:  Docetaxel ................................................................ 31 
Table 6-1.  Study Treatments ........................................................................................ 65 
Table 6-2.  Dose Reductions for AMG 510 .................................................................... 69 
Table 6-3.  AMG 510 Dose Modification Guidelines for Hematologic and 
Non-hematologic Toxicities ..................................................................... 69 
Table 6-4.  Dose Decrements for Docetaxel .................................................................. 70 
Table 6-5.  Docetaxel Dose Modification Guidelines for Hematologic and 
Non-hematologic Toxicities ..................................................................... 71 
Table 6-6.  AMG 510 Hepatoxicity Guidelines ............................................................... 73 
Table 8-1.  Accepted Methods for Central Confirmation or Detection of  KRAS 
G12C Mutation for Enrollment ................................................................ 97 
Table 9-1:  Potential Interim and Primary Analysis of PFS and OS .............................. 108 
Table 9-2.  Censoring Rules for PFS Analyses per BICR ............................................ 111 
Table 11-1.  Analyte Listing ......................................................................................... 126 
Table 11-2.  Conditions for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other Protocol-required 
Therapies Due to Potential Hepatotoxicity ............................................ 156 
 
List of Figures 
Figure 1-1.  Study Schema ............................................................................................ 23 
Figure 9-1.  Initial Graph of Maurer-Bretz Multiple Testing Procedure for PFS, 
OS, and ORR. ...................................................................................... 102 
Figure 9-2.  Holm’s Procedure for Change From Baseline Over Time to 
Week 12 in 3 Lung Cancer Symptoms .................................................. 102 
Figure 9-3.  Holm’s Procedure for Change From Baseline Over Time to 
Week 12 on Physical Functioning and Global Health Status ................. 103 
Figure 11-1.  Sample Electronic Serious Adverse Event Contingency Report 
Form ..................................................................................................... 142 
Figure 11-2.  Pregnancy and Lactation Notification Forms ........................................... 151 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 10 of 179 
CONFIDENTIAL  
 
 
1. 
Protocol Summary 
1.1 
Synopsis 
Protocol Title:  A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, 
Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated Locally 
Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated KRAS p.G12C 
Short Protocol Title:  A Phase 3 Study to Compare AMG 510 With Docetaxel 
in NSCLC Subjects With KRAS p.G12C Mutation (CodeBreak 200)    
Study Phase:  3 
Indication:  Previously treated locally advanced and unresectable or metastatic 
non-small cell lung cancer (NSCLC) with KRAS p.G12C mutation 
Rationale 
Lung cancer is the most common type of cancer occurring in both males and females 
worldwide (WHO statistics, 2018), and the 5-year survival rate for advanced NSCLC is 
low (between 6% and 33%, depending on the stage (American Cancer Society, 2019).  
The rat sarcoma (RAS) proto-oncogene has been identified as an oncogenic driver of 
tumorigenesis in several cancers, including NSCLC.  The RAS proteins can be 
mutationally activated at codons 12, 13, or 61, leading to human cancers.  Different 
tumor types are associated with mutations in certain isoforms of RAS, with Kirsten rat 
sarcoma viral oncogene homolog (KRAS) being the most frequently mutated isoform in 
most cancers (Prior et al, 2012).  While the role of KRAS mutations in human cancers 
has been known for decades, no anti-cancer therapies specifically targeting KRAS 
mutations have been successfully developed, largely because the protein has been 
intractable for inhibition by small molecules (McCormick, 2016).  AMG 510 is a small 
molecule that specifically and irreversibly inhibits the KRAS G12C mutated protein.  
Nonclinical studies of AMG 510 have demonstrated inhibition of growth and regression 
of cells and tumors harboring KRAS p.G12C, and in clinical Study 20170543, AMG 510 
demonstrated antitumor activity in KRAS p.G12C mutated NSCLC.  These data suggest 
that inhibition of KRAS G12C may have therapeutic benefit for subjects with 
KRAS p.G12C driven cancers.  Therefore, the aim of Study 20190009 is to evaluate the 
efficacy, safety, and tolerability of AMG 510 compared to docetaxel in subjects with 
previously treated, locally advanced, and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation.   

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 11 of 179 
CONFIDENTIAL  
 
 
Objective(s)/Endpoint(s) 
 
Objectives 
Endpoints 
Primary 
 
To compare the efficacy of 
AMG 510 versus docetaxel as 
assessed by progression-free 
survival (PFS) in previously 
treated subjects with 
KRAS p.G12C mutated 
non-small cell lung cancer 
(NSCLC)  
 
PFS - defined as time from randomization until 
disease progression or death from any cause, 
whichever occurs first for all subjects.  Progression 
will be based on blinded independent central review 
(BICR) of disease response per Response Evaluation 
Criteria in Solid Tumors version 1.1 (RECIST v1.1). 
Attributes 
Primary Estimand 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Primary Endpoint 
 
PFS 
 
Summary Measures 
 
Hazard Ratio (HR) 
 
Intercurrent Events and 
Strategies 
 
Start of new anti-cancer therapy prior to PFS 
event 
 PFS is censored at the date of last evaluable 
assessment before or on start of new anti-
cancer therapy.  
Primary Estimand Description 
HR of PFS between AMG 510 and docetaxel, for subjects with previously treated locally 
advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation, before or 
on start of new anti-cancer therapy 
Key Secondary 
 
To compare the efficacy of 
AMG 510 versus docetaxel as 
assessed by:   
 
Overall Survival (OS) 
 
Objective response rate 
(ORR)  
 
Overall survival - defined as time from randomization 
until death from any cause.   
 
Objective response (complete response [CR] + partial 
response [PR]), assessed per RECIST v1.1.  
Response will be assessed by BICR.  Complete 
response and PR require confirmatory repeat 
radiologic assessment at no less than 4 weeks after 
the original response.  The normal subsequent 
assessment is acceptable to confirm response. 
 
To compare patient-reported 
outcomes (PRO) as assessed 
by:  European Organization 
for Research and Treatment 
of Cancer Quality-of-life 
Questionnaire Core 13 
(EORTC QLQ-LC13) and 
European Organization for 
Research and Treatment of 
Cancer Quality-of-life 
 
Change from baseline (cycle 1 day 1) over time to 
week 12 in disease related symptoms of:  
o 
Dyspnea as measured by a 4-item 
dyspnea domain from QLQ-C30 and 
QLQ-LC13 
 
Cough as measured by QLQ-LC13 
 
Chest Pain as measured by QLQ-LC13  
 
Change from baseline over time to week 12 in 
 
Physical functioning as measured by QLQ-C30 

Product:  AMG 510 
Protocol Number:  20190009  
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CONFIDENTIAL  
 
 
Questionnaire Core 30 
(EORTC QLQ-C30) 
 
Global health status as measured by QLQ-C30 
Attributes 
Secondary Estimand - OS 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Key Secondary Endpoint 
 
OS 
 
Summary Measures 
 
Hazard Ratio (HR) 
 
Intercurrent Events and 
Strategies 
 
Start of new anti-cancer therapy  
 OS will be estimated regardless of subsequent 
anti-cancer therapy. 
 
Crossover from control group to treatment group  
 OS will be estimated regardless of crossover. 
Secondary Estimand Description - OS 
HR of OS between AMG 510 and docetaxel, for subjects with previously treated locally 
advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation, regardless 
of subsequent anti-cancer therapy and/or crossover. 
Attributes 
Secondary Estimand – Objective Response 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Key Secondary Endpoint 
 
Objective Response 
 
Summary Measures 
 
Odds Ratio 
 
Intercurrent Events and 
Strategies 
 
Discontinuation of treatment prior to achieving an 
objective response (PR or CR) 
 Subjects will be considered as non-responders. 
Secondary Estimand Description – Objective Response 
Odds ratio of objective response between AMG 510 and docetaxel, for subjects with 
previously treated locally advanced and unresectable or metastatic NSCLC with KRAS 
p.G12C mutation.  Subjects who discontinued treatment prior to achieving an objective 
response are considered as non-responders.  
Attributes 
Secondary Estimand - PRO 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Key Secondary Endpoint 
 
PRO 
 
Summary Measures 
 
Change from baseline to Week 12 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
 
Intercurrent Events and 
Strategies 
 
Start of new anti-cancer therapy including 
crossover before Week 12 
 PRO measurements before or on start of new 
anti-cancer therapy including crossover will be 
used to estimate treatment effect. 
Secondary Estimand Description - PRO 
Change from baseline to Week 12 in PRO endpoints between AMG 510 and docetaxel, for 
subjects with previously treated locally advanced and unresectable or metastatic NSCLC 
with KRAS p.G12C mutation.  PRO measurements before or on start of new anti-cancer 
therapy including crossover will be used to estimate treatment effect. 
Secondary 
 
To compare efficacy of 
AMG 510 versus docetaxel as 
assessed by:  duration of 
response (DOR), time to 
response (TTR), and disease 
control rate (DCR) 
 
Duration of response - defined as time from first 
evidence of PR or CR to disease progression or death 
due to any cause, whichever occurs first.  Progression 
will be based on an BICR assessment of disease 
response per RECIST v1.1. 
 
Time to response - defined as time from 
randomization to first evidence of PR or CR. 
 
Disease control rate - defined as rate of confirmed 
objective response (CR or PR) + stable disease per 
RECIST v1.1 of at least 6 weeks measured 
 
To compare the safety and 
tolerability of AMG 510 versus 
docetaxel  
 
Subject incidence of treatment-emergent adverse 
events, treatment-related adverse events, changes in 
vital signs, and clinical laboratory tests. 
 
To compare the effect of 
treatment with AMG 510 on 
other treatment and disease 
related symptoms, and health 
related quality of life relative 
to docetaxel  
 
Change from baseline over time to week 12 for the 
remaining subscales for QLQ-LC13 and QLQ-C30 
 
Time to deterioration for the subscales for QLQ-LC13 
and QLQ-C30 
 
Summary scores at each assessment and changes 
from baseline of visual analogue scale (VAS) scores 
as measured by EuroQol-5 Dimension (EQ5D5L)  
 
To characterize the 
pharmacokinetics (PK) of 
AMG 510 and its major 
metabolites 
 
Pharmacokinetic (PK) parameters of AMG 510 
including, but not limited to, maximum plasma 
concentration (Cmax), area under the plasma 
concentration-time curve (AUC) on Days 1 and 8, and 
pre-dose (trough) concentrations through cycle 4 
 
Overall Design 
This is a phase 3, multicenter, randomized, open label, active-controlled, study to 
evaluate the efficacy, safety, and tolerability of AMG 510 versus docetaxel in subjects 
with previously treated locally advanced and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation.  The study will be conducted at approximately 290 sites 
globally.  The study will consist of a screening period, a treatment period, a safety 
follow-up (SFU) period, and long-term follow-up period.  See Section 8.1.6 and 
Section 8.1.7 for AMG 510 and docetaxel treatment beyond radiologic progression.  See 
Section 8.1.8 for crossover.  Approximately 330 previously treated subjects with locally 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 14 of 179 
CONFIDENTIAL  
 
 
advanced and unresectable or metastatic NSCLC with centrally confirmed 
KRAS p.G12C mutation will be enrolled and randomized 1:1 to receive either AMG 510 
or docetaxel. 
Subjects will be stratified by number of prior lines of therapy in advanced disease 
(1 versus 2 versus > 2), race (Asian versus non-Asian), and history of central nervous 
system (CNS) involvement (present or absent).   
Cycle 1 day 1 will be defined as the first day subject receives study medication.  A cycle 
is 21 days in length  3 days, unless a delay is medically necessary.  A  3-day window 
is allowed for protocol required assessments, unless otherwise specified.  Tumor 
assessment will be conducted (by magnetic resonance imaging [MRI] and/or contrast 
enhanced computerized tomography [CT]) during screening (within 28 days of day 1); 
every 6 weeks from cycle 1 day 1; (± 7 days) (at weeks 7, 13, 19, 25, 31, 37, 43, and 
49), and then at 9 week intervals (± 7 days) thereafter until independent central 
confirmation of progression, start of another anti-cancer therapy, withdrawal of consent, 
lost to follow up, or death, whichever occurs earliest.  Subjects’ scans will undergo 
independent central confirmation of progression (COP) at the time of first progressive 
disease (PD).  Subjects that undergo treatment beyond progression or crossover, from 
docetaxel to AMG 510, will continue to receive scans after confirmation of first PD.  
Further details with regards to imaging assessments post treatment period are listed in 
Section 8.1.4.  
Once subjects on the docetaxel arm are determined to have radiological progression 
according to RECIST v1.1 by the investigator and progressive disease undergoes 
independent central confirmation, they will be given the opportunity to crossover and 
receive AMG 510.  Alternatively, should an early efficacy of the study be noted by the 
DMC, crossover will be considered for all subjects who randomized into the docetaxel 
arm (so that they will be able to immediately receive AMG 510).  All subjects remaining 
on study will be followed for survival, as specified in the Schedule of Activities 
(Section 1.3), until the pre-specified OS events are reached, regardless of the OS 
analysis result at the PFS primary analysis.  
Tumor assessment and response will be confirmed by BICR who will evaluate disease 
progressions and responses without the knowledge of randomization assignments, in 
accordance with the RECIST v1.1.   

Product:  AMG 510 
Protocol Number:  20190009  
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Subjects will continue treatment until independent central confirmation of progression, 
intolerance of treatment leading to treatment discontinuation, initiation of another 
anticancer therapy or withdrawal of consent.  Subjects that consent to treatment beyond 
progression or consent to crossover, from docetaxel to AMG 510, will continue to receive 
investigational product after independent central confirmation of progression at the time 
of first progressive disease (PD).  
In select cases, subjects may continue on treatment following radiologic progression if 
they are continuing to demonstrate clinical benefit (see Section 8.1.6 and 8.1.7).  
In all subjects, after end of investigational product, information regarding date of 
progression, the type and duration of subsequent therapies, response to subsequent 
therapy, date of progression on subsequent therapy, and survival data will be collected.  
Subjects who discontinue treatment prior to RECIST v1.1 disease progression (eg, due 
to unacceptable toxicity) will also continue to be followed with tumor assessments until 
independent central confirmation of disease progression, withdrawal of consent, or start 
of another anti-cancer therapy, then followed for subsequent anti-cancer therapy and 
survival. 
The assessments to be conducted in this study are described below and will be carried 
out at the timepoints designated in the Schedule of Activities (SOA) (Table 1-1 and 
Table 1-2). 
 
Central confirmation of KRAS p.G12C mutation status for all enrolling subjects. 
 
Disease progression will be assessed using RECIST v1.1.   
 
Primary efficacy objective will be assessed by BICR.  
 
Expedited independent confirmation of progression (COP), at time of first progressive 
disease (PD), will be performed by a single radiologist separate from the central 
radiologist group reading the images for (as described in Section 8.2.2.1.2 ) prior to 
moving forward with treatment beyond progression or crossover.  
 
Safety will be monitored by assessing serious and non-serious adverse events, 
safety laboratory tests, vital signs and electrocardiograms (ECGs).  Adverse events 
will be graded according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0). 
 
Laboratory safety tests will include hematology, blood chemistry, cholesterol, 
coagulation, urinalysis, and thyroid function test.  Vital sign assessments will include 
oxygen saturation, respiratory rate, blood pressure, heart rate, and body 
temperature; additional vital signs will be collected only if clinically warranted.  The 
urine studies may be performed at a local laboratory and/or by the central laboratory, 
depending on the availability of the testing facility. 
 
PK characterization will be conducted using sparse sampling and population PK 
modeling approach. 

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Protocol Number:  20190009  
Date:  06 January 2022 
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 
PRO/quality of life (QOL) assessments will be assessed using the PRO instruments 
EORTC QLQ-C30, EORTC QLQ-LC13, EQ-5D-5L, and PRO-CTCAE plus a single 
item about symptom bother (GP5 of the Functional Assessment of Cancer Therapy 
Tool General form [FACT-G]).  Patient pain and patient impression of change and 
severity will be assessed using the brief pain inventory (BPI), patient global 
impression of change (PGIC) and patient global impression of severity (PGIS) 
questionnaires.  Patient-reported outcomes scores will be determined for all 
subjects at baseline (cycle 1 day 1) and at timepoints designated in the SOA and 
will be compared across treatment groups. 
 
Further tissue assessments at the time of independent central confirmation of 
progression 
 
If a subject is not continuing AMG 510 upon radiologic progression, they will be 
encouraged to enroll in an optional sub-study assessing exploratory biomarkers 
via an optional tumor biopsy (excisional, core needle, or fine needle aspirates) 
only if biomarker research is allowed according to local regulations and agreed 
by local EC/IRB 
 
If a subject plans to continue on AMG 510 treatment beyond radiologic 
progression, the subject must be willing to undergo biopsy, if clinically feasible or 
advisable, (excisional, core needle, or fine needle aspirates) of one of the new or 
progressing lesions (see Section 8.1.6 for additional criteria) only if biomarker 
research is allowed according to local regulations and agreed by local EC/IRB 
An independent (external to Amgen) data monitoring committee (DMC) will review safety 
and efficacy data as per DMC charter.  Interim safety analysis will be conducted after 
approximately 50, 100, and 200 subjects have been enrolled and have had the 
opportunity to complete at least 6 weeks of study treatment, and then at approximately 
6-month intervals until the primary analysis (PA) of PFS.  Interim analysis (IA) data will 
be reviewed by an independent (external to Amgen) DMC.  There will be 2 planned PFS 
efficacy analyses.  The PA of PFS will occur when approximately 230 PFS events have 
been observed.  The PFS PA may be delayed to ensure that the enrollment is finished 
and the delayed PA will be triggered when the last randomized subject has had the 
opportunity to have at least 6 weeks of follow up.  An IA of PFS for superiority is planned 
when approximately 70% (160 events) of the total PFS events have been observed from 
both arms, or when the enrollment is finished and the last randomized subject have had 
the opportunity to have 6 weeks of follow up, whichever occurs later.   
Early efficacy at the proposed PFS interim analysis will be claimed if the observed PFS 
difference meets the pre-specified statistical significance as well as being considered 
clinically meaningful.  More details will be included in the DMC charter.   

Product:  AMG 510 
Protocol Number:  20190009  
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If PFS achieves statistical significance at the interim analysis, an administrative interim 
summary for OS will be performed.  Otherwise, the OS will be assessed for superiority of 
AMG 510 over docetaxel at either the time of PFS primary analysis or after 175 OS 
events have been observed, whichever is later.  The OS primary analysis will occur 
when at least 198 OS events (~60% maturity) have been observed, which is expected to 
be at approximately 3 months after PFS primary analysis.  The analysis of ORR will be 
done at the time when PFS is claimed statistically significant and the last randomized 
subject has had the opportunity to have at least 12 weeks of follow up.  The final 
analysis will be performed after the last subject completes long-term follow-up (LTFU).  
Number of Subjects 
Approximately 330 subjects with locally advanced unresectable or metastatic NSCLC 
with centrally confirmed KRAS p.G12C mutation will be enrolled in the study, with 
approximately 165 subjects in each of the 2 treatment groups. 
Summary of Subject Eligibility Criteria 
Eligible subjects will have histologically or pathologically documented, locally-advanced 
and unresectable or metastatic NSCLC with KRAS p.G12C mutation (and no other 
known oncogenic driver mutation for which there is an approved targeted therapy 
(according to local standard of care or guidelines), and will have failed at least 1 prior 
systemic therapy.  For a full list of eligibility criteria, please refer to Section 5.1 to 
Section 5.2. 
Treatments 
Treatment begins on day 1 of cycle 1 when the first dose of investigational product is 
administered to a subject.  AMG 510 will be dispensed at 960 mg once daily (QD) orally 
(PO) administered to subjects at the beginning of each cycle.  Subjects are required to 
bring bottle(s) of AMG 510 as per guidance in the Investigational Product Instruction 
Manual, and return the remaining pills when they come off treatment.  For the first 
2 cycles, subjects will be instructed to take their AMG 510 dose in the clinic after all 
pre-dose assessments have been performed during clinic visit days.  For non-clinic 
days, subjects will be instructed to take their AMG 510 dose at home.  Docetaxel at 
75 mg/m2 will be administered intravenously over 1 hour (additional administration time 
allowed as per local guidelines) every 3 weeks  
(Taxotere® Summary of Product Characteristics [SmPC]; Taxotere® United States 
Prescribing Information [USPI]). 

Product:  AMG 510 
Protocol Number:  20190009  
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Procedures 
Tumor evaluation is to be performed by contrast-enhanced CT of the chest and one of 
the following:  contrast-enhanced CT abdomen with cuts through to the pubic symphysis, 
contrast-enhanced CT abdomen and pelvis, contrast-enhanced MRI abdomen and 
pelvis, or contrast-enhanced MRI abdomen with cuts through to the pubic symphysis.  
Contrast-enhanced images are strongly preferred.  If contrast enhanced CT imaging is 
contraindicated (allergy, medical contraindication, etc), radiological imaging to be 
performed as indicated by site imaging manual will be performed during screening 
(within 28 days of day 1); every 6 weeks after cycle 1 day 1 ( 7 days) at week 7, 13, 19, 
25, 31, 37, 43, and 49  7 days, and then at 9 week intervals thereafter ( 7 days) until 
end of investigational product.  Investigational product is either AMG 510, or docetaxel, 
depending on the treatment group to which the subject is randomized.  If investigational 
product was ended before radiologically documented and independently confirmed 
progressive disease, radiologic imaging and tumor assessment will continue to be 
performed until independently confirmed disease progression, start of new anticancer 
treatment, death, withdrawal of consent or until end of study, whichever occurs first.  
Baseline brain imaging by contrast enhanced MRI will be obtained for all subjects at 
screening.  For subjects with known brain metastases, brain MRI should also be 
obtained at every subsequent imaging assessment.  Computerized tomography scan 
with contrast of the brain may be used in lieu of MRI for those subjects who cannot 
undergo an MRI.  Non-contrast only CT of the brain is not acceptable.  Patient-reported 
outcomes questionnaires including the EQ-5D-5L, QLQ-C30, the disease specific 
module QLQ-LC13, and PRO-CTCAE, plus a single item about symptom bother (GP5 of 
the FACT-G) will be administered to all subjects, and collected as indicated in the 
Schedule of Activities (Section 1.3 and Table 1-2).  For a full list of study procedures, 
including safety assessments and the timing of each procedure, please refer to the study 
assessments and procedures in Section 8.2 and the Schedule of Activities in Section 1.3 
and Table 1-2.  
Statistical Considerations 
The efficacy analyses of primary endpoint and key secondary endpoints to compare 
AMG 510 vs docetaxel will be conducted on the full analysis set (intention-to-treat [ITT] 
population).  The PA of PFS and key secondary endpoint of ORR will be based on BICR 
assessed outcomes.  

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Protocol Number:  20190009  
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The hypotheses of the primary efficacy endpoint and key secondary efficacy endpoints 
will be tested using the graphical multiple testing procedure (Maurer and Bretz, 2013) to 
control the study-level overall type I error rate (α) below 1-sided 0.025 levels.  A 
hypothesis can be re-tested repeatedly with a different nominal level that is propagated 
from rejecting other hypothesis test(s).  
Starting with PFS, if the hypothesis of PFS is rejected, ORR will be tested using 1-sided 
α/5 (0.005) level.  With the rejection of ORR hypothesis, OS will be tested using 1-sided 
full α (0.025) level.  If ORR hypothesis is failed to be rejected, OS will be tested using 
1-sided 0.001 level if at PFS IA, otherwise using 4 α/5 (0.02) level.  With the rejection of 
OS hypothesis, ORR can be retested using 1-sided full α (0.025) level.   
If all 3 hypotheses of PFS, OS, ORR are rejected, the next 3 endpoints of change from 
baseline over time to week 12 in 3 lung cancer symptoms will be tested using Holm’s 
procedure, including change from baseline over time to week 12 for the symptom of 
dyspnea as measured by a 4 item dyspnea domain from QLQ-C30 and  QLQ-LC13 
(dyspnea), change from baseline over time to week 12 for the symptom of cough as 
measured by QLQ-LC13 (cough), and change in baseline over time to week 12 for the 
symptom of chest pain as measured by QLQ-LC13 (pain).  Hypotheses are rejected 
sequentially based on the smallest p-value.  If all 6 hypotheses listed above are rejected, 
the next two PRO endpoints will be tested using the Holm’s procedure, including change 
from baseline over time to week 12 in physical functioning as measured by QLQ-C30 
(physical), change from baseline over time to week 12 in global health status as 
measured by QLQ-C30 (global health status).  Hypotheses are rejected sequentially 
based on the smallest p-value.   
As designed, the trial will not be terminated at PFS analyses and subjects will continue 
to be followed for OS data until the targeted number of events are reached, regardless of 
the OS analysis result at the PFS primary analysis, to enable OS analyses and a robust 
description of the totality of the data. 
Sample size:  The planned enrollment is approximately 330 subjects with locally 
advanced unresectable or metastatic NSCLC with centrally confirmed KRAS p.G12C 
mutation.  A total of 230 PFS events are required to provide at least 90% power to 
demonstrate superiority at an alternative Hazard Ratio (HR) of 0.65 for the AMG 510 
arm versus control arm with 1-sided overall type I error of 0.025, in a group sequential 
design setting with 1 potential IA for superiority and 1 PA.  The PA of PFS will occur 
when approximately 230 PFS events have been observed.  With 230 PFS events, the 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
study will have ~90% power to show a statistically significant PFS at the 2.5% 1-sided 
significance level if the true treatment effect hazard ratio (HR) is assumed 0.65 for the 
AMG 510 arm versus the control arm.  The sample size is chosen to have 70% maturity 
realizing PFS events, which is approximately 330 subjects with 1:1 randomization ratio 
into the AMG 510 arm and the docetaxel arm.  The PFS PA may be delayed to ensure 
that the enrollment is finished and the delayed PA will be triggered when the last 
randomized subject has had the opportunity to have at least 6 weeks of follow up.   
An IA is planned when approximately 70% (160) of the target PFS events have been 
observed from both arms, or when the enrollment is finished and the last randomized 
subject has had the opportunity to have 6 weeks of follow up, whichever occurs later.  
The monitoring boundary for early stopping for efficacy will be based on an 
O’Brien-Fleming type alpha spending function for multiplicity adjustment.  The actual 
information fraction will be calculated based on the number of observed events at the 
time of the analysis.  Under exponential distribution, the minimum detectable difference 
for success in this design is an HR of 0.68 between AMG 510 arm and the docetaxel 
arm with 160 PFS events, 70% of the target PFS events, and an HR of 0.769 at the PA 
with 230 PFS events.  Assuming an enrollment rate of 40 subjects per month after a 
3-month ramp-up period, with a total sample size of 330, it is estimated that 
approximately 19 months will be required to reach 230 PFS events, and 13 months will 
be required to reach 70% (160) of the target PFS events.  This estimation is based on a 
median PFS of 5 months for the control arm (Charpidou et al, 2019) and 7.7 months for 
the AMG 510 arm, and a 10% dropout rate. 
If PFS achieves statistical significance at the interim analysis, an administrative interim 
summary for OS will be performed with approximately 107 OS events (~32% 
maturity) observed. A nominal alpha of 0.01% (negligible impact on overall type I error 
rate) will be spent on this OS interim summary.  Otherwise, the OS will be assessed for 
superiority of AMG 510 over docetaxel at either the time of PFS primary analysis or after 
175 OS events (~53% maturity) have been observed, whichever is later.  Assuming the 
actual crossover rate of approximately 30% at the time of PFS primary analysis for 
subjects on the control arm who have disease progression, then with 175 OS events, the 
study has ~96% probability to observe a HR < 1 when the true OS HR is 0.75. 
The OS primary analysis will occur when at least 198 OS events (~60% maturity) have 
been observed, which is expected to be at approximately 3 months after PFS primary 
analysis, with the same enrollment assumptions.  The estimation is based on a median 

Product:  AMG 510 
Protocol Number:  20190009  
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CONFIDENTIAL  
 
 
OS of 9 months for the control arm and 12 months for the AMG 510 arm (OS 
HR = 0.75).  The multiplicity will be adjusted as necessary based on O’Brien-Fleming 
type alpha spending function.   
Analysis Method:  The distribution of PFS and OS will be estimated using the 
Kaplan-Meier method.  The HR and its 95% CI will be estimated using a Cox 
proportional hazards model stratified by the randomization stratification factors.  The 
inferential comparison will be made using a stratified log rank test. Objective response 
rate will be calculated and the associated 95% CI will be estimated using the 
Clopper-Pearson method.  The inferential comparison for ORR will be made using the 
Cochran-Mantel-Haenszel chi-square test controlling for the randomization stratification 
factors.  The inferential comparison for the endpoints of change from baseline over time 
to week 12 in symptoms of dyspnea as measured by a 4 item dyspnea domain from 
QLQ-C30 and QLQ-LC13, change from baseline over time to week 12 in physical 
functioning, global health status as measured by QLQ-C30 will be made through a mixed 
model for repeated measurement (MMRM).  The inferential comparison for the 
endpoints of change from baseline over time to week 12 in symptoms of cough and 
chest pain as measured by a single question from QLQ-LC13 will be made through 
generalized estimating equations (GEE) method for cumulative logits model  
(Lipsitz et al, 1994).  Multiple imputation approach with non-ignorable missing pattern will 
be explored as the sensitivity analysis for all the key secondary PRO endpoints. 
Subgroup Analyses:  In addition to the stratification factors for randomization, number 
of prior lines of therapy in advanced disease (1 versus 2 versus > 2), race (Asian versus 
non-Asian), history of CNS involvement (yes versus no), primary and selected 
secondary endpoints will be examined in the following subgroups to investigate the 
consistency of treatment effects: 
 
region (North America and Europe vs rest of world)  
 
best response on prior therapy primary refractory (progression on first scan), 
suboptimal response (stable disease), recurrent (initial response with subsequent 
growth) 
 
age (< 65 vs  65) 
 
sex (male vs female) 
 
race (white, black, Asian, other) 
 
Eastern Cooperative Oncology Group (ECOG) status (0 vs 1) 
 
liver metastasis at baseline (yes vs no) 
 
stage (locally advanced and unresectable versus metastatic) 

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Protocol Number:  20190009  
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 
smoking history (yes vs no) 
 
histology (squamous vs non-squamous) 
 
presence of specific co-mutation at baseline (yes vs no).  Specific co-mutations to be 
specified in SAP. 
 
brain metastasis at baseline (yes vs no) 
 
bone metastasis at baseline (yes vs no) 
 
PD-L1 protein expression (< 1% vs ≥ 1%, and < 50% vs ≥ 50%)  
 
STK11 mutation   
 
KEAP1 mutation  
In the event that there are insufficient number of subjects in the subgroup (ie, less than 
10% of the whole population), relevant subgroups may be combined.  For a full 
description of statistical analysis methods, please refer to Section 9. 
Statistical Hypotheses 
The hypotheses of the primary efficacy endpoint and key secondary efficacy endpoints 
will be tested using the following graphical multiple testing procedure  
(Maurer and Bretz, 2013) to control the study-level overall type I error rate below 1-sided 
0.025 levels, as discussed above. 
Sponsor Name:  Amgen Inc. 

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 23 of 179 
CONFIDENTIAL  
 
 
1.2 
Study Schema 
Figure 1-1.  Study Schema 
 
Randomization (1:1)
Screening (28 days)
21-day cycles of
Docetaxel 75 mg/m2 Q3W (n = 165)  
21-day cycles of
AMG 510 960 mg QD (n = 165)
Safety Follow-upb
30 days
Long-term Follow-up Periodc
(12 weeks after SFU visit 
for up to 5 years)
EOS
Stratified by: 
• number of prior lines of therapy (1 versus 2 versus > 2),
• history of CNS involvement (yes vs no)
• race (Asian vs non-Asian)
Open-label Treatment Period
End of Investigational Producta
Continued Treatment Beyond 
Radiographic Progression *
Continued Treatment Beyond 
Radiographic Progression *
 
BID = twice daily; CNS = central nervous system; EOS = End of Study; LTFU = long term follow up; PI = Principal Investigator; QD = once a day; Q3W 
= every 3 weeks; RECIST = Response Evaluation Criteria in Solid Tumors; SFU = safety follow up 
a Treatment with investigational product continues until independent central confirmation of progression, intolerance of treatment, initiation of another 
anticancer therapy, withdrawal of consent, or death.  Subjects that consent to treatment beyond progression or consent to crossover, from docetaxel 
to AMG 510, will continue to receive investigational product after independent central confirmation of progression at the time of first progressive 
disease (PD).  
b Upon permanent discontinuation from the study treatment for any reason, a safety follow-up visit will be performed 30 days ( 7 days) after the end of 
the last dosing interval of investigational product.  
c Details with regards to imaging assessments post treatment period are listed in Section 8.1.4.   
* See Section 8.1.6 and 8.1.7 (respectively) for details on AMG 510 and docetaxel treatment beyond radiograph progression.  
Note:  See Section 8.1.8 for details on crossover from docetaxel to AMG 510.  

Product:  AMG 510  
Protocol Number:  20190009  
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1.3 
Schedule of Activities 
Table 1-1.  Schedule of Activities:  AMG 510 
 
Screening 
Treatment Cycle 
SFUb LTFUc 
Notes 
Cycle  
(1 Cycle is 
21 Days 
 3 days) 
 
1 
2 to 4 
5+ 
Day 
-28 
to 1 
1a 
5 
8 
1 
5 
1 
Hours (Relative 
to Dosing) 
 
Pre 0 0.5 1 
2 
4 NA Pre 
0 
0.5 
1 
2 
4 
Pre 
NA 
Pre 
GENERAL & SAFETY 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other anticancer 
therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
Physical exam 
X  
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
Physical 
measurements 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
Height collected at screening only.  Weight 
collected every clinic visit. 
Substance abuse 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECOG 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
Vital signs 
including oxygen 
saturation 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
ECG 
X 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
(X) 
 
 
X 
 
See Section 8.2.3.2.  ECGs must be performed 
at screening, C1D1 (predose and 1-hour post 
dose), C2D1 predose, and at safety follow-up.  
Screening ECG:  standardized method in 
triplicate.  All other ECGs: standardized method 
– single copy 

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Protocol Number:  20190009  
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Screening 
Treatment Cycle 
SFUb LTFUc 
Notes 
Cycle  
(1 Cycle is 
21 Days 
 3 days) 
 
1 
2 to 4 
5+ 
Day 
-28 
to 1 
1a 
5 
8 
1 
5 
1 
Hours (Relative 
to Dosing) 
 
Pre 0 0.5 1 
2 
4 NA Pre 
0 
0.5 
1 
2 
4 
Pre 
NA 
Pre 
Vital Assessments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
In addition to survival, LTFU period will collect 
data on the subjects’ health condition, disease 
status, and subsequent anticancer treatment. 
Concomitant 
medications 
X ←============================================================→ 
 
Concomitant therapy data to be collected should 
include supplemental oxygen volume usage per 
day. 
Adverse events 
 
←============================================================→ 
 
 
Serious adverse 
eventsd 
←======================================================================→  
LABORATORY 
Chemistry 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
Laboratory Assessments may be performed 
within ± 3 days before day 1 of each cycle.  The 
urine studies may be performed at a local 
laboratory and/or by the central laboratory, 
depending on the availability of the testing 
facility. 
Hematology 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Urinalysis 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
 
X 
 
Serum or urine 
pregnancy test  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
Only for females of childbearing potential.  
Pregnancy test must be within 3 days before 
day 1 of each cycle. 
Hepatitis B and 
Hepatitis C testing    X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Thyroid function 
tests 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
Thyroid function testing at screening, pre-dose 
on day 1 of each cycle (except cycle 1), at the 
end of treatment, and at safety follow-up.  They 
should also be obtained if the subject displays 
clinical signs or symptoms concerning for thyroid 
dysfunction. 

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Protocol Number:  20190009  
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CONFIDENTIAL  
 
 
 
Screening 
Treatment Cycle 
SFUb LTFUc 
Notes 
Cycle  
(1 Cycle is 
21 Days 
 3 days) 
 
1 
2 to 4 
5+ 
Day 
-28 
to 1 
1a 
5 
8 
1 
5 
1 
Hours (Relative 
to Dosing) 
 
Pre 0 0.5 1 
2 
4 NA Pre 
0 
0.5 
1 
2 
4 
Pre 
NA 
Pre 
Cholesterol and 
Triglycerides 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
(X) 
X 
 
Cholesterol and triglyceride levels on pre-dose 
on day 1 of every other cycle (ie, cycle 1, 3, 5, 7, 
etc). 
DOSING 
AMG 510e 
 
 
←===================================================→ 
 
 
 
AMG 510 is to be administered during the clinic 
visit on Day 1 and Day 8 of the first cycle, Day 1 
of the second cycle, and outside of the clinic on 
the other days of the cycle and during 
subsequent cycles.  Every effort should be 
made to administer IP at the same dosing time; 
in the event not possible, AMG 510 should not 
be taken 2 hours before the dosing time.  
AMG 510 dose should not be taken 6 hours 
after the dosing time (based on the previous 
day’s dose).  Do not take 2 doses at the same 
time to make up for the missed dose. 
 
AMG 510 will be administered daily on a 
repeated basis with no planned off treatment 
days until independent central confirmation of 
progression, intolerance to treatment 
necessitating treatment discontinuation, need for 
other anti-cancer therapy, withdrawal of 
consent, or death.  
**Please refer to footnote “e” for further dosing 
details.  

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 27 of 179 
CONFIDENTIAL  
 
 
 
Screening 
Treatment Cycle 
SFUb LTFUc 
Notes 
Cycle  
(1 Cycle is 
21 Days 
 3 days) 
 
1 
2 to 4 
5+ 
Day 
-28 
to 1 
1a 
5 
8 
1 
5 
1 
Hours (Relative 
to Dosing) 
 
Pre 0 0.5 1 
2 
4 NA Pre 
0 
0.5 
1 
2 
4 
Pre 
NA 
Pre 
Dosing diary 
 
 
←===================================================→  
 
A dosing diary will be provided for subjects to 
record their adherence to the oral medication 
TUMOR ASSESSMENTS 
CT/MRIf 
X 
 
Imaging every 6 weeks from cycle 1 day 1 ( 7 days) (at weeks 7, 13, 19, 25, 31, 
37, 43, and 49), and then at 9-week intervals ( 7 days) thereafter 
Contrast enhanced CT scan or MRI of the brain 
is required for all subjects at screening 
 
For subjects with brain metastases or history of 
brain metastases, contrast enhanced brain MRI 
(contrast enhanced CT scan if unable to have 
MRI) at screening and at each tumor evaluation 
is required. 
 
**Please refer to footnote “f” for further tumor 
assessment details. 
PK ASSESSMENT 
AMG 510 PK 
 
X 
 
X 
X 
X X 
 
X 
 
X 
X 
X 
X 
X 
 
 
 
 
PK blood samples should be collected within a 
10% window of the nominal time point (see hour 
post dose column ie, 0.5 hour 3 min, 1 hour 
6 min, 2 hours 12 min, 4 hours 24 min).  
Day 8 PK is to be collected 1 day.

