Phase 2a Study Evaluating the Efficacy, Safety, Tolerability and Pharmacokinetics of Tarlatamab in Chinese Subjects With Advanced Small Cell Lung Cancer After Two or More Prior Lines of Treatment (DeLLphi-307)
Phase: PHASE2
Conditions: Extensive Stage Small Cell Lung Cancer
Sponsor: Amgen

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 1 of 137 
CONFIDENTIAL 
 
Title Page 
Protocol Title: 
Phase 2a Study Evaluating the Efficacy, Safety, 
Tolerability and Pharmacokinetics of 
Tarlatamab in Chinese Subjects with Advanced 
Small Cell Lung Cancer after Two or More Prior 
Lines of Treatment (DeLLphi-307) 
Short Protocol Title: 
Phase 2a Study Evaluating Tarlatamab in 
Chinese Subjects with Advanced Small Cell 
Lung Cancer after Two or More Prior Lines of 
Treatment (DeLLphi-307)  
Protocol Number: 
20230273 
Investigational Product: 
Tarlatamab (AMG 757)  
Trade Name: 
Not Applicable 
Sponsor 
Name of Sponsor: 
Amgen Inc. 
 
Address: 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
 
Telephone Number: 
+1-805-447-1000 
Protocol 
Approver 
Name: 
 
 
Function: 
Vice President, Global Development 
Key 
Sponsor 
Contact 
Name: 
, MD, PhD 
 
Address: 
One Amgen Center Drive 
Thousand Oaks, CA 91320 
 
Telephone Number: 
 
 
Email Address: 
 
EU CT Number: 
Not Applicable 
NCT Number: 
NCT06502977 
Protocol Version Date: 
Document Version 
Date 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 2 of 137 
CONFIDENTIAL 
 
Original 
19 December 2023 
Amendment 1 
15 May 2024 
Amendment 2 
06 September 2024 
Data Elements Standards 
Version: 
9.0 
 
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 (International Council for Harmonisation 
[ICH] E6). 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 3 of 137 
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 external review bodies (eg, institutional review board/independent 
ethics committee/regulatory authorities). 
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.] 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 4 of 137 
CONFIDENTIAL 
 
Investigator’s Agreement: 
I have read the attached protocol entitled Phase 2a Study Evaluating the Efficacy, 
Safety, Tolerability and Pharmacokinetics of Tarlatamab in Chinese Subjects with 
Advanced Small Cell Lung Cancer after Two or More Prior Lines of Treatment (DeLLphi-
307), dated 06 September 2024, 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.  I agree not to share the confidential 
information contained in this document without the prior written consent of Amgen Inc. 
 
Signature 
 
_______________________________ 
____________________________ 
Name of Investigator  
 
 
Date (DD Month YYYY) 
 
Title and Role of Investigator 
 
Institution Name 
 
Address and Telephone Number of Institution 
 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 5 of 137 
CONFIDENTIAL 
 
Table of Contents  
Table of Contents ................................................................................................... 5 
1. 
Protocol Summary ................................................................................................ 11 
1.1 
Synopsis ................................................................................................... 11 
1.2 
Study Schema ........................................................................................... 15 
1.3 
Schedule of Activities (SoA) ...................................................................... 16 
2. 
Introduction ........................................................................................................... 26 
2.1 
Study Rationale ......................................................................................... 26 
2.2 
Background ............................................................................................... 26 
2.2.1 
Disease ..................................................................................... 26 
2.2.2 
Amgen Investigational Product Background:  
Tarlatamab ................................................................................ 27 
2.2.3 
Non-Amgen Investigational Product Background ....................... 28 
2.3 
Benefit/Risk Assessment ........................................................................... 28 
3. 
Objective(s) and Endpoint(s)/Estimand(s) ............................................................. 30 
4. 
Study Design ........................................................................................................ 31 
4.1 
Overall Design .......................................................................................... 31 
4.2 
Patient Input into the Study Design ........................................................... 32 
4.3 
Justification for Dose ................................................................................. 32 
4.3.1 
Justification for Investigational Product Dose............................. 32 
4.4 
Justification for Monitoring ......................................................................... 33 
4.5 
End of Study ............................................................................................. 33 
5. 
Study Population .................................................................................................. 34 
5.1 
Inclusion Criteria ....................................................................................... 34 
5.2 
Exclusion Criteria ...................................................................................... 35 
5.3 
Lifestyle Considerations ............................................................................ 39 
5.4 
Subject Enrollment .................................................................................... 39 
5.5 
Screen Failures ......................................................................................... 40 
6. 
Study Intervention ................................................................................................. 40 
6.1 
Study Interventions Administered .............................................................. 40 
6.1.1 
Investigational Products ............................................................ 40 
6.1.2 
Noninvestigational Products/Auxiliary Medicinal 
Products .................................................................................... 43 
6.1.2.1 
Pre- and Post-infusion Medications ......................... 43 
6.1.2.2 
Cytokine Release Syndrome Rescue 
Medication ............................................................... 43 
6.1.3 
Medical Devices ........................................................................ 43 
6.1.4 
Other Intervention Procedures ................................................... 43 
6.1.5 
Product Complaints ................................................................... 43 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
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6.1.6 
Excluded Treatments, Medical Devices, and/or 
Procedures During Study Period ............................................... 44 
6.1.7 
Continuation on Investigational Product Treatment 
After First Radiologic Disease Progression ............................... 45 
6.2 
Dose Modification ...................................................................................... 45 
6.2.1 
Dose-group Study Escalation/De-escalation and 
Stopping Rules .......................................................................... 45 
6.2.2 
Dosage Adjustments, Delays, Rules for Withholding or 
Restarting, Permanent Discontinuation ..................................... 46 
6.2.2.1 
Amgen Investigational Product:  
Tarlatamab .............................................................. 46 
6.2.3 
Hepatotoxicity Stopping and Rechallenge Rules ....................... 60 
6.3 
Preparation/Handling/Storage/Accountability ............................................ 60 
6.4 
Method of Treatment Assignment ............................................................. 60 
6.5 
Blinding ..................................................................................................... 60 
6.6 
Treatment Compliance .............................................................................. 60 
6.7 
Treatment of Overdose ............................................................................. 60 
6.8 
Prior and Concomitant Treatment ............................................................. 61 
6.8.1 
Prior Treatment ......................................................................... 61 
6.8.2 
Concomitant Treatment ............................................................. 61 
7. 
Discontinuation of Study Treatment and Subject 
Discontinuation/Withdrawal ................................................................................... 61 
7.1 
Discontinuation of Study Treatment........................................................... 61 
7.2 
Subject Discontinuation/Withdrawal From the Study ................................. 62 
7.2.1 
Reasons for Removal From Study ............................................. 63 
7.3 
Lost to Follow-up ....................................................................................... 63 
8. 
Study Assessments and Procedures .................................................................... 63 
8.1 
General Study Periods .............................................................................. 64 
8.1.1 
Screening and Enrollment ......................................................... 64 
8.1.2 
Treatment Period ....................................................................... 64 
8.1.3 
End of Treatment ....................................................................... 65 
8.1.4 
Safety Follow-up ........................................................................ 65 
8.1.5 
Long-term Follow-up .................................................................. 65 
8.1.6 
End of Study .............................................................................. 65 
8.2 
General Assessments ............................................................................... 66 
8.2.1 
Informed Consent ...................................................................... 66 
8.2.2 
Demographics ........................................................................... 66 
8.2.3 
Medical History .......................................................................... 66 
8.2.4 
Physical Examination ................................................................ 66 
8.2.5 
Neurological Examination .......................................................... 66 
8.2.6 
Physical Measurements ............................................................ 67 
8.2.7 
Performance Status ................................................................... 67 
8.3 
Efficacy Assessments ............................................................................... 67 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
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8.3.1 
Radiological Imaging Assessment ............................................. 67 
8.3.2 
Blinded Independent Central Review (BICR) ............................. 68 
8.4 
Safety Assessments .................................................................................. 69 
8.4.1 
Vital Signs ................................................................................. 69 
8.4.2 
Electrocardiograms.................................................................... 70 
8.4.3 
Clinical Laboratory Assessments ............................................... 70 
8.4.4 
Vital Status (Survival Status) ..................................................... 70 
8.4.5 
Other Safety .............................................................................. 71 
8.4.5.1 
Echocardiogram (ECHO)/Multigated 
Acquisition (MUGA) Scan ........................................ 71 
8.4.5.2 
Cytokine Release Syndrome ................................... 71 
8.4.5.3 
Immune Effector Cell-Associated 
Neurotoxicity Syndrome (ICANS) ............................ 71 
8.4.5.4 
Hepatitis B ............................................................... 71 
8.4.5.5 
Hypersensitivity ....................................................... 72 
8.4.6 
Adverse Events and Serious Adverse Events ............................ 72 
8.4.6.1 
Time Period and Frequency for Collecting 
and Reporting Safety Event Information .................. 72 
8.4.6.2 
Method of Detecting Adverse Events and 
Serious Adverse Events .......................................... 75 
8.4.6.3 
Follow-up of Adverse Events and Serious 
Adverse Events ....................................................... 75 
8.4.6.4 
Regulatory Reporting Requirements for 
Safety Information ................................................... 75 
8.4.6.5 
Safety Monitoring Plan ............................................ 76 
8.4.6.6 
Other Safety Findings/Special Situations ................. 76 
8.4.6.7 
Pregnancy and Lactation ......................................... 76 
8.5 
Pharmacokinetic Assessments .................................................................. 77 
8.6 
Pharmacogenetic Assessments ................................................................ 77 
8.7 
Antibody Testing Procedures .................................................................... 78 
8.8 
Medical Resource Utilization and Health Economics ................................. 78 
9. 
Statistical Considerations ...................................................................................... 78 
9.1 
Statistical Hypotheses ............................................................................... 78 
9.2 
Sample Size Determination ....................................................................... 79 
9.3 
Populations for Analysis ............................................................................ 79 
9.3.1 
Covariates ................................................................................. 79 
9.4 
Statistical Analyses ................................................................................... 79 
9.4.1 
Planned Analyses ...................................................................... 79 
9.4.1.1 
Primary Analysis ..................................................... 79 
9.4.1.2 
Final Analysis .......................................................... 80 
9.4.2 
Methods of Analyses ................................................................. 80 
9.4.2.1 
General Considerations ........................................... 80 
9.4.2.2 
Efficacy Analyses .................................................... 81 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
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9.4.2.3 
Safety Analyses ...................................................... 81 
9.4.2.4 
Other Analyses ........................................................ 82 
10. 
References ........................................................................................................... 83 
11. 
Appendices ........................................................................................................... 85 
11.1 
Appendix 1.  List of Abbreviations ............................................................. 86 
11.2 
Appendix 2.  Clinical Laboratory Tests ...................................................... 89 
11.3 
Appendix 3.  Study Governance Considerations ....................................... 92 
11.4 
Appendix 4.  Safety Events:  Definitions and Procedures for 
Recording, Evaluating, Follow-up and Reporting ..................................... 101 
11.5 
Appendix 5.  Contraceptive Guidance and Collection of 
Pregnancy and Lactation Information ...................................................... 109 
11.6 
Appendix 6.  Sample Storage and Destruction ........................................ 115 
11.7 
Appendix 7.  Hepatotoxicity Stopping Rules:  Suggested Actions 
and Follow-up Assessments and Study Treatment Rechallenge 
Guidelines ............................................................................................... 117 
11.7.1 
Criteria for Stopping Amgen Investigational Product 
and Noninvestigational Product(s)/Auxiliary Medicinal 
Product(s) Due to Potential Hepatotoxicity .............................. 117 
11.7.2 
Reporting Criteria .................................................................... 117 
11.7.3 
Follow up Actions .................................................................... 118 
11.7.3.1 
Investigating Alternative Causes of 
Hepatotoxicity........................................................ 118 
11.7.4 
Rechallenge and Dose Modification in Patients with 
Suspected Hepatotoxicity in Oncology Trials ........................... 120 
11.7.5 
Permanent Discontinuation of Study Drug(s) ........................... 120 
11.7.6 
Management Flow Chart ......................................................... 120 
11.8 
Appendix 8.  Protocol-specific Anticipated Serious Adverse 
Events ..................................................................................................... 122 
11.9 
Appendix 9.  ECOG Performance Status and NYHA Functional 
Classification ........................................................................................... 123 
11.10 Appendix 10.  Response Evaluation Criteria in Solid Tumors 
Version 1.1 (RECIST 1.1); Eisenhauer et al, 2009 .................................. 124 
11.10.1 
Definitions ............................................................................... 124 
11.10.1.1 Measurable Disease.............................................. 124 
11.10.1.2 Measurable Lesions .............................................. 124 
11.10.1.3 Non-measurable Lesions ...................................... 125 
11.10.2 
Methods of Measurement ........................................................ 125 
11.10.2.1 CT/MRI.................................................................. 125 
11.10.2.2 PET-CT ................................................................. 126 
11.10.2.3 Ultrasound ............................................................. 126 
11.10.2.4 Endoscopy, Laparoscopy ...................................... 126 
 