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 28 of 179 
CONFIDENTIAL  
 
 
 
Screening 
Treatment Cycle 
SFUb LTFUc 
Notes 
Cycle  
(1 Cycle is 
21 Days 
 3 days) 
 
1 
2 to 4 
5+ 
Day 
-28 
to 1 
1a 
5 
8 
1 
5 
1 
Hours (Relative 
to Dosing) 
 
Pre 0 0.5 1 
2 
4 NA Pre 
0 
0.5 
1 
2 
4 
Pre 
NA 
Pre 

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 29 of 179 
CONFIDENTIAL  
 
 
 
Screening 
Treatment Cycle 
SFUb LTFUc 
Notes 
Cycle  
(1 Cycle is 
21 Days 
 3 days) 
 
1 
2 to 4 
5+ 
Day 
-28 
to 1 
1a 
5 
8 
1 
5 
1 
Hours (Relative 
to Dosing) 
 
Pre 0 0.5 1 
2 
4 NA Pre 
0 
0.5 
1 
2 
4 
Pre 
NA 
Pre 
TREATMENT AND DISEASE RELATED SYMPTOMS AND HRQOL 
 
PRO/QOL 
assessments:  
FACT-G GP5, and 
PRO-CTCAE  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
  
Pain assessment 
(BPI) 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
Pain will be assessed at screening, on day 1 of 
every cycle and at the SFU by using the brief 
pain inventory (BPI) scale. 
PRO/QOL 
assessments:  
QLQ-C30 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
PRO/QOL 
assessments:  
QLQ-LC13,  
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
X 
X 
 
 
PRO/QOL 
assessments:  
PGIC  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
(X) 
 
 
PGIC will be collected in the clinic on day 1 of 
cycles 3 and cycle 5 (no collection needed at 
screening or cycle 1 for PGIC). 
PRO/QOL 
assessments:  
PGIS 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
(X) 
 
(X) 
 
 
PGIS will be collected in the clinic at screening 
and day 1 of cycles 1, 3, and 5.  
PRO/QOL 
assessments:  
EQ-5D-5L  
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
X 
(X) 
X 
X 
X 
The EQ-5D-5L questionnaire will be completed 
at screening, in the clinic on clinic visit days, 
including SFU, and at home (data collected by 
phone) for the scheduled non-clinic visit days 
(day 5 of cycles 1, 2 and 3).  EQ-5D-5L will also 
be collected during LTFU. 

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 30 of 179 
CONFIDENTIAL  
 
 
CxDx = cycle x day x; CT = computerized tomography; CTCAE = Common Terminology Criteria for Adverse Events; ctDNA = circulating tumor DNA;  
EC = Ethics Committee; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EQ-5D-5L = EuroQol-5 Dimension; FACT-G = Functional 
Assessment of Cancer Therapy Tool General form; FFPE = formalin fixed, paraffin embedded; HRQOL = health-related quality of life; IRB = Institutional Review 
Board; KRAS = Kirsten rat sarcoma viral oncogene homolog; LTFU = long-term follow-up; MRI = magnetic resonance imaging; NA = not applicable; PD = progressive 
disease; PGIC = patient global impression of change; PGIS = patient global impression of severity; PI = Principal Investigator; PK = pharmacokinetic; 
PRO = patient-reported outcome; QLQ-LC13 = Quality-of-life Questionnaire Core 13; QLQ-C30 = Quality-of-life Questionnaire Core 30; QOL = quality of life; 
RECIST = Response Evaluation Criteria in Solid Tumors; SFU = safety follow-up; (X) = parentheses indicate that the particular test is situational at that time point, as 
specified in the respective notes 
a Randomisation can take place up to 48 hours before first dose/C1D1.   
b SFU will be performed 30 days ( 7 days) after the last dose of investigational product.  Subjects who reach PD have a LTFU visit 12 weeks after SFU. 
c LTFU will be 5 years after last subject enrolled, or until withdrawal of consent, loss to follow-up, or subject death, whichever occurs first. Vital status and subsequent 
treatment for NSCLC will be recorded after the SFU period during the LTFU. 
d Serious adverse events observed by the investigator or reported by the subject that occur after the safety follow-up visit through the end of the long-term follow up 
period should be reported if there is a reasonable possibility that the event may have been caused by investigational product.   
e Below is applicable to AMG 510 dosing: 
 Subjects that consent to treatment beyond progression or consent to crossover, from docetaxel to AMG 510, will continue to receive investigational product after 
independent central confirmation of progression at the time of first progressive disease (PD). 
 Progressive disease must undergo independent central confirmation prior to crossover 
 See Section 8.1.6 for treatment beyond radiologic progression. 
 See Section 8.1.8 for docetaxel to AMG 510 crossover details, once the subject crosses over in the AMG 510 arm, the AMG 510 Schedule of Activities (Table 1-1) 
will be utilized.   
 Once the subject starts treatment beyond radiologic progression, they will adhere to the same schedule of events as long as they are receiving drug.  
 Once subject begins crossover, AMG 510 Schedule of Activities (Table 1-1) is to be followed.  See Section 8.1.8 for details on crossover. 
f Below is applicable to Tumor Assessments:   
 Tumor evaluation is to be performed by contrast-enhanced CT of the chest and one of the following:  contrast-enhanced CT abdomen with cuts through the pubic 
symphysis, contrast-enhanced CT abdomen and pelvis, contrast-enhanced MRI abdomen and pelvis, or contrast-enhanced MRI abdomen with cuts through to the 
pubic symphysis.  Contrast-enhanced images are strongly preferred. If contrast enhanced CT imaging is contraindicated (allergy, medical, etc), radiological 
imaging to be performed as indicated by site imaging manual.    
 Imaging assessments are indicated until independent central confirmation of progression, start of another anti-cancer therapy, withdrawal of consent, lost to follow 
up, or death, whichever occurs earliest.  Subjects’ scans will undergo independent central confirmation of progression (COP) at the time of first progressive 
disease (PD).   
 Subjects that undergo treatment beyond progression or crossover, from docetaxel to AMG 510, will continue to receive scans after confirmation of first PD.  
 Safety follow up CT/MRI should be performed only for subjects that discontinue treatment for a reason other than disease progression per RECIST v1.1.  Imaging 
should continue in LTFU until RECIST radiologic progression is documented.    
 Further details with regards to imaging assessments post treatment period are listed in Section 8.1.4. 
 Further details with regards to the process of independent central confirmation of progression are detailed in Section 8.2.2.1.2.   

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 31 of 179 
CONFIDENTIAL  
 
 
Table 1-2.  Schedule of Activities:  Docetaxel 
 
Screening 
Treatment Cycle 
Follow-up 
Visit 
Notes 
Cycle (1 Cycle is 21 Days  
 3 days) 
 
1a 
2 
3 
4+ 
SFUb LTFUc 
Day 
-28 to 1 
1 
5 
1 
5 
1 
5 
1 
GENERAL AND SAFETY 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility criteria 
X 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Other anticancer therapies 
X 
 
 
 
 
 
 
 
X 
X 
 
Physical exam 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
Physical measurements 
X 
X 
 
X 
 
X 
 
X 
X 
 
Height collected at screening only.  Weight collected every 
cycle. 
Substance abuse history 
X 
 
 
 
 
 
 
 
 
 
 
ECOG 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
Vital signs including oxygen 
saturation 
X 
X 
 
X 
 
X 
 
X 
X 
 
 
ECG 
X 
 
 
 
 
 
 
 
 
 
See Section 8.2.3.2.  Screening ECG: standardized method in 
triplicate.   
Vital Assessments 
 
 
X 
In addition to survival, LTFU period will collect data on the 
subjects’ health condition, disease status, and subsequent 
anticancer treatment. 
Concomitant medications 
X 
←=================================→ 
 
Concomitant therapy data to be collected should include 
supplemental oxygen volume usage per day. 
Adverse events 
 
←=================================→ 
 
 
Serious adverse eventsd 
←==================================================→  
LABORATORY 
Chemistry 
X 
X 
 
X 
 
X 
 
X 
X 
 
Laboratory Assessments may be performed within ± 3 days 
before day 1 of each cycle.  The urine studies may be 
performed at a local laboratory and/or by the central laboratory, 
depending on the availability of the testing facility. 
Hematology 
X 
X 
 
X 
 
X 
 
X 
X 
 
Coagulation 
X 
 
 
 
 
 
 
 
X 
 
Urinalysis  
X 
X 
 
X 
 
X 
 
X 
X 
 
Serum or urine pregnancy 
test 
X 
X 
 
X 
 
X 
 
X 
X 
 
Only for females of childbearing potential.  Pregnancy test must 
be within 3 days before day 1 of each cycle. 
Hepatitis B and Hepatitis C 
testing 
X 
 
 
 
 
 
 
 
 
 
 

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 32 of 179 
CONFIDENTIAL  
 
 
 
Screening 
Treatment Cycle 
Follow-up 
Visit 
Notes 
Cycle (1 Cycle is 21 Days  
 3 days) 
 
1a 
2 
3 
4+ 
SFUb LTFUc 
Day 
-28 to 1 
1 
5 
1 
5 
1 
5 
1 
Thyroid function tests 
X 
 
 
X 
 
X 
 
X 
X 
 
Thyroid function testing at screening, pre-dose on day 1 of each 
cycle (except cycle 1), at the end of treatment, and at safety 
follow-up.  They should also be obtained if the subject displays 
clinical signs or symptoms concerning for thyroid dysfunction 
Cholesterol and Triglyceride 
 
X 
 
 
 
X 
 
(X) 
X 
 
Cholesterol and triglyceride levels on pre-dose on day 1 of 
every other cycle (ie, cycle 1, 3, 5, 7, etc). 
DOSING 
 
Docetaxele 
 
X 
 
X 
 
X 
 
X 
 
 
Docetaxel will be administered every 3 weeks  3 days until 
independent central confirmation of progression, intolerance to 
treatment necessitating treatment discontinuation, need for 
other anti-cancer therapy, withdrawal of consent, or death.   
 
**Please refer to footnote “e” for further dosing details.  
TUMOR ASSESSMENTS 
CT/MRIf 
X 
Imaging every 6 weeks from cycle 1 day 1 ( 7 days) (at 
weeks 7, 13, 19, 25, 31, 37, 43, and 49), and then at 
9-week intervals ( 7 days) thereafter 
Contrast enhanced CT scan or MRI of the brain is required for 
all subjects at screening, and if positive for metastasis, must be 
performed at every subsequent tumor assessment. 
 
For subjects with brain metastases or history of brain 
metastases, contrast enhanced brain MRI (contrast enhanced 
CT scan if unable to have MRI) at screening and at each tumor 
evaluation is required. 
 
**Please refer to footnote “f” for further tumor assessment 
details.  

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 33 of 179 
CONFIDENTIAL  
 
 
 
Screening 
Treatment Cycle 
Follow-up 
Visit 
Notes 
Cycle (1 Cycle is 21 Days  
 3 days) 
 
1a 
2 
3 
4+ 
SFUb LTFUc 
Day 
-28 to 1 
1 
5 
1 
5 
1 
5 
1 
TREATMENT AND DISEASE RELATED SYMPTOMS AND HRQOL 
PRO/QOL assessments:  
FACT-G GP5 and PRO-
CTCAE  
 
X 
 
X 
 
X 
  
X 
X 
 
 
 
Pain assessment (BPI) 
X 
X 
 
X 
 
X 
 
X 
X 
 
Pain will be assessed at screening and on day 1 of every cycle 
and at the SFU by using the brief pain inventory (BPI) scale 
PRO/QOL assessments:  
QLQ-C30  
X 
X 
 
X 
 
X 
  
X 
X 
 
 
PRO/QOL assessments:  
QLQ-LC13 
X 
X 
 
X 
 
X 
  
X 
X 
 
 
PRO/QOL assessments:  
PGIC  
 
 
 
 
 
X 
 
(X) 
 
 
PGIC will be collected in the clinic on day 1 of cycle 3 and 
cycle 5 (no collection needed at screening or cycle 1 for PGIC). 
PRO/QOL assessments:  
PGIS  
X   
X 
 
 
 
X 
 
(X) 
 
 
PGIS will be collected in the clinic at screening and day 1 of 
cycles 1, 3, and cycle 5. 
PRO/QOL assessments: 
EQ-5D-5L  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
The EQ-5D-5L questionnaire will be completed at screening, in 
the clinic on clinic visit days, including SFU, and at home (data 
collected by phone) for the scheduled non-clinic visit days (day 
5 of cycles 1, 2 and 3).  EQ-5D-5L will also be collected during 
LTFU. 
CxDx = cycle x day x; CT = computerized tomography; CTCAE = Common Terminology Criteria for Adverse Events; ctDNA = circulating tumor DNA;  
EC = Ethics Committee; ECG = electrocardiogram; ECOG = Eastern Cooperative Oncology Group; EQ-5D-5L = EuroQol-5 Dimension; FACT-G = Functional 
Assessment of Cancer Therapy Tool General form; FFPE = formalin fixed, paraffin embedded; HRQOL = health-related quality of life; IRB = Institutional Review 
Board; KRAS = Kirsten rat sarcoma viral oncogene homolog; LTFU = long-term follow-up; MRI = magnetic resonance imaging; PGIC = patient global impression of 
change; PGIS = patient global impression of severity; PI = Principal Investigator; PRO = patient-reported outcome; QLQ-LC13 = Quality-of-life Questionnaire Core 
13; QLQ-C30 = Quality-of-life Questionnaire Core 30; QOL = quality of life; RECIST = Response Evaluation Criteria in Solid Tumors; SFU = safety follow-up;  
(X) = parentheses indicate that the particular test is situational at that time point, as specified in the respective notes 
a Randomisation can take place up to 48 hours before first dose/C1D1. 
b SFU will be performed 30 days ( 7 days) after the last dose of investigational product 

Product:  AMG 510  
Protocol Number:  20190009  
Date:  06 January 2022 
Page 34 of 179 
CONFIDENTIAL  
 
 
c LTFU will be 5 years after last subject enrolled, or until withdrawal of consent, loss to follow-up, or subject death, whichever occurs first. Vital status and subsequent 
treatment for NSCLC will be recorded after the SFU period during the LTFU. 
d Serious adverse events observed by the investigator or reported by the subject that occur after the safety follow-up visit through the end of the long-term follow up 
period should be reported if there is a reasonable possibility that the event may have been caused by investigational product.   
e Below is applicable to docetaxel dosing: 
 Subjects that consent to treatment beyond progression or consent to crossover, from docetaxel to AMG 510, will continue to receive investigational product after 
independent central confirmation of progression at the time of first progressive disease (PD). 
 Progressive disease must undergo independent central confirmation prior to crossover 
 See Section 8.1.7 for treatment beyond radiologic progression. 
 See Section 8.1.8 for crossover details, once the subject crosses over in the AMG 510 arm, the AMG 510 Schedule of Activities (Table 1-1) will be utilized.   
 Once the subject starts treatment beyond radiologic progression, they will adhere to the same schedule of events as long as they are receiving drug.  
 Once subject begins crossover, AMG 510 Schedule of Activities (Table 1-1) is to be followed.  See Section 8.1.8 for details on crossover. 
f Below is applicable to Tumor Assessments:   
 Tumor evaluation is to be performed by contrast-enhanced CT of the chest and one of the following:  contrast-enhanced CT abdomen with cuts through the pubic 
symphysis, contrast-enhanced CT abdomen and pelvis, contrast-enhanced MRI abdomen and pelvis, or contrast-enhanced MRI abdomen with cuts through to the 
pubic symphysis.  Contrast-enhanced images are strongly preferred. If contrast enhanced CT imaging is contraindicated (allergy, medical, etc), radiological 
imaging to be performed as indicated by site imaging manual.    
 Imaging assessments are indicated until independent central confirmation of progression, start of another anti-cancer therapy, withdrawal of consent, lost to follow 
up, or death, whichever occurs earliest.  Subjects’ scans will undergo independent central confirmation of progression (COP) at the time of first progressive 
disease (PD).   
 Subjects that undergo treatment beyond progression or crossover will continue to receive scans after confirmation of first PD.  
 Safety follow up CT/MRI should be performed only for subjects that discontinue treatment for a reason other than disease progression per RECIST v1.1.  Imaging 
should continue in LTFU until RECIST radiologic progression is documented.    
 Further details with regards to imaging assessments post treatment period are listed in Section 8.1.4. 
 Further details with regards to the process of independent central confirmation of progression are detailed in Section 8.2.2.1.2.   

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 35 of 179 
CONFIDENTIAL  
 
 
 
2. 
Introduction 
2.1 
Study Rationale 
Lung cancer is the most common type of cancer occurring in both males and females 
worldwide (WHO statistics, 2018), and the 5-year survival rate for advanced non-small 
cell lung cancer (NSCLC) is low (between 6% and 33%, depending on the stage 
[American Cancer Society, 2019]). 
The rat sarcoma (RAS) proto-oncogene has been identified as an oncogenic driver of 
tumorigenesis in several cancers, including NSCLC.  The RAS proteins can be 
mutationally activated at codons 12, 13, or 61, leading to human cancers.  Different 
tumor types are associated with mutations in certain isoforms of RAS, with Kirsten rat 
sarcoma viral oncogene homolog (KRAS) being the most frequently mutated isoform in 
most cancers (Prior et al, 2012).  While the role of KRAS mutations in human cancers 
has been known for decades, no anti-cancer therapies specifically targeting KRAS 
mutations have been successfully developed, largely because the protein had been 
intractable for inhibition by small molecules (McCormick, 2016).  AMG 510 is a small 
molecule that specifically and irreversibly inhibits the KRASG12C mutated protein.  
Nonclinical studies of AMG 510 have demonstrated inhibition of growth and regression 
of cells and tumors harboring KRAS p.G12C.  These data suggest that inhibition of 
KRAS G12C may have therapeutic benefit for subjects with KRAS p.G12C driven 
cancers.  Accordingly, the ongoing phase 1/2 study, Study 20170543, is evaluating the 
safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of AMG 510 
in subjects with KRAS p.G12C-mutated advanced NSCLC, colorectal cancer (CRC), and 
other solid tumors. 
Study 20170543 was the first clinical test of this hypothesis in subjects with 
KRAS p.G12C mutated solid tumors, including 27 subjects with NSCLC (as of the 
12 June 2019 data cutoff date).  In Study 20170543, AMG 510 demonstrated antitumor 
activity in KRAS p.G12C mutated NSCLC, with 7 of 17 evaluable subjects having a 
partial response (PR) (5 confirmed) and 8 subjects having stable disease (2 subjects 
had progression), as of the 12 June 2019 data cutoff date.  AMG 510 was well tolerated 
at the 180 mg once daily (QD) to 960 mg QD dose levels tested.  AMG 510 dose of 
960 mg QD orally administered (PO) was selected to be the dose for the phase 2 part of 
Study 20170543 and Study 20190009.  The types and frequency of adverse events at 
the 960 mg dose were consistent with those observed at lower doses. 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
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CONFIDENTIAL  
 
 
The aim of Study 20190009 is to evaluate the efficacy, safety, and tolerability of 
AMG 510 compared with docetaxel in subjects with previously treated, locally advanced, 
and unresectable or metastatic NSCLC with KRAS p.G12C mutation.  The target 
population is subjects with pathologically documented, locally advanced unresectable or 
metastatic lung malignancy with KRAS p.G12C mutation identified through molecular 
testing and no other previously identified driver mutation (eg, epidermal growth factor 
receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) fusion).  Subjects must 
have received at least 1 prior systemic therapy for advanced disease.  Prior treatment 
should include a platinum-based doublet chemotherapy and a checkpoint inhibitor, either 
in one line or separate lines of therapy, unless there is a contraindication to those 
therapies.  This target population represents previously treated, locally advanced, and 
unresectable or metastatic NSCLC patients with unmet medical need and is consistent 
with the NSCLC subjects who demonstrated clinical responses to AMG 510 in  
Study 20170543.  
2.1.1 
Choice of Docetaxel as Comparator 
Docetaxel is indicated (Taxotere® Summary of Product Characteristics [SmPC] 2019; 
Taxotere® United States Prescribing Information [USPI] 2019) for the treatment of 
patients with locally advanced or metastatic NSCLC after failure of prior chemotherapy 
or platinum-based chemotherapy.  In clinical practice, patients with NSCLC are usually 
treated in first line with platinum-based doublet therapy and/or checkpoint inhibitors 
either alone or in combination.  Patients whose tumors have been screened and 
identified to have “actionable” mutations (eg, EGFR, ALK, ROS, BRAF) will receive 
targeted therapies directed at these specific oncogenic drivers in first- or later-lines 
(NCCN, 2019).  Since the KRAS p.G12C mutation rarely occurs concomitantly with 
these other targetable mutations (Scheffler et al, 2018; Gainor et al, 2013), patients with 
KRAS p.G12C rarely have this option.  The European Society for Medical Oncology 
(ESMO) treatment guidelines list the checkpoint inhibitors and platinum-based 
chemotherapy, either alone or in combination, as the recommended first-line treatment 
in patients with NSCLC who test negative for mutations other than KRAS p.G12C.  For 
patients who did not receive both a checkpoint inhibitor and platinum-based 
chemotherapy concurrently in first-line treatment, the alternate treatment (ie, a 
checkpoint inhibitor for those patients who received platinum-based therapy in first line 
and vice versa) is the recommended second-line treatment.  For patients whose cancer 
progressed after treatment with both a checkpoint inhibitor and platinum-based 
chemotherapy, the taxanes, such as docetaxel, are the recommended treatment.  In 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 37 of 179 
CONFIDENTIAL  
 
 
Study 20190009, docetaxel has been chosen as the active control treatment; since 
subjects must have already failed or their tumors progressed on both checkpoint inhibitor 
therapy and platinum-containing doublet therapy, additional treatment with a 
programmed cell death-1 (PD-1) or programmed cell death ligand 1 (PD-L1) agent or 
another platinum-containing doublet agent would not be indicated.   
Although the REVEL study indicated an added benefit of docetaxel in combination with 
ramucirumab for second-line treatment of NSCLC (Garon et al, 2014), this additional 
benefit was small (survival gain of 1.4 months) and appeared primarily in younger 
patients (Ramalingam et al, 2018).  Some adverse events in the docetaxel plus 
ramucirumab group were notably worse than those of docetaxel alone, with greater 
incidences of grade 4 neutropenia, hospitalization for neutropenia, anemia, and bleeding 
events in the combination treatment group.  With the small increase in survival and the 
more severe toxicity profile, this combination is not widely used and may be best limited 
to younger patients with better Eastern Cooperative Oncology Group (ECOG) 
performance status (Uprety, 2019).  Patients who are not eligible for treatment with 
docetaxel (eg, patients with ECOG status  2) would most likely receive only palliative 
care, with outcomes significantly worse than those patients who are eligible for docetaxel 
treatment.  AMG 510 offers an alternative treatment option, with a favorable benefit-risk 
profile, for patients with KRAS pG12C mutations. 
Docetaxel combined with nintedanib has also shown an added benefit over docetaxel 
alone for the treatment of advanced NSCLC (Gottfried et al, 2017).  Nintedanib, 
however, is not available in all countries selected for this phase 3 study, and thus 
docetaxel alone was selected as the comparator. 
Individuals with other oncogenic driver mutations will be excluded from the 
Study 20190009 study population, and thus therapies targeting those mutations would 
not be indicated as second- or third-line therapy.  However, since other oncogenic driver 
mutations rarely occur concomitantly with the KRAS p.G12C mutation  
(Scheffler et al, 2018; Gainor et al, 2013), this exclusion is not expected to have a 
significant effect on study enrollment.   
A docetaxel dose of 75 mg/m2 every 3 weeks was chosen for the study as the 
recommended dose for treatment of NSCLC following failure of prior platinum-based 
therapy.  However, docetaxel dose reductions will be allowed as needed.  All subjects 
assigned to receive docetaxel will start at 75 mg/m2, with dose reductions allowed as 

Product:  AMG 510 
Protocol Number:  20190009  
Date:  06 January 2022 
Page 38 of 179 
CONFIDENTIAL  
 
 
described in Section 6.2.2.2, as the standard dosing regimen in Japan is 60 mg/m2 
based on the occurrence of myelosuppression at higher doses (Taguchi et al, 1994). 
In summary, Amgen considers that docetaxel is the appropriate comparator for this 
study because: 
 
Docetaxel is indicated for the treatment of NSCLC in patients who have 
progressed after checkpoint inhibitor and platinum-based doublet therapy and is 
regionally widely available.   
 
Alternative choices are not widely available or would be appropriately used in 
only a narrower population of younger, healthier patients.   
 
Compared with the overall population of patients with NSCLC, the subjects 
enrolled in this study must have better performance status (ECOG status  1).  
Docetaxel mortality in clinical studies was increased in subjects with ECOG 
status of 2.  In addition, because AMG 510 is expected to have better tolerability 
than docetaxel, enrolling subjects with better performance status is expected to 
maximize the tolerability of the docetaxel control group compared with AMG 510.  
2.1.2 
Primary Endpoints 
The primary endpoint of Study 20190009 is progression-free Survival (PFS).  
Progression-free survival is defined as time from randomization until disease 
progression or death from any cause, whichever occurs first for all subjects.  Subjects 
who do not progress or die will be censored at their last evaluable disease assessment 
date.  Progression will be based on an independent radiologic assessment of disease 
response per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).  
Often used as an endpoint in diseases with very low survival rates, PFS is considered an 
acceptable surrogate endpoint for overall survival (OS) (Clinical Trial Endpoints for the 
Approval of Cancer Drugs and Biologics Guidance for Industry, FDA 2018; Clinical Trial 
Endpoints for the Approval of Non-Small Cell Lung Cancer Drugs and Biologics, 
FDA 2015; Guideline on the evaluation of anticancer medicinal products in man, 
EMA/CHMP 2017).  Given the poor prognosis of refractory NSCLC, PFS is an 
appropriate early endpoint to evaluate efficacy in this setting.  The endpoint of PFS will 
be included in the planned early interim efficacy analyses for this study.  Estimand 
framework will be utilized to align the clinical trial design and analysis with the endpoints 
of interest while accounting for any intercurrent events.  See Section 3 and 
Section 9.4.2.2 for details of the estimand framework.  
2.1.3 
Key Secondary Endpoints 
The key secondary endpoints are OS, objective response rate (ORR), patient-reported 
outcomes (PRO), including change from baseline (cycle 1 day 1) over time to week 12 in 

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disease related symptoms (dyspnea, cough, and chest pain), physical functioning, and 
health related quality of life (QOL).   
Overall survival, defined as time from randomization until death from any cause 
(subjects who do not die will be censored at the date of last contact through the analysis 
trigger date), is considered the gold standard for demonstrating clinical benefit for cancer 
drugs.  This endpoint is precise and easy to measure, documented by the date of death 
and bias is not a factor in endpoint measurement (Clinical Trial Endpoints for the 
Approval of Cancer Drugs and Biologics Guidance for Industry, FDA 2018; Guideline on 
the evaluation of anticancer medicinal products in man, EMA/CHMP 2017). 
Objective response rate is defined as complete response (CR) + PR, as assessed by 
RECIST v1.1.  When defined in this manner, ORR is a direct measure of antitumor 
activity; therefore, this data will reflect any direct therapeutic effect of AMG 510.  Given 
the poor prognosis of refractory NSCLC, ORR is an appropriate early endpoint to 
evaluate efficacy in this setting. 
The effect of treatment with AMG 510 on treatment and disease related symptoms and 
health related QOL relative to docetaxel will be assessed.  The 5-year survival rate for 
advanced NSCLC cancer is between 6% and 33% depending on the stage  
(American Cancer Society, 2019).  Due to this poor prognosis, the effect of treatment on 
QOL is especially important.  The QOL in lung cancer patients is lower than both healthy 
people, and patients suffering from other malignancies.  It is affected by the severity and 
the number of symptoms such as fatigue, loss of appetite, dyspnea, cough, pain, and 
blood in sputum, which are specific for lung tumors (Polanski et al, 2016).  Assessing 
change from baseline over time to week 12 in dyspnea, cough, and chest pain in NSCLC 
subjects receiving AMG 510 compared to docetaxel is predicted to give a meaningful 
assessment of whether AMG 510 improves these disease related symptoms.  Change 
from baseline over time to week 12 in physical functioning and global health status will 
also be compared in subjects receiving AMG 510 compared to docetaxel, to allow 
assessment of possible impact on health related QOL.  
2.2 
Background 
2.2.1 
Disease 
Worldwide, lung cancer (small cell and non-small cell) is the most common type of 
cancer occurring in both males and females (WHO statistics, 2018).  It was estimated 
that in 2019 there would be approximately 228 150 new cases of lung cancer in the 
United States (US) alone (American Cancer Society, 2019).  The 5-year survival rate 

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for advanced NSCLC cancer is between 6% and 33% depending on the stage  
(American Cancer Society, 2019).  
2.2.1.1 
Oncogenic RAS Driven Tumorigenesis 
The RAS proto-oncogene has been identified as an oncogenic driver of tumorigenesis in 
NSCLC (Johnson et al, 2001; Der et al, 1982).  The RAS family consists of 3 closely 
related genes that express guanosine triphosphatases (GTPases) responsible for 
regulating cellular proliferation and survival (Simanshu et al, 2017; Barbacid et al, 1987).  
The RAS proteins, KRAS, Harvey rat sarcoma viral oncogene homolog (HRAS), and 
neuroblastoma RAS viral oncogene homolog (NRAS) (Hall et al, 1983; Taparowsky et al, 
1983; Chang et al, 1982; Kirsten and Mayer, 1967; Harvey, 1964), can be mutationally 
activated at codons 12, 13, or 61, leading to human cancers.  Different tumor types are 
associated with mutations in certain isoforms of RAS, with KRAS being the most 
frequently mutated isoform in most cancers (Prior et al, 2012).  While the role of KRAS 
mutations in human cancers has been known for decades, no anti-cancer therapies 
specifically targeting KRAS mutations have been successfully developed, largely because 
the protein had been intractable for inhibition by small molecules (McCormick, 2016).   
2.2.1.2 
KRAS p.G12C Mutation and AMG 510 
Of the KRAS mutations, it is estimated that approximately 80% occur at codon 12 
(Prior et al, 2012).  The KRAS p.G12C mutation is estimated to occur in approximately 
13% of lung adenocarcinoma (including NSCLC), 3% of CRC, and 1% to 2% of numerous 
other solid tumors (including pancreatic, endometrial, bladder, ovarian, and small cell lung 
tumors) (The AACR Project GENIE Consortium, 2017; Biernacka et al, 2016;  
Neumann et al, 2009).  This specific mutation has been identified as a putative oncogenic 
driver in several types of solid tumors including NSCLC (Fernández-Medarde and Santos, 
2011) and CRC (Jones et al, 2017) and other solid tumors such as pancreatic, 
endometrial, bladder, ovarian, and small cell lung tumors (The AACR Project GENIE 
Consortium, 2017; Zhou et al, 2016). 
The KRAS p.G12C mutation is a single guanine to thymine substitution that results in a 
glycine to cysteine substitution at amino acid position 12.  This structural change in the 
protein results in a defect in the association of GAPs, thereby reducing the hydrolysis of 
guanosine triphosphate (GTP) by KRAS.  The resulting accumulation of active, 
GTP-bound KRAS leads to enhanced proliferative and survival signaling in tumor cells 
(Jones et al, 2017).   

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AMG 510 is a small molecule that specifically and irreversibly inhibits the KRAS G12C 
mutated protein.  AMG 510 binds to the P2 pocket of KRAS adjacent to the mutated 
cysteine at position 12 and the nucleotide-binding pocket.  The inhibitor contains a 
thiol-reactive portion which covalently modifies the cysteine residue and locks KRAS 
G12C in an inactive, guanosine diphosphate (GDP)-bound conformation.  This blocks 
the interaction of KRAS with effectors such as Rapidly Accelerated Fibrosarcome (RAF) 
proto oncogene serine/threonine-protein kinase (RAF), thereby preventing downstream 
signaling, including the phosphorylation of extracellular signal-regulated kinase (ERK) 
(Simanshu et al, 2017; Ostrem et al, 2013; Cully and Downward, 2008).  Inactivation of 
KRAS by RNA interference (RNAi) or small-molecule inhibition has previously 
demonstrated an inhibition of cell growth and induction of apoptosis in tumor cell lines 
and xenografts harboring KRAS mutations (including the KRAS p.G12C mutation) 
(Janes et al, 2018; McDonald et al, 2017; Xie et al, 2017; Ostrem and Shokat, 2016; 
Patricelli et al, 2016).  Studies with AMG 510 have confirmed these in vitro findings and 
have likewise demonstrated inhibition of growth and regression of cells and tumors 
harboring KRAS p.G12C mutations.  These data suggest that inhibition of 
KRAS p.G12C may have therapeutic benefit for subjects with KRAS p.G12C-driven 
cancers.  Accordingly, the first-in-human (FIH) and phase 2 Study 20170543, were 
designed to evaluate the safety, tolerability, PK/PD, and efficacy of AMG 510 in subjects 
with KRAS p.G12C mutated advanced NSCLC, CRC, and other solid tumors.  
2.2.1.3 
Current Therapy for Cancers Harboring the KRAS p.G12C Mutation 
While the incidence of the G12C KRAS mutation in these tumor types is relatively low 
(approximately 13%) the overall incidence of NSCLC and the poor prognosis of subjects 
with advanced/metastatic disease makes this mutation an important molecular target.  
There is currently no anticancer therapy specifically targeting tumors that harbor the 
KRAS p.G12C mutation.  Subjects with metastatic or unresectable NSCLC, CRC and 
other solid tumors (including pancreatic, endometrial, bladder, ovarian, appendiceal, 
ampullary, and small intestine) with the KRAS p.G12C mutation are generally being 
treated with combinations of chemotherapy, immunotherapy or antiangiogenic agents.   
Although somatic mutations in EGFR, BRAF, and human epidermal growth factor 
receptor 2 (HER2), and rearrangements in ALK, ROS, Neurotrophic Tyrosine Receptor 
Kinase (NTRK), and Rearranged During Transfection (RET) have been validated as 
powerful predictive biomarkers, and have expanded treatment options for these 
molecularly defined subsets of subjects, since the KRAS mutation rarely occurs 

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concomitantly with these other molecular abnormalities, subjects with KRAS mutations 
are not usually candidates for these therapies (Scheffler et al, 2018; Gainor et al, 2013).  
Efforts to target KRAS mutated NSCLC by inhibiting downstream signaling mechanisms 
such as with Mitogen Activated Protein Kinase Kinases (MEK1/2) or Cyclin Dependent 
Kinase 4/6 (CDK4/6) inhibitors have been unsuccessful to date (Roman et al, 2018).  
More recently, NSCLC subjects with the KRAS p.G12C mutation are, like subjects 
without other molecularly defined targets, receiving anti-PD-1 inhibitors with or without 
chemotherapy in first and/or second line therapy, followed by therapy with a taxane with 
or without a Vascular Endothelial Growth Factor (VEGF) inhibitor.  
Preliminary literature review performed by Amgen on KRAS p.G12C mutated subjects 
(from 15 publications with NSCLC G12C specific data over the past 10 years) suggests 
that in general, in NSCLC subjects, the KRAS p.G12C mutation appeared to be 
associated with poorer progression-free and disease-free survival.  However, the 
magnitude of these differences was modest and there were a few studies that reported 
no difference or slightly better outcomes of subjects with KRAS p.G12C mutations.  
Based on the preliminary literature review described above, it is assumed that subjects 
with the KRAS p.G12C mutation respond similarly to chemotherapy, immunotherapy, 
and anti-angiogenic agents as subjects who do not harbor a KRAS p.G12C mutation. 
For advanced/metastatic NSCLC subjects, multiple large phase 3 trials have 
demonstrated ORR in  second line (following first line platinum-containing 
chemotherapy doublets, such as cisplatin/pemetrexed) of 5.5 to 13 % with 
chemotherapy (typically a taxane) and 9.7 to 22.5 % with chemotherapy plus a Vascular 
Endothelial Growth Factor Receptor (VEGFR) inhibitor (Gridell et al, 2018; 
Rittmeyer et al, 2017; Herbst et al, 2016; Borghaei et al, 2015; Herbst et al, 2007).  
These trials have also demonstrated PFS of 2.8 to 4.2 months and 4.8 to 5.4 months 
and OS of 6 to 11.4 months and 9.9 to 12.6 months for chemotherapy and 
chemotherapy plus a VEGFR inhibitor, respectively.  Recent studies of  second line 
NSCLC subjects receiving anti-PD1 therapy (post-chemo doublet therapy in first line) 
have yielded more substantial ORR and OS (Vokes et al, 2018; Herbst et al, 2016; 
Borghaei et al, 2015); however, due to recent approvals of anti-PD1 therapy for first line 
NSCLC the sequence of immunotherapy in NSCLC is in flux and the standard of care 
(and outcomes) for subjects who progress or recur after first line anti-PD1 therapy 
remains unclear.   