11.10.2.6 Cytology, Histology ............................................... 126 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
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11.10.2.7 FDG-PET .............................................................. 127 
11.10.3 
Lesion Evaluation .................................................................... 127 
11.10.3.1 Baseline documentation of “Target” and 
“Non-target” lesions ............................................... 127 
11.10.4 
Response Criteria .................................................................... 128 
11.10.5 
Evaluation of Best Overall Response ...................................... 128 
11.10.6 
Special Notes on Response Assessment ................................ 130 
11.10.7 
Confirmation Measurement ..................................................... 132 
11.11 Appendix 11.  Specific Guidance for Cytokine Release 
Syndrome, Immune-effector Cell-associated Neurologic 
Syndrome, and Tumor Lysis Syndrome .................................................. 133 
11.11.1 
Specific Guidance for Cytokine Release Syndrome ................. 133 
11.11.2 
Specific Guidance for Immune-effector 
Cell-associated Neurologic Syndrome ..................................... 135 
11.11.3 
Tumor Lysis Syndrome ............................................................ 137 
 
List of Tables 
Table 1-1.  Schedule of Activities:  Cycle 1 only ............................................................ 17 
Table 1-2.  Schedule of Activities:  Cycle 2+ .................................................................. 23 
Table 6-1.  Investigational Products ............................................................................... 43 
Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events ..................... 49 
Table 6-3.  Step dose Rechallenge Requirement After Tarlatamab Delay ..................... 61 
Table 8-1.  Vital Signs for Subjects Receiving Tarlatamab............................................. 71 
Table 9-1.  Probabilities of Observed ORR Greater Than Thresholds With 
Sample Size of 30 .................................................................................. 81 
Table 11-1.  Analyte Listing ........................................................................................... 92 
Table 11-2.  DILI Potential Analyte Listing ..................................................................... 93 
Table 11-3.  Evaluation of Target Lesions ................................................................... 130 
Table 11-4.  Evaluation of Non-target Lesions ............................................................. 130 
Table 11-5.  Time Point Overall Response .................................................................. 131 
Table 11-6.  Best Overall Response When Confirmation of Complete 
Response (CR) and Partial Response (PR) Required ........................... 132 
Table 11-7.  ASBMT Immune-effector Cell-associated Neurotoxicity 
Syndrome (ICANS) Consensus Grading for Adults ............................... 138 
Table 11-8.  Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome ................. 139 
 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
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CONFIDENTIAL 
 
List of Figures 
Figure 1-1.  Study Schema ............................................................................................ 15 
Figure 11-1.  Sample Electronic Serious Adverse Event Contingency Report 
Form (Paper-based Form) .................................................................... 108 
Figure 11-2.  Pregnancy and Lactation Notification Forms (Paper-based 
Form) .................................................................................................... 113 
Figure 11-3.  Management of Potential Hepatotoxicity ................................................. 121 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 11 of 137 
CONFIDENTIAL 
 
1. 
Protocol Summary  
1.1 
Synopsis  
Protocol Title:  Phase 2a Study Evaluating the Efficacy, Safety, Tolerability and 
Pharmacokinetics of Tarlatamab in Chinese Subjects with Advanced Small Cell Lung 
Cancer after Two or More Prior Lines of Treatment (DeLLphi-307)  
Short Protocol Title:  Phase 2a Study Evaluating Tarlatamab in Chinese Subjects with 
Advanced Small Cell Lung Cancer after Two or More Prior Lines of Treatment (DeLLphi-
307) 
Study Phase:  2a 
Indication:  Small Cell Lung Cancer (SCLC) 
Study Rationale 
Small cell lung cancer (SCLC) is a grave diagnosis, marked by high initial response 
rates to platinum-based first-line chemotherapy.  However, resistance to subsequent 
treatments quickly emerges, resulting in a median survival of 10 to 12 months 
post-diagnosis (Rudin et al, 2015).  Delta-like ligand 3 (DLL3) is typically intracellular in 
normal tissues but often overexpressed on the cell surface in most SCLC tumors, 
making it an attractive target for T-cell therapies (Saunders et al, 2015).  Notably, 
minimal cytoplasmic staining is observed in the brain, pituitary, and pancreatic islets in 
normal tissues (Study 123377), suggesting the potential for tumor-specific 
DLL3-targeted therapy. 
Tarlatamab (INN; AMG 757) is a novel, extended half-life (HLE) bispecific T-cell engager 
(BiTE) designed to direct T effector cells toward DLL3-expressing cells using a tandem 
single-chain fragment crystallizable (scFc) for prolonged half-life.  In an ongoing phase 2 
study (Study 20200491), tarlatamab has demonstrated efficacy in SCLC patients with a 
manageable safety profile (Ahn et al, 2023). 
Tarlatamab received accelerated approval from the United States Food and Drug 
Administration (FDA) for the treatment of adult patients with extensive-stage 
SCLC with disease progression on or after platinum-based chemotherapy. 
Study 20230273 aims to assess tarlatamab's efficacy, safety, tolerability, and 
pharmacokinetics (PK) in Chinese subjects with advanced SCLC who have progressed 
on or recurred following 1 platinum-based regimen as first-line (1L) therapy (including a 
Programmed Cell Death Protein 1 [PD-1]/Programmed Cell Death Ligand 1 [PD-(L)1]) 
and at least 1 other prior line of therapy (re-treatment with a platinum-based regimen is 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
Page 12 of 137 
CONFIDENTIAL 
 
considered a second-line of therapy).  Detailed information about tarlatamab's chemistry, 
pharmacology, efficacy, and safety is available in the investigator’s brochure. 
Objective(s) and Endpoint(s)/Estimand(s) 
 
Objectives 
Endpoints 
Primary 
 
Evaluate efficacy of tarlatamab as 
assessed by objective response rate 
(ORR) based on blinded independent 
central review (BICR) per Response 
Evaluation Criteria in Solid Tumors 
version 1.1 (RECIST 1.1) 
 
ORR BICR, defined as proportion with 
best overall response (BOR) of 
complete response (CR) plus partial 
response (PR) 
 
Secondary 
 
Evaluate efficacy of Tarlatamab as 
assessed by duration of response 
(DOR), disease control (DC), and 
progression-free survival (PFS) based 
on BICR per RECIST 1.1 
 
DOR, defined as time from the first 
documentation of objective response 
(OR) until the first documentation of 
disease progression or death due to 
any cause, whichever occurs first.  
Only subjects who have achieved OR 
will be evaluated for DOR  
 
DC, defined as CR + PR + stable 
disease (SD) 
 
Duration of DC, defined as time from 
the first documentation of CR, PR, or 
SD until the first documentation of 
disease progression or death due to 
any cause, whichever occurs first.  
Only subjects who have achieved CR, 
PR, or SD will be evaluated for 
Duration of DC 
 
PFS, defined as time from enrollment 
until disease progression or death 
from any cause, whichever occurs 
first.  Progression will be based on 
RECIST 1.1. 
 
Evaluate efficacy of Tarlatamab as 
assessed by ORR, DOR, DC, and 
PFS based on investigator 
assessment per RECIST 1.1 
 
ORR (Investigator) 
 
DOR  
 
DC 
 
Duration of DC 
 
PFS 
 
Evaluate efficacy of Tarlatamab as 
assessed by overall survival (OS) 
 
OS, defined as time from enrollment 
until death from any cause 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
Date:  06 September 2024 
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CONFIDENTIAL 
 
 
Evaluate safety and tolerability 
 
Incidence of treatment-emergent 
adverse events  
 
Characterize the pharmacokinetics of 
tarlatamab 
 
Serum concentration of tarlatamab  
 
Evaluate the immunogenicity of 
tarlatamab 
 
Incidence of anti-tarlatamab antibody 
formation 
Estimand(s) for Primary Objective(s) 
Objective response rate (ORR) by blinded independent central review (BICR) per 
RECIST 1.1 in Chinese subjects with advanced SCLC who have progressed on or 
recurred following 1 platinum-based regimen as 1L therapy (including a PD-1/ PD [L]1) 
and at least 1 other prior line of therapy (re treatment with a platinum-based regimen is 
considered a second line of therapy) prior to start of new cancer therapy 
(while-on-treatment strategy). 
Overall Design 
This is a phase 2a, multicenter, single arm, open-label study in Chinese subjects with 
advanced SCLC who have progressed on or recurred following 1 platinum-based 
regimen as 1L therapy (including a PD-1/PD-[L]1) and at least 1 other prior line of 
therapy (re-treatment with a platinum-based regimen is considered a second-line of 
therapy).   
The study consists of a 21-day screening period, a treatment period, a safety follow-up 
(SFU) period, and a long-term follow-up (LTFU) period.  Enrolled subjects will receive 
tarlatamab per protocol. 
Number of Subjects 
Approximately 30 Chinese subjects are planned to be enrolled in the study.  
Summary of Subject Eligibility Criteria 
Male and female subjects who are residents in China and of Chinese ancestry, aged 
≥ 18 years (or legal adult age), with confirmed advanced SCLC after 1 platinum-based 
regimen as 1L therapy (including PD-1/PD-[L]1) and at least one other prior line of 
therapy.  
Upon study consent, subjects undergo protocol-mandated screening assessments to 
confirm eligibility.  They must have measurable lesions (per RECIST 1.1) within 21 days 
before the first dose of study treatment and adequate organ function.   
For a full list of eligibility criteria, please refer to Section 5.1 to Section 5.2. 