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2.2.2 
Amgen Investigational Product Background:  AMG 510 
AMG 510 is a small molecule that specifically and irreversibly inhibits the KRAS G12C 
mutated protein.  AMG 510 binds to the P2 pocket of KRAS adjacent to the mutated 
cysteine at position 12 and the nucleotide-binding pocket.  The inhibitor contains a 
thiol-reactive portion which covalently modifies the cysteine residue and locks KRAS 
G12C in the inactive GDP-bound conformation.  This blocks the interaction of KRAS 
with effectors like RAF, thus preventing downstream signaling, including the 
phosphorylation of ERK (Ostrem et al, 2013; Simanshu et al, 2017).  Inactivation of 
KRAS through a small molecule inhibitor has previously demonstrated an inhibition of 
cell growth and induction of apoptosis in tumor cell lines and xenografts with the 
KRAS p.G12C mutation (Janes et al, 2018; Ostrem and Shokat, 2016; Patricelli et al, 
2016).  Likewise, studies of AMG 510 have demonstrated inhibition of growth and 
regression of cells and tumors harboring KRAS p.G12C (Section 2.2.1.3).  These data 
suggest that inhibition of KRAS G12C may have therapeutic benefit for subjects with 
KRAS p.G12C-driven cancers.  Accordingly, the FIH and phase 2 Study 20170543, was 
designed to evaluate the safety and efficacy of AMG 510 in subjects with KRAS p.G12C 
mutated advanced NSCLC, CRC, and other solid tumors. 
AMG 510 Preclinical Experience 
In vitro AMG 510 inhibited nucleotide exchange of recombinant mutated KRAS 
G12C/C118A (half maximal inhibitory concentration (IC50) = 0.09 µM), but had minimal 
effect on KRAS C118A, which is wildtype at G12.  In cells, AMG 510 covalently modified 
KRAS G12C and inhibited KRAS signaling as measured by phosphorylation of ERK1/2 
in all KRAS p.G12C-mutated cell lines tested (IC50 values from 0.01 to 0.12 µM), but did 
not inhibit phospho-ERK1/2 in cell lines with various other KRAS mutations.  AMG 510 
also impaired viability in all but one p.G12C-mutated cell lines (IC50 values from 0.004 to 
0.032 µM), but did not affect the viability of cell lines that did not harbor the 
KRAS p.G12C mutation.  The cellular maximum potential rate (kinact) and inhibitor 
concentration (Ki) values for AMG 510 were also experimentally determined in the 
human pancreatic cell line MIA PaCa-2 to be 0.00133 sec-1 and 6.97×10-7 M, 
respectively, with kinact/Ki ratio of 1.9×103 M-1 sec-1. 
In vivo AMG 510 covalently modified KRAS G12C and significantly inhibited 
phosphor-ERK1/2 in human KRAS p.G12C MIA PaCa-2 T2 pancreatic and 
KRAS p.G12C NCI-H358 NSCLC tumor xenografts in mice in a dose-dependent manner 
at doses as low as 1 mg/kg in the MIA PaCa-2 T2 model.  After a single, 10 mg/kg dose 

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in mice bearing MIA PaCa-2 T2 tumors, exposure of AMG 510 peaked at 0.5 hours, 
followed closely by maximal inhibition of phospho-ERK1/2 by 1 hour to 2 hours. 
Covalent modification of KRAS G12C by AMG 510 tracked with inhibition and maximal 
modification occurred after 2 hours.  Significant inhibition and modification of 
KRAS G12C persisted for 48 hours after a single, 10 mg/kg dose.  In tumor xenograft 
studies AMG 510 significantly inhibited the growth of MIA PaCa-2 T2 and NCI-H358 
tumors at doses as low as 3 mg/kg and achieved 62% and 49% regression, 
respectively, at 100 mg/kg.  Notably AMG 510 had no effect on SW480-1AC (KRAS 
p.G12V) tumor xenografts at 100 mg/kg and did not impact body weight in any study. 
AMG 510 Clinical Experience in NSCLC and Other Tumor Types 
The FIH study (which later was amended to phase 1/2), Study 20170543, was initiated in 
August 2018 to evaluate the safety and tolerability of AMG 510 as an oral therapeutic in 
subjects with advanced or metastatic KRAS p.G12C mutated NSCLC, CRC, or other 
solid tumors.  
The phase 1 monotherapy dose exploration part of Study 20170543 has yielded early 
evidence of activity (even in this heavily pretreated population), as demonstrated by 
preliminary data.  As of the 12 June 2019 data cutoff date, Study 20170543 had enrolled 
62 subjects, 27 with NSCLC, 31 with CRC, and 4 with other solid tumors.  Thirty-nine of 
the 62 enrolled subjects were evaluable for efficacy as of the 12 June 2019 data cutoff 
date.  Preliminary results demonstrated antitumor activity in KRAS p.G12C mutated 
NSCLC, with 7 of 17 evaluable subjects having a PR (5 confirmed) and 8 subjects 
having stable disease (2 subjects had progression).   
AMG 510 was well tolerated at the 180 mg QD to 960 mg QD dose levels tested. 
As of the data cut-off date of 28 August 2019, preliminary safety data were available for 
95 subjects who had received AMG 510 doses between 180 and 960 mg QD.  In the 
preliminary safety data, none of these 95 subjects had dose-limiting toxicities (DLTs).  
Eighty-one subjects (85.3%) had at least 1 treatment-emergent adverse event during the 
study.  The most frequently reported adverse events (reported in ≥ 10% subjects in all 
the cohorts combined) were diarrhea (25 subjects [26.3%]), nausea (20 subjects 
[21.1%]), fatigue (18 subjects [18.9%]), vomiting (12 subjects [12.6%]), abdominal pain, 
decreased appetite (11 subjects [11.6%] each), and headache (10 subjects [10.5%]).  
Most adverse events were grade 1 or 2 in severity.  Thirty-five subjects (36.8%) had 
adverse events that were grade ≥ 3 in severity; anemia (5 subjects [5.3%]), diarrhea 

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(4 subjects [4.2%]), metastatic CRC, increased alanine aminotransferase (ALT) 
(3 subjects [3.2%] each), and dyspnea, metastatic lung cancer, adult failure to thrive, 
respiratory failure, and vomiting (2 subjects [2.1%] each) were reported in > 1 subject; 
the remaining adverse events were all reported in 1 subject (1.1%) each. 
Treatment-related (as reported by the investigator) treatment-emergent adverse events 
were reported for 43 subjects (45.3%).  The most frequently reported treatment-related 
adverse events were diarrhea (16 subjects, 16.8%), nausea (8 subjects, 8.4%), 
increased ALT (6 subjects [6.3%] each), vomiting (5 subjects [5.3%]), increased blood 
alkaline phosphatase (ALP), fatigue (4 subjects [4.2%] each), abdominal pain, dry 
mouth, anemia (3 subjects [3.2%] each), increased blood creatine phosphokinase, 
decreased white blood cell count, decreased appetite, peripheral neuropathy, and 
pruritus (2 subjects [2.1%] each).  Most treatment-related adverse events were grade 1 
or 2 in severity; grade 3 treatment-related adverse events that were reported in 
> 1 subject were diarrhea (4 subjects [4.2%]), increased ALT, and anemia (3 subjects 
[3.2%] each).  No grade 4 related adverse events were reported.   
Twenty-seven subjects (28.4%) had serious adverse events.  Two subjects (2.1%) had 
treatment-related serious adverse events: lung infection (1 subject) and increased ALT 
(1 subject); both these events were grade 3 in severity.  Eight subjects (8.4%) had fatal 
adverse events; all were considered unrelated to AMG 510 treatment by the investigator. 
Phase 2 portion, which further evaluate efficacy of AMG 510 monotherapy in previously 
treated NSCLC, CRC, and other tumor types, is ongoing. 
2.2.3 
Non-Amgen Investigational Product Background:  Docetaxel 
Docetaxel is a semisynthetic taxane, a class of anticancer agents that bind to β tubulin, 
thereby stabilizing microtubules and inducing cell-cycle arrest and apoptosis.  
Docetaxel Clinical Experience as Second Line Treatment in NSCLC 
Two trials have shown the benefit of docetaxel as a second-line agent in subjects with 
non-small-cell lung cancer who had platinum-resistant tumors.  The first trial (TAX 317) 
assigned patients with stage IIIB or IV disease that was refractory to platinum-based 
regimens to either docetaxel or best supportive care.  Subjects in the docetaxel group 
were assigned 100 mg/m2 as a 1-h intravenous infusion once every 21 days, but 
because of an unexpectedly high incidence of febrile neutropenia and deaths from 
sepsis, the dose was lowered to 75 mg/m2.  Median time to progression favored 
docetaxel over supportive care.  In an intention-to-treat (ITT) analysis of all subjects 

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allocated docetaxel, median OS was significantly extended compared with controls 
(7·0 months vs 4·6 months, p = 0·047).  One-year OS was also enhanced in the 
docetaxel group compared with controls (29% vs 19%).  Febrile neutropenia was less 
frequent with 75 mg/m2 docetaxel (2%) than at the higher dose (22%), with no deaths 
from sepsis. 
TAX 320 assigned 373 subjects with stage IIIB or IV non-small-cell lung cancer who 
had disease progression during or after one or more platinum-based chemotherapy 
regimens to 1 of 3 treatments: 100 mg/m2 docetaxel every 3 weeks; 75 mg/m2 docetaxel 
every 3 weeks; or to either 30 mg/m2 weekly vinorelbine or 2 g/m2 ifosfamide for 3 days 
every 3 weeks.  About 90% of subjects had stage IV disease at the time of enrollment.  
Overall response was 11% with 100 mg/m2 docetaxel and 7% with 75 mg/m2 docetaxel, 
both of which were significantly greater than the 1% response noted for those assigned 
vinorelbine or ifosfamide.  Intention-to-treat analysis showed a modest but significant 
improvement in time to progression and 26-week PFS in favor of docetaxel.  Groups did 
not differ in median OS.  However, 1 year OS favored 75 mg/m2 docetaxel compared 
with vinorelbine or ifosfamide.  Moreover, a third of subjects in each group received 
subsequent chemotherapy on removal from the trial (including taxane treatment in 21% 
of subjects in the control group) and thus an ITT survival curve, in which survival 
observations were censored when subjects received subsequent chemotherapy, was 
generated.  In this analysis, 1-year survival significantly favored docetaxel over 
vinorelbine or ifosfamide.  Quality-of-life analysis, which was assessed prospectively, 
suggested that docetaxel was more effective than control treatment.  Grade 4 
neutropenia and febrile neutropenia were more frequent in both groups assigned 
docetaxel compared with the control group.  However, documented infection and grade 
4 thrombocytopenia were much the same for all 3 groups (reviewed in  
Montero et al, 2005). 
Indication 
Docetaxel 75 mg/m2 administered intravenously over 1 hour every 3 weeks as a 
monotherapy is approved by the Food and Drug Administration (FDA) and the European 
Medicines Agency (EMA) for the treatment of patients with locally advanced or 
metastatic NSCLC after failure of prior platinum-based chemotherapy.  It is also 
approved by the FDA and the EMA in combination with cisplatin for the treatment of 
chemotherapy naïve unresectable, locally advanced, or metastatic NSCLC.  Refer to the 

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regional manufacturer package insert for additional information (for example; Taxotere® 
SmPC; Taxotere® United States Prescribing Information [USPI]). 
2.3 
Benefit/Risk Assessment 
Based on preclinical data, nonclinical toxicity studies, and the clinical experience with 
AMG 510, the overall benefit/risk profile favors clinical development of AMG 510 for 
NSCLC subjects with KRAS p.G12C mutation. 
Preliminary efficacy data from Study 20170543 demonstrated anti-tumor activity of 
AMG 510 monotherapy in NSCLC subjects with KRASG12C.  As of the 12 June 2019 data 
cutoff date, Study 20170543 had enrolled 62 subjects, 27 with NSCLC, 31 with CRC, 
and 4 with other solid tumors.  Thirty-nine of the 62 enrolled subjects were evaluable for 
efficacy as of the 12 June 2019 data cutoff date.  Preliminary results demonstrated 
antitumor activity in KRAS p.G12C mutated NSCLC, with 7 of 17 evaluable subjects 
having a PR (5 confirmed) and 8 subjects having stable disease (2 subjects had 
progression).   
In addition, no cumulative toxicities were noted with extended treatment, suggesting that 
AMG 510 may provide a safe and novel therapeutic option for subjects with advanced 
cancer. 
Based on nonclinical toxicity studies of AMG 510, the key safety information to be 
monitored in clinical studies of AMG 510 includes renal toxicity, anemia, leukocytosis, 
and splenomegaly.  Based on the clinical study data of AMG 510, the key risks to be 
monitored include increases to aspartate aminotransferase (AST) and alanine 
aminotransferase (ALT) and interstitial lung disease (ILD)/pneumonitis.  Clinical 
signs and symptoms along with safety laboratories, such as liver enzymes, will be 
monitored during the study to ensure the subjects’ safety.  More detailed 
information about the safety profile and risks of AMG 510, including the most 
recent information on adverse drug reactions based on the ongoing clinical 
program, may be found in the AMG 510 Investigator’s Brochure and the regional 
Prescribing Information (if applicable). 
The above benefit risk assessment supports the conduct of this clinical trial.  Refer to the 
AMG 510 Investigator’s Brochure for further data on AMG 510. 

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3. 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
 
To compare the efficacy of 
AMG 510 versus docetaxel as 
assessed by progression-free 
survival (PFS) in previously 
treated subjects with 
KRAS p.G12C mutated 
non-small cell lung cancer 
(NSCLC)  
 
PFS - defined as time from randomization until 
disease progression or death from any cause, 
whichever occurs first for all subjects.  Progression 
will be based on blinded independent central review 
(BICR) of disease response per Response Evaluation 
Criteria in Solid Tumors version 1.1 (RECIST v1.1). 
Attributes 
Primary Estimand 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Primary Endpoint 
 
PFS 
 
Summary Measures 
 
Hazard Ratio (HR) 
 
Intercurrent Events and 
Strategies 
 
Start of new anti-cancer therapy prior to PFS 
event 
 PFS is censored at the date of last evaluable 
assessment before or on start of new anti-
cancer therapy.  
Primary Estimand Description 
HR of PFS between AMG 510 and docetaxel, for subjects with previously treated locally 
advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation, before or 
on start of new anti-cancer therapy 
Key Secondary 
 
To compare the efficacy of 
AMG 510 versus docetaxel as 
assessed by:   
 
Overall Survival (OS) 
 
Objective response rate 
(ORR)  
 
Overall survival - defined as time from randomization 
until death from any cause.   
 
Objective response (complete response [CR] + partial 
response [PR]), assessed per RECIST v1.1.  
Response will be assessed by BICR.  Complete 
response and PR require confirmatory repeat 
radiologic assessment at no less than 4 weeks after 
the original response.  The normal subsequent 
assessment is acceptable to confirm response. 
 
To compare patient-reported 
outcomes (PRO) as assessed 
by:  European Organization 
for Research and Treatment 
of Cancer Quality-of-life 
Questionnaire Core 13 
(EORTC QLQ-LC13) and 
European Organization for 
Research and Treatment of 
Cancer Quality-of-life 
 
Change from baseline (cycle 1 day 1) over time to 
week 12 in disease related symptoms of:  
o 
Dyspnea as measured by a 4-item 
dyspnea domain from QLQ-C30 and 
QLQ-LC13 
 
Cough as measured by QLQ-LC13 
 
Chest Pain as measured by QLQ-LC13  
 
Change from baseline over time to week 12 in 
 
Physical functioning as measured by QLQ-C30 

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Questionnaire Core 30 
(EORTC QLQ-C30) 
 
Global health status as measured by QLQ-C30 
Attributes 
Secondary Estimand - OS 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Key Secondary Endpoint 
 
OS 
 
Summary Measures 
 
Hazard Ratio (HR) 
 
Intercurrent Events and 
Strategies 
 
Start of new anti-cancer therapy  
 OS will be estimated regardless of subsequent 
anti-cancer therapy. 
 
Crossover from control group to treatment group  
 OS will be estimated regardless of crossover. 
Secondary Estimand Description - OS 
HR of OS between AMG 510 and docetaxel, for subjects with previously treated locally 
advanced and unresectable or metastatic NSCLC with KRAS p.G12C mutation, regardless 
of subsequent anti-cancer therapy and/or crossover. 
Attributes 
Secondary Estimand – Objective Response 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Key Secondary Endpoint 
 
Objective Response 
 
Summary Measures 
 
Odds Ratio 
 
Intercurrent Events and 
Strategies 
 
Discontinuation of treatment prior to achieving an 
objective response (PR or CR) 
 Subjects will be considered as non-responders. 
Secondary Estimand Description – Objective Response 
Odds ratio of objective response between AMG 510 and docetaxel, for subjects with 
previously treated locally advanced and unresectable or metastatic NSCLC with KRAS 
p.G12C mutation.  Subjects who discontinued treatment prior to achieving an objective 
response are considered as non-responders.  
Attributes 
Secondary Estimand - PRO 
 
Target Population 
 
Subjects with previously treated locally advanced 
and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation 
 
Key Secondary Endpoint 
 
PRO 
 
Summary Measures 
 
Change from baseline to Week 12 

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 
Intercurrent Events and 
Strategies 
 
Start of new anti-cancer therapy including 
crossover before Week 12 
 PRO measurements before or on start of new 
anti-cancer therapy including crossover will be 
used to estimate treatment effect. 
Secondary Estimand Description - PRO 
Change from baseline to Week 12 in PRO endpoints between AMG 510 and docetaxel, for 
subjects with previously treated locally advanced and unresectable or metastatic NSCLC 
with KRAS p.G12C mutation.  PRO measurements before or on start of new anti-cancer 
therapy including crossover will be used to estimate treatment effect. 
Secondary 
 
To compare efficacy of 
AMG 510 versus docetaxel as 
assessed by:  duration of 
response (DOR), time to 
response (TTR), and disease 
control rate (DCR) 
 
Duration of response - defined as time from first 
evidence of PR or CR to disease progression or death 
due to any cause, whichever occurs first.  Progression 
will be based on an BICR assessment of disease 
response per RECIST v1.1. 
 
Time to response - defined as time from 
randomization to first evidence of PR or CR. 
 
Disease control rate - defined as rate of confirmed 
objective response (CR or PR) + stable disease per 
RECIST v1.1 of at least 6 weeks measured 
 
To compare the safety and 
tolerability of AMG 510 versus 
docetaxel  
 
Subject incidence of treatment-emergent adverse 
events, treatment-related adverse events, changes in 
vital signs, and clinical laboratory tests. 
 
To compare the effect of 
treatment with AMG 510 on 
other treatment and disease 
related symptoms, and health 
related quality of life relative 
to docetaxel  
 
Change from baseline over time to week 12 for the 
remaining subscales for QLQ-LC13 and QLQ-C30 
 
Time to deterioration for the subscales for QLQ-LC13 
and QLQ-C30 
 
Summary scores at each assessment and changes 
from baseline of visual analogue scale (VAS) scores 
as measured by EuroQol-5 Dimension (EQ5D5L)  
 
To characterize the 
pharmacokinetics (PK) of 
AMG 510 and its major 
metabolites 
 
Pharmacokinetic (PK) parameters of AMG 510 
including, but not limited to, maximum plasma 
concentration (Cmax), area under the plasma 
concentration-time curve (AUC) on Days 1 and 8, and 
pre-dose (trough) concentrations through cycle 4 
 
 
Exploratory 

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4. 
Study Design 
4.1 
Overall Design 
This is a phase 3, multicenter, randomized, open label, active-controlled, study to 
evaluate the efficacy, safety, and tolerability of AMG 510 versus docetaxel in subjects 
with previously treated locally advanced and unresectable or metastatic NSCLC with 
KRAS p.G12C mutation.  The study will be conducted at approximately 290 sites 
globally.  The study will consist of a screening period, a treatment period, a safety 
follow-up (SFU) period, and long term follow up period.  See Section 8.1.6 and 
Section 8.1.7 for AMG 510 and docetaxel treatment beyond radiologic progression.  See 
Section 8.1.8 for crossover.  Approximately 330 previously treated subjects with locally 
advanced and unresectable or metastatic NSCLC with centrally confirmed 
KRAS p.G12C mutation will be enrolled. 

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Subjects must have documentation of KRAS p.G12C mutation identified by central 
laboratory testing with the Qiagen KRAS therascreen® KRAS Rotor-Gene Q (RGQ) PCR 
Kit through Amgen Study 20190294 or through this protocol. 
Subjects will be randomized 1:1 to receive either AMG 510 or docetaxel and stratified by 
number of prior lines of therapy in advanced disease (1 versus 2 versus > 2), race 
(Asian versus non-Asian), and history of CNS involvement (present or absent).  Prior 
lines of therapy will be assessed using the criteria below: 
 
Chemoradiation for locally advanced and unresectable disease is a line of 
therapy for advanced disease if progression occurs within 6 months of end of 
treatment. 
 
Chemoradiation followed by planned systemic therapy (including checkpoint 
inhibitor) or vice versa without documented intervening progression is considered 
one line of therapy if progression occurs within 6 months of end of treatment 
 
Adjuvant therapy is a line of therapy for advanced disease if progression occurs 
within 6 months of end of treatment. 
 
Each new systemic anti-cancer regimen for progressive locally advanced and 
unresectable or metastatic disease is a line of therapy. 
 
Maintenance therapy is not considered a new line of therapy. 
 
Chemotherapy regimen adjustments for intolerability is not a new line of therapy. 
Cycle 1 day 1 will be defined as the first day subject receives study medication.  A cycle 
is 21 days in length  3 days, unless a delay is medically necessary.  A  3-day window 
is allowed for protocol required assessments, unless otherwise specified.  Tumor 
assessment will be conducted (by magnetic resonance imaging [MRI] and/or contrast 
enhanced computerized tomography [CT]) during screening (within 28 days of day 1); 
every 6 weeks from cycle 1 day 1; (± 7 days) (at weeks 7, 13, 19, 25, 31, 37, 43, and 
49), and then at 9 week intervals (± 7 days) thereafter until independent central 
confirmation of progression, start of another anti-cancer therapy, withdrawal of consent, 
lost to follow up, or death, whichever occurs earliest.  Subjects’ scans will undergo 
independent central confirmation of progression (COP) at the time of first progressive 
disease (PD).  Subjects that undergo treatment beyond progression or crossover, from 
docetaxel to AMG 510, will continue to receive scans after confirmation of first PD.  
Further details with regards to imaging assessments post treatment period are listed in 
Section 8.1.4. 
Once subjects on the docetaxel arm are determined to have radiological progression 
according to RECIST v1.1 by the investigator and progressive disease is confirmed by 
independent central imaging review, they will be given the opportunity to crossover and 

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receive AMG 510.  Alternatively, should an early efficacy of the study be noted by the 
DMC, crossover will be considered for all subjects who randomized into the docetaxel 
arm (so that they will be able to immediately receive AMG 510).  All subjects remaining 
on study will be followed for survival, as specified in the Schedule of Activities 
(Section 1.3), until the pre-specified OS events are reached, regardless of the OS 
analysis result at the PFS primary analysis.  
Tumor assessment and response will be confirmed by BICR who will evaluate disease 
progressions and responses without the knowledge of randomization assignments, in 
accordance with the RECIST v1.1.  This assessment will be used for the primary 
analysis (PA) of endpoints.  
In all subjects, after the end of IP, information regarding the date of progression, type 
and duration of subsequent therapies following disease progression, response to 
subsequent therapy, date of progression on subsequent therapy, and survival data will 
be collected.  Subjects who discontinue treatment prior to RECIST v1.1 disease 
progression (eg, due to unacceptable toxicity) will also continue to be followed with 
tumor assessments until independent central confirmation of progression, withdrawal of 
consent, or start of another anti-cancer therapy then followed for subsequent anti-cancer 
therapy and survival.  Subjects that consent to treatment beyond progression or 
consent to crossover, from docetaxel to AMG 510, will continue to receive investigational 
product after independent central confirmation of progression at the time of first 
progressive disease (PD).  In select cases, subjects may continue on treatment following 
radiologic progression if they are continuing to demonstrate clinical benefit (see 
Section 8.1.6 and 8.1.7). 
The assessments to be conducted in this study are described below and will be carried 
out at the timepoints designated in the Schedule of Activities (Table 1-1 and Table 1-2): 
 
Central confirmation of KRAS p.G12C mutation status for all enrolling subjects. 
 
Disease progression will be assessed using RECIST v1.1.  The primary efficacy 
objective will be assessed by BICR.  
 
Expedited independent confirmation of progression (COP), at time of first progressive 
disease (PD), will be performed by a single radiologist separate from the central 
radiologist group reading the images for (as described in Section 8.2.2.1.2 ) prior to 
moving forward with treatment beyond progression or crossover.  
 
Safety will be monitored by assessing serious and non-serious adverse events, 
safety laboratory tests, vital signs and electrocardiograms (ECGs).  Adverse events 
will be graded according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).  

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 
Laboratory safety tests will include hematology, blood chemistry, cholesterol, 
coagulation, urinalysis, and thyroid function test.  Vital sign assessments will include 
blood pressure, heart rate, oxygen saturation, respiratory rate, and body 
temperature; additional vital signs will be collected only if clinically warranted.  The 
urine studies may be performed at a local laboratory and/or by the central laboratory, 
depending on the availability of the testing facility. 
 
PK characterization will be conducted using sparse sampling and population PK 
modeling approach. 
 
PRO/QOL assessments will be assessed using the PRO instruments QLQ-C30, 
QLQ-LC13, EQ-5D-5L, and PRO-CTCAE, plus a single item about symptom bother 
(GP5 of the FACT-G).  Patient pain and patient impression of change and severity 
will be assessed using the brief pain inventory (BPI), patient global impression of 
change (PGIC) and patient global impression of severity (PGIS) questionnaires.  
Patient-reported outcomes scores will be determined for all subjects at baseline 
(cycle 1 day 1) and at timepoints designated in the SOA and will be compared across 
treatment groups. 
 
Further tissue assessments at the time of independent central confirmation of 
progression:   
 
If a subject is not continuing AMG 510 upon radiologic progression, they will be 
encouraged to enroll in an optional sub-study assessing exploratory biomarkers 
via an optional tumor biopsy (excisional, core needle, or fine needle aspirates) 
only if biomarker research is allowed according to local regulations and agreed 
by local EC/IRB. 
 
If a subject plans to continue on AMG 510 treatment beyond radiologic 
progression, the subject must be willing to undergo biopsy, if clinically feasible or 
advisable, (excisional, core needle, or fine needle aspirates) of one of the new or 
progressing lesions (see Section 8.1.6 for additional criteria) only if biomarker 
research is allowed according to local regulations and agreed by local EC/IRB. 
An independent data monitoring committee (DMC) will be convened for this study and 
will act in an advisory capacity to the sponsor with respect to safeguarding the interests 
of study subjects, assessing interim safety and efficacy data, monitoring the overall 
conduct of the study, and providing recommendations relating to continuing, modifying, 
or stopping the study based on these findings (International Council for Harmonisation 
Good Clinical Practice [ICH GCP 5.5.2]).  Details of the DMC will be described in the 
DMC Charter.   
Data monitoring committee will review safety and efficacy data as per DMC charter.  
Data monitoring committee will meet to review safety after 50, 100, and 200 subjects are 
enrolled and have had the opportunity to be treated for at least 6 weeks and thereafter at 

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approximately 6-month intervals, until the PA of PFS.  The DMC will also review the IA 
data for PFS and OS, whenever these are triggered.   
There will be 2 planned PFS efficacy analyses.  The PA of PFS will occur when 
approximately 230 PFS events have been observed.  The PFS PA may be delayed to 
ensure that the enrollment is finished and the delayed PA will be triggered when the last 
randomized subject have had the opportunity to have at least 6 weeks of follow up.  An 
IA of PFS for superiority is planned when approximately 70% (160 events) of the total 
PFS events have been observed from both arms, or when the enrollment is finished and 
the last randomized subject have had the opportunity to have 6 weeks of follow up, 
whichever occurs later.  
Early efficacy at the proposed PFS interim analysis will be claimed if the observed PFS 
difference meets the pre-specified statistical significance as well as being considered 
clinically meaningful.  More details will be included in the DMC charter.   
If PFS achieves statistical significance at the interim analysis, an administrative interim 
summary for OS will be performed.  Otherwise, the OS will be assessed for superiority of 
AMG 510 over docetaxel at either the time of PFS primary analysis or after 175 OS 
events have been observed, whichever is later.  The OS primary analysis will occur 
when at least 198 OS events (~60% maturity) have been observed, which is expected to 
be at approximately 3 months after PFS primary analysis.  The analysis of ORR will be 
done at the time when PFS is claimed statistically significant and the last randomized 
subject has had the opportunity to have at least 12 weeks of follow up.  The final 
analysis will be performed when the last subject has completed long-term follow-up 
(LTFU).   
As designed, the trial will not be terminated at PFS analyses and subjects will continue 
to be followed for OS data until the targeted number of events are reached, regardless of 
the OS analysis result at the PFS primary analysis, to enable OS analyses and a robust 
description of the totality of the data.  
The overall study design is described by a study schema in Section 1.2.  The endpoints 
are defined in Section 3. 
4.2 
Number of Subjects 
Approximately 330 subjects with locally advanced unresectable or metastatic centrally 
confirmed KRAS p.G12C mutation will be enrolled in the study (approximately 
165 subjects in each of the 2 treatment groups).  Subjects will be randomized 1:1 to 

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receive either monotherapy AMG 510 or docetaxel.  Once subjects on the docetaxel arm 
are determined to have radiological progression according to RECIST v1.1 by the 
investigator and progressive disease is confirmed by independent central imaging 
review, they will be given the opportunity to crossover and receive AMG 510.  
Alternatively, should an early efficacy of the study be noted by the DMC, crossover will 
be considered for all subjects who randomized into the docetaxel arm (so that they will 
be able to immediately receive AMG 510). All subjects remaining on study will be 
followed for survival, as specified in the Schedule of Activities (Section 1.3), until the 
pre-specified OS events are reached, regardless of the OS analysis result at the PFS 
primary analysis.  
Subjects in this clinical investigation shall be referred to as “subjects”.  For the sample 
size justification, see Section 9.2. 
4.2.1 
Replacement of Subjects 
Subjects who are withdrawn or removed from treatment or the study will not be replaced. 
4.2.2 
Number of Sites 
Approximately 290 investigative sites globally will be included in the study.  Sites that do 
not enroll subjects within 6 months of site initiation may be closed. 
4.3 
Justification for Investigational Product Dose 
4.3.1 
Amgen Investigational Product Dose 
The nonclinical profile of AMG 510 suggests that a high initial exposure (Cmax), with 
enough residual exposure to inhibit a resynthesized pool of KRASG12C could be ideal for 
inhibition of mutated KRAS in humans, while limiting exposure to non-target tissues. 
Study 20170543 is the first clinical test of this hypothesis in subjects with KRAS p.G12C 
mutated solid tumors.  Study 20170543 is a phase 1/2, multicenter, nonrandomized, 
open-label study of PO AMG 510 in subjects with KRAS p.G12C mutated advanced or 
metastatic NSCLC, CRC, or other solid tumors.  The phase 1 portion of the study was 
conducted in 2 parts:  part 1 - dose exploration and part 2 - dose expansion.  Phase 1 
part 1 was aimed at evaluating the safety, tolerability, PK, and pharmacodynamics of 
AMG 510 and determining the maximum tolerated dose (MTD) and/or a biologically 
active dose (eg, recommended phase 2 dose [RP2D]) of repeat QD dosing schedule in 
subjects with advanced KRAS p.G12C mutated solid tumors using a Bayesian Logistics 
Regression Model (BLRM) design.  The evaluation period for DLTs was the first 

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treatment cycle (ie, 21 days after the first dose) of the dose exploration part of the study 
(part 1).  
The phase 1 monotherapy dose exploration part of Study 20170543 has yielded early 
evidence of activity (even in this heavily pretreated population), as demonstrated by 
preliminary data.  As of the 12 June 2019 data cutoff date, Study 20170543 had enrolled 
62 subjects, 27 with NSCLC, 31 with CRC, and 4 with other solid tumors.  Thirty-nine of 
the 62 enrolled subjects were evaluable for efficacy as of the 12 June 2019 data cutoff 
date.  Preliminary results demonstrated antitumor activity in KRAS p.G12C mutated 
NSCLC, with 7 of 17 evaluable subjects having a PR (5 confirmed) and 8 subjects 
having stable disease (2 subjects had progression).   
AMG 510 was well tolerated at the 180 mg QD to 960 mg QD dose levels tested 
(Section 2.2.2).   
In conclusion, 960 mg QD PO AMG 510 was recommended as the dose to be 
administered for the phase 2 portion of the study.  From a PK perspective, correlations 
were observed between AUC, Cmax, and concentration at 24 hours (C24-hour) (on both 
day 1 and day 8) and the percent change in sum of tumor lesion from screening to 
cycle 3, day 1.  The types and frequency of adverse events at the 960 mg dose were 
consistent with those observed at lower doses, suggesting that the overall benefit-risk 
profile at 960 mg QD PO will be favorable.  
4.3.2 
Non-Amgen Investigational Product Dose 
Docetaxel at a dose of 75 mg/m2 was tolerable and yielded a favorable outcome in 
patients previously treated with platinum-based chemotherapy.  Docetaxel at a dose of 
100 mg/m2, however, was associated with unacceptable hematologic toxicity, infections, 
and treatment-related mortality and this dose should not be used (eg, Taxotere® SmPC; 
Taxotere® United States Prescribing Information [USPI]).  The dose of docetaxel in 
Study 20190009 is 75 mg/m2 administered intravenously over 1 hour every 3 weeks, in 
accordance with the terms of the Taxotere® product information documentation. 
 
4.4 
End of Study 
4.4.1 
End of Study Definition 
Primary Completion:  The primary completion date is defined as the date when the last 
subject is assessed or receives an intervention for the final collection of data for the 
primary and key secondary endpoint(s).  

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If the study concludes prior to the primary completion date originally planned in the 
protocol (ie, early termination of the study), then the primary completion will be the date 
when the last subject is assessed or receives an intervention for evaluation in the study 
(ie, last subject last visit). 
End of Study:  The end of study date is defined as the date when the last subject 
across all sites is assessed or receives an intervention for evaluation in the study (ie, last 
subject last visit), following any additional parts in the study (eg, LTFU, additional 
antibody testing), as applicable. 
4.4.2 
Study Duration for Subjects 
The total study duration is estimated to be up to 6.5 years.  This includes a screening 
period of up to 28 days, duration of treatment for an individual subject of approximately 
8 months followed by an SFU visit that occurs 30 days ( 7 days) after the last dose of 
all study drug.  After the SFU visit, subjects enter LTFU for up to 5 years.   
4.5 
Patient Input on Study Design 
Feedback on general concepts around study design (eg, screening requirements, 
hospitalization, length of study), procedures, and the informed consent form (ICF) were 
considered based on a patient panel conducted by Amgen in patients with NSCLC.   
5. 
Study Population 
Investigators will be expected to maintain a screening log of all potential study 
candidates that includes limited information about the potential candidate (eg, date of 
screening).   
Eligibility criteria will be evaluated during the screening period. 
Before any study-specific activities/procedures, the appropriate written informed consent 
must be obtained (see Section 11.3). 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, will not be provided. 
5.1 
Inclusion Criteria 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
101. 
Subject or subject’s legally acceptable representative has provided informed 
consent prior to initiation of any study specific activities/procedures. 
102. 
Age  18 years of age 
103. 
Histologically or pathologically documented, locally-advanced and unresectable or 
metastatic NSCLC. 

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104. 
Have documentation of KRAS p.G12C mutation confirmed by central testing 
through the current protocol or have documentation of KRAS p.G12C mutation 
through Amgen Study 20190294 prior to enrollment.   
105. 
Subjects will have received and progressed or experienced disease recurrence on 
or after receiving at least 1 prior systemic therapy for locally advanced and 
unresectable or metastatic disease.  Prior treatment must include a platinum-
based doublet chemotherapy and checkpoint inhibitor for advanced or metastatic 
disease, either given as one line of therapy or as individual lines of therapy 
unless the subject has a medical contraindication to one of the required 
therapies.  If the subject has a medical contraindication to a required therapy, the 
subject may be enrolled only after the investigator discusses and obtains 
approval from the Amgen medical monitor. 
a) Adjuvant therapy will count as a line of therapy if the subject 
progressed on or within 6 months of adjuvant therapy administration.  
b) In locally advanced and unresectable NSCLC, disease progression on 
or within 6 months of end of prior curatively intended multimodal 
therapy will count as a line of therapy.  If chemoradiation is followed 
by planned systemic therapy without documented progression 
between chemoradiation and systemic therapy, the entire treatment 
course counts as one line of therapy. 
c) Maintenance therapy following platinum doublet-based chemotherapy 
is not considered as a separate line of therapy. 
106. 
Subjects must have archived tumor tissue samples (formalin fixed, paraffin 
embedded [FFPE] sample [FFPE of excisional, core needle, or fine needle 
aspirate] collected within 5 years) or be willing to undergo pre-treatment tumor 
biopsy (excisional, core needle, or fine needle aspirate) for tissue prior to 
enrollment.  
107. 
Measurable disease per RECIST v1.1 criteria.  Lesions previously radiated are 
not considered measurable unless they have progressed after radiation. 
108. 
ECOG Performance Status of  1  
109. 
Adequate hematologic laboratory assessments, defined as the following within 
10 days prior to start of study therapy:  
a) Absolute neutrophil count (ANC)  1500 cells/l (without granulocyte 
colony-stimulating factor support within 10 days of laboratory test 
used to determine eligibility) 
b) Hemoglobin  9.0 g/dL (without transfusion within 2 weeks of 
laboratory test used to determine eligibility) 
c) Platelet count  100 000/l (without transfusion within 2 weeks of 
laboratory test used to determine eligibility) 
110. 
Life expectancy of > 3 months, in the opinion of the investigator 
111. 
Adequate liver function, defined as the following: 
a) Aspartate aminotransferase (AST) and, alanine aminotransferase 
(ALT)  2.5 times the upper limit of normal (ULN), except if alkaline 
phosphatase > 2.5 times the ULN, then AST and/or ALT must be 
 1.5 times the ULN 
b) Serum bilirubin  1.0 x ULN 

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112. 
International normalized ratio (INR) and activated partial thromboplastin time 
 1.5 x ULN  
113. 
Serum creatinine  1.5 x ULN OR creatinine clearance  60 mL/min.  Cockcroft-
Gault formula will be used for creatinine clearance calculation.  Twenty-four hour 
urine collection is not required but is allowed. 
114. 
QTc  470 msec in females and  450 msec in males (based on average of 
screening triplicates) 
115. 
Ability to take oral medications and willing to record daily adherence to 
investigational product 
5.2 
Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria apply: 
Disease Related 
201. 
Subjects have received prior docetaxel in unresectable or metastatic setting 
(including subjects who received prior docetaxel in first line for metastatic 
disease, but not including subjects who received prior docetaxel neoadjuvantly or 
adjuvantly and did not progress within 6 months of end of therapy). 
202. 
Mixed small-cell lung cancer or mixed NSCLC histology   
203. 
Previously identified driver mutation (according to local standard of care or 
guidelines) other than KRAS p.G12C for which an approved therapy is available 
(including EGFR, ALK, etc). 
204. 
Active brain metastases.  Subjects who have had brain metastases resected or 
have received whole brain radiation therapy ending at least 4 weeks (or 
stereotactic radiosurgery ending at least 2 weeks) prior to study day 1 are eligible 
if they meet all of the following criteria:  a) residual neurological symptoms grade 
 2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if 
applicable; and c) follow-up MRI performed within 30 days prior to enrollment 
shows no progression or new lesions appearing.  
Active brain metastases are defined as:  Untreated brain lesions (new or 
progressing) and/or symptomatic brain lesions (symptoms as determined by the 
investigator), present at the time of study entry.  
205. 
Leptomeningeal disease. 
206. 
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent 
drainage procedures at a frequency greater than monthly.  Subjects with PleurX 
catheters in place may be considered for the study with Medical Monitor 
approval. 
Other Medical Conditions  
207. 
Known history of Human Immunodeficiency Virus (HIV) infection  
208. 
Exclusion of hepatitis infection based on the following results and/or criteria: 
a) Positive hepatitis B surface antigen (HepBsAg) (indicative of chronic 
Hepatitis B or recent acute hepatitis B) 
b) Negative HepBsAg with a positive for hepatitis B core antibody (Hepatitis B 
core antibody testing is not required for screening, however if this is done and 
is positive, then hepatitis B surface antibody [Anti-HBs] testing is necessary.  