Product:  Tarlatamab (AMG 757) 
Protocol Number:  20230273  
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CONFIDENTIAL 
 
Treatments 
Tarlatamab will be administered as a 60-minute ( 10 minutes) intravenous (IV) infusion 
with 1 mg step dose on cycle 1 day 1 (C1D1) followed by a 10 mg target dose on cycle 1 
day 8 (C1D8), and cycle 1 day 15 (C1D15) in a 28-day cycle.  Subsequent doses 
(10 mg) will be administered every 2 weeks (Q2W) (ie, cycle 2+ day 1/day 15 dosing) in 
a 28-day cycle. 
 
Monitoring during cycle 1: 
o Monitoring – cycle 1:  Monitoring required for 6 to 8 hours post-infusion at C1D1 
and C1D8.   
- Cohabitant (caregiver) support for 24 hours post-infusion and the ability to 
stay within 1 hour of a hospital for 24 hours is required.   
- Counseling the subject and caregiver on signs and symptoms of cytokine 
release syndrome (CRS), and immune effector cell-associated 
neurotoxicity syndrome (ICANS) by a health care provider is required 
prior to discharge.   
- Subjects return to site on cycle 1 day 2 (C1D2) and cycle 1 day 9 (C1D9) 
for vital signs and physical examination.   
- At subsequent visits, additional monitoring may be required post-infusion.  
Refer to Section 6.1.1 (Table 6-1).   
 
Pre- and Post-infusion medication requirements: 
o Dexamethasone:  8 mg IV (or equivalent) will be administered within 1 hour prior 
to tarlatamab infusion on C1D1 and C1D8. 
o Intravenous Hydration:  1 L normal saline over 2 to 4 hours following tarlatamab 
administration on C1D1 and C1D8.  
Statistical Considerations 
For a full description of statistical analysis methods, please refer to Section 9. 
Statistical Hypotheses 
No statistical hypotheses will be tested. 
Sponsor Name: 
 Amgen Inc. 
 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
Page 15 of 137 
CONFIDENTIAL 
 
1.2 
Study Schema  
Figure 1-1.  Study Schema  
SCREENING
ENROLLMENT
END OF TREATMENT b
Tarlatamab IV Infusion
1mg C1D1
10 mg C1D8, C1D15, then Q2W a
n = 30
SAFETY FOLLOW-UP c
LONG-TERM FOLLOW-UP
 
C1D1  cycle 1 day 1; C1D8  cycle 1 day 8; C1D15  cycle 1 day 15; IV  intravenous; Q2W  every 2 weeks; RECIST 1.1 = Response Evaluation Criteria in Solid 
Tumors 1.1 
a Subjects will receive study treatment until blinded independent central review (BICR)-confirmed disease progression per RECIST 1.1, death, withdrawal of consent, 
start of new anticancer therapy, unacceptable toxicity, or end of study as determined by the sponsor (whichever occurs first). 
b End of Treatment visit will occur at the time the decision is made to discontinue study treatment (preferably within 14 days after last dose of study treatment) and prior 
to start of new anti-cancer therapy. 
c Safety Follow-up visit will occur 60 ( 5) days after last dose of study treatment. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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1.3 
Schedule of Activities (SoA)  
Table 1-1.  Schedule of Activities:  Cycle 1 only  
Procedurea 
Screening 
Treatment Periodb 
As clinically 
indicated 
Notes 
Cycle 1 
Day 
(Up to 21 
Days 
Before 
Day 1) 
1 
2 
8 
9 
15 
GENERAL AND SAFETY ASSESSMENTS 
Informed consent 
X 
 
 
 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
 
 
 
Medical history 
X 
 
 
 
 
 
 
Includes medical, surgical, and cancer. 
Demographics 
X 
 
 
 
 
 
 
 
Physical examination (including 
neurological exam) 
(X) 
[X] 
X 
X 
X 
X 
X 
Physical exam must be completed prior to 
start of infusion on treatment days. 
(X):  Height to be collected at screening 
ONLY. 
[X]:  Must include weight on Day 1. 
Vital Signs 
X 
(X) 
X 
(X) 
X 
X 
X 
Includes systolic/diastolic blood pressure, 
heart rate, respiratory rate, pulse oximetry, 
and temperature. 
(X):  Refer to Section 8.4.1 for detailed vital 
sign collection time points. 
ECOG PS 
X 
X 
 
 
 
 
 
 
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Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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Table 1-1.  Schedule of Activities:  Cycle 1 only 
 
Procedurea 
Screening 
Treatment Periodb 
As clinically 
indicated 
Notes 
Cycle 1 
Day 
(Up to 21 
Days 
Before 
Day 1) 
1 
2 
8 
9 
15 
NYHA 
X 
 
 
 
 
 
 
Collected at screening only for patients with 
a known history of heart disease. 
ECG 
X 
 
 
 
 
 
X 
 
ECHO or MUGA scan 
X 
 
 
 
 
 
X 
 
Adverse events 
 
continuous 
X 
 
Serious adverse events 
continuous 
X 
 
Prior and Concomitant therapies 
review 
continuous 
X 
 
LABORATORY ASSESSMENTS 
HIV, Hepatitis B and C screening 
X 
 
 
 