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Undetectable anti-HBs in this setting would suggest unclear and possible 
infection, and needs exclusion). 
c) Positive Hepatitis C virus antibody:  Hepatitis C virus RNA by polymerase 
chain reaction is necessary.  Detectable Hepatitis C virus RNA renders the 
subject ineligible. 
If above antibody/antigen testing is not able to be obtained, positive hepatitis B or 
C viral load 
209. 
Malignancy other than NSCLC within 3 years prior to randomization, with the 
exception of those with a negligible risk of metastases or death and treated with 
expected curative outcome (such as adequately treated carcinoma in situ of the 
cervix, basal cell carcinoma, cutaneous squamous cell carcinoma, localized 
prostate cancer treated with curative intent, or ductal carcinoma in situ treated 
surgically with curative intent). 
210. 
Major surgery within 28 days of study day 1 
211. 
Significant gastrointestinal disorder that results in significant malabsorption, 
requirement for intravenous alimentation, or inability to take oral medication. 
212. 
Significant cardiovascular disease, such as New York Heart Association cardiac 
disease (Class II or greater), myocardial infarction within 6 months prior to study 
day 1, unstable arrhythmias or unstable angina. 
213. 
Severe infections within 4 weeks prior to randomization including, but not limited 
to hospitalization for complications of infection, bacteremia or severe pneumonia. 
214. 
Therapeutic oral or intravenous antibiotics within 2 weeks prior to randomization.  
Prophylactic antibiotics are allowed with Amgen medical monitor approval. 
215. 
Current CTCAE version 5.0 grade  2 peripheral neuropathy  
Prior/Concomitant Therapy 
216. 
Unresolved toxicities from prior anti-tumor therapy, defined as not having 
resolved to CTCAE version 5.0 grade 0 or 1, or to levels dictated in the eligibility 
criteria with the exception of alopecia (any grade allowed) or toxicities from prior 
anti-tumor therapy that are considered irreversible (defined as having been 
present and stable for > 6 months), endocrine adverse events that are stably 
maintained on appropriate replacement therapy. 
217. 
Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, 
retinoid therapy, hormonal therapy [except for subjects with history of completely 
resected breast cancer with no active disease for over 3 years on long term 
adjuvant endocrine therapy], or investigational agent) within 4 weeks of study 
day 1; Please note that bisphosphonates or anti-Receptor Activator of Nuclear 
Factor Kappa Beta Ligand (anti-RANKL) antibody therapy is allowed if needed for 
management of hypercalcemia or for prevention of skeletal events. 
218. 
Therapeutic or palliative radiation therapy within 2 weeks of study day 1.  
Subjects must have recovered from all radiotherapy related toxicity to CTCAE 
version 5.0 grade 1 or less with the exception of alopecia (any grade of alopecia 
allowed). 
219. 
Other investigational procedures are excluded 
220. 
Previous treatment with AMG 510 or other KRAS G12C inhibitor 

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221. 
History of severe hypersensitivity to docetaxel or to other drugs formulated with 
polysorbate 80, or known sensitivity to any of the products or components to be 
administered during dosing. 
222. 
Use of known cytochrome P450 (CYP) 3A4 or P-gp sensitive substrates (with a 
narrow therapeutic window), within 14 days or 5 half-lives of the drug or its major 
active metabolite, whichever is longer, prior to study day 1 that was not reviewed 
and approved by the principal investigator and the Amgen medical monitor. 
223. 
Use of strong inducers of CYP3A4 (including herbal supplements such as 
St. John’s wort) within 14 days or 5 half-lives (whichever is longer) prior to study 
day 1 that was not reviewed and approved by the principal investigator and the 
Amgen medical monitor.  
224. 
Use of warfarin.  Other anticoagulation may be allowed with Amgen medical 
monitor approval 
Prior/Concurrent Clinical Study Experience 
225. 
Currently enrolled in another investigational device or drug study, or less than 
4 weeks since ending another investigational device or drug(s), or receiving other 
investigational agent(s)  
Other Exclusions 
226. 
Female subject is pregnant or breastfeeding or planning to become pregnant or 
breastfeed during treatment and for an additional 7 days after the last dose of 
AMG 510 or during treatment with docetaxel and 6 months after last dose of 
docetaxel if planning to become pregnant. 
227. 
Female subjects of childbearing potential unwilling to use 1 highly effective 
method of contraception during treatment and for an additional 7 days after the 
last dose of AMG 510 and 6 months after the last dose of docetaxel. 
228. 
Female subjects of childbearing potential with a positive pregnancy test 
assessed at Screening or day 1 by a serum pregnancy test and/or urine 
pregnancy test.  
229. 
Male subjects with a female partner of childbearing potential who are unwilling to 
practice sexual abstinence (refrain from heterosexual intercourse) or use 
contraception during treatment and for an additional 7 days (AMG 510) or 
6 months (docetaxel) after the last dose of investigational product. 
230. 
Male subjects with a pregnant partner who are unwilling to practice abstinence or 
use a condom during treatment and for an additional 7 days (AMG 510) or 
6 months (docetaxel) after the last dose of investigational product. 
231. 
Male subjects unwilling to abstain from donating sperm during treatment and for 
an additional 7 days (AMG 510) or 6 months (docetaxel) after the last dose of 
investigational product.  Refer to Section 11.5 for additional contraceptive 
information. 
232. 
Subject likely to not be available to complete all protocol-required study visits or 
procedures, and/or to comply with all required study procedures (eg, Clinical 
Outcome Assessments) to the best of the subject and investigator’s knowledge. 
233. 
History or evidence of any other clinically significant disorder, condition or 
disease (with the exception of those outlined above) that, in the opinion of the 
investigator or Amgen physician, if consulted, would pose a risk to subject safety 

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or interfere with the study evaluation, procedures or completion, or interpretation 
of results. 
5.3 
Subject Enrollment 
Before subjects begin participation in any study-specific activities/procedures, Amgen 
requires a copy of the site’s written IRB/independent ethics committee (IEC) approval of 
the protocol, ICF, (and all other subject information and/or recruitment material, if 
applicable [see Section 11.3]). 
The subject or the subject’s legally acceptable representative must personally sign and 
date the IRB/IEC and Amgen approved informed consent before commencement of 
study-specific procedures. 
A subject is considered enrolled when the investigator decides that the subject has met 
all eligibility criteria.  The investigator is to document this decision and date, in the 
subject’s medical record and on the enrollment case report form (CRF). 
Each subject who enters into the screening period for the study (defined as when the 
subject signs the informed consent) receives a unique subject identification number 
before any study-related activities/procedures are performed.  The subject identification 
number will be assigned by Interactive Response Technology (IRT).  This number will be 
used to identify the subject throughout the clinical study and must be used on all study 
documentation related to that subject. 
The subject identification number must remain constant throughout the entire clinical 
study; it must not be changed after initial assignment, including if a subject is 
rescreened.  This number will not necessarily be the same as the randomization number 
assigned for the study. 
5.4 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study 
but are not subsequently enrolled in the study.  A minimal set of screen failure 
information will be collected that includes demography, screen failure details, eligibility 
criteria, medical history, prior therapies, and any serious adverse events.  
Individuals who do not meet the criteria for participation in this study (screen failure) due 
to reasons other than KRAS p.G12C mutation status may be rescreened once (total 
number of possible screenings  2).  Refer to Section 8.1.1.  
Subjects who experience a technical failure of laboratory samples at screening (for 
example sample is lost or damaged in transit, or otherwise cannot be analyzed) will not 

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be considered a screen failure.  Lab samples may be retested during screening in such 
cases, provided the screening window will not be exceeded. 
Central confirmation of KRAS p.G12C status (if applicable), and the following 
assessments do not have to be repeated during rescreening, if they were performed as 
standard of care or during the initial screening attempt within the time frames specified 
below: 
 
Infectious hepatitis serology assessments and/or viral load does not need to be 
repeated if it was performed within 6 weeks prior to enrollment with AMG 510 or 
docetaxel. 
 
Imaging assessments do not need to be repeated if they were performed within 
28 days prior to cycle 1 day 1 with AMG 510 or docetaxel. 
Any other assessments do not need to be repeated if they were performed within the 
specified time frame prior to enrollment with AMG 510 or docetaxel; 
6. 
Treatments 
Study treatment is defined as any investigational product(s), non-investigational 
product(s), placebo, or medical device(s) intended to be administered to a study subject 
according to the study protocol. 
Note that in several countries, investigational product and non-investigational product 
are referred to as investigational medicinal product and non-investigational medicinal 
product, respectively. 
The Investigational Product Instruction Manual (IPIM), a document external to this 
protocol, contains detailed information regarding the storage, preparation, destruction, 
and administration of each treatment.  
6.1 
Treatment(s) Administered 
6.1.1 
Investigational Products 
AMG 510 and docetaxel are the investigational products used in this study.  The details 
of these drug treatments are shown in Table 6-1 below. 
 

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Table 6-1.  Study Treatments 
Study Treatment Name 
Amgen Investigational Product:a  
AMG 510 
Non-Amgen Investigational Product: 
Docetaxel 
Dosage Formulation 
Solid dosage form in strengths of 120 mg.  The 120 mg coated tablet is presented as 
film-coated yellow, oblong, debossed tablet.  Excipients used in the tablets include 
lactose monohydrate, microcrystalline cellulose, croscarmellose sodium, magnesium 
stearate and Opadry® II Yellow. 
20 mg/1 mL single dose vial:  20 mg 
docetaxel in 1 mL in 50/50 (v/v) ratio 
polysorbate 80/dehydrated alcohol  
80 mg/4 mL single-dose vial:  80 mg 
docetaxel in 4 mL 50/50 (v/v) ratio 
polysorbate 80/dehydrated alcohol 
Unit Dose Strength(s)/ 
Dosage Level(s) and 
Dosage Frequency 
960 mg/QD 
75 mg/m2 every 3 weeks 
Route of Administration 
Oral 
IV 
Accountability 
The amount dispensed, amount returned, date dispensed, start and stop date, date 
returned, and lot number of investigational product are to be recorded on each subject's 
CRF 
The planned dose, quantity administered, 
start date/time, stop date/time, lot number 
are to be recorded on each subject's CRF 
Dosing Instructions 
AMG 510 will be dispensed at the clinic by a qualified staff member.  For the first 
2 cycles, subjects will be instructed to take their AMG 510 dose in the clinic after all 
pre-dose assessments have been performed during clinic visit days. Subjects will take 
AMG 510 at home on non-clinic visit days.  Subject should take the AMG 510 dose (all 
tablets at the same time) with or without food at approximately the same time every day 
(see Section 6.7.2 for concomitant administration of AMG 510 with proton-pump 
inhibitors [PPIs]).  The AMG 510 dose should also not be taken more than 2 hours 
earlier than the scheduled time.  The AMG 510 dose should not be taken more than 
6 hours after the dosing time (based on the previous day’s dose).  Do not take 2 
doses at the same time to make up for the missed dose.  A dose of AMG 510 can be 
replaced in the event of vomiting if the vomiting occurs within 15 minutes of the dosing, 
all tablets administered have been accounted for (eg, 4 tablets must be collected if 4 
tablets were administered) and are intact by visual inspection (not broken, partially 
dissolved, chewed, or crushed).  A dosing diary will be provided for subjects to record 
their adherence to the oral medication.  Additional information relating to pH-elevating 
agents may be collected for subjects randomized to AMG-510, if needed.   
Docetaxel will be infused at the clinic by a 
qualified staff member over a time frame of  
1 hour (additional administration time 
allowed as per local guidelines). 
CRF = case report form; IV = intravenous; QD = once daily; PPIs = proton-pump inhibitor(s) 
a AMG 510 will be manufactured and packaged by Amgen and distributed using Amgen clinical study drug distribution procedures. 

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6.1.2 
Non-investigational Products 
There will be no non-investigational products in Study 20190009. 
6.1.3 
Medical Devices 
No investigational medical devices will be used in the conduct of this study. 
Other non-investigational medical devices may be used in the conduct of this study as 
part of standard care. 
Non-Amgen non-investigational medical devices (eg, syringes, sterile needles), that are 
commercially available are not usually provided or reimbursed by Amgen (except, for 
example, if required by local regulation).  The investigator will be responsible for 
obtaining supplies of these devices. 
6.1.4 
Other Protocol-required Therapies 
All other protocol-required therapies including, pre- and post-infusion medications for 
docetaxel, that are commercially available will not be provided or reimbursed by Amgen 
(except if required by local regulation).  The investigator will be responsible for obtaining 
supplies of these protocol-required therapies. 
6.1.4.1 
Pre- and Post-infusion Medications for Docetaxel 
Subjects receiving docetaxel should be premedicated with oral corticosteroids, such as 
dexamethasone 8 mg twice daily for 3 days starting 1 day prior to docetaxel 
administration (or as per local guidance) to reduce the incidence and severity of fluid 
retention and severity of hypersensitivity reactions.  Antiemetic medication may be 
administered on the day of docetaxel infusion as per institutional guidelines. 
6.1.5 
Other Treatment Procedures 
6.1.5.1 
Biopsies 
Tumor Biopsy for Enrollment:  When archival tumor tissue is not available, collection 
of new tumor tissue is required, as described in Section 8.2.7.3. 
Optional Tumor Biopsy for Biomarkers:  Additional tissue biopsy samples will be 
collected at disease progression for exploratory biomarkers related to mechanisms of 
primary and secondary resistance. 
Biomarker assessment can be done only if the biomarker research is allowed according 
to local regulations and agreed by the local EC/IRB. 
Mandatory Tumor Biopsy for Continued Treatment with AMG 510 Beyond 
Radiologic Progression:  In order to continue to receive AMG 510 beyond radiologic 

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progression, the subject must be willing to undergo biopsy of one of the new or 
progressing lesions as well as meet criteria listed in Section 8.1.6.  If tumor biopsy is not 
clinically feasible or advisable, the subject may continue on treatment with AMG 510 
beyond radiologic progression only upon agreement with investigator and the Amgen 
Medical Monitor. 
Biomarker assessment can be done only if the biomarker research is allowed according 
to local regulations and agreed by the local EC/IRB. 
6.1.6 
Product Complaints 
A product complaint is any written, electronic or oral communication that alleges 
deficiencies related to the identity, quality, durability, reliability, safety, effectiveness, or 
performance of a drug, or device after it is released for distribution to market or clinic by 
either (1) Amgen or (2) distributors or partners for whom Amgen manufactures the 
material.  This includes all components distributed with the drug, such as 
packaging drug containers, delivery systems, labeling, and inserts. 
This includes any investigational/non-investigational products provisioned and/or 
repackaged/modified by Amgen.  AMG 510 and docetaxel are the investigational 
products in this study for which Amgen wants to collect complaints.  
Any product complaint(s) associated with an investigational product supplied by Amgen 
are to be reported according to the instructions provided in the IPIM. 
6.1.7 
Excluded Treatments, Medical Devices, and/or Procedures During 
Study Period 
The following medications and supplements to be avoided for times stated prior to study 
day 1, and during the study period unless reviewed and approved by the principal 
investigator and the Amgen medical monitor: 
 
Known strong inducers of CYP 3A4 including herbal supplements, such as 
St. John’s wort within 14 days or 5 half-lives (whichever is longer) prior to 
study day 1 
 
Known CYP 3A4 or P-gp sensitive substrates with a narrow therapeutic window 
within 14 days or 5 half-lives of the drug or its major active metabolite, whichever 
is longer, prior to study day 1 
If a subject needs palliative radiotherapy for pain control during the course of the study, 
the sponsor should be notified prior to initiation of therapy (as soon as possible) 
and all study drugs should be withheld during radiation therapy and for 7 days after 
completion of radiation therapy.  A subject may be allowed to resume study drug after 

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discussion between the Amgen medical monitor and the investigator to determine the 
appropriateness of treatment resumption. 
Subjects must not schedule any major elective surgeries within 28 days of study day 1, 
during the treatment period, and for at least 28 days after the last administration of 
AMG 510.  Minor elective surgery may be allowed after discussion with the Amgen 
medical monitor.  If a subject undergoes any unexpected surgery during the course of 
the study, all study drugs must be withheld, and the investigator or designee should 
notify the sponsor as soon as possible.  A subject may be allowed to resume 
investigational product only if both the investigator and Amgen medical monitor agree to 
restart study therapy. 
See Section 6.7.2 for more details about concomitant medications. 
A complete list of excluded treatments are listed in the exclusion criteria (Section 5.2). 
6.2 
Dose Modification 
6.2.1 
Dose-cohort Study Escalation/De-escalation and Stopping Rules 
There are no dose-cohort study escalation/de-escalation and/or stopping rules in 
Study 20190009. 
6.2.2 
Dosage Adjustments, Delays, Rules for Withholding or Restarting, 
Permanent  
6.2.2.1 
Amgen Investigational Product:  AMG 510 
The reason for dose change of AMG 510 is to be recorded on each subject’s CRF.  All 
subjects randomized to the AMG 510 group will receive AMG 510 at a starting dose of 
960 mg QD.  Dose reduction levels of AMG 510 for toxicity management of individual 
subjects are provided in Table 6-2.  AMG 510 will be discontinued, temporarily delayed 
or dosage temporarily reduced, in the event of a toxicity that, in the opinion of the 
investigator, warrants the discontinuation, or dose reduction as indicated in Table 6-3.  
Up to two dose reductions are allowed.  Dose reductions below 240 mg are not allowed.  
Subjects who experience an adverse event requiring dose reductions below 240 mg 
should be permanently discontinued from AMG 510 treatment. 
If day 1 of a cycle is delayed, day 1 of subsequent cycles should be adjusted accordingly 
to maintain the 21-day cycle duration.  However, if a within-cycle dose is held the missed 
dose will not be made up and day 1 of subsequent cycles should not be adjusted.  

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Table 6-2.  Dose Reductions for AMG 510 
AMG 510 Doses  
Starting Dose 
Dose -1 
Dose -2 
960 mg QD 
480 mg QD 
240 mg QD 
QD = once daily. 
Table 6-3.  AMG 510 Dose Modification Guidelines for Hematologic and 
Non-hematologic Toxicities 
Toxicity 
Recommended Action a 
Hold Until: 
Restart Dose: 
Hematologic toxicities 
Grade > 3 thrombocytopenia 
Recovery to grade 1 or less 
or to baseline grade 
(without platelet transfusion 
in last 7 days)  
 resume dosing at 1 dose 
decrement 
Grade > 3 febrile 
neutropenia, or grade > 3 
neutropenia lasting longer 
than 7 days 
Recovery to grade 1 or less 
or to baseline grade  
 resume dosing at 1 dose 
decrement  
Grade 4 hemoglobin 
decrease 
Recovery to grade 1 or less 
or to baseline grade  
 resume dosing at 1 dose 
decrement  
Nonhematologic toxicities 
Grade > 3 nausea, vomiting, or 
diarrhea lasting longer than 3 
days despite optimal medical 
support 
Recovery to grade 1 or less 
or to baseline grade 
 resume dosing at 1 dose 
decrement 
Suspected interstitial lung 
disease (ILD)/pneumonitis of 
any grade 
ILD/pneumonitis 
confirmed or excluded 
 if confirmed, permanently 
discontinue AMG 510 
 if excluded, restart at 
same dose if no other 
AMG 510 dose 
modification guidelines 
are applicable. 
Any other drug-related 
nonhematologic toxicity 
≥ grade 3c 
Recovery to grade 1 or less 
or to baseline grade ≤ 4 
weeks from toxicity event 
 resume dosing at 1 dose 
decrement 
Recovery to grade 1 or less 
or to baseline grade > 4 
weeks from toxicity event 
 resume dosing at 2 dose 
decrement b 
a If these toxicity events occur after the first dose reduction, then a second dose reduction is permitted.  If 
toxicities continue after 2 dose decrements, then the subject should be discontinued from the study and 
enter the follow-up phase. 
b If 2 dose decrements are not possible (for example if the subject has already had 2 dose reductions), 
subject should be discontinued from the study and enter the follow-up phase. 
c For suspected hepatotoxicity, refer to Section 6.2.3 and Section 11.7. 
Note:  Subjects may be resumed at a lower dose with the recommended restarting dose after discussion 
with the medical monitor.  

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Note:  If renal dysfunction has a clear etiology unrelated to AMG 510 and in the opinion of the investigator, is 
not expected to recur, no dose reduction may be needed after recovery, but this requires investigator 
discussion with Amgen medical monitor for approval. 
6.2.2.2 
Non-Amgen Investigational Product(s):  Docetaxel 
The reason for dose change of docetaxel is to be recorded on each subject’s CRF.  
Dose reduction levels of docetaxel for toxicity management of individual subjects are 
provided in Table 6-4.  Docetaxel will be discontinued or dosage reduced, in the event of 
a toxicity that, in the opinion of the investigator, warrants the discontinuation, or dose 
reduction as indicated in Table 6-5. 
If docetaxel treatment was held or delayed by > 21 days, that dose will be deemed to 
have been missed and the subject will proceed to the next scheduled treatment visit.  If 
docetaxel administration is held or delayed  21 days, day 1 of subsequent cycles 
should be adjusted accordingly to maintain the 21-day cycle duration. 
Table 6-4.  Dose Decrements for Docetaxel  
Docetaxel Doses (mg/m2) 
Starting Dose 
Dose -1 
Dose -2 
Dose -3 
75 
55 
37.5 
Discontinue 

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Table 6-5.  Docetaxel Dose Modification Guidelines for Hematologic and 
Non-hematologic Toxicities 
Toxicityc 
Recommended Actiona 
Hold Untilb: 
Restart Dose: 
Hematologic toxicities 
 grade 3 drug related 
thrombocytopenia associated with 
bleeding 
No restart permitted 
 permanently discontinue 
treatment 
Febrile neutropenia  
Recovery to grade 1 
neutropenia or less or to 
baseline grade 
 resume dosing at 1 dose 
decrement 
Neutrophils < 500 cells/mm3 for 
more than 1 week 
Recovery to grade 1 or less or 
to baseline grade  
 resume dosing at 1 dose 
decrement  
Grade 4 anemia (low hemoglobin) 
Recovery to grade 1 or less or 
to baseline grade (without 
blood transfusion in last 
7 days)  
 resume dosing at 1 dose 
decrement  
ANC < 1500 cells/mm3 
Recovery to a level 
> 1500 cells/mm3 
 resume dosing at 1 dose 
decrement 
Nonhematologic toxicities 
Severe or cumulative cutaneous 
reactions 
Recovery to grade 1 or less or 
to baseline grade 
 resume dosing at 1 dose 
decrement 
Other grade 3 or 4  
non-hematological toxicities 
Recovery to grade 1 or less or 
to baseline grade  
 resume dosing at 1 dose 
decrement 
 grade 3 peripheral neuropathy 
No restart permitted 
 permanently discontinue 
treatment 
Bilirubin > ULN or if AST and/or 
ALT > 1.5 x ULN concomitant with 
alkaline phosphatase > 2.5 x ULN. 
 
Recovery to normal liver 
function  
 resume dosing at 1 dose 
decrement 
 grade 3 AST or ALT elevation 
related to drug for > 2 weeks 
 
No restart permitted 
 permanently discontinue 
treatment 
Concurrent AST or ALT > 3 x ULN 
and total bilirubin > 2 x ULN if 
related to drug 
 
No restart permitted 
 permanently discontinue 
treatment 
Severe hypersensitivity reactions 
No restart permitted 
 permanently discontinue 
treatment 
ALT = alanine aminotransferase; ANC = absolute neutrophil count; AST = aspartate aminotransferase;  
ULN = upper limit of normal. 
a If these toxicity events occur after the first dose reduction, then a second dose reduction is permitted.  A 
third dose reduction is not permitted, and if toxicities continue after 2 dose decrements, then the subject 
should be discontinued from the study and enter the follow-up phase 
b Subjects requiring more than 4 weeks to recover from docetaxel related grade  3 toxicities should be 
discontinued from study 
c Subjects with impaired vision should undergo prompt and comprehensive ophthalmologic examination.  If 
cystoid macular edema is diagnosed, docetaxel should be discontinued and appropriate treatment initiated 

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6.2.3 
Hepatotoxicity Stopping and Re-Challenge Rules 
Unless specified otherwise in Section 6.2.2.2, refer to Section 11.7 for details regarding 
drug-induced liver injury guidelines, as specified in the Guidance for Industry 
Drug-Induced Liver Injury:  Premarketing Clinical Evaluation, July 2009.  
Guidelines for management and monitoring of subjects with increased AST, ALT, or ALP 
are presented in Table 6-6. 
 

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Table 6-6.  AMG 510 Hepatoxicity Guidelines 
If the conditions for permanent discontinuation are met (below):  Participant to be permanently discontinued 
AST or ALT >3x ULN and INR > 1.5x ULN (for subjects not on anticoagulation therapy) in the presence of no important alternative causes for elevated AST/ALT 
values 
OR 
AST or ALT > 3x ULN and TBL > 2x ULN in the presence of no important alternative causes for elevated AST/ALT and/or TBL values 
If conditions are not met:  Exclude other causesa 
Upon failure to identify any other causes and AMG 510 relation to increase in LFTs cannot be excluded, proceed with guidelines below: 
CTCAE Grade 
AMG 510 Action 
Medical Management 
Monitoring and Follow-up 
Grade 2 AST or ALT and ALP ≤ 8 x 
ULN with no clinical symptoms 
consistent with hepatitis 
(right upper quadrant pain/tenderness, 
fever, nausea, vomiting, and jaundice) 
Continue 
Consider steroidsb 
Closely monitor liver function tests 
Grade 2 AST or ALT 
with symptoms 
Or 
Grade 3 or 4 
AST or ALT 
Or 
> 8 x ULN ALPd 
First Occurrence 
Initiate steroidsb 
Closely monitor liver function tests 
Await resolution to baseline or grade 1 and resolution or 
improvement of hepatitis symptoms  
Restart at 1 dose level reductionc, e 
Withhold 
Second Occurrence 
Initiate steroidsb 
Closely monitor liver function tests 
Await resolution to baseline or grade 1 and resolution or 
improvement of hepatitis symptoms 
Resume at an additional 1 dose level reduction only with 
MEDICAL MONITOR approvalc, e 
Withhold 
Third Occurrence 
NOT APPLICABLE 
Permanently discontinue 
AMG 510 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; CTCAE = Common Terminology Criteria for Adverse Events; 
INR = international normalized ratio; LFT = liver function test; TBL = total bilirubin; ULN = upper limit of normal 
a If increase in AST/ALT is likely related to alternative agent, discontinue causative agent and await resolution to baseline or grade 1 prior to resuming AMG 510. 
b Example: prednisone 1.0 to 2.0 mg/kg/day, dexamethasone equivalent, or methylprednisolone equivalent, followed by a taper.  The taper may occur after 
restarting AMG 510. 
c Close monitoring at restart (eg, daily LFTs x 2, then weekly x 4).   
d  AMG 510 dose may be increased after discussion with medical monitor. 
e. There is no limit to the number of AMG 510 re-challenges for isolated alkaline phosphatase elevations that resolve to baseline or grade 1. 
f.  Dose decrements below 240 mg are not allowable. 

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6.3 
Preparation/Handling/Storage/Accountability 
Guidance and information on preparation, handling, storage, accountability, destruction, 
or return of the investigational product during the study are provided in the IPIM. 
6.4 
Measures to Minimize Bias:  Randomization and Blinding 
6.4.1 
Method of Treatment Assignment 
Subjects will be randomized in a 1:1 allocation ratio, to either AMG 510 or docetaxel, in 
an open-label manner after meeting all enrollment requirements.  
The randomization will be performed by IRT and the randomization number will be 
provided to the site by the IRT system. 
The randomization will be stratified by number of prior lines of therapy in advanced 
disease (1 versus 2 versus > 2), race (Asian versus non-Asian), and history of CNS 
involvement (present or absent).   
The randomization date is to be documented in the subject’s medical record and on the 
enrollment CRF. 
6.4.2 
Blinding 
This is an open-label study; blinding procedures are not applicable.  
Amgen pre-defined authorized roles with a business need for access and handling of 
data should follow standard operational procedures for restricted data in open-label 
randomized trials (SOP-428127, effective 08 Jan 2018).  Aggregated safety and efficacy 
data should only be disclosed to the study team at protocol prespecified analyses.  
Authorized roles with access to ongoing clinical trial data should emphasize precautions 
to maintain aggregated-level data confidentiality in study team interactions and not let it 
influence their input into any changes to the study design or conduct. 
6.5 
Treatment Compliance 
Treatment compliance on AMG 510 will be documented in the medical records and will 
be collected in the CRF and through subject input into an electronic diary.  Subjects are 
required to bring bottle(s) of AMG 510 as per guidance in the Investigational Product 
Instruction Manual and return the remaining pills when they come off treatment.  Pill 
counts will be collected by the study staff, and at treatment discontinuation, or SFU.  
eDiary must be completed daily with the response yes (if IP taken) or no (in the event of 
dose interruption due to adverse event, etc).  

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6.6 
Treatment of Overdose 
6.6.1 
AMG 510 Overdose 
The effects of overdose of AMG 510 are not known.  There are no AMG 510 specific 
antidotes.  Consultation with the Amgen medical monitor is required for prompt reporting 
of clinically apparent or laboratory adverse events possibly related to overdosage.  
Consultation with the Amgen medical monitor is also required even if there are no 
adverse events, in order to discuss further management of the subject.  If the overdose 
results in clinically apparent or symptomatic adverse events, the subject should be 
followed carefully until all signs of toxicity are resolved or returned to baseline and the 
adverse event(s) should be recorded/reported per Section 11.4. 
6.6.2 
Docetaxel Overdose 
There is no known antidote for docetaxel overdosage.  In case of overdosage, the 
subject should be kept in a specialized unit where vital functions can be closely 
monitored.  Anticipated complications of overdosage include:  bone marrow suppression, 
peripheral neurotoxicity, and mucositis.  Subjects should receive therapeutic 
Granulocyte-colony stimulating factor (G-CSF) as soon as possible after discovery of 
overdose.  Other appropriate symptomatic measures should be taken, as needed (see 
regional labeling for Taxotere®). 
6.7 
Prior and Concomitant Treatment 
6.7.1 
Prior Treatment 
Prior anticancer therapies must date back to the original diagnosis and will be collected 
through enrollment on the appropriate eCRF.  For prior anticancer therapies collect the 
regimen/agent, type of therapy, setting, start date, stop date, reason for stopping 
therapy, dose, unit, route, frequency, best response, date of best response, and date of 
progression documented.  For prior radiotherapy for current malignancy, collect body 
site, sub site, setting, type, start date, stop date, total dose, unit, best response, was 
chemotherapy part of concurrent therapy, did documented progression occur in this 
area, date progression documented.  For prior surgeries for current malignancies collect 
date of surgery, surgery, reason for surgery, body site, subsite, intent of surgery, 
residual disease. 
All other prior therapies that were being taken 28 days before enrollment through 
enrollment should be collected on each subject’s eCRF(s).  Collect therapy name, 
indication, dose, unit, frequency, route, start date and stop date. 

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6.7.2 
Concomitant Treatment 
Avoid coadministration with proton pump inhibitors (PPIs) and H2 receptor antagonists.  
If an acid-reducing agent cannot be avoided, administer AMG 510 4 hours before or 
10 hours after a local antacid.  Breast cancer resistance protein (BCRP) substrates 
should be used with caution when co-administered with AMG 510, which may 
increase the circulating concentrations of BCRP substrates. 
Throughout the study, investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care except for those 
listed in Section 6.1.7.  
Concomitant therapies are to be collected from enrollment through the end of SFU 
period (30 days after the last dose of all study drugs).  Subsequent treatment for NSCLC 
will be recorded after the SFU period during the LTFU.  For all concomitant therapies, 
collect therapy name, indication, dose, unit, frequency, route, start date and stop date 
and record on Concomitant Medications eCRF.  Supplemental oxygen use should be 
captured in the concomitant medication eCRF. 
7. 
Discontinuation Criteria 
Subjects have the right to withdraw from investigational product and/or other 
protocol-required therapies, protocol procedures, or the study as a whole at any time 
and for any reason without prejudice to their future medical care by the physician or at 
the institution. 
The investigator and/or sponsor can decide to withdraw a subject(s) from investigational 
product, device, and/or other protocol-required therapies, protocol procedures, or the 
study as a whole at any time prior to study completion for the reasons listed in 
Sections 7.1, 7.2.1, and 7.2.2. 
7.1 
Discontinuation of Study Treatment 
Subjects (or a legally acceptable representative) can decline to continue receiving 
investigational product and/or other protocol-required therapies or procedures at any 
time during the study but continue participation in the study.  If this occurs, the 
investigator is to discuss with the subject the appropriate processes for discontinuation 
from investigational product or other protocol-required therapies and must discuss with 
the subject the possibilities for continuation of the Schedule of Activities (Table 1-1 and 
Table 1-2) including different options of follow-up (eg, in person, by phone/mail, through 
family/friends, in correspondence/communication with other treating physicians, from the 

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review of medical records) and collection of data, including endpoints, adverse events, 
and must document this decision in the subject’s medical records. Subjects who have 
discontinued investigational product and/or other protocol-required therapies or 
procedures should not be automatically removed from the study.  Whenever safe and 
feasible, it is imperative that subjects remain on-study to ensure safety surveillance 
and/or collection of outcome data. 
Subjects may be eligible for continued treatment with Amgen investigational product(s) 
and/or other protocol-required therapies in a separate protocol or as provided for by the 
local country’s regulatory mechanism, based on parameters consistent with 
Section 11.3. 
Reasons for early removal from protocol-required investigational product(s) or 
procedural assessments may include any of the following: 
 Decision by Sponsor 
 Lost to follow-up 
 Death 
 Adverse event 
 Subject request 
 Ineligibility determined 
 Protocol deviation 
 Non-compliance 
 Disease progression 
 Requirement for alternative therapy 
 Pregnancy 
7.2 
Discontinuation From the Study 
Withdrawal of consent for a study means that the subject does not wish to receive 
further protocol-required therapies or procedures, and the subject does not wish to or is 
unable to continue further study participation, including long-term follow up.  Subject 
data up to withdrawal of consent will be included in the analysis of the study, and where 
permitted, publicly available data can be included after withdrawal of consent.  The 
investigator is to discuss with the subject appropriate procedures for withdrawal from the 
study, and must document the subject’s decision to withdraw in the subject’s medical 
records. 
If a subject withdraws from the study, he/she may request destruction of any samples 
taken and not tested, and the investigator must notify Amgen accordingly (see 
Section 11.6 for further details).  Refer to the Schedule of Activities (Table 1-1 and  

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Table 1-2) for data to be collected at the time of study discontinuation and follow-up and 
for any further evaluations that need to be completed. 
7.2.1 
Reasons for Removal From Washout Period, Run-in Period, or 
Invasive Procedures 
Not Applicable. 
7.2.2 
Reasons for Removal From Study 
Reasons for removal of a subject from the study are: 
 Decision by sponsor 
 Withdrawal of consent from study 
 Death 
 Lost to follow-up 
7.3 
Lost to Follow-up 
A subject 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.  
The following actions must be taken if a subject fails to return to the clinic for a required 
study visit: 
 The site must attempt to contact the subject and reschedule the missed visit as soon 
as possible and counsel the subject on the importance of maintaining the assigned 
visit schedule and ascertain whether or not the subject wishes to and/or is able to 
continue in the study. 
 In cases in which the subject is deemed lost to follow-up, the investigator or 
designee must make every effort to regain contact with the subject (where possible, 
3 telephone calls and, if necessary, a certified letter to the subject’s last known 
mailing address or local equivalent methods).  These contact attempts are to be 
documented in the subject’s medical record. 
 If the subject continues to be unreachable, he/she will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
 For subjects who are lost to follow-up, the investigator can search publicly available 
records, where permitted, to ascertain survival status.  This ensures that the data 
set(s) produced as an outcome of the study is/are as comprehensive as possible. 
8. 
Study Assessments and Procedures 
Study procedures and their time points are summarized in the Schedule of Activities 
(see Table 1-1 and Table 1-2).  
As protocol waivers or exemptions are not allowed if an enrolled subject is subsequently 
determined to be ineligible for the study, this must be discussed with the sponsor 
immediately upon occurrence or awareness to determine if the subject is to continue or 
discontinue study treatment. 

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Adherence to the study design requirements, including those specified in the Schedule 
of Activities, is essential and required for study conduct. 
Ongoing subjects who are unable or unwilling to attend protocol-specified trial 
visits and procedures, due to COVID-19, should generally remain on study even if 
AMG 510 is interrupted, as continued collection of even limited clinical 
information is valuable for safety and efficacy assessments.  In cases where the 
subject is unable to visit the site, Amgen has explored alternative methods for 
safety assessments and continuation of study medication (eg, phone contact, 
virtual visit, alternative location for assessment including local labs or 
radiological assessment, direct to subject shipment of Investigational Product 
where possible).  Each case should be discussed with the medical monitor before 
temporary adjustments are made to the subject’s schedule of activities. 
8.1 
General Study Periods 
8.1.1 
Screening, Enrollment and/or Randomization 
Informed consent must be obtained before completing any screening procedure or 
discontinuation of standard therapy for any disallowed therapy.  After the subject has 
signed the ICF, the site will register the subject in the IRT and screen the subject in 
order to assess eligibility for participation.  Imaging scans obtained as part of standard of 
care prior to signing consent may be used for screening provided they meet the time 
windows specified in the study.  The screening window is up to 28 days from C1D1. 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria, including confirmation of positive KRAS p.G12C 
mutation status.  Central confirmation of KRAS p.G12C mutation status is required 
before randomization.  The investigator will maintain a screening log to record details of 
all subjects screened and to confirm eligibility or record reasons for screening failure, 
(see Section 5.4) as applicable. 
If a subject has not met all eligibility criteria at the end of the screening period, the 
subject will be registered as a screen fail.  Screen fail subjects may be eligible for 
re-screening 1 additional time, unless the failure was due to KRAS p.G12C mutation 
status, in which case the subject cannot rescreen. 
Rescreen subjects must first be registered as screen failures in IRT and subsequently 
registered as rescreens.  Once the subject is registered as rescreened, a new 28-day 
screening window will begin.  Subjects will retain the same subject identification number 

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assigned at the original screening.  If the rescreening period begins more than 28 days 
after the original signing of the ICF, all screening procedures, including informed 
consent, must be repeated if they are out of window. 
8.1.2 
Treatment Period 
Visits will occur per the Schedule of Activities (Table 1-1 and Table 1-2).  On-study visits 
may be completed within 3 days of the scheduled visit.  The date of the first dose of 
investigational product is defined as day 1.  All subsequent doses and study visits will be 
scheduled based on the day 1 date.  For subjects randomized to AMG 510, 
administration of AMG 510 is to be administered during the clinic visit on day 1 and day 
8 of the first cycle, day 1 of the second cycle, and outside of the clinic on other days of 
the cycle, and during subsequent cycles. 
Images are to undergo independent central confirmation of progression as described in 
Section 8.2.2.1.2. 
8.1.3 
Safety Follow-up 
Upon permanent discontinuation from the study treatment for any reason, a SFU visit will 
be performed 30 days ( 7 days) after the end of the last dosing interval of 
investigational product.  
Safety follow-up is to be performed upon completion of any and all of the 
following:  initial study treatment, crossover treatment, and treatment beyond 
progression treatment.  
8.1.4 
Long-term Follow-up 
Following the SFU visit (30 days  7 days after the end of the last dosing interval of 
investigational product), there will be an LTFU period, during which data will be collected 
on the subjects’ health condition, disease status, and subsequent anticancer treatment.  
Safety follow-up must be completed prior to moving into LTFU. 
For subjects who discontinued study treatment without independent central confirmation 
of progression or without start of subsequent anticancer treatment (excluding the 
administration of single agent docetaxel), tumor assessments will continue at the same 
frequency during LTFU, but with a larger window in which assessments can be 
completed (every 6 weeks from cycle 1 day 1; [at weeks 7, 13, 19, 25, 31, 37, 43, and 
49], and then at 9 week intervals thereafter [± 4 weeks]) from SFU until independent 
central confirmation of progression per RECIST v1.1, start of subsequent anticancer 
treatment, death, withdrawal of consent, loss to follow-up, or end of study. 

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Subjects who have had independent central confirmation of progression or started 
subsequent anticancer treatment (other than single agent docetaxel), will be followed via 
telephone or visit (clinic or virtual [eg, Tele-Health]) every 12 weeks (± 4 weeks) (or ad 
hoc to support analysis) for assessment of survival and documentation of anticancer 
treatment.  Subjects will be followed for 5 years after last subject enrolled, or until 
withdrawal of consent, loss to follow-up, or subject death, whichever occurs first.  When 
the last subject has completed LTFU, the final analysis will occur. 
8.1.5 
End of Study 
The end of study visit for an individual subject is defined as the date of the final study 
contact (eg, LFTU visit) when assessments or procedures are done.  
8.1.6 
Continuation on AMG 510 Treatment After Independent Central 
Confirmation of Progression at the time of First PD  
This section details the conditions necessary to allow continued treatment with AMG 510 
post disease progression.  If, in the investigator’s opinion, it is believed that the subject 
will continue to have clinical benefits from AMG 510, the subject may continue on AMG 
510 after radiographic progression provided all of the following criteria below are met. 
The decision to continue on treatment beyond progression is at the discretion of the PI.   
 
Documentation of progressive disease per RECIST v1.1  
 
PD imaging must undergo independent central confirmation. If a subject has been 
deemed to have objective disease progression according to investigator tumor 
assessment by RECIST v1.1, but is imaging does not undergo independent central 
confirmation, subject is not eligible to continue AMG 510 beyond progression  
 
Signed separate informed consent for AMG 510 treatment beyond radiologic 
progression. 
 
Absence of threat to vital organs or critical anatomical sites (eg, CNS metastasis, 
respiratory failure due to tumor compression, spinal cord compression) requiring 
urgent alternative medical intervention. 
 
No other treatment discontinuation criteria are met (Table 6-6 and Table 11-2). 
 
No significant, unacceptable, or irreversible toxicities related to any dose of the study 
treatment or treatment-related adverse events of CTCAE grade 4 at the current dose 
at the time of progression.  
 
No current signs or symptoms of clinical disease progression that have decreased 
the ECOG performance status to  2.   
 
Disease progression is in one of the following settings:  small or oligometastasis 
candidate for stereotactic body radiation therapy (SBRT), palliative radiation, or 
surgery 
 
The subject is willing to undergo biopsy of one of the new or progressing lesions 
(only if biomarker research is allowed according to local regulations and agreed by 

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local EC/IRB).  If tumor biopsy is not clinically feasible or advisable, the subject may 
continue only upon agreement with investigator and the Amgen Medical Monitor. 
 
Approval for continuation from the Amgen Medical Monitor 
 
Palliative radiation and/or surgery for new, progressive, or symptomatic lesions is 
permitted prior to crossover, but AMG 510 must be held until after completion of 
these treatments and until 7 days after completion of radiation.  
 
If the time between the subject’s initial progression scan and the restart of AMG 510 
is > 28 days, the scan must be repeated to serve as the new baseline. 
 
All protocol-mandated procedures must be performed as noted in the protocol 
(imaging, labs, and clinic visits may be obtained earlier per clinical judgment and if 
clinically indicated). 
 
Continued growth of tumor(s) on a subsequent scan should result in permanent 
discontinuation of the study drug. 
For subjects who continue treatment beyond radiologic progression, the date of first 
progression, will be used for PFS analysis and subject’s response post first progression 
will not be used for the primary analyses to evaluate objective response endpoints 
including PFS, ORR, DOR, TTR, and DCR.   
Biomarker assessment can be done only if the biomarker research is allowed according 
to local regulations and agreed by the local EC/IRB. 
8.1.7 
Continuation on Docetaxel Treatment After Independent Central 
Confirmation of Progression at the Time of First PD  
This section details the conditions necessary to allow continued treatment with docetaxel 
post disease progression.  If, in the investigator’s opinion, it is believed that the subject 
will continue to have clinical benefits from docetaxel, the subject may continue on 
docetaxel after radiographic progression provided all of the following criteria below are 
met.  The decision to continue on treatment beyond progression is at the discretion of 
the PI.   
 
Documentation of progressive disease per RECIST v1.1  
 
PD imaging must undergo independent central confirmation. If a subject has been 
deemed to have objective disease progression according to investigator tumor 
assessment by RECIST v1.1, but is imaging does not undergo independent central 
confirmation, subject is not eligible to continue docetaxel beyond progression  
 
Signed separate informed consent for docetaxel treatment beyond radiologic 
progression. 
 
Absence of threat to vital organs or critical anatomical sites (eg, CNS metastasis, 
respiratory failure due to tumor compression, spinal cord compression) requiring 
urgent alternative medical intervention. 
 
No other treatment discontinuation criteria are met (Table 6-6 and Table 11-2). 

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 
No significant, unacceptable, or irreversible toxicities related to any dose of the study 
treatment or treatment-related adverse events of CTCAE grade 4 at the current dose 
at the time of progression.  
 
No current signs or symptoms of clinical disease progression that have decreased 
the ECOG performance status to  2.   
 
Disease progression is in one of the following settings:  small or oligometastasis 
candidate for stereotactic body radiation therapy (SBRT), palliative radiation, or 
surgery 
 
Approval for continuation from the Amgen Medical Monitor. 
 
Palliative radiation and/or surgery for new, progressive, or symptomatic lesions is 
permitted, but docetaxel must be held until after completion of these treatments and 
until 7 days after completion of radiation  
 
If the time between the subject’s initial progression scan and the restart of 
docetaxel is > 28 days, the scan must be repeated to serve as the new baseline.   
 
All protocol-mandated procedures must be performed as noted in the protocol 
(imaging, labs, and clinic visits may be obtained earlier per clinical judgment and if 
clinically indicated). 
 
Continued growth of tumor(s) on a subsequent scan should result in permanent 
discontinuation of the study drug. 
For subjects who continue treatment beyond radiologic progression, the first date of 
progression will be used for PFS analysis and subject’s response post first progression 
will not be used for the primary analyses to evaluate objective response endpoints 
including PFS, ORR, DOR, TTR, and DCR.   
8.1.8 
Crossover  
This section details the conditions necessary to allow crossover for subjects in the 
docetaxel arm to the AMG 510 arm.  The decision to crossover, from docetaxel to 
AMG 510, is at the discretion of the PI.  Subjects that crossover may not initiate 
treatment with AMG  510 any earlier than 14 days after their last dose of docetaxel 
(regardless of the time of progression, if applicable).  Safety follow up visit may occur on 
the same day as the first dose of AMG 510 in the crossover phase (see Section 8.1.3).  
Subjects who are in LTFU at the time of crossover assessment cannot crossover, from 
docetaxel to AMG 510, if they have received any other systemic anti-cancer therapeutic 
administered other than docetaxel.  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, unless otherwise stated.  Subjects who permanently 
discontinue the crossover phase will follow the same SFU and LTFU assessments 
outlined in the AMG 510 Schedule of Activities (Section 1.3).   

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For subjects who crossover from docetaxel to AMG 510, the subject’s response post first 
progression or post crossover will not be used for the primary analyses to evaluate 
objective response endpoints including PFS, ORR, DOR, TTR, and DCR.   
Once a subject crossover, the subject will begin a new cycle.  For example:  If a subject 
progress on cycle 2, day 15, once disease progression undergoes independent central 
confirmation, the PI will obtain approval from the medical monitor.  Once approval is 
obtained, the subject will initiate cycle 3 for AMG 510 administration and follow the 
AMG 510 Schedule of Activities (Section 1.3).  All assessments listed in the prior cycle 
(eg, cycle 2) must be completed prior to crossover and initiation of cycle 3. 
Crossover Condition 1:  Subjects who permanently discontinue chemotherapy due to 
an adverse event, or for any reason other than progressive disease, will not be eligible 
for crossover until they have had radiographic progression and have undergone 
independent central confirmation of progression at the time of first PD as per 
Section 8.2.2.1.2.  Crossover from docetaxel to AMG 510 after Progressive Disease can 
be considered if the following conditions below are met.  
1. Documentation of progressive disease per RECIST v1.1  
2. PD imaging must undergo independent central confirmation. If a subject has been 
deemed to have objective disease progression according to investigator tumor 
assessment by RECIST v1.1, but is imaging does not undergo independent central 
confirmation, subject is not eligible to crossover. 
3. Disease progression limited to CNS only must be treated prior to crossover 
4. Subjects with symptomatic brain metastasis will not be permitted to crossover 
5. Signed separate informed consent for AMG 510 crossover  
6. Absence of threat to vital organs or critical anatomical sites (eg, CNS metastasis, 
respiratory failure due to tumor compression, spinal cord compression) requiring 
urgent alternative medical intervention.  Subject may re-evaluate appropriateness for 
crossover after therapeutic intervention.   
7. Brain imaging (CT/MRI with contrast) must be obtained prior to initiating therapy with 
AMG 510 in crossover (if brain scan has been performed > 28 days from the date of 
first crossover dose of AMG 510, brain scan must be repeated)   
8. Subject must meet inclusion criteria requirements:  109, 110, 111, 112, and 113 
(Section 5.1) on AMG 510 administration day 1 of crossover (labs to be obtained on 
crossover day 1 ( 3 days).  
9. No AMG 510 treatment discontinuation criteria are met (Table 6-6 and Table 11-2). 
10. No significant, unacceptable, or irreversible toxicities related to any dose of 
docetaxel or treatment-related adverse events of CTCAE (grade 1) at the current 
dose at the time of progression (with the exception of alopecia and nail 
discoloration).  Additional non-significant toxicities may be allowed but will 
need to be discussed with and approved by the medical monitor prior to 
crossover.  

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11. No current signs or symptoms of clinical disease progression that have decreased 
the ECOG performance status to  2.   
12. Palliative radiation and/or surgery for new, progressive, or symptomatic lesions is 
permitted prior to crossover, but AMG 510 must be held until after completion of 
these treatments and until 7 days after completion of radiation  
13. If the time between the subject’s initial progression scans and the start of AMG 510 
is > 28 days, the imaging scans must be repeated to serve as the new baseline. 
14. All protocol-mandated procedures must be performed as noted in the protocol 
(imaging, labs, and clinic visits may be obtained earlier per clinical judgment and if 
clinically indicated) as dictated by the AMG 510 Schedule of Activities (Table 1-1) 
15. No other systemic anti-cancer directed therapeutic agents are to be administered 
during crossover 
16. Subject has not received any other systemic anti-cancer therapies other than 
docetaxel administered during the treatment phase. 
17. Approval for crossover from the Amgen Medical Monitor  
Crossover Condition 2:  Should an early efficacy of the study be noted by the DMC, 
crossover will be considered for all subjects who randomized into the docetaxel arm (so 
that they will be able to immediately receive AMG 510). 
8.2 
Description of General Study Assessments and Procedures 
The sections below provide a description of the individual study procedures for required 
time points. 
8.2.1 
General Assessments  
8.2.1.1 
Informed Consent 
All subjects or their legally authorized representative must sign and personally date the 
IRB/IEC and Amgen approved informed consent before any study-specific procedures 
are performed. 
8.2.1.2 
Demographics 
Demographic data collection including sex, age, race, and ethnicity will be collected in 
order to study their possible association with subject safety and treatment effectiveness.  
Additionally, demographic data will be used to study the impact on biomarkers variability 
and PK of the protocol-required therapies  
8.2.1.3 
Medical History 
The Investigator or designee will collect a complete medical history from 28 days prior to 
enrollment through enrollment.  Medical history will include information on the subject's 
concurrent medical conditions.  Record all findings on the medical history CRF.  The 
current toxicity grade will be collected for each condition that has not resolved.  Cancer 
history will be collected dating back to the original diagnosis. 

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8.2.1.4 
Physical Examination  
Physical examination will be performed as per standard of care.  Physical examination 
findings should be recorded on the appropriate CRF page (eg, Medical history, Adverse 
event). 
8.2.1.5 
Physical Measurements 
Height in centimeters should be measured without shoes.  Weight in kilograms should 
be measured without shoes.  Height should only be recorded at screening, and weight 
should be recorded at every clinic visit (Schedule of Activities; Table 1-1 and Table 1-2).  
8.2.1.6 
Substance Abuse History  
Obtain a detailed history of prior and/or concurrent use of tobacco.  Tobacco usage must 
include current and any prior smoking history (number of pack years). 
8.2.1.7 
Performance Status  
The subject’s performance status will be assessed using the ECOG Performance Status. 
8.2.2 
Efficacy Assessments 
8.2.2.1 
Disease Assessments 
8.2.2.1.1 
Radiological Imaging Assessment 
The extent of disease will be evaluated by contrast-enhanced MRI/CT according to 
RECIST v1.1 (Section 11.8).  All radiological imaging will be performed as indicated in 
the Site Imaging Manual provided by the central imaging core laboratory.  In order to 
reduce radiation exposure for subjects, low dose CT should be utilized whenever 
possible. 
Contrast-enhanced CT of the chest, and one of the following: contrast-enhanced CT 
abdomen with cuts through to the pubic symphysis, contrast-enhanced CT abdomen and 
pelvis, contrast-enhanced MRI abdomen and pelvis, or contrast-enhanced MRI 
abdomen with cuts through to the pubic symphysis, and brain MRI with contrast (or brain 
CT scan with contrast) will be obtained at screening.  The screening scans must be 
performed within 28 days prior to cycle 1 day 1 and will be used as baseline.  Scans 
obtained as part of standard of care prior to signing informed consent may be used if 
they are within the window specified prior to cycle 1 day 1.  All subsequent scans will 
be performed in the same manner as at screening, with the same contrast, preferably on 
the same scanner.  Tumor evaluation is to be performed by contrast-enhanced CT of the 
chest and one of the following:  contrast-enhanced CT abdomen with cuts through to the 
pubic symphysis, contrast-enhanced CT abdomen and pelvis, contrast-enhanced MRI 

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abdomen and pelvis, or contrast-enhanced MRI abdomen with cuts through to the pubic 
symphysis.  Contrast-enhanced images are strongly preferred.  If contrast enhanced CT 
imaging is contraindicated (allergy, medical contraindication, etc), radiological imaging to 
be performed as indicated by site imaging manual.  Magnetic resonance imaging of the 
brain should be performed if subject has history of brain metastases, or if signs or 
symptoms suggestive of CNS metastases are present.  All subjects with brain 
metastasis must have MRI of the brain performed within 28 days prior to cycle 1 day 1 of 
AMG 510 or docetaxel. 
The same MRI field strength used at screening should be used for all subsequent 
assessments.  Liver specific MRI contrast agents should not be used.  To reduce 
potential safety concerns, macrocyclic gadolinium contrast agents are recommended 
per United States National Institute of Health guidelines, or follow local standards if 
more rigorous.  All brain scans on protocol are required to be MRI unless MRI is 
contraindicated, and then CT with contrast is acceptable.  Non-contrast only CT of the 
brain is not acceptable.   
Imaging may also be performed more frequently if clinically necessitated at the discretion 
of the managing physician.  Radiographic response (CR, PR) requires confirmation by a 
repeat, consecutive scan at a minimum of 4 weeks after the first documentation of 
response and may be delayed until the next scheduled scan to avoid unnecessary 
procedures.  
Determination of disease response for clinical management of subjects will be assessed 
at the clinical sites per RECIST v1.1.  Scans will be submitted to a central imaging core 
laboratory for archival, response assessment including RECIST v1.1, and/or exploratory 
analysis eg, volumetric and viable tumor measurements.  Detailed information regarding 
submission of images to the central imaging core laboratory is found in the Site Imaging 
Manual. 
In the event of crossover or treatment beyond progression imaging schedule is per 
Schedule of Activities (Table 1-1). 
8.2.2.1.2 
Independent Central Confirmation of Progression (COP) at Time of 
First Progressive Disease (PD) 
All scheduled images for all study participants from the sites will be submitted to the 
central imaging vendor.  In addition, images (including via other modalities) that are 
obtained at an unscheduled time point to determine disease progression, as well as 

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imaging obtained for other reasons, but captures radiologic progression based on 
investigator assessment should also be submitted to the central imaging vendor. 
The purpose of the independent confirmation of progression is to provide the site PI with 
a second independent opinion regarding whether the participant has reached progressive 
disease according to RECIST v1.1.  The expedited independent confirmation of 
progression (COP) will be performed by a single radiologist from a pool of highly qualified 
central radiologists that is entirely separate from the central radiologist group reading the 
images for efficacy.  The results of the single radiologist COP review will not be discussed 
with the central efficacy reviewers and thus, will not influence the determination of 
response or progression by the efficacy reviewers.  The COP will only be utilized to 
provide a second opinion on the presence or absence of progression at the current time 
point to the site PI, no clinical subject data is to be discussed.  
When the investigator identifies radiographic progression per RECIST v1.1, the current 
imaging plus all images to date must be immediately sent to the central imaging vendor 
who, once any critical queries (as defined in the imaging manual) are resolved, will 
perform an expedited confirmation of radiologic disease progression and communicate 
the results to study site and Sponsor within 3 business days after receiving the images.  
If the evaluation of radiologic disease progression, via central imaging vendor, does not 
confirm progression of disease at this timepoint, a web conference may be organized, by 
the central imaging vendor, to be held between the single radiologist and the site 
radiologist to review the participants’ images for determination of confirmation of 
radiological disease progression.  The site PI will make final treatment and subject 
management decisions.  The results of the web conference will be documented and 
provided to the study team within 1 business day.  
Progression of radiologic disease should be verified centrally prior to cessation of 
investigational product, local intervention, or initiation of new anti-cancer therapy, 
treatment beyond progression, or crossover.  If there are no safety concerns and the 
study participant is clinically stable, the participant is to remain on investigational product 
while central confirmation of progression is ongoing and until confirmation of radiologic 
disease progression is complete. 
8.2.2.1.3 
Clinical Outcome Assessments 
Patient-reported outcomes questionnaires include the, EORTC QLQ-C30 General 
Cancer Instrument, the disease specific module QLQ-LC13, a single item about 

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symptom bother (GP5 of the FACT-G), and the EQ-5D-5L.  The patient Global 
Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), and Brief 
pain Inventory (BPI), will provide additional context to interpret patient reported on the 
prespecified lung cancer symptoms of dyspnea, cough and chest pain.  PRO-CTCAE 
will be administered to all subjects, and collected as indicated in the Schedule of 
Activities (Table 1-1 and Table 1-2).  The PRO questionnaires completed in the clinic 
should be completed by the subject prior to any other clinical assessments and before 
receiving any study medications.  
8.2.2.1.3.1 
QLQ-C30 
Physical function and the impact of treatment on disease-related symptoms and  
health-related quality of life (HRQOL) will be evaluated in all subjects using EORTC 
QLQ-C30.  EORTC QLQ-C30 (Section 11.9):  The EORTC QLQ-C30 was developed to 
assess the QOL in cancer subjects across tumor types.  The QLQ-C30 has been tested 
and validated with multiple myeloma subjects (Leleu et al, 2013;  
Wisløff et al, 1996) and has also been used in NSCLC (Aaronson et al, 1993;  
Niezgoda and Pater, 1993).  It is a self-reporting 30-item generic instrument which 
assesses 5 functional domains (physical, role, emotional, cognitive, social), 9 symptom 
scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, 
constipation, diarrhea, financial difficulties), and a global health status/QOL scale 
(Aaronson et al, 1993).  The recall period is the past week.  Subjects will complete the 
QLQ-C30 at clinic visits only.  
8.2.2.1.3.2 
EQ-5D-5L 
Health-related QOL will also be assessed in all subjects using the EQ-5D-5L 
(Section 11.10).  EuroQol-5 Dimension will be collected at timepoints listed in the SOAs 
(Table 1-1 and Table 1-2).  The EQ-5D-5L questionnaire is a 2-page, standardized 
instrument for use as a measure of health outcome developed by the EuroQol group 
(Rabin and de Charro, 2001).  It is comprised of a 5-dimension health status measure 
and a visual analogue scale (VAS), as applicable.  The 5-dimension health status 
measure evaluates:  mobility, self-care, usual activities, pain/discomfort, and 
anxiety/depression based on a 5-level scale:  no problems, slight problems, moderate 
problems, severe problems, and extreme problems.  The VAS records the subject's 
self-rated health on a vertical, visual analogue scale where the endpoints are labelled 
‘The best health you can imagine' and ‘The worst health you can imagine'.  The 
EQ-5D-5L questionnaire will be completed in the clinic on clinic visit days, including 

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SFU, and at home (data collected by phone) for the scheduled non-clinic assessment 
days (day 5 of cycles 1, 2, and 3), and during LTFU.  
8.2.2.1.3.3 
QLQ-LC13 
The supplementary disease specific module, QLQ-LC13, is a validated questionnaire to 
assess the impact of treatment on lung cancer-associated symptoms (cough, 
hemoptysis, dyspnea and site-specific pain) and treatment-related side effects (sore 
mouth, dysphagia, peripheral neuropathy and alopecia) and pain medication  
([Koller et al, 2015; Bergman et al, 1994]; Section 11.11).  It contains 13 questions.  
QLQ-LC13 includes: 1 multi-item scale and 9 single items that assess the specific 
symptoms (dyspnea, cough, hemoptysis, and site-specific pain), side effects (sore 
mouth, dysphagia, neuropathy, and alopecia), and pain medication use of patients with 
lung cancer receiving chemotherapy.  Subjects will complete the QLQ-LC13 
questionnaire at clinic visits only. 
8.2.2.1.3.4 
PGIS and PGIC 
PGIS (Section 11.12) will be collected in the clinic at screening and on day 1 of cycles 1, 
3, and 5 to assess patients’ global impression of symptom severity of cough, dyspnea, 
and chest pain.  PGIC (Section 11.13) will be collected in the clinic on day 1 of cycles 3 
and cycle 5 to provide context for interpretation of change in key lung cancer symptoms 
as measured by the EORTC QLQ-C30 and QLQ-LC13 
8.2.2.1.3.5 
PRO-CTCAE  
Treatment-related symptoms and impact on the subject will be assessed in all subjects 
(regardless of tumor types) using selected questions from the PRO version of the 
CTCAE (PRO-CTCAE) library (Section 11.14).  PRO-CTCAE is a subject-reported 
outcome measure developed to evaluate symptomatic toxicity in subjects on cancer 
clinical trials.  The questionnaire was designed to be used as a companion to the 
CTCAE, the standard lexicon for adverse event reporting in cancer trials.  PRO-CTCAE 
item library version 1.0 is comprised of 124 individual questions developed to elicit 
78 symptomatic AEs from subjects using between 1 to 3 attribute questions (ie, 
frequency, severity, and/or interference of the adverse event),  
(Basch et al, 2014).  The recall period for PRO-CTCAE is the past 7 days.  The  
PRO-CTCAE has been tested and validated in terms of construct validity, test-retest 
reliability, and item responsiveness (Dueck et al, 2015).  Amgen has selected questions 
from the PRO-CTCAE for inclusion in the trial which represent symptoms of adverse 
events which are not addressed directly by questions in the EORTC QLQ-C30 or the 

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EORTC QLQ-LC13.  The specific questions were selected based on a review of the 
symptoms most commonly observed with AMG 510 as of the June 12 2019  
(AMG 510 Investigator’s Brochure June 12 2019) and a review of the USPI for docetaxel 
for symptoms among patients treated with docetaxel and prior exposure to a platinum 
based chemotherapy.  The specific questions to be asked in this study are composed of 
the general mouth sores, muscle aches, itchy skin, numbness and pain components 
from the library.  Subjects will complete the PRO-CTCAE questionnaire at clinic visits 
only (with the exception of screening visit). 
8.2.2.1.3.6 
GP5 of the FACT-G 
The GP5 of the FACT-G is a single item “I am bothered by side effects of treatment” 
rated on a 5-point Likert scale from “not at all” to “very much” is an item included in the 
Physical Well-Being subscale of the PRO assessment instrument FACT-G 
(Section 11.15).  It has been evaluated and validated as a useful summary index of side 
effect impact or burden to the individual subject (Pearman et al, 2018). Subjects will 
complete the GP5 of the FACT-G on day 1 (administered by tablet in the clinic) of each 
cycle, and at the SFU. 
8.2.2.1.3.7 
Brief pain Inventory (BPI)  
Pain will be assessed on day 1 of every cycle and at the SFU by using the BPI, which 
assesses the severity of pain and its impact on functioning (Section 11.16).  The BPI will 
be administered in the clinic to provide context for interpretation of change in patient 
reported symptoms of chest pain. 
8.2.3 
Safety Assessments 
Planned time points for all safety assessments are listed in the Schedule of Activities 
see (Table 1-1 and Table 1-2). 
8.2.3.1 
Vital Signs 
The following measurements must be performed:  systolic/diastolic blood pressure, heart 
rate, respiratory rate, oxygen saturation, and body temperature.  Subject must be in a 
supine position in a rested and calm state for at least 5 minutes before blood pressure 
assessments are conducted.  If the subject is unable to be in the supine position, the 
subject should be in most recumbent position as possible.  The position selected for a 
subject should be the same that is used throughout the study and documented on the 
vital sign CRF.  The temperature location selected for a subject should be the same that 
is used throughout the study and documented on the vital signs CRF.  All measurements 
will be recorded on the vital signs CRF. 

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8.2.3.2 
Electrocardiograms 
Subject must be in supine position in a rested and calm state for at least 5 minutes 
before ECG assessment is conducted.  If the subject is unable to be in the supine 
position, the subject should be in most recumbent position as possible.  The ECG must 
include the following measurements:  Heart Rate, QRS, QT, QTc, and PR intervals.  The 
Principal Investigator (PI) or delegate assigned via the Delegation of Authority log will 
review all ECGs.  Once signed, the original ECG tracing will be retained with the 
subject's source documents.  At the request of the sponsor, a copy of the original ECG 
will be made available to Amgen.  
8.2.3.3 
Vital Status 
Vital status must be obtained for all subjects within the limits of local law.  This includes 
subjects who may have discontinued study visits with or without withdrawing consent 
and should include interrogation of public databases, if necessary.  If deceased, the date 
and reported cause of death should be obtained. 
8.2.3.4 
Other Safety 
Patient recorded outcome questionnaires are described in Section 8.2.2.1.3. 
8.2.4 
Adverse Events and Serious Adverse Events  
8.2.4.1 
Time Period and Frequency for Collecting and Reporting Safety 
Event Information 
8.2.4.1.1 
Adverse Events 
The adverse event grading scale to be used for this study will be the CTCAE version 5.0 
and is described in Section 11.4. 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur after enrollment through the SFU visit 
are reported using the Events CRF. 
8.2.4.1.2 
Serious Adverse Events 
The investigator is responsible for ensuring that all serious adverse events observed by 
the investigator or reported by the subject that occur after signing of the informed 
consent through the safety follow-up visit or 30 days after the last day of dosing 
interval of investigational product(s)/protocol-required therapies, whichever 
occurs later are reported using the Events CRF.   
All serious adverse events will be collected, recorded and reported to the sponsor or 
designee within 24 hours of the investigator’s awareness of the event, as indicated in 

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Section 11.4.  The investigator will submit any updated serious adverse event data to the 
sponsor within 24 hours of it being available. 
The criteria for grade 4 in the CTCAE grading scale differs from the regulatory criteria for 
serious adverse events.  It is left to the investigator’s judgment to report these grade 4 
abnormalities as serious adverse events. 
8.2.4.1.3 
Serious Adverse Events After the Protocol-required Reporting 
Period 
After End of Study, there is no requirement to actively monitor study subjects after 
the study has ended with regards to study subjects treated by the investigator.  
However, if the investigator becomes aware of serious adverse events suspected to 
be related to investigational products after the protocol-required reporting period (as 
defined in Section 8.2.4.1.2), then these serious adverse events will be reported to 
Amgen within 24 hours following the investigator’s awareness of the event. 
Since overall survival is a study endpoint, the investigator will also need to 
collect/report fatal serious adverse events (regardless of causality) to Amgen within 
24 hours following the investigator’s awareness of the event. 
Serious adverse events reported outside of the protocol-required reporting period will be 
captured within the safety database as clinical trial cases and handled accordingly based 
on relationship to investigational product.  
If further safety-related data is needed to fulfill any regulatory reporting 
requirements for a reportable event, then additional information may need to be 
collected from the subject’s medical records - even after the subject has ended 
the study (as long as the subject did not withdraw consent). 
The method of recording, evaluating, and assessing causality of adverse events, and 
serious adverse events and the procedures for completing and transmitting serious 
adverse event reports are provided in Section 11.4. 
8.2.4.2 
Reporting a Safety Endpoint as a Study Endpoint 
Safety endpoints (eg, mortality) that are study endpoints are reported on the Events 
CRF.  All endpoints that also meet the criteria of serious adverse event must also be 
transmitted to safety within 24 hours of the investigator’s awareness of the event (refer 
to Section 11.4). 

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8.2.4.3 
Method of Detecting Adverse Events and Serious Adverse Events 
Care will be taken not to introduce bias when detecting adverse events and/or serious 
adverse events.  Open-ended and non-leading verbal questioning of the subject is the 
preferred method to inquire about adverse event occurrence. 
8.2.4.4 
Follow-up of Adverse Events and Serious Adverse Events 
After the initial adverse event/serious adverse event report, the investigator is required to 
proactively follow each subject at subsequent visits/contacts.  All adverse events and 
serious adverse events will be followed until resolution, stabilization, until the event is 
otherwise explained, or the subject is lost to follow-up (as defined in Section 7.3).  
Further information on follow-up procedures is given in Section 11.4. 
All new information for previously reported serious adverse events must be sent to 
Amgen within 24 hours following awareness of the new information.  If specifically 
requested, the investigator may need to provide additional follow-up information, such as 
discharge summaries, medical records, or extracts from the medical records.  
Information provided about the serious adverse event must be consistent with that 
recorded on the Events CRF. 
8.2.4.5 
Regulatory Reporting Requirements for Serious Adverse Events 
If subject is permanently withdrawn from protocol-required therapies because of a 
serious adverse event, this information must be submitted to Amgen. 
Prompt notification by the investigator to the sponsor of serious adverse events is 
essential so that legal obligations and ethical responsibilities towards the safety of 
subjects and the safety of a study treatment under clinical investigation are met.  
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study treatment under clinical 
investigation.  The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRBs/IECs, and investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse 
reactions according to local regulatory requirements and sponsor policy and forwarded 
to investigators as necessary. 
An investigator who receives an individual safety report describing a serious adverse 
event or other specific safety information (eg, summary or listing of serious adverse 
events) from the sponsor will file it along with the Investigator’s Brochure and will notify 
the IRB/IEC, if appropriate according to local requirements. 

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8.2.4.6 
Safety Monitoring Plan 
Subject safety will be routinely monitored as defined in Amgen’s safety surveillance and 
signal management processes. 
8.2.4.7 
Pregnancy and Lactation 
Details of all pregnancies and/or lactation in female subjects and female partners of 
male subjects will be collected after the start of study treatment and until 7 days 
(AMG 510) or 6 months (docetaxel) post dose for female subjects and 7 days 
(AMG 510) or 6 months (docetaxel) post dose for female partners of male subjects.  
Female subjects who become pregnant while on study or within 7 days after receiving 
the last dose of AMG 510 will not receive subsequent scheduled doses and will be 
followed for safety until end of study visit. 
If a pregnancy is reported, the investigator is to inform Amgen within 24 hours of learning 
of the pregnancy and/or lactation and is to follow the procedures outlined in 
Section 11.5.  Amgen Global Patient Safety will follow-up with the investigator regarding 
additional information that may be requested. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Section 11.5. 
8.2.5 
Clinical Laboratory Assessments 
Refer to Section 11.2 for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Table 1-1 and Table 1-2) for the timing and frequency.  
The investigator is responsible for reviewing laboratory test results and recording any 
clinically relevant changes occurring during the study on the Adverse Event CRF.  The 
investigator must determine whether an abnormal value in an individual study subject 
represents a clinically significant change from the subject’s baseline values.  In general, 
abnormal laboratory findings without clinical significance (based on the investigator's 
judgment) are not to be recorded as adverse events.  However, laboratory value 
changes that require treatment or adjustment in current therapy are considered adverse 
events.  Where applicable, clinical sequelae (not the laboratory abnormality) are to be 
recorded as the adverse event.  

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8.2.6 
Pregnancy Testing 
A highly sensitive (urine or serum) pregnancy test should be completed at screening and 
within 3 days before initiation of investigational product for females of childbearing 
potential.   
Note:  Females who have undergone a bilateral tubal ligation/occlusion should have 
pregnancy testing per protocol requirements.  (If a female subject, or the partner of a 
male subject, becomes pregnant it must be reported on the Pregnancy Notification 
Form, see Figure 11-2).  Refer to Section 11.5 for contraceptive requirements.  
Additional pregnancy testing should be performed as outlined in the Schedule of 
Activities (Table 1-1 and Table 1-2).  
Additional on-treatment pregnancy testing may be performed at the investigator’s 
discretion or as required per local laws and regulations. 
8.2.7 
Pharmacokinetic Assessments 
All subjects randomized to AMG 510 will have PK samples assessed.  Whole blood 
samples will be collected for measurement of plasma concentrations of AMG 510, 
metabolites, and for exploratory exposure-response analyses as specified in the 
Schedule of Activities (Table 1-1 and Table 1-2).  Instructions for the collection and 
handling of biological samples will be provided by the sponsor.  The actual date and time 
(24-hour clock time) of each sample will be recorded. 
8.2.7.1 
Biomarker Assessment to Determine Eligibility (KRAS G12C):  
Tumor Tissue 
Biomarkers are objectively measured and evaluated indicators of normal biologic 
processes, pathogenic processes, or pharmacologic responses to a therapeutic 
intervention.  In oncology, there is particular interest in the molecular changes underlying 
the oncogenic processes that may identify cancer subtypes, stage of disease, assess 
the amount of tumor growth, or predict disease progression, metastasis, and responses 
to investigational product(s) or protocol required therapies.  In this study, a specific 
genomic biomarker (KRAS p.G12C) needs to be identified as part of the screening 
process. 
A subject must have confirmation of KRAS p.G12C mutation by central laboratory testing 
prior to enrollment.  Positivity for KRAS G12C will be determined at the central testing 
lab with an in vitro diagnostic device (Qiagen KRAS therascreen® KRAS RGQ PCR Kit).  

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This central laboratory testing can occur through the current protocol or Amgen Study 
20190294. 
The method used to confirm or detect KRAS G12C mutation by central testing should 
depend on whether the subject has KRAS G12C mutation results from a local test and 
whether they have sufficient archival tissue available or need to undergo a biopsy. 
(Table 8-1). 
Table 8-1.  Accepted Methods for Central Confirmation or Detection of  
KRAS G12C Mutation for Enrollment 
Subject Presentation 
Method 
Local KRAS G12C results available 
(tissue or liquid) 
Archived tissue through the Study 20190009 
protocol 
Local KRAS G12C results available, but 
no available tissue to confirm 
Tumor biopsy through the Study 20190009 
protocol 
No local KRAS G12C result available 
Receive confirmation of KRAS G12C mutation 
through screening protocol (Amgen 
Study 20190294) 
No local KRAS G12C result available, 
and no available tissue to confirm 
Tumor biopsy through the Study 20190009 
protocol 
If confirmation of KRAS G12C mutation is not available through participation in Amgen 
Study 20190294, tumor tissue will be required to identify KRAS p.G12C status prior to 
enrollment.  Tumor tissue samples (FFPE of excisional, core needle, or fine needle 
aspirates) may be collected after informed consent is obtained.  Tumor sample must be 
submitted to the central laboratory either as FFPE blocks or unstained slides (see study 
laboratory manual for details) for confirmation of mutation status.  Tissue sample should 
be submitted along with the corresponding pathology report. 
If archived tumor samples are not available, subjects will have the option to undergo a 
tumor biopsy to identify KRAS p.G12C status which must be sent as an FFPE block or 
unstained slides.   
The FFPE tumor block or unstained slides of tissue (excisional, core needle, or fine 
needle aspirates) is to be carefully selected by a pathologist or a skilled experienced 
histology associate to include generous tumor tissue using the Pathology Report as a 
guide.  In lieu of a block, unstained sections on superfrost or positively charged slides 
from the same block can be submitted according to the procedures defined in the study 
lab manual. 

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Subjects will submit tumor tissue samples (formalin fixed, paraffin embedded [FFPE] 
sample [FFPE of excisional, core needle, or fine needle aspirate] collected within 5 years) 
or be willing to undergo pre-treatment tumor biopsy (excisional, core needle, or fine 
needle aspirate) for tissue prior to enrollment.  Tissue samples will be used for biomarker 
testing (If biomarker assessments are allowable under local regulations and if allowable 
by local IRB/EC) and Qiagen KRAS therascreen® testing for KRAS G12C.  
8.2.7.2 
Central KRAS p.G12C Laboratory Methods Summary 
The therascreen® KRAS PCR Kit from QIAGEN is a real-time qualitative PCR assay 
performed on the RGQ MDx instrument for the detection of 7 somatic mutations in the 
human KRAS oncogene using DNA extracted from FFPE tissue.  The mutations 
detected are:  G12A, G12D, G12R, G12C, G12S, G12V, G13D.  The therascreen® 
KRAS RGQ PCR Kit is an in vitro diagnostic device that will be used to confirm that the 
subjects, who are to be enrolled in the study, have tumors that are KRAS G12C positive. 