 
 
X 
 
Pregnancy test (females of 
childbearing potential only)c 
X 
X 
 
 
 
 
X 
Serum pregnancy test at screening within 
7 days of C1D1; serum or urine pregnancy 
test on Day 1 of every cycle should be 
collected. 
Coagulationd 
X 
X 
 
X 
 
X 
X 
 
Hematologyd 
X 
X 
 
X 
 
X 
X 
  
Chemistryd 
X 
(X) 
 
X 
 
X 
X 
(X):  Includes LDH and uric acid.   
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Product:  Tarlatamab (AMG 757)  
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Date:  06 September 2024 
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Table 1-1.  Schedule of Activities:  Cycle 1 only 
Procedurea 
Screening 
Treatment Periodb 
As 
clinically 
indicated 
Notes 
Cycle 1 
Day 
(Up to 21 
Days 
Before 
Day 1) 
1 
2 
8 
9 
15 
Urinalysisd 
X 
X 
 
 
 
 
X 
 
Lipase and amylasee 
X 
X 
 
 
 
 
X 
 
TSH and FT4e 
X 
X  
 
 
 
 
X 
 
CENTRAL LABORATORY ASSESSMENTS 
PK sample 
 
 
X 
 
 
 
 
 
X:  Collect pre dose sample on C1D1. 
The time of dosing and PK sample collection 
should be accurately recorded. 
Anti-tarlatamab antibody sample 
 
X 
 
 
 
 
 
X:  Collect pre dose sample on C1D1.  
Refer to Section 8.7 for additional details.  
IMAGING ASSESSMENTS 
MRI brain 
Xf 
 
 
 
 
 
X 
All brain scans on protocol are required to be 
MRI unless MRI is contraindicated, then CT 
with contrast is acceptable.  Subsequently 
after screening, MRI brain can be performed at 
any time if clinically indicated per standard of 
care. 
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Date:  06 September 2024 
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Table 1-1.  Schedule of Activities:  Cycle 1 only 
Procedurea 
Screening 
Treatment Periodb 
As clinically 
indicated 
Notes 
Cycle 1 
Day 
(Up to 21 
Days Before 
Day 1) 
1 
2 
8 
9 
15 
Radiological imaging and tumor 
assessmentg 
Xf 
Weeks 1 to 48:  Q6W ( 1 week) 
Weeks 49 Q12W ( 1 week) 
by BICR per RECIST 1.1 
X 
Refer to Section 8.3.1 for additional details. 
For subjects who end study treatment for 
reasons other than specified in Section 8.3.2, 
every effort should be made to perform 
scheduled radiographic imaging (CT/MRI) 
until radiographic progression. 
STUDY TREATMENT AND MONITORING 
Other protocol-required therapy: 
Dexamethasone 
 
X 
 
X 
 
 
 
Refer to Section 6.1.2 for details for pre-
treatment with dexamethasone (or equivalent 
dose of other corticosteroids).  
Dexamethasone will be administered within 
1 hour prior to tarlatamab infusion on days 1 
and 8 of cycle 1 only. 
Tarlatamab Infusion 
 
X 
 
X 
 
X 
 
 
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Product:  Tarlatamab (AMG 757)  
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Date:  06 September 2024 
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Table 1-1.  Schedule of Activities:  Cycle 1 only 
Procedurea 
Screening 
Treatment Periodb 
As clinically 
indicated 
Notes 
Cycle 1 
Day 
(Up to 21 
Days Before 
Day 1) 
1 
2 
8 
9 
15 
Monitoring post-tarlatamab infusion 
 
X 
 
X 
 
 
X 
Subject will remain at study site for 
6 to 8 hours post‑infusion at C1D1 and C1D8.  
Cohabitant (caregiver) support for 24 hours 
post-infusion and the ability to stay within 
1 hour of a hospital for 24 hours is required.  
Counseling the subject and caregiver on 
signs and symptoms of CRS and ICANS by a 
health care provider is required prior to 
discharge.  Subjects return to site on C1D2 
and C1D9 for vital signs and physical 
examination.  At subsequent visits, additional 
monitoring may be recommended 
post-tarlatamab infusion based on occurrence 
of CRS, ICANS, or ICANS-related 
neurological events. 
Refer to Table 6-1.   
Other protocol-required therapy: IV 
hydration 
 
X 
 
X 
 
 
 
Refer to Section 6.1.2 for details related to IV 
hydration.  IV hydration (1 L normal saline) 
over 2 to 4 hours following tarlatamab 
administration. 
Page 5 of 5 
BICR  Blinded Independent Central Review; C1D1  cycle 1 day 1; C1D2  cycle 1 day 2; C1D8 cycle 1 day 8; C1D9  cycle 1 day 9; 
CRS  cytokine release syndrome; CT  computed tomography; ECG  electrocardiogram; ECHO  echocardiogram; ECOG PS  Eastern 
Cooperative Oncology Group Performance Status; EOI  end of infusion; FT4  free T4; HIV  human immunodeficiency virus; ICANS  immune 
effector cell-associated neurotoxicity syndrome; IV  intravenous; LDH  Lactate dehydrogenase; MUGA Scan  multigated acquisition scan; 
MRI  magnetic resonance imaging; NYHA  New York Heart Association; PK  pharmacokinetic; Q6W  every 6 weeks; Q12W  every 12 weeks; 
RECIST 1.1 = Response Evaluation Criteria in Solid Tumors 1.1; TSH  thyroid-stimulating hormone 
a All procedures and assessments on dosing days are to be completed prior to study drug administration unless otherwise indicated.  Assessments 
should not be performed from the infusion line.   
b Each visit week and day is relative to day 1 of each cycle.  Cycle 1 visits have a ± 1-day window from designated time point unless otherwise 
specified.  

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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c Additional on-treatment pregnancy testing may be performed at the investigator’s discretion if there is suspicion that a female subject is pregnant or 
per local laws and regulations. 
d If screening local labs are obtained within 48 hours prior to cycle 1 day 1 dose, pre-infusion cycle 1 day 1 samples do not have to be repeated.  
Where applicable, cycle 1 day 8 and day 15 local labs must be obtained within 48 hours prior to dose (day 8 and day 15).  Results must be 
reviewed prior to study drug administration.   
e If screening local labs are obtained within 72 hours prior to cycle 1 day 1 dose, the pre-infusion cycle 1 day 1 samples do not have to be 
repeated.  Results must be reviewed prior to study drug administration. 
f Imaging assessments must be within 21 days prior to the first dose of tarlatamab. 
g Timing is based on first dose of tarlatamab (C1D1). 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
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Table 1-2.  Schedule of Activities:  Cycle 2+  
Procedurea 
Treatment Periodb 
EOT c SFUd LTFUe,f 
As 
clinically 
indicated 
Notes 
Cycle 2 Cycle 3 
Day 
1 
15 
1 
15 
GENERAL AND SAFETY ASSESSMENTS 
Physical examination 
(including neurological 
exam) 
[X] 
X 
[X] 
X 
X 
X 
 
X 
Physical exam must be completed prior to start of infusion on 
treatment days. 
[X]:  Must include weight on Day 1 of every cycle. 
Vital Signs 
X 
X 
X 
X 
X 
X 
 
X 
Includes systolic/diastolic blood pressure, heart rate, respiratory 
rate, pulse oximetry, and temperature 
ECOG PS 
X 
 
X 
 
X 
X 
 
 
 
ECG 
 
 
 
 
X 
 
 
X 
  
Adverse events 
continuous 
 
X 
 
Serious adverse events 
continuous g 
X 
 
Prior and Concomitant 
therapies review 
continuous 
 
X 
 
Survival Status 
 
 
 
 
 
 
X 
 
 
Subsequent anticancer 
therapy 
 
 
 
 
X 
X 
X 
 
 
LABORATORY ASSESSMENTS 
Pregnancy test 
(females of 
childbearing potential 
only)h 
X 
 
X 
 
X 
X 
(X) 
X 
Serum or urine pregnancy test on Day 1 of every cycle should be 
collected. 
(X):  60 days after the last dose of tarlatamab. 
Page 1 of 3 
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Protocol Number:  20230273 
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Table 1-2.  Schedule of Activities:  Cycle 2+ 
Procedurea 
Treatment Periodb 
EOT c SFUd LTFUe,f 
As 
clinically 
indicated 
Notes 
Cycle 2 Cycle 3 
Day 
1 
15 
1 
15 
Coagulationi 
X 
X 
X 
 
X 
X 
 
X 
 
Hematologyi 
X 
X 
X 
(X) 
X 
X 
 
X 
(X):  Cycle 3, 4, and 5 only. 
Chemistryi 
[X] 
X 
X 
(X) 
X 
X 
 
X 
[X]:  Includes LDH and uric acid on C2D1 only.  
(X):  Cycle 3, 4, and 5 only. 
Urinalysis 
X 
 
(X) 
 
X 
X 
 
X 
(X):  Collect on cycle 3, cycle 4 and then every other cycle (ie, cycle 
6, 8, etc) on Day 1 only. 
Lipase and amylasej 
X 
 
X 
 
X 
X 
 
X 
 
TSH and FT4j 
 
 
 
 
X 
 
 
X 
 
CENTRAL LABORATORY ASSESSMENTS 
PK samplek 
X 
 
(X) 
 
 
 
 
 
All PK samples are collected pre-dose (ie, prior to start of tarlatamab 
infusion). 
(X):  Collect C3D1, C4D1, and then every other cycle (ie, cycle 6, 
cycle 8, etc) on Day 1 only.   
PK samples to be collected up to cycle 12 only. 
The time of dosing and PK sample collection should be accurately 
recorded.  
Anti-tarlatamab 
antibody sample 
X 
 
(X) 
 
X 
X  
 
 
All anti-tarlatamab antibody samples are collected pre-dose 
(ie, prior to start of tarlatamab infusion). 
The time of dosing and anti-tarlatamab antibody sample 
collection should be accurately recorded. 
(X):  Collect C3D1, C4D1, and then every other cycle (ie, cycle 6, 
cycle 8, etc) on Day 1 only. 
Anti-tarlatamab antibody samples are to be collected until EOT and 
SFU. 
Page 2 of 3 
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Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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Table 1-2.  Schedule of Activities:  Cycle 2+ 
Procedurea 
Treatment Periodb 
EOT c SFUd LTFUe,f 
As 
clinically 
indicated 
Notes 
Cycle 2 Cycle 3 
Day 
1 
15 
1 
15 
IMAGING ASSESSMENTS 
Radiological imaging 
and tumor assessmentk 
Weeks 1 to 48:  
Q6W (± 1 week) 
Weeks 49+ Q12W 
(± 1 week) 
by BICR per 
RECIST 1.1 
(X)  
(X) 
[X] 
X 
Refer to Section 8.3.1 for additional details.   
(X):  For subjects who discontinued treatment for any reason other 
than radiographic PD, imaging is required at the EOT or SFU visit if 
the subject has not had radiologic imaging performed within 6 weeks 
of the visit (if ending treatment on or before week 48) or within 
12 weeks of the visit (if ending treatment after week 48). 
[X]:  For subjects who discontinued treatment for any reason other 
than specified in Section 8.3.2, every effort should be made to 
perform scheduled radiographic imaging (CT/MRI) until radiographic 
progression.  
STUDY TREATMENT AND MONITORING 
Tarlatamab Infusionl 
X 
X 
X 
X 
 