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8.2.8 
Medical Resource Utilization and Health Economics 
 
Medical resource utilization and health economics data, associated with medical 
encounters, will be collected in the CRF by the investigator and study-site personnel 
for all subjects throughout the study.  Protocol-mandated procedures, tests, and 
encounters are excluded.  
9. 
Statistical Considerations 
9.1 
Statistical Hypotheses 
The following 2-sided hypotheses will be tested in this trial. 
Primary endpoint: 
H01:  PFS survival distribution of AMG 510 arm is the same as for docetaxel arm versus 
H11:  the 2 PFS survival distributions are different. 
Key secondary endpoints: 
H02:  odds ratio of ORR between AMG 510 arm and docetaxel arm = 1 versus H12:  odds 
ratio of ORR between AMG 510 arm and docetaxel arm ≠ 1 
H03:  OS survival distribution of AMG 510 arm is the same as for docetaxel arm versus 
H13:  the 2 OS survival distributions are different. 
H04:  difference in mean change from baseline over time to week 12 in symptom of 
dyspnea as measured by a 4-item dyspnea domain from QLQ-C30 and QLQ-LC13 = 0 
versus H14:  difference in mean change from baseline over time to week 12 in symptom 

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of dyspnea as measured by a 4-item dyspnea domain from QLQ-C30 and  
QLQ-LC13 ≠ 0 
H05:  difference in mean change from baseline over time to week 12 in symptom of 
cough as measured by QLQ-LC13 = 0 versus H15:  difference in mean change from 
baseline over time to week 12 in symptom of cough as measured by QLQ-LC13 ≠ 0 
H06:  difference in mean change from baseline over time to week 12 in symptom of chest 
pain as measured by QLQ-LC13 = 0 versus H16:  difference in mean change from 
baseline over time to week 12 in symptom of chest pain as measured by QLQ-LC13 ≠ 0 
H07:  difference in mean change from baseline over time to week 12 in physical 
functioning as measured by QLQ-C30 = 0 versus H17:  difference in mean change from 
baseline over time to week 12 in physical functioning as measured by QLQ-C30 ≠ 0 
H08:  difference in mean change from baseline over time to week 12 in global health 
status as measured by QLQ-C30 = 0 versus H18:  difference in mean change from 
baseline over time to week 12 in global health status as measured by QLQ-C30 ≠ 0 
The hypotheses of the primary efficacy endpoint and key secondary efficacy endpoints 
will be tested using the following graphical multiple testing procedure  
(Maurer and Bretz, 2013) to control the study-level overall type I error rate below 1-sided 
0.025 levels.  A hypothesis can be re-tested repeatedly with a different nominal level that 
is propagated from rejecting other hypothesis test(s).  
Figure 9-1 illustrates the Maurer-Bretz multiple testing procedure among PFS, OS and 
ORR.  The fractions on the directed arrows indicate the proportion of α propagated from 
one hypothesis to the other when its hypothesis is rejected.  Starting with PFS, if the 
hypothesis of PFS is rejected, ORR will be tested using 1-sided α/5 (0.005) level.  With 
the rejection of ORR hypothesis, OS will be tested using 1-sided full α (0.025) level.  If 
ORR hypothesis is failed to be rejected, OS will be tested using 1-sided 0.001 level if at 
PFS IA, otherwise using 4α/5 (0.02) level.  With the rejection of OS hypothesis, ORR can 
be retested using 1-sided full α (0.025) level.  

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Figure 9-1.  Initial Graph of Maurer-Bretz Multiple Testing Procedure for PFS, OS, 
and ORR. 
 
ORR = objective response rate; OS = overall survival; PFS = progression-free survival 
If all 3 hypotheses of PFS, OS, ORR are rejected, the next 3 endpoints of change from 
baseline over time to week 12 in 3 lung cancer symptoms will be tested using Holm’s 
procedure, illustrated in Figure 9-2, including change from baseline over time to week 12 
for the symptom of dyspnea as measured by a 4 item dyspnea domain from QLQ-C30 
and QLQ-LC13 (dyspnea), change from baseline over time to week 12 for the symptom 
of cough as measured by QLQ-LC13 (cough), and change from baseline over time to 
week 12 for the symptom of chest pain as measured by QLQ-LC13 (pain).  Hypotheses 
are rejected sequentially based on the smallest p-value.  
Figure 9-2.  Holm’s Procedure for Change From Baseline Over Time to Week 12 in 
3 Lung Cancer Symptoms 
 
Dysp = dyspnea 
If all 6 hypotheses listed above are rejected, the next 2 PRO endpoints will be tested 
using the Holm’s procedure, illustrated in Figure 9-3, including change from baseline 
over time to week 12 in physical functioning as measured by QLQ-C30 (phys.), change 

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from baseline over time to week 12 in global health status as measured by QLQ-C30 
(ghs).  Hypotheses are rejected sequentially based on the smallest p-value.   
Figure 9-3.  Holm’s Procedure for Change From Baseline Over Time to Week 12 on 
Physical Functioning and Global Health Status  
 
phys = physical; ghs = global health status 
9.2 
Sample Size Determination 
The PA of PFS will occur when approximately 230 PFS events have been observed.  
With 230 PFS events, the study will have ~90% power to show a statistically significant 
PFS at the 2.5% 1-sided significance level if the true treatment effect hazard ratio (HR) 
is assumed 0.65 for the AMG 510 arm versus the control arm.  The sample size is 
chosen to have 70% maturity realizing PFS events, which is approximately 330 subjects 
with 1:1 randomization ratio into the AMG 510 arm and the docetaxel arm.  The PFS PA 
may be delayed to ensure that the enrollment is finished and the delayed PA will be 
triggered when the last randomized subject have had the opportunity to have at least 
6 weeks of follow up.   
An IA is planned when approximately 70% (160) of the target PFS events have been 
observed from both arms, or when the enrollment is finished and the last randomized 
subject have had the opportunity to have 6 weeks of follow up, whichever occurs later.  
The monitoring boundary for early stopping for efficacy will be based on an 
O’Brien-Fleming type alpha spending function for multiplicity adjustment.  The actual 
information fraction will be calculated based on the number of observed events at the 
time of the analysis.  Under exponential distribution, the minimum detectable difference 
for success in this design is an HR of 0.68 between AMG 510 arm and the docetaxel 
arm with 160 PFS events, 70% of the target PFS events, and an HR of 0.769 at the PA 
with 230 PFS events.  Assuming an enrollment rate of 40 subjects per month after a 
3-month ramp-up period, with a total sample size of 330, it is estimated that 
approximately 19 months will be required to reach 230 PFS events, and 13 months will 
be required to reach 70% (160) of the target PFS events.  This estimation is based on a 

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median PFS of 5 months for the control arm (Charpidou et al, 2019) and 7.7 months for 
the AMG 510 arm, and a 10% dropout rate. 
If PFS achieves statistical significance at the interim analysis, an administrative interim 
summary for OS will be performed with approximately 107 OS events (~32% 
maturity) observed.  A nominal alpha of 0.01% (negligible impact on overall type I error 
rate) will be spent on this OS interim summary.  Otherwise, the OS will be assessed for 
superiority of AMG 510 over docetaxel at either the time of PFS primary analysis or after 
175 OS events (~53% maturity) have been observed, whichever is later.  Assuming the 
actual crossover rate of approximately 30% at the time of PFS primary analysis for 
subjects on the control arm who have disease progression, then with 175 OS events, the 
study has ~96% probability to observe a HR < 1 when the true OS HR is 0.75. 
The OS primary analysis will occur when at least 198 OS events (~60% maturity) have 
been observed, which is expected to be at approximately 3 months after PFS primary 
analysis, with the same enrollment assumptions.  The estimation is based on a median 
OS of 9 months for the control arm and 12 months for the AMG 510 arm (OS HR=0.75).  
The multiplicity will be adjusted as necessary based on O’Brien-Fleming type alpha 
spending function. 
As designed, the trial will not be terminated at PFS analyses and subjects will continue 
to be followed for OS data until the targeted number of events are reached, regardless of 
the OS analysis result at the PFS primary analysis, to enable OS analyses and a robust 
description of the totality of the data. 
9.3 
Analysis Sets, Subgroups, and Covariates 
9.3.1 
Analysis Sets 
9.3.1.1 
Full Analysis Set 
The full analysis set (ITT population) will include all randomized subjects.  All subjects 
will be analyzed according to treatment to which they are randomized.  Full analysis set 
will be used for the primary and key secondary efficacy endpoints. 
9.3.1.2 
Safety Analysis Set 
The safety analysis set will include subjects in the full analysis set who received at least 
1 dose of investigational product.  Subjects in the analyses based on safety analysis set 
will be analyzed according to actual treatment received. 

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9.3.1.3 
Per Protocol Analysis Set 
The per protocol analysis set is a subset of the full analysis set which includes subjects 
who do not have important protocol deviations.  The list of important protocol deviations 
is maintained by the sponsor on an ongoing basis and will be finalized before the PA of 
the study. 
9.3.2 
Covariates 
Covariates may be incorporated in selected models of efficacy endpoints.  In addition to 
the stratification factors for randomization, number of prior lines of therapy in advanced 
disease (1 versus 2 versus > 2), race (Asian versus non-Asian), history of CNS 
involvement (yes versus no), the following additional covariates may be included: 
 
region 
 
best response on prior therapy  
 
age 
 
sex 
 
race 
 
ECOG status 
 
Liver metastasis at baseline 
 
Disease stage  
 
smoking history 
 
histology 
 
brain metastasis at baseline 
 
bone metastasis at baseline 
 
presence of specific co-mutations at baseline (specific co-mutations to be specified 
in statistical analysis plan [SAP]) 
 
PD-L1 protein expression (< 1%, ≥ 1%, and < 50%; ≥ 50%)  
 
STK11 mutation   
 
KEAP1 mutation  
Detailed description of covariates to incorporate for each appropriate model will be 
pre-specified in the SAP. 
9.3.3 
Subgroups 
In addition to the stratification factors for randomization, number of prior lines of therapy 
in advanced disease (1 versus 2 versus > 2), race (Asian versus non-Asian), history of 

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CNS involvement (yes versus no), primary and selected secondary endpoints will be 
examined in the following subgroups to investigate the consistency of treatment effects: 
 
region (North America and Europe vs rest of world)  
 
best response on prior therapy primary refractory (progression on first scan), 
suboptimal response (stable disease), recurrent (initial response with subsequent 
growth) 
 
age (< 65 vs  65) 
 
sex (male vs female) 
 
race (white, black, Asian, other) 
 
ECOG status (0 vs 1) 
 
Liver metastasis at baseline (yes vs no) 
 
stage (locally advanced and unresectable versus metastatic) 
 
smoking history (yes vs no) 
 
histology (squamous vs non-squamous) 
 
presence of specific co-mutation at baseline (yes vs no).  Specific co-mutations to be 
specified in SAP. 
 
brain metastasis at baseline (yes vs no) 
 
bone metastasis at baseline (yes vs no) 
 
PD-L1 protein expression (< 1% vs ≥ 1%, and < 50% vs ≥ 50%) 
 
STK11 mutation   
 
KEAP1 mutation  
In the event that there are insufficient number of subjects in the subgroup (ie, less than 
10% of the whole population), relevant subgroups may be combined. 
9.3.4 
Handling of Missing and Incomplete Data 
Incomplete adverse event start dates, concomitant medications start or stop dates, and 
death date will be imputed and the detailed rules will be specified in SAP.  No imputation 
will be done for the PA of the primary and key secondary endpoints.  The frequency of 
missing disease assessments and deviation of the actual disease assessment times 
from the scheduled assessment times will be summarized by treatment arms.  Sensitivity 
analyses will be performed to assess the impact on the analysis of PFS due to any 
missing data/assessment, and any lost to follow-up or discontinuation of assessment of 

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PFS not due to an event.  Similar analysis will be performed for Clinical Outcome 
Assessments (COA) endpoints. 
Details of missing data analysis and imputation rules will be described in the SAP.  
9.4 
Statistical Analyses 
The SAP will be developed and finalized before database lock.  Below is a summary of 
the timing and methods for the planned statistical analyses.  To preserve study integrity, 
the final analysis will be conducted and reported following the end of study, as defined in 
Section 4.4. 
9.4.1 
Planned Analyses 
9.4.1.1 
Interim Analysis and Early Stopping Guidelines 
An IA of PFS for superiority is planned when approximately 70% (160 events) of the total 
PFS events have been observed, or when the enrollment is finished and the last 
randomized subject have had the opportunity to have 6 weeks of follow up, whichever 
occurs later.  Early efficacy at the proposed PFS interim analysis will be claimed if the 
observed PFS difference meets the pre-specified statistical significance as well as being 
considered clinically meaningful. 
If PFS achieves statistical significance at the interim analysis, an administrative interim 
summary for OS will be performed.  Otherwise, the OS will be assessed for superiority of 
AMG 510 over docetaxel at either the time of PFS primary analysis or after 175 OS 
events (~53% maturity) have been observed, whichever is later. 

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Table 9-1:  Potential Interim and Primary Analysis of PFS and OS 
Analysis 
PFS 
Information 
Fraction 
Expected Timing 
from FSE 
Analysis Trigger 
PFS IA 
70% 
13 months 
160 PFS events or LSE + 
6 weeks, whichever occurs 
later 
PFS PA 
100% 
19 months 
230 PFS events or LSE + 
6 weeks, whichever occurs 
later 
OS at PFS 
PA 
N.A. 
19 months 
175 OS events 
OS PA 
N.A. 
22 months 
198 OS events 
IA = interim analysis; OS = overall survival; PA = primary analysis; PFS = progression-free survival. 
9.4.1.2 
Primary Analysis 
The timing for the PA of PFS will be event driven and will happen when approximately 
230 PFS events are reached cumulatively in 2 treatment groups.  If PFS early success is 
achieved in the IA, the IA will serve the purpose of PA of PFS.  The PFS PA may be 
delayed to ensure that the enrollment is finished and the delayed PA will be triggered 
when the last randomized subject have had the opportunity to have at least 6 weeks of 
follow up.  The PA for OS will be event driven and will occur when approximately 198 OS 
events have been reached.  There will be only one analysis for ORR (no interim analysis 
for ORR is planned).  The primary analysis of ORR will be done when PFS is claimed 
statistically significant and the last randomized subject has had the opportunity to have 
at least 12 weeks of follow up. 
9.4.1.3 
Final Analysis 
The final analysis of the study will be done when the last subject completes LTFU. 
9.4.2 
Methods of Analyses 
9.4.2.1 
General Considerations 
The efficacy analyses of PFS and key secondary endpoints will be conducted on the full 
analysis set.  In principle, summary statistics including mean, standard deviation, 
median, first and third quartiles, will be provided for continuous variables.  Frequency 
and percentage will be summarized by treatment arm for binary and categorical 
variables.  The distribution of PFS and OS will be estimated using the Kaplan-Meier 
method.  The HR and its 95% CI will be estimated using a Cox proportional hazards 
model stratified by the randomization stratification factors.  The inferential comparison 

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will be made using a stratified log rank test.  Objective response rate will be calculated 
and the associated 95% CI will be estimated using the Clopper-Pearson method.  The 
inferential comparison for ORR will be made using the Cochran-Mantel-Haenszel 
chi-square test controlling for the randomization stratification factors.  For subjects who 
continue treatment post-progression or subjects who crossover from docetaxel to 
AMG 510, the first date of progression will be used for PFS analysis and subject’s 
response post first progression or post crossover will not be used the primary analyses 
to evaluate objective response endpoints including PFS, ORR, DOR, TTR, and DCR.  
The inferential comparison for the endpoints of change from baseline over time to 
week 12 in symptoms of dyspnea as measured by a 4 item dyspnea domain from 
QLQ-C30 and QLQ-LC13, change from baseline over time to week 12 in physical 
functioning, global health status as measured by QLQ-C30 will be made through a mixed 
model for repeated measurement (MMRM).  The inferential comparison for the 
endpoints of change from baseline over time to week 12 in symptoms of cough and 
chest pain as measured by a single question from QLQ-LC13 will be made through 
generalized estimating equations (GEE) method for cumulative logits model (Lipsitz et 
al, 1994).  Multiple imputation approach with non-ignorable missing pattern will be 
explored as the sensitivity analysis for all the key secondary PRO endpoints. 
Further details of secondary endpoint testing will be described in the SAP.  
9.4.2.2 
Efficacy Analyses 
 
Estimand 
Primary Analysis 
Sensitivity Analysis 
HR of PFS between 
AMG 510 and docetaxel, for 
subjects with previously 
treated locally advanced and 
unresectable or metastatic 
NSCLC with KRAS p.G12C 
mutation, before or on start 
of new anti-cancer therapy 
The PA of PFS will be 
conducted on the full 
analysis set. 
The primary comparison for 
PFS between treatment and 
control will use the log rank 
test stratified by 
randomization factors per 
IRT.  The HR and its 95% 
CI will be estimated using a 
Cox proportional hazards 
model stratified by the 
randomization stratification 
factors per IRT.  Kaplan 
Meier curve will also be 
provided by treatment arm.  
The PA of PFS will be 
based on BICR centrally 
assessed outcomes. 
The analysis based on 
investigator-assessed local 
To evaluate the robustness of 
the PFS endpoint for the 
intercurrent event of start of new 
anti-cancer therapy prior to PFS 
event, a sensitivity analysis 
based on a different set of 
censoring rules will be 
performed (see Table 9-2). 

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Estimand 
Primary Analysis 
Sensitivity Analysis 
outcome will serve as 
supportive analyses. 
HR of OS between AMG 
510 and docetaxel, for 
subjects with previously 
treated locally advanced and 
unresectable or metastatic 
NSCLC with KRAS p.G12C 
mutation, regardless of 
subsequent anti-cancer 
therapy and/or crossover. 
The analysis of OS will be 
conducted on the full 
analysis set.  Overall 
survival will be analyzed 
using the same method as 
described for the PFS 
endpoints.   
To address the intercurrent 
event of crossover from control 
group to treatment group, the 
primary comparison of OS 
between treatment and control 
will use one or more methods 
such as Rank preserving 
structural failure time (RPSFT) 
model to adjust for crossover 
effect.  It will provide the 
randomization-based estimate of 
estimate of treatment effect 
(RBEE) corrected for the bias 
induced by crossover and the 
95% CI of the OS HR adjusted 
for crossover effect.  Additional 
methods will be explored to 
check the robustness of the 
model assumptions. 
Odds ratio of objective 
response between AMG 510 
and docetaxel, for subjects 
with previously treated 
locally advanced and 
unresectable or metastatic 
NSCLC with KRAS p.G12C 
mutation. Subjects who 
discontinued treatment prior 
to achieving an objective 
response are considered as 
non-responders. 
The inferential comparison 
between treatment and 
control for ORR will be 
made using the Cochran-
Mantel-Haenszel chi-square 
test controlling for the 
stratification factors per IRT.  
An estimate of the common 
odds ratio (95% CI) will be 
provided as a measure of 
the relative treatment effect. 
Change from baseline to 
Week 12 in PRO endpoints 
between AMG 510 and 
docetaxel, for subjects with 
previously treated locally 
advanced and unresectable 
or metastatic NSCLC with 
KRAS p.G12C mutation. 
PRO measurements before 
or on start of new anti-
cancer therapy including 
crossover will be used to 
estimate treatment effect. 
Change from baseline over 
time to week 12 in 
symptoms of dyspnea as 
measured by a 4 item 
dyspnea domain from 
QLQ-C30 and QLQ-LC13, 
change from baseline over 
time to week 12 in physical 
functioning, global health 
status as measured by 
QLQ-C30 will be compared 
between treatment arms 
using MMRM (Mallinckrodt 
et al, 2008).  The dependent 
variable of this model will be 
the change from baseline 
score over time to week 12.  
The model will include 
intercept, time, baseline 
score, treatment, treatment 
by time interaction, and 
randomization stratification 
factors as fixed effects and 
Multiple imputation approach 
with non-ignorable missing 
pattern will be explored as the 
sensitivity analysis for all the key 
secondary PRO endpoints. 

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Estimand 
Primary Analysis 
Sensitivity Analysis 
subject random intercept 
and subject random slope of 
time on score as random 
effect. 
Change from baseline over 
time to week 12 in 
symptoms of cough and 
chest pain as measured by 
a single question from 
QLQ-LC13 will be 
compared between 
treatment arms using GEE 
method for cumulative logits 
model.  The model will 
include intercept, time, 
baseline score, treatment, 
treatment by time 
interaction and 
randomization stratification 
factors. 
Subgroup analysis for key 
secondary endpoints will be 
performed in subgroups 
defined in Section 9.3.3. 
Table 9-2.  Censoring Rules for PFS Analyses per BICR 
Situation (before data 
cutoff) 
Primary Analysis 
Sensitivity Analysis 
Date of Event or 
Censor 
Out 
come 
Date of Event or 
Censor 
Out 
come 
Radiological disease 
progression per 
BICR prior to death 
Date of first 
observation of 
radiological disease 
progression per BICR 
Event 
  
  
No radiological 
disease progression 
per BICR, but death 
record 
Date of death 
Event 
  
  
No evaluable 
post-baseline tumor 
assessments per 
BICR, no death 
recorded  
Date of randomization 
date 
Censor  
  
  
No radiological 
disease progression 
per BICR, no death, 
but start of new 
anti-cancer therapy 
recorded 
Date of last evaluable 
assessment per BICR 
before start of new 
anti-cancer therapy 
Censor  
If on study therapy, 
date of last evaluable 
assessment 
per BICR 
Censor 
if not on study therapy, 
date of treatment 
discontinuation 
Event 

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Situation (before data 
cutoff) 
Primary Analysis 
Sensitivity Analysis 
Date of Event or 
Censor 
Out 
come 
Date of Event or 
Censor 
Out 
come 
No radiological 
disease progression 
per BICR, no death 
recorded, no start of 
new anti-cancer 
therapy 
Date of last evaluable 
assessment per BICR 
Censor  
Date of start of new 
anti-cancer therapy 
Event 
Death or radiological 
disease progression 
per BICR 
immediately after 
more than one 
missed tumor 
assessment 
Date of last evaluable 
assessment per BICR 
with documented 
non-progression prior 
to missing 
assessment(s) 
Censor  
  
  
 
 
Endpoint 
Statistical Analysis Methods 
Primary 
The PA of PFS will be conducted on the full analysis set.  The primary 
comparison for PFS between treatment and control will use the log-rank test 
stratified by randomization factors per IRT.  The HR and its 95% CI will be 
estimated using a Cox proportional hazards model stratified by the 
randomization stratification factors per IRT.  Kaplan-Meier curve will also be 
provided by treatment arm.  The PA of PFS will be based on BICR centrally 
assessed outcomes.  The analysis based on investigator-assessed local 
outcome will serve as supportive analyses. 
As stated in Section 9.2, the PA of PFS will occur when approximately 
230 events have been reached.  The PFS PA may be delayed to ensure that 
the enrollment is finished and the delayed PA will be triggered when the last 
randomized subject have had the opportunity to have at least 6 weeks of 
follow up.  An IA is planned when approximately 70% (160) of the target PFS 
events have been observed from both arms or when the enrollment is finished 
and the last randomized subject have had the opportunity to have 6 weeks of 
follow up, whichever occurs later.  The monitoring boundary for early stopping 
for efficacy will be based on an O’Brien-Fleming type alpha spending function 
for multiplicity adjustment; the early stopping information fraction will be based 
on the actual PFS events observed and monitoring boundaries will be adjusted 
accordingly.  Deviation from the scheduled IA will not affect the overall Type I 
error.  The primary endpoint will be analyzed within each of the subgroups listed 
in Section 9.3.3.  The estimate of the hazard ratios (95% CI) will be provided 
using Cox proportional hazard model.  

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Endpoint 
Statistical Analysis Methods 
Key 
Secondary 
Objective response is defined as a complete response or partial response, as 
defined by RECIST v1.1.  Confirmation is done by a repeat, consecutive 
assessment no less than 4 weeks from the date of first documented 
assessment.  Response will be assessed by blinded independent central review 
(BIRC).  ORR is therefore defined as the proportion of subjects with a best 
overall response of confirmed CR or confirmed PR. 
The analysis of ORR will be done at the time when PFS reaches statistical 
significance and the last randomized subject has had the opportunity to have at 
least 12 weeks of follow up, whichever is later.  The inferential comparison 
between treatment and control for ORR will be made using the Cochran-Mantel-
Haenszel chi-square test controlling for the stratification factors per IRT.  An 
estimate of the common odds ratio (95% CI) will be provided as a measure of 
the relative treatment effect.  The PA of ORR will be based on BICR centrally 
assessed outcomes.  The analysis based on investigator-assessed local 
outcome will serve as supportive analyses. 
Overall survival is defined as the time from the date of randomization until event 
of death due to any cause.  Subjects still alive will be censored at the date last 
known to be alive.  If the date last known to be alive is after the date that 
triggers the analysis (ie, the data cutoff date), the subject will be censored at the 
date of last contact through the analysis trigger date. 
Overall survival will be analyzed using the same method as described for the 
PFS endpoints.  The PA of OS will be performed when approximately 198 OS 
events have been reached.  In addition, OS will also be tested at the PFS IA 
and/or PFS PA when PFS is claimed statistically significant.  The monitoring 
boundary for early stopping for efficacy will be based on an O’Brien-Fleming 
type alpha spending function for multiplicity adjustment.  The early stopping 
information fraction will be based on the actual OS events observed and 
monitoring boundaries will be adjusted accordingly.  Deviation from the 
scheduled IA will not affect the overall type I error. 
Change from baseline over time to week 12 in symptoms of dyspnea as 
measured by a 4 item dyspnea domain from QLQ-C30 and QLQ-LC13, change 
from baseline over time to week 12 in physical functioning, global health status 
as measured by QLQ-C30 will be compared between treatment arms using 
MMRM (Mallinckrodt et al, 2008). The dependent variable of this model will be 
the change from baseline score over time to week 12.  The model will include 
intercept, time, baseline score, treatment, treatment by time interaction and 
randomization stratification factors as fixed effects and subject random intercept 
and subject random slope of time on score as random effect. Change from 
baseline over time to week 12 in symptoms of cough and chest pain as 
measured by a single question from QLQ-LC13 will be compared between 
treatment arms using GEE method for cumulative logits model.  The model will 
include intercept, time, baseline score, treatment, treatment by time interaction 
and randomization stratification factors. Multiple imputation approach with non-
ignorable missing pattern will be explored as the sensitivity analysis for all the 
key secondary PRO endpoints.  Subgroup analysis for key secondary endpoints 
will be performed in subgroups defined in Section 9.3.3. 
Secondary 
and 
Exploratory 
Will be described in the SAP finalized before database lock 
 

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9.4.2.3 
Safety Analyses 
9.4.2.3.1 
Analyses of Primary Safety Endpoint(s) 
There is no primary safety endpoint in Study 20190009.  The safety and tolerability of 
AMG 510 compared to docetaxel will be assessed as a secondary endpoint.  Unless 
otherwise specified, analyses of safety endpoints will be done in safety analysis set. 
9.4.2.3.2 
Adverse Events 
Subject incidence of all treatment-emergent adverse events will be tabulated by system 
organ class and preferred term.  Tables of fatal adverse events, serious adverse events, 
adverse events leading to discontinuation from investigational product or other 
protocol-required therapies, and significant treatment emergent adverse events will also 
be provided.   
9.4.2.3.3 
Laboratory Test Results 
The analyses of safety laboratory endpoints will include summary statistics over time by 
treatment.  Shifts in grades of safety laboratory values between baseline and the worst 
on-study value will be tabulated by treatment group.  
9.4.2.3.4 
Vital Signs 
The analyses of vital signs will include summary statistics over time by treatment group.  
Shifts in vital sign values between baseline and the worst on-study value will be 
tabulated by treatment group. 
9.4.2.3.5 
Physical Measurements 
The analyses of physical measurements will include summary statistics over time by 
treatment group. 
9.4.2.3.6 
Electrocardiogram 
The ECG measurements from this clinical study were performed as per standard of care 
for routine safety monitoring, rather than for purposes of assessment of potential QTc 
effect.  Since these evaluations may not necessarily be performed under the rigorous 
conditions expected to lead to meaningful evaluation of QTc data; summaries and 

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statistical analyses of ECG measurements are not planned, and these data would not be 
expected to be useful for meta-analysis with data from other trials. 
9.4.2.3.7 
Exposure to Investigational Product 
The number of days on investigational product, the daily dose, and the total dose of 
investigational product will be summarized using descriptive statistics.  Subject-level 
data may be provided instead of the summary if the subject incidence is low. 
9.4.2.3.8 
Exposure to Concomitant Medication 
Number and proportion of subjects receiving therapies of interest will be summarized by 
preferred term for each treatment group as coded by the World Health Organization 
Drug dictionary.  The subject incidence and time to first use of subsequent anti-cancer 
therapies will be summarized. 

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Janes MR, Zhang J, Li LS, et al.  Targeting KRAS mutant cancers with a covalent 
G12C-specific inhibitor.  Cell.  2018;172(3):578-589. 
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early onset lung cancer in mice.  Nature.  2001;410:1111-1116. 
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clinical perspectives on the treatment of an old target.  Mol Cancer.  2018;17(1):33. 
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Co-occuring Mutations in Other Oncogenic Pathways.  J Thoras Oncol.  2018;1-9. 
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11. 
Appendices 

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11.1 
Appendix 1.  List of Abbreviations and Definitions of Terms 
 
Abbreviation or Term 
Definition/Explanation 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
AST 
aspartate aminotransferase 
AUC 
area under the plasma concentration-time curve 
BCRP 
breast cancer resistance protein 
BCT 
blood collection tubes 
BICR 
blinded independent central review committee 
BLRM 
Bayesian Logistics Regression Model 
cfDNA 
cell-free DNA 
CFR 
U.S. Code of Federal Regulations 
Cmax 
maximum plasma concentration 
CNA 
copy number amplifications 
CNS 
central nervous system 
COA 
Clinical outcome assessment 
COP 
confirmation of progression 
CR  
complete response  
CRC 
colorectal cancer 
CRF 
case report form 
CT 
computerized tomography  
ctDNA 
circulating tumor DNA 
CTCAE 
Common Terminology Criteria for Adverse Events 
ctDNA 
circulating tumor DNA 
CYP 
cytochrome P450 
DCR 
disease control rate 
DILI 
drug induced liver injury 
DLT 
dose-limiting toxicity 
DMC 
data monitoring committee 
DOR 
duration of response 
EC 
Ethics Committee 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group  
EDC 
electronic data capture 
EMA  
European Medicines Agency  
EMR 
electronic medical record 

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Abbreviation or Term 
Definition/Explanation 
EORTC QLQ-C30 
European Organization for Research and Treatment of Cancer 
Quality-of-life Questionnaire Core 30 
EORTC QLQ-LC13 
European Organization for Research and Treatment of Cancer 
Quality-of-life Questionnaire Core 13 
EQ-5D-5L 
EuroQol-5 Dimension 
End of Study (primary 
completion) 
defined as the date when the last subject is assessed or 
receives an intervention for the final collection of data for the 
primary and key secondary endpoint(s), for the purposes of 
conducting the primary analysis, whether the study concluded as 
planned in the protocol or was terminated early  
End of Study (end of trial) 
defined as the date when the last subject across all sites is 
assessed or receives an intervention for evaluation in the study 
(ie, last subject last visit), following any additional parts in the 
study (eg, long-term follow-up), as applicable 
End of Treatment 
defined as the last assessment for the protocol-specified 
treatment phase of the study for an individual subject 
ERK 
extracellular signal-regulated kinase 
ESMO 
European Society for Medical Oncology 
FACT-G 
Functional Assessment of Cancer Therapy Tool General form 
FDA 
Food and Drug Administration 
FFPE 
formalin fixed, paraffin embedded 
FIH 
first-in-human 
FSH 
follicle stimulating hormone 
GCP 
Good Clinical Practice 
GDP 
guanosine diphosphate 
GTP 
guanosine triphosphate 
GTPase 
guanosine triphosphatase 
HepBsAg 
Hepatitis B Surface Antigen 
HIV 
Human immunodeficiency virus 
HR 
Hazard ratio 
HRQOL  
health-related quality of life  
HRAS 
Harvey rat sarcoma viral oncogene homolog 
HRQOL  
health-related quality of life  
HRT 
hormone replacement therapy 
IA 
interim analysis 
IBG 
Independent Biostatistics Group 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
independent ethics committee 
ILD 
interstitial lung disease 

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Abbreviation or Term 
Definition/Explanation 
INR 
international normalized ratio 
IPIM 
Investigational Product Instruction Manual 
IRB 
institutional review board 
IRT 
interactive response technology that is linked to a central 
computer in real time as an interface to collect and process 
information 
ITT 
intention-to-treat 
IUD 
intrauterine device 
IUS 
intrauterine hormonal-releasing system 
IV 
intravenous 
KRAS 
Kirsten rat sarcoma viral oncogene homolog 
LTFU 
long-term follow-up 
MMRM 
mixed model for repeated measurement 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
NCI 
National Cancer Institute 
NCT 
National Clinical Trials 
NRAS 
neuroblastoma RAS viral oncogene homolog 
NSCLC 
non-small cell lung cancer 
ORR 
objective response rate 
OS 
overall survival 
PA 
primary analysis 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PD-1 
programmed cell death-1 
PFS 
progression-free survival 
PGIC 
Patient global impression of change 
PGIS 
Patient global impression of severity 
PI 
Principal Investigator 
PK 
pharmacokinetic 
PO 
orally-administered 
PPI 
proton-pump inhibitor 
PR 
partial response 
PRO 
patient-reported outcomes 
QD 
once daily 
QOL 
quality of life 
RAS 
rat sarcoma 

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Abbreviation or Term 
Definition/Explanation 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RGQ 
Rotor-Gene Q 
RNAi 
RNA interference 
RP2D 
recommended phase 2 dose 
rSDR/V 
Source Data Review and Verification 
SAP 
statistical analysis plan 
SD 
stable disease 
SFU 
safety follow up 
SmPC 
Summary of Product Characteristics 
SOA 
Schedule of Activities 
Source Data 
information from an original record or certified copy of the 
original record containing patient information for use in clinical 
research.  The information may include, but is not limited to, 
clinical findings, observations, or other activities in a clinical trial 
necessary for the reconstruction and evaluation of the trial.  
Source data are contained in source documents (original records 
or certified copies).  (ICH Guideline [E6]).  Examples of source 
data include Subject identification, Randomization identification, 
and Stratification Value. 
Study Day 1 
defined as the first day that protocol-specified investigational 
product(s)/protocol-required therapies is/are administered to the 
subject 
TBL 
total bilirubin 
TMF 
trial master folder 
TTR 
time to response  
VAS 
visual analogue scale 
VEGF 
Vascular Endothelial Growth Factor 
ULN 
upper limit of normal 
US 
United States 
USPI 
United States Prescribing Information 
 
 
 

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11.2 
Appendix 2.  Clinical Laboratory Tests 
The tests detailed in Table 11-1 will be performed by the local laboratory and/or by the 
central laboratory. 
Sites without local capabilities to perform protocol-required urine studies may send 
samples to the central laboratory for testing.  Results will be provided to investigative 
sites.   
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Sections 5.1 to 5.2 of the protocol. 
Additional tests, including pregnancy tests, may be performed at any time during the 
study as determined necessary by the investigator or required by local regulations. 

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Table 11-1.  Analyte Listing 
Local Laboratory/Local/Centralf Laboratory Urinalysis 
Central Laboratory 
Chemistry 
Hematology 
Coagulation 
PK and Biomarker 
(If allowable under local 
regulations and if 
allowable by local 
IRB/EC) 
Sodium  
Potassium  
Chloride 
Bicarbonatee 
Total CO2e 
Triglycerides 
Cholesterol  
Total protein  
Albumin 
Calcium  
Magnesium 
Phosphorous 
Glucose 
Blood urea nitrogen 
Ureaa 
Creatinine 
Creatinine clearance 
Total creatine kinase 
Total bilirubin 
Direct bilirubin 
Alkaline phosphatase 
Alanine 
aminotransferase 
Aspartate 
aminotransferase 
 
Other Labs 
Serum or Urine 
Pregnancyb 
 
Hemoglobin  
Hematocrit 
Mean corpuscular volume 
Platelets  
RBC 
WBC 
ANC 
White blood cell 
Differential 
 
Total neutrophils 
 
Eosinophils 
 
Basophils 
 
Lymphocytes 
 
Monocytes 
PT and INR 
aPTT  
 
 
 
 
 
 
 
 
 
 
  
 
PK sampling 
Plasma ctDNA  
Plasma cell pellet 
Serum 
PB Paxgene RNA 
Tumor biopsy
d 
 
Serologyc 
Urinalysisf 
HepBsAg 
HepCAb 
(if above cannot be 
obtained hepatitis viral 
load can be utilized)  
 
Thyroid Function Tests 
 
TSH 
 
Total T3 (or Free T3 
per local standard) 
 
Free T4 
Specific gravity 
pH 
Blood  
protein  
glucose  
bilirubin  
ketones  
leukocyte (esterase) 
nitrite 
ANC = absolute neutrophil count; aPTT = activated partial thromboplastin time; BUN = blood urea nitrogen; 
ctDNA = circulating tumor DNA; FT4 = free thyroxine; HepBsAg = hepatitis B surface antigen; 
HepCAb = hepatitis C antibody; INR = international normalized ratio; PB = peripheral blood; 
PCR = polymerase chain reaction; PK = pharmacokinetic; PT = prothrombin time; RBC = red blood cell; 
T3 = triiodothyronine; TCO2 = total carbon dioxide; TSH = thyroid stimulating hormone; WBC = white 
blood cell 
a Urea collection is acceptable in absence of BUN. 
b these data are collected separately from the chemistry form. 
c Hepatitis B surface antigen, hepatitis C antibody, PCR for Hepatitis C RNA (if Hepatitis C antibody is 
positive). 

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d Archived tumor tissue is acceptable for screening for KRAS G12C mutation status. 
e Bicarbonate/TCO2 can also be obtained via capillary testing 
f Investigative sites without local capability to perform urine studies may submit samples to central 
laboratory. 
 

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11.3 
Appendix 3.  Study Governance Considerations 
Data Monitoring Committee 
The data monitoring committee (DMC) will be comprised of 2 clinical oncologists, and 
1 independent biostatistician.  The DMC will act in an advisory capacity to the sponsor 
with respect to safeguarding the interests of study subjects, assessing interim safety and 
efficacy data, monitoring the overall conduct of the study, and providing with 
recommendations relating to continuing, modifying, or stopping the study based on these 
findings (International Council for Harmonisation Good Clinical Practice [ICH GCP 
5.5.2]).  Details of the DMC will be described in the DMC Charter.  Data monitoring 
committee will review safety and efficacy data as per DMC charter.  Data monitoring 
committee will meet to review safety after 50, 100, and 200 subjects are enrolled and 
have had the opportunity to be treated for at least 6 weeks and thereafter at 
approximately 6 month intervals, until the primary analysis of progression-free survival 
(PFS).  The DMC will also review the IA data for PFS and overall survival (OS), 
whenever these are triggered.  An Independent Biostatistics Group (IBG) will perform the 
IA and provide the interim report to an independent DMC.  The IBG and DMC will have 
access to subjects’ individual treatment assignments.  To minimize the potential 
introduction of bias to the conduct of the study, members of the DMC will not have any 
direct contact with study site personnel or subjects.  The DMC will communicate major 
concerns and recommendations regarding study modification or termination to Amgen in 
accordance with the DMC charter. 
Records of all meetings will be maintained by the DMC for the duration of the study.  
Records of all meetings will be transferred and stored in the trial master folder (TMF) at 
the conclusion of the study.  Further details are provided in the DMC charter. 
Blinded Independent Central Review Committee (BICR) 
A BICR committee will perform independent assessment of individual subject efficacy 
outcomes in accordance with the Response Evaluation Criteria in Solid Tumors 
version 1.1 (RECIST v1.1). The committee will centrally review the disease related tests 
and assessments (Section 8.2.2.1.1) to evaluate disease progressions and responses 
without the knowledge of randomization assignments.  This assessment will be used for 

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the primary analysis of endpoints.  The membership criteria and operational details of 
the BICR will be described in the BICR Charter.   
Regulatory and Ethical Considerations 
This study will be conducted in accordance with the protocol and with: 
 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines 
 
Applicable ICH GCP Guidelines 
 
Applicable ICH laws and regulations 
The protocol, protocol amendments, informed consent form (ICF), Investigator’s 
Brochure, and other relevant documents (eg, subject recruitment advertisements) must 
be submitted to an institutional review board (IRB)/independent ethics committee (IEC) 
by the investigator and reviewed and approved by the IRB/IEC and Amgen.  A copy of 
the written approval of the protocol and ICF must be received by Amgen before 
recruitment of subjects into the study and shipment of Amgen investigational product. 
Amgen may amend the protocol at any time.  The investigator must submit and, where 
necessary, obtain approval from the IRB/IEC for all subsequent protocol amendments 
and changes to the informed consent document.  The investigator must send a copy of 
the approval letter from the IRB/IEC and amended protocol Investigator’s Signature 
page to Amgen prior to implementation of the protocol amendment at their site. 
The investigator will be responsible for the following: 
 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
 
Obtaining annual IRB/IEC approval/renewal throughout the duration of the study.  
Copies of the investigator’s reports and the IRB/IEC continuance of approval 
must be sent to Amgen 
 
Notifying the IRB/IEC of serious adverse events occurring at the site, deviations 
from the protocol or other adverse event reports received from Amgen, in 
accordance with local procedures 
 
Overall conduct of the study at the site and adherence to requirements of Title 21 
of the U.S. Code of Federal Regulations (CFR), ICH guidelines, the IRB/IEC, and 
all other applicable local regulations 
Recruitment Procedures 
Site staff will identify potential subjects from their existing patient population or may seek 
referral patients through existing professional networks or other community sources such 

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as patient advocacy groups.  All patient-facing materials must be reviewed/approved by 
the sponsor and the local IRB/IEC. 
Informed Consent Process 
An initial sample ICF is provided for the investigator to prepare the informed consent 
document to be used at his or her site.  Updates to the sample ICF are to be 
communicated formally in writing from the Amgen Trial Manager to the investigator.  The 
written ICF is to be prepared in the language(s) of the potential patient population. 
The investigator or his/her delegated representative will explain to the subject, or his/her 
legally authorized representative, the aims, methods, anticipated benefits, and potential 
hazards of the study before any protocol-specific screening procedures or any 
investigational product(s) is/are administered, and answer all questions regarding the 
study.   
Subjects must be informed that their participation is voluntary.  Subjects or their legally 
authorized representative [defined as an individual or other body authorized under 
applicable law to consent, on behalf of a prospective subject, to the subject’s 
participation in the clinical study] will then be required to sign a statement of informed 
consent that meets the requirements of 21 CFR 50, local regulations, ICH guidelines, 
Health Insurance Portability and Accountability Act requirements, where applicable, and 
the IRB/IEC or study site.  
The medical record must include a statement that written informed consent was obtained 
before the subject was enrolled in the study and the date the written consent was 
obtained.  The authorized person obtaining the informed consent must also sign the ICF. 
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have his/her primary care physician informed 
of the subject’s participation in the clinical study unless it is a local requirement.  The 
investigator shall then inform the primary care physician.  If the subject agrees to such 
notification, the investigator is to inform the subject’s primary care physician of the 
subject’s participation in the clinical study.  If the subject does not have a primary care 
physician and the investigator will be acting in that capacity, the investigator is to 
document such in the subject’s medical record. 
The acquisition of informed consent, and the subject’s agreement or refusal of his/her 
notification of the primary care physician, is to be documented in the subject’s medical 
records, and the ICF is to be signed and personally dated by the subject or a legally 

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acceptable representative and by the person who conducted the informed consent 
discussion.  Subject withdrawal of consent or discontinuation from study treatment 
and/or procedures must also be documented in the subject’s medical records; refer to 
Section 7. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study.  
The original signed ICF is to be retained in accordance with institutional policy, and a 
copy of the ICF(s) must be provided to the subject or the subject’s legally authorized 
representative.  
A subject who is rescreened is not required to sign another ICF if the rescreening occurs 
within 28 days from the previous ICF signature date. 
The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional future research.  The investigator or authorized designee will 
explain to each subject the objectives of the future research.  Subjects will be told that 
they are free to refuse to participate and may withdraw their specimens at any time and 
for any reason during the storage period.  A separate signature will be required to 
document a subject’s agreement to allow any remaining specimens to be used for future 
research.  Subjects who decline to participate will not provide this separate signature. 
Data Protection/Subject Confidentiality 
The investigator must ensure that the subject’s confidentiality is maintained for 
documents submitted to Amgen. 
Subject will be assigned a unique identifier by the sponsor.  Any subject records or 
datasets that are transferred to the sponsor will contain the identifier only; subject names 
or any information which would make the subject identifiable will not be transferred.  
On the case report form (CRF) demographics page, in addition to the unique subject 
identification number, include the age at time of enrollment. 
For serious adverse events reported to Amgen, subjects are to be identified by their 
unique subject identification number, initials (for faxed reports, in accordance with local 
laws and regulations), and age (in accordance with local laws and regulations). 
Documents that are not submitted to Amgen (eg, signed ICFs) are to be kept in 
confidence by the investigator, except as described below. 

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In compliance with governmental regulations/ICH GCP Guidelines, it is required that the 
investigator and institution permit authorized representatives of the company, of the 
regulatory agency(s), and the IRB/IEC direct access to review the subject’s original 
medical records for verification of study-related procedures and data.  Direct access 
includes examining, analyzing, verifying, and reproducing any records and reports that 
are important to the evaluation of the study.   
The investigator is obligated to inform and obtain the consent of the subject to permit 
such individuals to have access to his/her study-related records, including personal 
information. 
Publication Policy 
To coordinate dissemination of data from this study, Amgen may facilitate the formation 
of a publication committee consisting of several investigators and appropriate Amgen 
staff, the governance and responsibilities of which are set forth in a Publication Charter.  
The committee is expected to solicit input and assistance from other investigators and to 
collaborate with authors and Amgen staff, as appropriate, as defined in the Publication 
Charter.  Membership on the committee (both for investigators and Amgen staff) does 
not guarantee authorship.  The criteria described below are to be met for every 
publication. 
Authorship of any publications resulting from this study will be determined on the basis 
of the Uniform Requirement for Manuscripts Submitted to Biomedical Journals 
International Committee of Medical Journal Editors Recommendations for the Conduct of 
Reporting, Editing, and Publications of Scholarly Work in Medical Journals, which states:  
Authorship credit is to be based on:  (1) substantial contributions to conception and 
design, acquisition of data, or analysis and interpretation of data; (2) drafting the article 
or revising it critically for important intellectual content; (3) final approval of the version to 
be published; and (4) agreement 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.  Authors need to meet conditions 1, 2, 3, and 4. 
When a large, multicenter group has conducted the work, the group is to identify the 
individuals who accept direct responsibility for the manuscript.  These individuals must 
fully meet the criteria for authorship defined above.  Acquisition of funding, collection of 
data, or general supervision of the research group, alone, does not justify authorship.  All 
persons designated as authors must qualify for authorship, and all those who qualify are 

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to be listed.  Each author must have participated sufficiently in the work to take public 
responsibility for appropriate portions of the content.  All publications (eg, manuscripts, 
abstracts, oral/slide presentations, book chapters) based on this study must be 
submitted to Amgen for review.  The Clinical Trial Agreement among the institution, 
investigator, and Amgen will detail the procedures for, and timing of, Amgen’s review of 
publications. 
Investigator Signatory Obligations 
Each clinical study report is to be signed by the investigator or, in the case of multicenter 
studies, the coordinating investigator. 
The coordinating investigator, identified by Amgen, will be any or all of the following: 
 
A recognized expert in the therapeutic area 
 
An Investigator who provided significant contributions to either the design or 
interpretation of the study 
 
An Investigator contributing a high number of eligible subjects 
Data Quality Assurance 
All subject data relating to the study will be recorded on printed or electronic CRF unless 
transmitted to the sponsor or designee electronically (eg, laboratory data, centrally or 
adjudicated data).  The investigator is responsible for verifying that data entries are 
accurate and correct by physically or electronically signing the CRF.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.  
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.   
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  
Clinical monitors will perform ongoing source data verification to confirm that data 
entered into the CRF by authorized site personnel are accurate, complete, and verifiable 
from source documents; that the safety and rights of subjects are being protected; and 
that the study is being conducted in accordance with the currently approved protocol and 
any other study agreements, ICH GCP, and all applicable regulatory requirements per 
the sponsor’s monitoring plan.  

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If permitted by national and/or local regulations, remote Source Data Review and 
Verification (rSDR/V) can be implemented.  The clinical monitor should be 
provided with a secure, read-only access to the Electronic Medical Record (EMR) 
system, including all modules relevant for review.  This access should be 
restricted to the records of only those subjects who participate in the trial and 
who did not object to remote access to their medical records.  A list of the 
monitors to whom remote access has been granted should be maintained.  In 
order to prevent unauthorized access, access rights should be revoked once 
rSDR/V tasks have been completed for the trial.  If EMR is to be utilized, the site 
should attempt to ensure that the EMR system has an audit trail and is be able to 
log information on who accessed data and when.  In addition, the site should 
attempt to ensure that remote access to the EMR should only be possible using a 
two-factor authentication.  
The investigator agrees to cooperate with the clinical monitor to ensure that any 
problems detected in the course of these monitoring visits, including delays in 
completing CRFs, are resolved. 
The Amgen representative(s) and regulatory authority inspectors are responsible for 
contacting and visiting the investigator for the purpose of inspecting the facilities and, 
upon request, inspecting the various records of the clinical study (eg, CRFs and other 
pertinent data) provided that subject confidentiality is respected. 
In accordance with ICH GCP and the sponsor’s audit plans, this study may be selected 
for audit by representatives from Amgen’s Global Research and Development 
Compliance and Audit function (or designees).  Inspection of site facilities (eg, 
pharmacy, protocol-required therapy storage areas, laboratories) and review of 
study-related records will occur to evaluate the study conduct and compliance with the 
protocol, ICH GCP, and applicable regulatory requirements. 
Retention of study documents will be governed by the Clinical Trial Agreement. 
Case report forms must be completed in English.  TRADENAMES® (if used) for 
concomitant medications may be entered in the local language.  Consult the 
country-specific language requirements. 
All written information and other material to be used by subjects and investigative staff 
must use vocabulary and language that are clearly understood. 

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Source Documents 
The investigator is to maintain a list of appropriately qualified persons to whom he/she 
has delegated study duties.  All persons authorized to make entries and/or corrections 
on CRFs will be included on the Amgen Delegation of Authority Form. 
Source documents provide evidence for the existence of the subject and substantiate 
the integrity of the data collected.  Source documents are filed at the investigator’s site. 
Source documents are original documents, data, and records from which the subject’s 
CRF data are obtained.  These include but are not limited to hospital records, clinical 
and office charts, laboratory and pharmacy records, diaries, microfiches, radiographs, 
and correspondence.  Source documents may also include data captured in the 
Interactive Response Technology (IRT) system (if used, such as subject identifier (ID) 
and randomization number) and CRF entries if the CRF is the site of the original 
recording (ie, there is no other written or electronic record of data, such as paper 
questionnaires for a clinical outcome assessment). 
Data reported on the CRF or entered in the electronic CRF that are transcribed from 
source documents must be consistent with the source documents or the discrepancies 
must be explained.  The investigator may need to request previous medical records or 
transfer records, depending on the study.  Also, current medical records must be 
available. 
The Investigator and study staff are responsible for maintaining a comprehensive and 
centralized filing system of all study-related (essential) documentation, suitable for 
inspection at any time by representatives from Amgen and/or applicable regulatory 
authorities. 
Elements to include: 
 
Subject files containing completed CRFs, ICFs, and subject identification list 
 
Study files containing the protocol with all amendments, Investigator’s Brochure, 
copies of prestudy documentation, and all correspondence to and from the 
IRB/IEC and Amgen 
 
Investigational product-related correspondence including Proof of Receipts, 
Investigational Product Accountability Record(s), Return of Investigational 
Product for Destruction Form(s), Final Investigational Product Reconciliation 
Statement, as applicable 
 
Non-investigational product(s), and/or medical device(s) or combination 
product(s) documentation, as applicable 
 
Retention of study documents will be governed by the Clinical Trial Agreement. 

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Remote Source Data Review and Verification 
If permitted by national and/or local regulations, remote Source Data Review and 
Verification (rSDR/V) can be implemented.  The clinical monitor should be 
provided with a secure, read-only access to the Electronic Medical Record (EMR) 
system, including all modules relevant for review.  This access should be 
restricted to the records of only those subjects who participate in the trial and 
who did not object to remote access to their medical records.  A list of the 
monitors to whom remote access has been granted should be maintained.  In 
order to prevent unauthorized access, access rights should be revoked once 
rSDR/V tasks have been completed for the trial.  The EMR system should have an 
audit trail and be able to log information on who accessed data and when.  
Remote access to the EMR should only be possible using a two-factor 
authentication. 
Study and Site Closure 
Amgen or its designee may stop the study or study site participation in the study for 
medical, safety, regulatory, administrative, or other reasons consistent with applicable 
laws, regulations, and GCP.  
Both Amgen and the Investigator reserve the right to terminate the Investigator’s 
participation in the study according to the Clinical Trial Agreement.  The investigator is to 
notify the IRB/IEC in writing of the study’s completion or early termination and send a 
copy of the notification to Amgen. 
Subjects may be eligible for continued treatment with Amgen investigational product(s) 
by an extension protocol or as provided for by the local country’s regulatory mechanism.  
However, Amgen reserves the unilateral right, at its sole discretion, to determine 
whether to supply Amgen investigational product(s) and by what mechanism, after 
termination of the study and before the product(s) is/are available commercially. 
Compensation 
Any arrangements for compensation to subjects for injury or illness that arises in the 
study are described in the Compensation for Injury section of the Informed Consent that 
is available as a separate document. 

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11.4 
Appendix 4.  Safety Events:  Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting 
Definition of Adverse Event 
Adverse Event Definition 
 
An adverse event is any untoward medical occurrence in a clinical study subject 
irrespective of a causal relationship with the study treatment.   
 
Note:  An adverse event can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of a treatment, combination 
product, medical device or procedure. 
 
Note:  Treatment-emergent adverse events will be defined in the statistical 
analysis plan (SAP). 
 
Events Meeting the Adverse Event Definition 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, ECG, radiological scans, vital signs 
measurements), including those that worsen from baseline, that are considered 
clinically significant in the medical and scientific judgment of the investigator  
(ie, not related to progression of underlying disease). 
 
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
 
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication.  Overdose per se will not be reported as an 
adverse event/serious adverse event unless it is an intentional overdose taken with 
possible suicidal/self-harming intent.  Such overdoses are to be reported 
regardless of sequelae. 
 
For situations when an adverse event or serious adverse event is due to non-small 
cell lung cancer (NSCLC), report all known signs and symptoms.  Death due to 
disease progression in the absence of signs and symptoms should be reported as 
the primary tumor type (eg, metastatic pancreatic cancer).  Note:  The term 
“disease progression” should not be used to describe the adverse event. 
 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an adverse event or serious adverse event.  Such instances will be 
captured in the efficacy assessments.  However, the signs, symptoms, and/or 
clinical sequelae resulting from lack of efficacy will be reported as adverse event or 
serious adverse event if they fulfill the definition of an adverse event or serious 
adverse event.  
 

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Events NOT Meeting the Adverse Event Definition 
 
Medical or surgical procedure (eg, endoscopy, appendectomy):  the condition that 
leads to the procedure is the adverse event. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
Definition of Serious Adverse Event 
A Serious Adverse Event is defined as any untoward medical occurrence that, 
meets at least 1 of the following serious criteria: 
Results in death (fatal) 
Immediately life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event.  It does not refer to an event, 
which hypothetically might have caused death, if it were more severe. 
Requires in-patient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting.  Complications that occur during hospitalization are an adverse 
event.  If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious.  When in doubt as to whether “hospitalization” occurred or was 
necessary, the adverse event is to be considered serious.  Hospitalization for elective 
treatment of a pre-existing condition that did not worsen from baseline is not 
considered an adverse event. 
Results in persistent or significant disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.  This definition is not intended to include experiences of relatively 
minor medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (eg, sprained ankle) which may interfere 
with or prevent everyday life functions but do not constitute a substantial disruption. 

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Is a congenital anomaly/birth defect 
Other medically important serious event 
Medical or scientific judgment is to be exercised in deciding whether serious adverse 
event reporting is 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 subject or may require medical or surgical intervention to prevent 1 of 
the other outcomes listed in the above definition.  These events are typically to be 
considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in 
an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
Recording Adverse Events and Serious Adverse Events 
Adverse Event and Serious Adverse Event Recording 
 
When an adverse event or serious adverse event occurs, it is the responsibility of 
the investigator to review all documentation (eg, hospital progress notes, 
laboratory, and diagnostics reports) related to the event. 
 
The investigator will then record all relevant adverse event/serious adverse event 
information in the Events case report form (CRF). 
 
The investigator must assign the following adverse event attributes: 
o Adverse event diagnosis or syndrome(s), if known (if not known, signs or 
symptoms); 
o Dates of onset and resolution (if resolved); 
o Did the event start prior to first dose of investigational product, other protocol-
required therapies; 
o Assessment of seriousness; 
o Severity (or toxicity defined below); 
o Assessment of relatedness to investigational product (AMG 510, docetaxel), or 
other protocol-related therapies, and/or study-mandated activity and/or 
procedures; 
o Action taken; and 
o Outcome of event. 
 
If the severity of an adverse event changes from the date of onset to the date of 
resolution, record a single event for each level of severity on the Events CRF 
 
It is not acceptable for the investigator to send photocopies of the subject’s 
medical records to Amgen in lieu of completion of the Events CRF page. 
 
If specifically requested, the investigator may need to provide additional follow-up 
information, such as discharge summaries, medical records, or extracts from the 
medical records.  In this case, all subject identifiers, with the exception of the 
subject number, will be blinded on the copies of the medical records before 
submission to Amgen. 

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 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information.  In such cases, the diagnosis (not the 
individual signs/symptoms) will be documented as the adverse event/serious 
adverse event. 
Evaluating Adverse Events and Serious Adverse Events 
Assessment of Severity 
The investigator will make an assessment of severity for each adverse event and 
serious adverse event reported during the study.  The assessment of severity will be 
based on:  
The Common Terminology Criteria for Adverse Events, version 5.0 which is 
available at the following location:  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
 
Assessment of Causality 
 
The investigator is obligated to assess the relationship between investigational 
product (AMG 510, docetaxel), protocol-related therapies, and/or study mandated 
activity and/or procedures and each occurrence of each adverse event/serious 
adverse event. 
 
Relatedness means that there are facts or reasons to support a relationship 
between investigational product and the event. 
 
The investigator will use clinical judgment to determine the relationship. 
 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study treatment 
administration will be considered and investigated. 
 
The investigator will also consult the Investigator’s Brochure and/or Product 
Information, for marketed products, in his/her assessment. 
 
For each adverse event/serious adverse event, the investigator must document in 
the medical notes that he/she has reviewed the adverse event/serious adverse 
event and has provided an assessment of causality. 
 
There may be situations in which a serious adverse event has occurred and the 
investigator has minimal information to include in the initial report.  However, it is 
very important that the investigator always make an assessment of causality for 
every event before the initial transmission of the serious adverse event data. 
 
The investigator may change his/her opinion of causality in light of follow-up 
information and send a serious adverse event follow-up report with the updated 
causality assessment. 
 
The causality assessment is 1 of the criteria used when determining regulatory 
reporting requirements. 
 

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Follow-up of Adverse Event and Serious Adverse Event 
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
Amgen to elucidate the nature and/or causality of the adverse event or serious 
adverse event as fully as possible.  This may include additional laboratory tests or 
investigations, histopathological examinations, or consultation with other health 
care professionals. 
 
If a subject is permanently withdrawn from protocol-required therapies because of 
a serious adverse event, this information must be submitted to Amgen. 
 
If a subject dies during participation in the study or during a recognized follow-up 
period, the investigator should provide Amgen with a copy of any post-mortem 
findings including histopathology, if available. 
 
New or updated information will be recorded in the originally completed Event 
CRF. 
 
The investigator will submit any updated serious adverse event data to Amgen 
within 24 hours of receipt of the information. 
Reporting of Serious Adverse Event 
Serious Adverse Event Reporting via Electronic Data Collection Tool 
 
The primary mechanism for reporting serious adverse event will be the electronic 
data capture (EDC) system.  
 
If the EDC system is unavailable for more than 24 hours, then the site will report 
the information to Amgen using a paper-based Serious Adverse Event 
Contingency Report Form (also referred to as the electronic Serious Adverse 
Event [eSAE] Contingency Report Form; see Figure 11-1) within 24 hours of the 
investigator’s awareness of the event. 
 
The site will enter the serious adverse event data into the electronic system as 
soon as it becomes available. 
 
After the study is completed at a given site, the EDC system will be taken off-line to 
prevent the entry of new data or changes to existing data. 
 
If a site receives a report of a new serious adverse event from a study subject or 
receives updated data on a previously reported serious adverse event after the 
EDC has been taken off-line, then the site can report this information on a 
paper-based Serious Adverse Event Contingency Report Form (see 
Figure 11-1). 
 
Once the study has ended, serious adverse event(s) suspected to be related to 
investigational products should be reported to Amgen (regardless of causality) if 
the investigator becomes aware of a serious adverse event.  The investigator 
should use the paper-based Serious Adverse Event Contingency Report Form to 
report the event. 

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Figure 11-1.  Sample Electronic Serious Adverse Event Contingency Report Form 
General Instructions 
The protocol will provide instruction on what types of events to report for the study.  This form is to be used 
ONLY to report events that must be captured in the Amgen safety database. *Indicates a mandatory field. 
Types of Events to be reported on this form  
 
Serious Adverse Events (regardless of causal relationship to investigational product [IP])  
   
1. Site Information  
Site Number* – Enter your assigned site number for this study  
Investigator*, Country*, Reporter*, Phone No., and Fax No. – Enter information requested   
2. Subject Information  
Subject ID Number* – Enter the entire number assigned to the subject  
Age at event onset, Sex, and Race – Enter the subject’s demographic information  
End of Study date – If the subject has already completed the study or terminated the study early, enter the End of 
Study date  
If you are submitting follow-up information to a previous report, provide the serious adverse event term for the 
previous report as well as the start date for the initial event.   
3. Serious Adverse Event 
Provide the date the Investigator became aware of this Information 
Serious Adverse Event Diagnosis or Syndrome* –   
➢ If the diagnosis is known, it should be entered.  Do not list all signs/symptoms if they are included in the 
diagnosis.  
➢ If a diagnosis is not known, the relevant signs/symptoms should be entered.  
➢ If the event is fatal, the cause of death should be entered and autopsy results should be submitted, when 
available.   
Date Started* – Enter date the adverse event first started (not the date on which the event met serious criteria) 
rather than the date of diagnosis or hospitalization.  This is a mandatory field. 
Date Ended – Enter date the adverse event ended and not the date when the event no longer met serious criteria.  If 
the event has not ended at the time of the initial report, a follow-up report should be completed when the end date is 
known.  If the event is fatal, enter the date of death as the end date. 
If event occurred before the first dose of Investigational Product /drug under study, add a check mark in the 
corresponding box. 
Is event serious?* – Indicate Yes or No.  This is a mandatory field. 
Serious Criteria Code* – This is a mandatory field for serious events.  Enter all reasons why the reported event 
has met serious criteria: 
➢ Immediately life-threatening – Use only if the subject was at immediate risk of death from the event as it 
occurred.  Emergency treatment is often required to sustain life in this situation. 
➢ If the investigator decides an event should be reported in an expedited manner, but it does not meet other 
serious criteria, “Other Medically Important Serious Event” may be the appropriate serious criterion. 
Relationship to Investigational Product – The Investigator must determine and enter the relationship of the event 
to the investigational product at the time the event is initially reported.  This is a mandatory field. 
Relationship to Amgen device* – The Investigator must determine and enter the relationship of the event to the 
Amgen device (eg, prefilled syringe, auto-injector) at the time the event is initially reported.  If the study involves 
an Amgen device, this is a mandatory field.  This question does not apply to non-Amgen devices used in the 
study (eg, heating pads, infusion pumps) 
Outcome of Event* – Enter the code for the outcome of the event at the time the form is completed.  This is a 
mandatory field.  
➢ Resolved – End date is known 
➢ Not resolved / Unknown – End date is unknown 
➢ Fatal – Event led to death 
If event is related to a study procedure, such as a biopsy, radiotherapy or withdrawal of a current drug treatment 
during a wash-out period, add a check mark to the corresponding box.  This does not include relationship to 
investigational product or concomitant medication – only diagnostic tests or activities mandated by the protocol. 

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4. Hospitalization 
If the subject was hospitalized, enter admission and discharge dates.  Hospitalization is any in-patient hospital 
admission for medical reasons, including an overnight stay in a healthcare facility, regardless of duration.  A pre-
existing condition that did 
 
not worsen while on study which involved a hospitalization for an elective treatment, is not considered an adverse 
event.  Protocol specified hospitalizations are exempt.   
At the top of Page 2, provide your Site Number and the Subject ID Number in the designated section. 
5. Investigational Product Administration including Lot # and Serial # when known / available. 
Blinded or open-label – If applicable, indicate whether the investigational product is blinded or open-label 
Initial Start Date – Enter date the product was first administered, regardless of dose.  
Date of Dose Prior to or at the time of the Event – Enter date the product was last administered prior to, or at the 
time of, the onset of the event.  
Dose, Route, and Frequency at or prior to the event – Enter the appropriate information for the dose, route and 
frequency at, or prior to, the onset of the event.  
Action Taken with Product – Enter the status of the product administration.   
6. Concomitant Medications  
Indicate if there are any medications.  
Medication Name, Start Date, Stop Date, Dose, Route, and Frequency – Enter information for any other 
medications the subject is taking.  Include any study drugs not included in Section 5 (Product Administration) such 
as chemotherapy, which may be considered co-suspect.  
Co-suspect – Indicate if the medication is co-suspect in the event  
Continuing – Indicate if the subject is still taking the medication  
Event Treatment – Indicate if the medication was used to treat the event    
7. Relevant Medical History  
Enter medical history that is relevant to the reported event, not the event description.  This may include pre-existing 
conditions that contributed to the event allergies and any relevant prior therapy, such as radiation.  Include dates if 
available.   
8. Relevant Laboratory Tests   
Indicate if there are any relevant laboratory values.  
For each test type, enter the test name, units, date the test was run and the results.  
9. Other Relevant Tests  
Indicate if there are any tests, including any diagnostics or procedures.  
For each test type, enter the date, name, results and units (if applicable).   
At the top of Page 3, provide your Site Number and the Subject ID Number in the designated section.  
10. Case Description  
Describe Event – Enter summary of the event.  Provide narrative details of the events listed in Section 3.  Include 
any therapy administered, such as radiotherapy; (excluding medications, which will be captured in Section 6).  If 
necessary, provide additional pages to Amgen.  
Complete the signature section at the bottom of page 3 and fax the form to Amgen.  If the reporter is not the 
investigator, designee must be identified on the Delegation of Authority form. 

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11.5 
Appendix 5.  Contraceptive Guidance and Collection of Pregnancy 
and Lactation Information 
Study-specific contraception requirements for male and female of childbearing potential 
are outlined in Section 5.2. 
Male and female subjects of childbearing potential must receive pregnancy prevention 
counseling and be advised of the risk to the fetus if they become pregnant or father a 
child during treatment and for 7 days after the last dose of AMG 510 for female subjects 
and 7 days after the last dose of AMG 510 for male subjects, and during treatment with 
docetaxel and 6 months after the last dose of docetaxel for male and female subjects. 
Additional medications given during the study may alter the contraceptive requirements.  
These additional medications may require female subjects to use highly effective 
methods of contraception and/or for an increased length of time.  In addition, male 
subjects may also be required to use contraception.  The investigator must discuss 
these contraceptive changes with the subject. 
Definition of Females of Childbearing Potential 
A female is considered fertile following menarche and until becoming post-menopausal 
unless permanently sterile.  Permanent sterilization methods include hysterectomy, 
bilateral salpingectomy, and bilateral oophorectomy. 
Females in the following categories are not considered female of childbearing potential: 
 
Premenopausal female with 1 of the following: 
o Documented hysterectomy; 
o Documented bilateral salpingectomy; or 
o Documented bilateral oophorectomy. 
Note:  Site personnel documentation from the following sources is acceptable:   
1) review of subject’s medical records; 2) subject’s medical examination; or  
3) subject’s medical history interview. 
 
Premenarchal female 
 
Postmenopausal female 
o A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause.  A high follicle stimulating hormone (FSH) level in the 
postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT).  However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient. 

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o Females on HRT and whose menopausal status is in doubt will be required to 
use 1 of the non-hormonal highly effective contraception methods if they wish to 
continue their HRT during the study.  Otherwise, they must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment 
Contraception Methods for Female Subjects 
Highly Effective Contraceptive Methods 
Note:  Failure rate of < 1% per year when used consistently and correctly. 
 
Intrauterine device (IUD) 
 
Bilateral tubal ligation/occlusion 
 
Vasectomized partner (provided that partner is the sole sexual partner of the female 
subject of childbearing potential and that the vasectomized partner has received 
medical assessment of the surgical success) 
 
Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatments; the reliability of sexual 
abstinence must be evaluated in relation to the duration of the trial and the preferred 
and usual lifestyle of the subject) 
Contraception Methods for Male Subjects 
 
Sexual abstinence (defined as refraining from heterosexual intercourse during the 
entire period of risk associated with protocol-required therapies; the reliability of 
sexual abstinence must be evaluated in relation to the duration of the trial and the 
preferred and usual lifestyle of the subject)  
 
Use a condom during treatment and for an additional 7 days (AMG 510) or 6 months 
(docetaxel) after the last dose of protocol-required therapies 
The female partner should consider using an acceptable method of effective 
contraception such as:  hormonal IUD, intrauterine hormonal-releasing system (IUS), 
female barrier method (diaphragm, cap, sponge [a female condom is not an option 
because there is a risk of tearing when both partners use a condom]). 
Note:  If the male’s sole female partner is of non-childbearing potential or has had a 
bilateral tubal ligation/occlusion, he is not required to use additional forms of 
contraception during the study. 
Unacceptable Methods of Birth Control for Male and Female Subjects 
Birth control methods that are considered unacceptable in clinical trials include: 
 
Periodic abstinence (calendar, symptothermal, post-ovulation methods) 
 
Withdrawal (coitus interruptus) 
 
Spermicides only 
 
Lactational amenorrhea method 

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Collection of Pregnancy Information 
Female Subjects Who Become Pregnant 
 
Investigator will collect pregnancy information on any female subject who becomes 
pregnant while taking protocol-required therapies through 7 days after last dose of 
AMG 510 and 6 months after the last dose of docetaxel. 
 
Information will be recorded on the Pregnancy Notification Form (see Figure 11-2).  
The form must be submitted to Amgen Global Patient Safety within 24 hours of 
learning of a subject’s pregnancy.  (Note:  Sites are not required to provide any 
information on the Pregnancy Notification Form that violates the country or regions 
local privacy laws). 
 
After obtaining the female subject’s signed authorization for release of pregnancy 
and infant health information, the investigator will collect pregnancy and infant health 
information and complete the pregnancy questionnaire for any female subject who 
becomes pregnant while taking protocol-required therapies through 7 days after the 
last dose of AMG 510 and 6 months after the last dose of docetaxel.  This 
information will be forwarded to Amgen Global Patient Safety.  Generally, infant 
follow-up will be conducted up to 12 months after the birth of the child (if applicable). 
 
Any termination of pregnancy will be reported to Amgen Global Patient Safety, 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure.  
 
While pregnancy itself is not considered to be an adverse event or serious adverse 
event, any pregnancy complication or report of a congenital anomaly or 
developmental delay, fetal death, or suspected adverse reactions in the neonate will 
be reported as an adverse event or serious adverse event.  Note that an elective 
termination with no information on a fetal congenital malformation or maternal 
complication is generally not considered an adverse event, but still must be reported 
to Amgen as a pregnancy exposure case. 
 
If the outcome of the pregnancy meets a criterion for immediate classification as a 
serious adverse event (eg, female subject experiences a spontaneous abortion, 
stillbirth, or neonatal death or there is a fetal or neonatal congenital anomaly) the 
investigator will report the event as a serious adverse event. 
 
Any serious adverse event occurring as a result of a post-study pregnancy which is 
considered reasonably related to the study treatment by the investigator, will be 
reported to Amgen Global Patient Safety as described in Section 11.4.  While the 
investigator is not obligated to actively seek this information in former study subjects, 
he or she may learn of a serious adverse event through spontaneous reporting.  
 
Any female subject who becomes pregnant while participating will discontinue study 
treatment (see Section 7.1 for details). 

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Male Subjects With Partners Who Become Pregnant  
 
In the event a male subject fathers a child during treatment, and for an additional 
7 days (AMG 510) or 6 months (docetaxel) after discontinuing protocol-required 
therapies, the information will be recorded on the Pregnancy Notification Form.  The 
form (see Figure 11-2) must be submitted to Amgen Global Patient Safety within 
24 hours of the site’s awareness of the pregnancy.  (Note:  Sites are not required to 
provide any information on the Pregnancy Notification Form that violates the country 
or regions local privacy laws). 
 
The investigator will attempt to obtain a signed authorization for release of pregnancy 
and infant health information directly from the pregnant female partner to obtain 
additional pregnancy information. 
 
After obtaining the female partner’s signed authorization for release of pregnancy 
and infant health information, the investigator will collect pregnancy outcome and 
infant health information on the pregnant partner and her baby and complete the 
pregnancy questionnaires.  This information will be forwarded to Amgen Global 
Patient Safety. 
 
Generally, infant follow-up will be conducted up to 12 months after the birth of the 
child (if applicable).  
 
Any termination of the pregnancy will be reported to Amgen Global Patient Safety 
regardless of fetal status (presence or absence of anomalies) or indication for 
procedure. 
Collection of Lactation Information 
 
Investigator will collect lactation information on any female subject who breastfeeds 
while taking protocol-required therapies through 7 days post final dose. 
 
Information will be recorded on the Lactation Notification Form (see below) and 
submitted to Amgen Global Patient Safety within 24 hours of the investigator’s 
knowledge of event. 
 
Study treatment will be discontinued if female subject breastfeeds during the study 
as described in exclusion criterion 226. 
 
With the female subjects signed authorization for release of mother and infant 
health information, the investigator will collect mother and infant health information 
and complete the lactation questionnaire on any female subject who breastfeeds 
while taking protocol-required therapies through 7 days after discontinuing 
protocol-required therapies. 

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Figure 11-2.  Pregnancy and Lactation Notification Forms 
 
Amgen Proprietary - Confidential 
Pregnancy Notification Form 
 
Report to Amgen at: USTO fax: +1-888-814-8653, Non-US fax: +44 (0)207-136-1046 or email (worldwide): svc-ags-in-us@amgen.com 
 
1. Case Administrative Information 
Protocol/Study Number:  20190009 
 
 
Study Design: 
Interventional 
Observational (If Observational: 
Prospective 
Retrospective) 
 
2. Contact Information 
Investigator Name   
_ 
Site #   
 
 
Phone (  
)  
_ 
Fax (_     _)  
 
 
Email   
 
Institution   
 
Address    
 
 
3.  Subject Information 
Subject ID #   
_ 
Subject Gender: 
Female 
Male 
Subject age (at onset):       (in years) 
 
4.  Amgen Product Exposure 
 
 
Amgen Product 
Dose at time of 
conception 
Frequency 
Route 
Start Date 
AMG 510 
mm  
/dd  
/yyyy  
 
 
Was the Amgen product (or study drug) discontinued? 
Yes 
No 
If yes, provide product (or study drug) stop date: mm    
/dd   
/yyyy  
 
Did the subject withdraw from the study? 
Yes 
No 
 
 
5.  Pregnancy Information 
Pregnant female’s last menstrual period (LMP) 
mm   
/ dd______/ yyyy  
  
Unknown 
N/A 
 Estimated date of delivery   mm  
/ dd  
_/ yyyy  
 
If N/A, date of termination (actual or planned) mm   
 
/ dd   _/ yyyy  
 
 
Has the pregnant female already delivered? 
Yes 
No  
Unknown 
N/A 
If yes, provide date of delivery:  mm    
 
/ dd   
 
/ yyyy  
 
Was the infant healthy? 
Yes 
No 
Unknown 
N/A 
If any Adverse Event was experienced by the infant, provide brief details:  
 
 
 
 
 
 
Form Completed by: 
 
Print Name:    
 
 
 
 
 
Title:    
 
 
Signature:    
 
 
Date:    
 
 
 
 
FORM-115199                                                                                       Version 1.0                                                                         Effective Date: 24-Sept-2018 

Product:  AMG 510  
Protocol Number:  20190009 
Date:  06 January 2022 
Page 152 of 179 
CONFIDENTIAL  
 
 
 
Amgen Proprietary - Confidential 
Lactation Notification Form 
 
 
Report to Amgen at: USTO fax: +1-888-814-8653, Non-US fax: +44 (0)207-136-1046 or email (worldwide): svc-ags-in-us@amgen.com 
1. Case Administrative Information 
Protocol/Study Number:  20190009 
 
 
Study Design: 
Interventional 
Observational (If Observational: 
Prospective 
Retrospective) 
 
2.  Contact Information 
Investigator Name   
 
 
 
Site #   
 
 
Phone (  
)  
 
 
Fax (  
)  
 
 
Email   
 
Institution   
 
Address    
 
 
 3.  Subject Information 
Subject ID #   
 
 
 
 
 
Subject age (at onset):       (in years)
 
4.  Amgen Product Exposure 
 
Amgen Product 
Dose at time of 
breast feeding 
Frequency 
Route 
Start Date 
AMG 510 
mm  
/dd  
/yyyy  
 
 
Was the Amgen product (or study drug) discontinued? 
Yes 
No 
If yes, provide product (or study drug) stop date: mm    
/dd   
/yyyy  
 
Did the subject withdraw from the study? 
Yes 
No 
 
5.  Breast Feeding Information 
 
Did the mother breastfeed or provide the infant with pumped breast milk while actively taking an Amgen product? 
Yes 
No 
 
If No, provide stop date:  mm   
 /dd   
/yyyy  
 
Infant date of birth: mm  
/dd  
/yyyy  
  
Infant gender: 
Female 
Male 
 
Is the infant healthy? 
Yes 
No 
Unknown 
N/A 
 
 
If any Adverse Event was experienced by the mother or the infant, provide brief details:  
 
 
 
 
 
 
 
  Form Completed by: 
 
Print Name:    
 
 
 
Title:    
 
 
Signature:    
 
 
Date:    
 
 
FORM-115201                                                                                      Version 1.0                                                                           Effective Date: 24-Sept-2018 

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11.6 
Appendix 6.  Sample Storage and Destruction 
Any blood, biopsy, biomarker, or pharmacokinetic (PK) sample collected according to 
the Schedule of Activities (Table 1-1 and Table 1-2) can be analyzed for any of the tests 
outlined in the protocol and for any tests necessary to minimize risks to study subjects.  
This includes testing to ensure analytical methods produce reliable and valid data 
throughout the course of the study.  This can also include, but is not limited to, 
investigation of unexpected results, incurred sample reanalysis, and analyses for 
method transfer and comparability.  
Biomarker assessment can be done only if the biomarker research is allowed according 
to local regulations and agreed by the local Ethics Committee (EC)/Institutional Review 
Board (IRB). 
All samples and associated results will be coded prior to being shipped from the site for 
analysis or storage.  Samples will be tracked using a unique identifier that is assigned to 
the samples for the study.  Results are stored in a secure database to ensure 
confidentiality.  
If informed consent is provided by the subject or legally acceptable representative, 
Amgen can do additional testing on remaining samples (ie, residual and back-up) to 
investigate and better understand the oncology, the dose response and/or prediction of 
response to AMG 510 and characterize aspects of the molecule (eg, mechanism of 
action/target, metabolites).  Results from this analysis are to be documented and 
maintained, but are not necessarily reported as part of this study.  Samples can be 
retained for up to 20 years.   
Since the evaluations are not expected to benefit the subject directly or to alter the 
treatment course, the results of pharmacogenetic, biomarker development, or other 
exploratory studies are not placed in the subject’s medical record and are not to be 
made available to the subject, members of the family, the personal physician, or other 
third parties, except as specified in the informed consent. 
The subject retains the right to request that the sample material be destroyed by 
contacting the investigator.  Following the request from the subject, the investigator is to 
provide the sponsor with the required study and subject number so that any remaining, 
blood or tumor samples and any other components from the cells can be located and 
destroyed.  Samples will be destroyed once all protocol-defined procedures are 

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completed.  However, information collected from samples prior to the request for 
destruction, will be retained by Amgen. 
The sponsor is the exclusive owner of any data, discoveries, or derivative materials from 
the sample materials and is responsible for the destruction of the sample(s) at the 
request of the subject through the investigator, at the end of the storage period, or as 
appropriate (eg, the scientific rationale for experimentation with a certain sample type no 
longer justifies keeping the sample).  If a commercial product is developed from this 
research project, the sponsor owns the commercial product.  The subject has no 
commercial rights to such product and has no commercial rights to the data, information, 
discoveries, or derivative materials gained or produced from the sample.  See 
Section 11.3 for subject confidentiality. 

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11.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions and 
Follow-up Assessments and Study Treatment Rechallenge 
Guidelines 
Subjects with abnormal hepatic laboratory values (ie, alkaline phosphatase [ALP], 
aspartate aminotransferase [AST], alanine aminotransferase [ALT], total bilirubin [TBL]) 
and/or international normalized ratio (INR) and/or signs/symptoms of hepatitis (as 
described below) may meet the criteria for withholding or permanent discontinuation of 
Amgen investigational product or other protocol-required therapies, as specified in the 
Guidance for Industry Drug-Induced Liver Injury:  Premarketing Clinical Evaluation, 
July 2009. 
Criteria for Withholding and/or Permanent Discontinuation of Amgen 
Investigational Product and Other Protocol-required Therapies Due to 
Potential Hepatotoxicity 
The following stopping and/or withholding rules apply to subjects for whom another 
cause of their changes in liver biomarkers (TBL, INR, and transaminases) has not been 
identified.  
Important alternative causes for elevated AST/ALT and/or TBL values include, but are 
not limited to: 
 
Hepatobiliary tract disease 
 
Viral hepatitis (eg, hepatitis A/B/C/D/E, Epstein-Barr Virus, cytomegalovirus, herpes 
simplex virus, varicella, toxoplasmosis, and parvovirus) 
 
Right sided heart failure, hypotension, or any cause of hypoxia to the liver causing 
ischemia 
 
Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal and dietary 
supplements, plants and mushrooms 
 
Heritable disorders causing impaired glucuronidation (eg, Gilbert’s syndrome, 
Crigler-Najjar syndrome) and drugs that inhibit bilirubin glucuronidation (eg, indinavir, 
atazanavir) 
 
Alpha-one antitrypsin deficiency 
 
Alcoholic hepatitis 
 
Autoimmune hepatitis 
 
Wilson’s disease and hemochromatosis 
 
Nonalcoholic fatty liver disease including steatohepatitis 
 
Non-hepatic causes (eg, rhabdomyolysis, hemolysis) 

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If investigational product(s) is/are withheld, the subject is to be followed for possible drug 
induced liver injury (DILI) according to recommendations in the last section of this 
appendix.  
Re-challenge may be considered if an alternative cause for impaired liver tests (ALT, 
AST, ALP) and/or elevated TBL, is discovered and/or the laboratory abnormalities 
resolve to normal or baseline (see next section in this appendix). 
Table 11-2.  Conditions for Withholding and/or Permanent Discontinuation of 
Amgen Investigational Product and Other Protocol-required Therapies Due to 
Potential Hepatotoxicity 
Analyte 
Temporary Withholding 
Permanent Discontinuation 
TBL 
> 3 x ULN 
at any time 
> 2 x ULN 
 
 
OR 
INR 
-- 
> 1.5 x (for subjects not on 
anticoagulation therapy) 
 
OR 
AND 
AST/ALT 
> 5 x ULN at any time 
> 3 x ULN with clinical signs or symptoms 
that are consistent with hepatitis (such as 
right upper quadrant pain/tenderness, 
fever, nausea, vomiting, and jaundice) 
In the presence of no important 
alternative causes for elevated 
AST/ALT and/or TBL values 
> 3 x ULN (when baseline was < ULN) 
 
OR 
 
ALP 
> 8 x ULN at any time 
-- 
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase;  
INR = international normalized ratio; TBL = total bilirubin; ULN = upper limit of normal. 
Criteria for Re-challenge of Amgen Investigational Product and Other 
Protocol-required Therapies After Potential Hepatotoxicity 
The decision to re-challenge the subject is to be discussed and agreed upon 
unanimously by the subject, investigator, and Amgen. 
Subjects who clearly meet the criteria for permanent discontinuation (as described in 
Table 11-2.) are never to be re-challenged. 

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Drug-induced Liver Injury Reporting and Additional Assessments 
Reporting 
To facilitate appropriate monitoring for signals of DILI, cases of concurrent AST or ALT 
and TBL and/or INR elevation, according to the criteria specified in the above, require 
the following: 
 
The event is to be reported to Amgen as a serious adverse event within 24 hours of 
discovery or notification of the event (ie, before additional etiologic investigations 
have been concluded) 
 
The appropriate case report form (CRF) (eg, Event CRF) that captures information 
necessary to facilitate the evaluation of treatment-emergent liver abnormalities is to 
be completed and sent to Amgen  
Other events of hepatotoxicity and potential DILI are to be reported as serious adverse 
events if they meet the criteria for a serious adverse event defined in Section 11.4. 
Additional Clinical Assessments and Observation 
All subjects in whom investigational product(s) or protocol-required therapies is/are 
withheld (either permanently or conditionally) due to potential DILI as specified in  
Table 11-2. or who experience AST or ALT elevations > 3 x upper limit of normal (ULN) 
or 2-fold increases above baseline values for subjects with elevated values before drug 
are to undergo a period of “close observation” until abnormalities return to normal or to 
the subject’s baseline levels.   
Assessments that are to be performed during this period include:  
 
Repeat AST, ALT, ALP, bilirubin (BIL) (total and direct), and INR within 24 hours  
 
In cases of TBL > 2 x ULN or INR > 1.5, retesting of liver tests, BIL (total and direct), 
and INR is to be performed every 24 hours until laboratory abnormalities improve 
Testing frequency of the above laboratory tests may decrease if the abnormalities 
stabilize or the investigational product(s) or protocol-required therapies has/have been 
discontinued AND the subject is asymptomatic. 
Initiate investigation of alternative causes for elevated AST or ALT and/or elevated TBL.  
The following are to be considered depending on the clinical situation: 
 
Complete blood count with differential to assess for eosinophilia 
 
Serum total immunoglobulin (Ig)G, anti-nuclear antibody, anti-smooth muscle 
antibody, and liver kidney microsomal antibody-1 to assess for autoimmune hepatitis 
 
Serum acetaminophen (paracetamol) levels 
 
A more detailed history of:  
o Prior and/or concurrent diseases or illness 

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o Exposure to environmental and/or industrial chemical agents  
o Symptoms (if applicable) including right upper quadrant pain, hypersensitivity-
type reactions, fatigue, nausea, vomiting, and fever 
o Prior and/or concurrent use of alcohol, recreational drugs and special diets 
o Concomitant use of medications (including non-prescription medicines and 
herbal and dietary supplements), plants, and mushrooms 
 
Viral serologies 
 
Creatine phosphokinase, haptoglobin, lactate dehydrogenase, and peripheral blood 
smear 
 
Appropriate liver imaging if clinically indicated 
 
Appropriate blood sampling for pharmacokinetic analysis if this has not already been 
collected 
Hepatology consult (liver biopsy may be considered in consultation with a hepatologist) 
Follow the subject and the laboratory tests (ALT, AST, TBL, INR) until all laboratory 
abnormalities return to baseline or normal or considered stable by the investigator.  The 
“close observation period” is to continue for a minimum of 4 weeks after discontinuation 
of all investigational product(s) and protocol-required therapies. 
The potential DILI event and additional information such as medical history, concomitant 
medications, and laboratory results must be captured in the corresponding CRFs.  

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11.8 
Appendix 8.  Response Evaluation Criteria in Solid Tumors Version 
1.1 (RECIST v1.1) 
MEASUREMENT OF EFFECT 
Please provide response criteria.  If the criteria for solid tumors below are not applicable, 
the investigator(s) should provide disease-appropriate criteria (eg, for specific 
hematologic malignancies) with references, and all solid tumor criteria should be 
deleted. 
Antitumor Effect – Solid Tumor 
For the purposes of this study, subjects should be re-evaluated for response every 
6 weeks for the first 48 weeks and then every 9 weeks thereafter until progressive 
disease.  In addition to a baseline scan, confirmatory scans should also be obtained at 
least 4 weeks following initial documentation of objective response. 
Response and progression will be evaluated in this study using the new international 
criteria proposed by the revised Response Evaluation Criteria in Solid Tumors (RECIST) 
guideline (version 1.1) (RECIST v1.1 2009).  Changes in the largest diameter 
(unidimensional measurement) of the tumor lesions and the shortest diameter in the 
case of malignant lymph nodes are used in the RECIST criteria. 
Definitions 
Evaluable for toxicity.  All subjects will be evaluable for toxicity from the time of their first 
treatment with AMG 510 or docetaxel 
Evaluable for objective response.  Only those subjects who have measurable disease 
present at baseline, have received at least 1 cycle of therapy, and have had their 
disease re-evaluated will be considered evaluable for response.  These subjects will 
have their response classified according to the definitions stated below.  
(Note:  subjects who exhibit objective disease progression prior to the end of cycle 1 will 
also be considered evaluable). 
Evaluable Non-Target Disease Response.  Subjects who have lesions present at 
baseline that are evaluable but do not meet the definitions of measurable disease, have 
received at least 1 cycle of therapy, and have had their disease re-evaluated will be 
considered evaluable for non-target disease.  The response assessment is based on the 
presence, absence, or unequivocal progression of the lesions.  

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Disease Parameters 
Measurable disease.  Measurable lesions are defined as those that can be accurately 
measured in at least 1 dimension (longest diameter to be recorded) as  20 mm by chest 
x-ray, as  10 mm with computerized tomography (CT) scan, or  10 mm with calipers 
by clinical exam.  All tumor measurements must be recorded in millimeters (or decimal 
fractions of centimeters). 
Note:  Tumor lesions that are situated in a previously irradiated area might or might not 
be considered measurable.   
Malignant lymph nodes.  To be considered pathologically enlarged and measurable, a 
lymph node must be  15 mm in short axis when assessed by CT scan (CT scan slice 
thickness recommended to be no greater than 5 mm).  At baseline and in follow-up, only 
the short axis will be measured and followed. 
Non-measurable disease.  All other lesions (or sites of disease), including small lesions 
(longest diameter < 10 mm or pathological lymph nodes with  10 to < 15 mm short 
axis), are considered non-measurable disease.  Bone lesions, leptomeningeal disease, 
ascites, pleural/pericardial effusions, lymphangitis cutis/pulmonitis, inflammatory breast 
disease, and abdominal masses (not followed by CT or magnetic resonance imaging 
[MRI]), are considered as non-measurable. 
Note:  Cystic lesions that meet the criteria for radiographically defined simple cysts 
should not be considered as malignant lesions (neither measurable nor non-measurable) 
since they are, by definition, simple cysts. 
‘Cystic lesions’ thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above.  However, if 
non-cystic lesions are present in the same subject, these are preferred for selection as 
target lesions. 
Target lesions.  All measurable lesions up to a maximum of 2 lesions per organ and 
5 lesions in total, representative of all involved organs, should be identified as target 
lesions and recorded and measured at baseline.  Target lesions should be selected on 
the basis of their size (lesions with the longest diameter), be representative of all 
involved organs, but in addition should be those that lend themselves to reproducible 
repeated measurements.  It may be the case that, on occasion, the largest lesion does 
not lend itself to reproducible measurement in which circumstance the next largest lesion 
which can be measured reproducibly should be selected.  A sum of the diameters 

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(longest for non-nodal lesions, short axis for nodal lesions) for all target lesions will be 
calculated and reported as the baseline sum diameters.  If lymph nodes are to be 
included in the sum, then only the short axis is added into the sum.  The baseline sum 
diameters will be used as reference to further characterize any objective tumor 
regression in the measurable dimension of the disease. 
Non-target lesions.  All other lesions (or sites of disease) including any measurable 
lesions over and above the 5 target lesions should be identified as non-target lesions 
and should also be recorded at baseline.  Measurements of these lesions are not 
required, but the presence, absence, or in rare cases unequivocal progression of each 
should be noted throughout follow-up.  
Methods for Evaluation of Measurable Disease 
All measurements should be taken and recorded in metric notation using a ruler or 
calipers.  All baseline evaluations should be performed as closely as possible to the 
beginning of treatment and never more than 4 weeks before the beginning of the 
treatment. 
The same method of assessment and the same technique should be used to 
characterize each identified and reported lesion at baseline and during follow-up.  
Imaging-based evaluation is preferred to evaluation by clinical examination unless the 
lesion(s) being followed cannot be imaged but are assessable by clinical exam. 
Clinical lesions:  Clinical lesions will only be considered measurable when they are 
superficial (eg, skin nodules and palpable lymph nodes) and  10 mm diameter as 
assessed using calipers (eg, skin nodules).  In the case of skin lesions, documentation 
by color photography, including a ruler to estimate the size of the lesion, is 
recommended.  
Chest x-ray:  Lesions on chest x-ray are acceptable as measurable lesions when they 
are clearly defined and surrounded by aerated lung.  However, CT chest is preferred and 
as specified in the Imaging manual, CT chest is to be utilized for scheduled imaging 
assessment.  
Conventional CT and MRI:  This guideline has defined measurability of lesions on CT 
scan based on the assumption that CT slice thickness is 5 mm or less.  If CT scans have 
slice thickness greater than 5 mm, the minimum size for a measurable lesion should be 
twice the slice thickness.  Magnetic resonance imaging is also acceptable in certain 
situations (eg, for body scans).   

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Use of MRI remains a complex issue.  Magnetic resonance imaging has excellent 
contrast, spatial, and temporal resolution; however, there are many image acquisition 
variables involved in MRI, which greatly impact image quality, lesion conspicuity, and 
measurement.  Furthermore, the availability of MRI is variable globally.  As with CT, if an 
MRI is performed, the technical specifications of the scanning sequences used should 
be optimized for the evaluation of the type and site of disease.  It is beyond the scope of 
the RECIST guidelines to prescribe specific MRI pulse sequence parameters for all 
scanners, body parts, and diseases.  Ideally, the same type of scanner should be used 
and the image acquisition protocol should be followed as closely as possible to prior 
scans.  Body scans should be performed with breath-hold scanning techniques, if 
possible. 
Positron Emission Tomography-Computer Tomography (PET-CT):  At present, the low 
dose or attenuation correction CT portion of a combined PET-CT is not always of optimal 
diagnostic CT quality for use with RECIST measurements.  However, if the site can 
document that the CT performed as part of a PET-CT is of identical diagnostic quality to 
a diagnostic CT (with Intravenous (IV) and oral contrast), then the CT portion of the 
PET-CT can be used for RECIST measurements and can be used interchangeably with 
conventional CT in accurately measuring cancer lesions over time.  Note, however, that 
the PET portion of the CT introduces additional data which may bias an investigator if it 
is not routinely or serially performed.   
Ultrasound:  Ultrasound is not useful in assessment of lesion size and should not be 
used as a method of measurement.  Ultrasound examinations cannot be reproduced in 
their entirety for independent review at a later date and, because they are operator 
dependent, it cannot be guaranteed that the same technique and measurements will be 
taken from one assessment to the next.  If new lesions are identified by ultrasound in the 
course of the study, confirmation by CT or MRI is advised.  If there is concern about 
radiation exposure at CT, MRI may be used instead of CT in selected instances. 
Endoscopy, Laparoscopy:  The utilization of these techniques for objective tumor 
evaluation is not advised.  However, such techniques may be useful to confirm complete 
pathological response when biopsies are obtained or to determine relapse in trials where 
recurrence following complete response (CR) or surgical resection is an endpoint. 
Tumor markers:  Tumor markers alone cannot be used to assess response.  If markers 
are initially above the upper normal limit, they must normalize for a subject to be 
considered in complete clinical response.  Specific guidelines for both CA-125 response 

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(in recurrent ovarian cancer) and Prostate Specific Antigen (PSA) response (in recurrent 
prostate cancer) have been published [JNCI 96:487-488, 2004; J Clin Oncol 17, 
3461-3467, 1999; J Clin Oncol 26:1148-1159, 2008].  In addition, the Gynecologic 
Cancer Intergroup has developed CA-125 progression criteria which are to be integrated 
with objective tumor assessment for use in first-line trials in ovarian cancer 
[JNCI 92:1534-1535, 2000]. 
Cytology, Histology:  These techniques can be used to differentiate between partial 
responses (PRs) and CRs in rare cases (eg, residual lesions in tumor types, such as 
germ cell tumors, where known residual benign tumors can remain). 
Response Criteria 
Evaluation of Target Lesions 
Complete Response: Disappearance of all target lesions.  Any pathological lymph 
nodes (whether target or non-target) must have reduction in short axis to < 10 mm. 
Partial Response: 
At least a 30% decrease in the sum of the diameters of target 
lesions, taking as reference the baseline sum diameters. 
Progressive Disease (PD): 
At least a 20% increase in the sum of the diameters of 
target lesions, taking as reference the smallest sum on study (this includes the baseline 
sum if that is the smallest on study).  In addition to the relative increase of 20%, the sum 
must also demonstrate an absolute increase of at least 5 mm.  (Note:  the appearance of 
one or more new lesions is also considered progressions). 
Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient 
increase to qualify for PD, taking as reference the smallest sum diameters while on 
study. 
Evaluation of Non-target Lesions 
Complete Response: Disappearance of all non-target lesions and normalization of 
tumor marker level.  All lymph nodes must be non-pathological in size (< 10 mm short 
axis). 
Note:  If tumor markers are initially above the upper normal limit, they must normalize for 
a subject to be considered in complete clinical response. 
Non-CR/Non-PD:  Persistence of one or more non-target lesion(s) and/or maintenance 
of tumor marker level above the normal limits. 

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Progressive Disease: Appearance of one or more new lesions and/or unequivocal 
progression of existing non-target lesions.  Unequivocal progression should not normally 
trump target lesion status.  It must be representative of overall disease status change, 
not a single lesion increase.   
Although a clear progression of “non-target” lesions only is exceptional, the opinion of 
the treating physician should prevail in such circumstances, and the progression status 
should be confirmed at a later time by the review panel (or Principal Investigator). 
Evaluation of Best Overall Response 
The best overall response is the best response recorded from the start of the treatment 
until disease progression/recurrence (taking as reference for PD the smallest 
measurements recorded since the treatment started).  The subject's best response 
assignment will depend on the achievement of both measurement and confirmation 
criteria. 
For Subjects With Measurable Disease (ie, Target Disease) 
Target 
Lesions 
Non-target 
Lesions 
New Lesions 
Overall 
Response 
Best Overall Response 
when Confirmation is 
Required* 
CR 
CR 
No 
CR 
 4 wks Confirmation** 
CR 
Non-CR/Non-PD 
No 
PR 
 4 wks Confirmation** 
CR 
Not evaluated 
No 
PR 
PR 
Non-PD/Not all 
evaluated 
No 
PR 
SD 
Non-PD/Not all 
evaluated 
No 
SD 
Documented at least 
once  4 wks from 
baseline** 
PD 
Any 
Yes or No 
PD 
No prior SD, PR, or CR 
Any 
PD*** 
Yes or No 
PD 
Any 
Any 
Yes 
PD 
CR = complete response; PD = progressive disease; PR = partial response; RECIST = Response 
Evaluation Criteria in Solid Tumors; SD = stable disease. 
* See RECIST v1.1 manuscript for further details on what is evidence of a new lesion. 
** Only for non-randomized trials with response as primary endpoint. 
*** In exceptional circumstances, unequivocal progression in non-target lesions may be accepted as disease 
progression. 
Note: Subjects with a global deterioration of health status requiring discontinuation of treatment without 
objective evidence of disease progression at that time should be reported as “symptomatic deterioration.”  
Every effort should be made to document the objective progression even after discontinuation of 
treatment. 

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For Subjects With Non-measurable Disease (ie, Non-target Disease) 
Non-target Lesions 
New Lesions 
Overall Response 
CR 
No 
CR 
Non-CR/non-PD 
No 
Non-CR/non-PD* 
Not all evaluated 
No 
Not evaluated 
Unequivocal PD 
Yes or No 
PD 
Any 
Yes 
PD 
CR = complete response; PD = progressive disease; SD = stable disease 
* ‘Non-CR/non-PD’ is preferred over ‘stable disease’ for non-target disease since SD is increasingly used as 
an endpoint for assessment of efficacy in some trials so to assign this category when no lesions can be 
measured is not advised. 
Duration of Response 
Duration of overall response:  The duration of overall response is measured from the 
time measurement criteria are met for CR or PR (whichever is first recorded) until the 
first date that recurrent or PD is objectively documented, or death, whichever is earlier 
(taking as reference for PD the smallest measurements recorded since the treatment 
started). 
The duration of overall CR is measured from the time measurement criteria are first met 
for CR until the first date that PD is objectively documented or death, whichever is 
earlier. 
Duration of SD:  Stable disease is measured from the start of the treatment until the 
criteria for progression are met, or death, whichever is earlier, taking as reference the 
smallest measurements recorded since the treatment started, including the baseline 
measurements.  
Progression-Free Survival 
PFS is defined as the duration of time from start of treatment to time of progression or 
death, whichever occurs first. 
Response Review 
A blinded independent central review committee (BICR) will perform independent 
assessment of individual subject efficacy outcomes in accordance with the 
RECIST v1.1.  The committee will centrally review the disease related tests and 
assessments (Section 8.2.2.1.1) to evaluate disease progressions and responses 
without the knowledge of randomization assignments.  This assessment will be used for 
the primary analysis of endpoints.  The membership criteria and operational details of 
the BICR will be described in the BICR Charter.  

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Any locoregional therapy not allowed per protocol 
Any subject receiving locoregional therapy not allowed in the protocol while on study that 
directly affects one or more of the target lesions selected at baseline will be considered 
to be non-evaluable at all disease assessments that occur on or after the date of 
locoregional therapy with the exception of disease progression.  However, if a lesion was 
completely resected where pathology was benign the subject will still be evaluable for 
response with 0 dimension reported.  
If locoregional therapy was performed on a non-target lesion, that lesion will always be 
assessed as present unless pathology was benign.  

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11.9 
Appendix 9.  QLQ-C30 
 
 

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11.10 
Appendix 10.  EQ-5D-5L 
 

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11.11 
Appendix 11.  QLQ-LC13 
 

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11.12 
Appendix 12.  PGIS 
 
Patient Global Impression of Severity 
Please choose one answer for each of the following questions.  
1. How would you rate any cough you experienced in the past week? 
 None 
 Mild 
 Moderate 
 Severe 
2. How would you rate any chest pain you experienced in the past week? 
 None 
 Mild 
 Moderate 
 Severe 
 
3. How would you rate any shortness of breath  you experienced in the past 
week? 
 None 
 Mild 
 Moderate 
 Severe 

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11.13 
Appendix 13.  PGIC 
 
Patient Global Impression of Change (PGIC) 
 
1. Compared to the beginning of this study, how would you rate your cough 
now? 
 Much better 
 A little better 
 About the same 
 A little worse 
 Much worse 
2. Compared to the beginning of this study, how would you rate your chest 
pain now? 
 Much better 
 A little better 
 About the same 
 A little worse 
 Much worse 
 
3. Compared to the beginning of this study, how would you rate your 
shortness of breath  now? 
 Much better 
 A little better 
 About the same 
 A little worse 
 Much worse 

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11.14 
Appendix 14.  PRO-CTCAE 
 

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11.15 
Appendix 15.  GP5 of the FACT-G 
 

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11.16 
Appendix 16.  Pain (BPI short form) 
 
 

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Product:  AMG 510 
Protocol Number:  20190009 
Date:  06 January 2022 
Page 1 of 12 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 4 
Protocol Title:  A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, 
Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated 
Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated 
KRAS p.G12C 
Amgen Protocol Number AMG 510 (20190009) 
EudraCT Number:  2019-003582-18 
NCT Number:  NCT04303780 
 
Amendment Date: 
06 January 2022 
 
Rationale: 
This protocol is being amended to include program wide pneumonitis safety language, to 
clarify the definition of an “Amgen product”, to include language inadvertently left out of 
protocol amendment 3 with regards to hepatotoxicity, and to relax the crossover criteria 
for subjects in competitor arm.  Key changes are summarized below:  
Added Language:  
 
Language added to provide details on drug administration with regards to timing. 
(Table 1-1 and Table 6-1).  Language has been added to be consistent with other 
study protocols within the AMG 510 program.  
 
Language added to Section 2.3 regarding the known risk/adverse drug reaction 
of increased aspartate aminotransferase and increased alanine 
aminotransferase. Text is listed in IB and was inadvertently left out of previous 
protocol version.   
 
Language added to Section 2.3 to inform investigators on new risk/adverse drug 
reaction of pneumonitis, as determined through Amgen safety governance.  
 
Language added to formally define, what is considered an Amgen product in 
Section 6.1.6.  This update provides sites and investigators with additional 
guidance in the event of a product complaint.  
 
Section 6.2.2.1 (Table 6-3). Language added as ILD/pneumonitis was 
determined to be a risk/adverse drug reaction with sotorasib through Amgen 

Product:  AMG 510 
Protocol Number:  20190009 
Date:  06 January 2022 
Page 2 of 12 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
safety governance.  This update provides investigators with dose modification 
guidance in the event pneumonitis is suspected or confirmed. 
 
Language added to Section 6.7.2 regarding breast cancer resistance protein 
(BCRP) to be consistent to other study protocols within the program.  During the 
review of the NSCLC marketing application, Amgen received a postmarket 
requirement to conduct a clinical drug interaction study to assess the effect of 
concomitant AMG 510 administration on the systemic exposure of BCRP 
transporter substrates.  This study is ongoing.   
 
Language added to align with the existing language in the Schedule of Activities 
and clarify SAE reporting requirements after end of study in Sections 8.2.4.1.3 
and Appendix 4. 
Relocated and Clarified Language:  
 
 
Language located in previous protocol versions but moved to Section 6.7.2, 
Section 8.1.3, and Section 8.1.8 to ensure clarity for sites and investigators as 
well as for protocol cohesion. 
 
Language added for clarification with regards to type of steroid(s) that can be 
utilized in the event of increased LFTs in Section 6.2.3 (Table 6-6, footnotes).  In 
addition to provide guidance on timing of steroid administration with regards to 
resuming AMG 510.  This clarification will ensure adequate treatment of 
increased LFTs and reduce early termination of study drug. 
 
Language added for further clarification in Section 8 and Appendix 3.  This 
language will accommodate any restrictions with regards subject visits/data 
monitoring due to COVID-19.  
 
Language clarified in Section 8.1.8 (Crossover Condition 1) to accommodate 
crossover in subjects who have non-significant adverse events (alopecia and nail 
discoloration) related to docetaxel.  This will allow more subjects the opportunity 
to access to crossover and not limiting subjects from crossing over if there are 
non-significant adverse events noted.  
 

Product:  AMG 510 
Protocol Number:  20190009 
Date:  15 February 2021 
Page 1 of 1 
Confidential 
 
 
Amendment 3 
Protocol Title:  A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, 
Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated 
Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated 
KRAS p.G12C 
 
Amgen Protocol Number Sotorasib (AMG 510) 20190009 
 
Amendment Date: 
15 February 2021 
 
Rationale: 
This protocol is being amended to: 
 
Reduction of sample size, from n = 650 to n = 330 
 
Incorporation of progression-free survival (PFS) interim analysis planned at ~70% 
information fraction when approximately 160 PFS events observed from both arms.  
 
Allow subjects enrolled into docetaxel arm to crossover to AMG 510 upon disease 
progression confirmed by blinded independent central review (BICR) or should early 
efficacy of the study be noted by the Data Monitoring Committee (DMC) at the PFS 
interim analysis 
 
Removal of urine microscopy and urine electrolytes from lab assessments schedule 
of activities (SOA) and analyte table  
 
Update to “AMG 510 Dose Modification Guidelines for Hematologic and 
Non-hematologic Toxicities Table 6-3”, Section “Renal Dysfunction” updated to 
“Non-hematologic Toxicities”  
 
Addition of P-gp sensitive substrates (with a narrow therapeutic index) to exclusion 
criterion 222 
 
Addition of language detailing independent central confirmation of progression (COP) 
at the time of first progressive disease (PD) prior to discontinuation of investigational 
product (Section 8.2.2.1.2) 
 
Addition of Estimands Framework 
 
General administrative (typographical, editorial) fixes 

Product:  AMG 510 
Protocol Number:  20190009 
Date:  29 June 2020 
Page 1 of 67 
Confidential 
 
 
Superseding Amendment 2 
Protocol Title:  A Phase 3 Multicenter, Randomized, Open Label, Active-controlled. 
Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated 
Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated 
KRAS p G12C 
Amgen Protocol Number AMG 510 20190009 
EudraCT Number:  2019-003582-18 
 
Amendment Date: 
03 June 2020 
Superseding Amendment 
Date: 
29 June 2020 
 
Rationale: 
The following changes were made to the protocol dated 03 June 2020: 
• 
Schedule of assessments was updated to include identification and quantification of 
biomarker expression at protein, RNA, and DNA levels.   
• 
In the case the subject chooses to continue on treatment beyond radiologic 
progression, the subject must meet certain criteria and the subject must undergo 
biopsy of the progressing lesions 
• 
Schedule of assessments was updated to notate that collection of pharmacokinetic 
(PK) samples are to be within a 10% window of the nominal time points. 
• 
Objectives and Endpoints, Exploratory:  
 
 
 
• 
Exclusion criteria updated to include clarification of previously identified driver 
mutation language to include identified driver mutations that are identified as per 
local standard of care guidelines 
• 
Deleted the exclusion criteria for use of strong inhibitors of CYP3A4 or 
P-glycoproteins  
• 
Revised the contraceptive guidance and collection of pregnancy and lactation 
information to exclude females who are pregnant planning to become pregnant 
within 6 months after last dose of docetaxel based on docetaxel guidelines  
• 
List of analytes table updated to collect urine potassium and urine fraction (24 hour) 
or fractional excretion urine/potassium. 
• 
Eligibility criteria notated to specify that If hepatitis B and C cannot be obtained 
hepatitis viral load to be utilized 
• 
Subgroup analysis revised to include brain and bone metastasis at baseline and 
PD-L1 protein expression 

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Protocol Number:  20190009 
Date:  29 June 2020 
Page 2 of 67 
Confidential 
 
 
• 
Additional changes to the protocol include: 
• 
For selected cases, subjects may continue in the study post radiologic 
progression if they are continuing to demonstrate clinical benefit 
• 
A clarification for a ± 3 day window for lab assessments is allowed, unless 
otherwise specified. 
• 
For select PRO assessments, evaluation at screening has been added Infectious 
hepatitis serology and assessments and/or viral load need not be repeated 
6 weeks prior to enrollment. 
• 
Tumor evaluation should be performed by contrast-enhanced imaging and in the 
case contrast administration is contraindicated radiological imaging is as per 
guidance in the imaging manual is to be followed. 
• 
Updated the collection of biopsy information with addition of mandatory biopsy 
collection for continuation of treatment beyond radiologic progression. 
• 
Text with regards to concomitant administration of proton pump inhibitors is 
included in the protocol.   
• 
AMG 510 dose modification allowances have been modified biomarker 
assessments to determine eligibility of subjects via tumor biopsy should be sent 
as an FFPE block or unstained slides. 
 

Product:  Sotorasib (AMG 510) 
Protocol Number:  20190009 
Date:  03 June 2020 
Page 1 of 68 
Confidential 
 
 
Amendment 2 
Protocol Title:  A Phase 3 Multicenter, Randomized, Open Label, Active-controlled. 
Study of Sotorasib Versus Docetaxel for the Treatment of Previously Treated 
Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated 
KRAS p G12C 
Amgen Protocol Number Sotorasib 20190009 
EudraCT Number:  2019-003582-18 
 
Amendment Date: 
03 June 2020 
 
Rationale: 
The following changes were made to the protocol dated 03 June 2020: 
• 
Schedule of Assessments was updated to include identification and quantification of 
biomarker expression at protein, RNA, and DNA levels.  Also, in case of progression 
of disease, if subject is not continuing sotorasib shall be encouraged to enroll in an 
optional sub-study and in case if the subject continues on treatment beyond 
radiologic progression, the subject must undergo biopsy of the progressing lesions 
• 
Schedule of Assessments was updated to collect pharmacokinetic (PK) samples 
within a 10% window of the nominal time points. 
• 
Objectives and Endpoints, Exploratory: 
• 
Exclusion criteria updated to include clarification for previously identified driver 
mutation as per local standard of care guidelines 
• 
Statistical analysis plan updated with inferential comparison for the endpoints of 
change from baseline over to week 12 in symptoms of chest pain and cough as 
measured by QLQ LC13. 
• 
Deleted the exclusion criteria for use of strong inhibitors of CYP3A4 or 
P-glycoproteins 
• 
Revised the Contraceptive Guidance and Collection of Pregnancy and Lactation 
Information to exclude females who are pregnant or breastfeeding or planning to 
become pregnant within 6 months after last dose of docetaxel 
• 
List of analytes updated to collect urine potassium and urine fraction (24 hour) or 
fractional excretion urine. 
• 
If hepatitis B and C cannot be obtained hepatitis viral load to be utilized 
• 
Subgroup analysis revised to include brain and bone metastasis at baseline and 
PD-L1 protein expression 
• 
Additional changes to the protocol include: 
• 
For selected cases, subjects may continue in the study post radiologic 
progression if they are continuing to demonstrate clinical benefit 

Product:  Sotorasib (AMG 510) 
Protocol Number:  20190009 
Date:  03 June 2020 
Page 2 of 68 
Confidential 
 
 
• 
A clarification for a ± 3 day window is allowed, unless otherwise specified. 
• 
For baseline visits cycle 1 day 1 is added 
• 
Infectious hepatitis serology and assessments and/or viral load need not be 
repeated 6 weeks prior to enrollment. 
• 
Tumor evaluation should be performed by contrast-enhanced imaging and in 
case if it is contraindicated radiological imaging to be performed. 
• 
Additional plasma and blood samples will not be collected for exploratory 
biomarkers (optional). 
• 
Updated the collection of biopsy information with additional mandatory biopsy 
collection for continuation of treatment beyond radiologic progression. 
• 
From the available study results it is known that the concomitant administration of 
proton-pump inhibitors decreased sotorasib concentrations which can affect 
efficacy.  Text included in the protocol to avoid use of PPIs with sotorasib. 
• 
Sotorasib doses modified as dose -2 at 240 mg, dose -1 at 480 mg, and starting 
dose at 960 mg. 
• 
For biomarker assessment to determine eligibility subjects can undergo tumor 
biopsy which should be sent as an FFPE block or unstained slides. 
• 
Potential interim and primary analysis of overall survival guideline included. 
 

Product:  AMG 510 
Protocol Number:  20190009 
Date:  21 January 2020 
Page 1 of 38 
CONFIDENTIAL 
 
 
Amendment 1 
Protocol Title:  A Phase 3 Multicenter, Randomized, Open Label, Active-controlled, 
Study of AMG 510 Versus Docetaxel for the Treatment of Previously Treated 
Locally Advanced and Unresectable or Metastatic NSCLC Subjects With Mutated 
KRAS p.G12C 
 
Amgen Protocol Number AMG 510 20190009 
 
Amendment Date: 
21 January 2020 
Rationale: 
This protocol is being amended to address the following regulatory agency feedback:  
 
Section 1.3, Schedule of Activities, Table 1-1 and Table 1-2 was updated to 
include Thyroid Function Test Assessments:  Thyroid function tests assesements 
added to schedule of activities at screening, pre-dose on day 1 of each cycle, at 
the end of treatment, and safety follow up.  They should also be obtained if the 
subject displays clinical signs or symptoms concerning for thyroid dysfucntion 
 
Additon of AMG 510 Hepatotoxicity Guidelines for management and monitoring 
of subjects with increased AST, ALT, or ALP while on trial 
 
Clarify the sample size determination section to note the trial will not be 
terminated at PFS analyses and subjects will continue to be followed for OS data 
until the targeted number of events are reached to enable OS analyses and a 
robust description of the totality of the data 
 
Section 1.3, Schedule of Activities, Table 1-2 was updated to include Cholesterol 
and Triglyceride Levels Assessments:  Cholesterol and triglyceride levels on  
pre-dose on day 1 of every other cycle (ie, cycle 1, 3, 5, 7, etc). 
 
Section 3, Objectives and Endpoints, Exploratory:  
 
 
 
 
Stratification Factors for randomization, number of prior lines of therapy revised 
to 1 versus 2 versus > 2 
Additional changes to the protocol include: 
 
Food restriction around the time of AMG 510 administration was removed as the 
studies evaluating the effect of food (high fat meal) on pharmacokinetic 
characteristics of AMG 510 demonstrated that high-fat meal does not appear to 
result in clinically meaningful alteration of AMG 510 exposure  
 
Revised the Contraceptive Guidance and Collection of Pregnancy and Lactation 
Information based on data from recently completed nonclinical studies (absence 
of genotoxic risk for AMG 510 based on recently completed GLP-compliant in 
vitro bacterial mutagenicity Ames assay and in vivo genotoxicity study including 
the erythrocyte micronucleus test and the alkaline comet assay). 

Product:  AMG 510 
Protocol Number:  20190009 
Date:  21 January 2020 
Page 2 of 38 
CONFIDENTIAL 
 
 
 
Data from the most recent datacut from the Phase 1/2 Study 20170543 
presented 
 
Dose modification section is updated to outline the dose reduction steps 
allowable  on the study 
 
Guidelines for management and monitoring of subjects with increased AST, ALT 
or ALP are added 
 
Editiorial changes for clarification  
o Indication statement 
o Additional tumor evaluation technigues that are acceptable  
o Introduction under the rationale for choice of docetaxel as comparator, to 
clarify and reduce redundancy 
o Inclusion criteria 105, clarify that the subjects will have reiceved at least 1 
prior systemic therapy