 
 
 
 
Monitoring 
post-tarlatamab 
infusion 
 
 
 
 
X 
At subsequent visits, additional monitoring may be recommended 
post-tarlatamab infusion based on occurrence of CRS, ICANS, or 
ICANS-related neurological events.  Refer to Table 6-1.   
Page 3 of 3 
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Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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BICR  Blinded Independent Central Review; C1D1  cycle 1 day 1; C2D1  cycle 2 day 1; CRS  cytokine release syndrome; ECHO  
echocardiogram; ECG  electrocardiogram; ECOG PS  Eastern Cooperative Oncology Group Performance Status; EOI  end of infusion; 
EOT  end of treatment; FT4  free T4; HIV  human immunodeficiency virus; ICANS  immune effector cell-associated neurotoxicity syndrome; 
LDH  Lactate dehydrogenase; LTFU  long-term follow-up; MUGA scan  multigated acquisition scan; PD  progressive disease; 
PK  pharmacokinetic; Q6W  every 6 weeks; Q12W  every 12 weeks; RECIST 1.1 = Response Evaluation Criteria in Solid Tumors Version 1.1; 
SFU  safety follow-up; TSH  thyroid-stimulating hormone.  
a All procedures and assessments on dosing days are to be completed prior to study drug administration unless otherwise indicated.  Assessments 
should not be performed from the infusion line.   
b Cycle 2 and all subsequent visits have a  3-day window, unless otherwise specified. 
c Subjects who permanently discontinue treatment for any reason are encouraged to complete all remaining study visits and procedures through LTFU 
to ensure safety surveillance and/or collection of outcome data.  Upon permanent discontinuation from tarlatamab treatment for any reasons, an EOT 
visit will be performed as soon as possible (within 14 days) after last dose of tarlatamab and prior to start of subsequent anticancer therapy. 
d Safety follow-up visit will occur 60 ( 5) days after the last dose of tarlatamab.  Safety follow-up visits will occur regardless of initiation of subsequent 
anticancer therapy within that period. 
e Assessed every 12 weeks ( 14 days) up to 1 year after the last subject’s last dose of tarlatamab or 5 years from first subject enrolled, whichever 
occurs first.  The study duration for subjects will be approximately up to 24 months, however this duration will be extended as needed to ensure all 
subjects have the opportunity to be followed in LTFU for at least 1 year after the last subject’s last dose of tarlatamab.   
f During LTFU, any serious adverse events suspected to be related to investigational product that the investigator becomes aware of will be reported to 
Amgen immediately and no later than 24 hours of awareness.   
g After end of study, serious adverse events suspected to be related to investigational product will be reported to Amgen.  Please refer to 
Section 8.4.6.4 for additional details. 
h Additional on-treatment pregnancy testing may be performed at the investigator’s discretion if there is suspicion that a female subject is pregnant or 
per local laws and regulations 
i Local labs must be obtained within 48 hours prior to dose on dosing days for tarlatamab.  Laboratory results must be reviewed prior to study drug 
administration.   
j Labs must be obtained within 72 hours prior to dose on dosing days for tarlatamab and must be reviewed by the investigator before each dose.  If 
labs are to be obtained more than 72 hours before the dose, prior approval by the medical monitor is required.  
k Timing is based on first dose of tarlatamab (C1D1). 
l For information on tarlatamab treatment beyond progression, refer to Section 6.1.7.  Subjects who continue on treatment should follow assessments 
as shown in the Schedule of Activities.

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273  
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2. 
Introduction  
2.1 
Study Rationale  
Small cell lung cancer (SCLC) is a grave diagnosis, marked by high initial response 
rates to platinum-based first-line chemotherapy.  However, resistance to subsequent 
treatments quickly emerges, resulting in a median survival of 10 to 12 months 
post-diagnosis (Rudin et al, 2015).  Delta-like ligand 3 (DLL3) is typically intracellular in 
normal tissues but often overexpressed on the cell surface in most SCLC tumors, 
making it an attractive target for T-cell therapies (Saunders et al, 2015).  Notably, 
minimal cytoplasmic staining is observed in the brain, pituitary, and pancreatic islets in 
normal tissues (Study 123377), suggesting the potential for tumor-specific 
DLL3-targeted therapy. 
Tarlatamab (INN; AMG 757) is a novel, extended half-life (HLE) bispecific T-cell engager 
(BiTE) designed to direct T effector cells toward DLL3-expressing cells using a tandem 
single-chain fragment crystallizable (scFc) for prolonged half-life.  In an ongoing phase 2 
study (Study 20200491), tarlatamab has demonstrated efficacy in SCLC patients with a 
manageable safety profile (Ahn et al, 2023). 
Tarlatamab received accelerated approval from the United States Food and Drug 
Administration (FDA) for the treatment of adult patients with extensive-stage 
SCLC with disease progression on or after platinum-based chemotherapy. 
Study 20230273 aims to assess tarlatamab's efficacy, safety, tolerability, and 
pharmacokinetics (PK) in Chinese subjects with advanced SCLC who have progressed 
on or recurred following 1 platinum-based regimen as first-line (1L) therapy (including a 
Programmed Cell Death Protein 1 [PD-1]/Programmed Cell Death Ligand 1 
[PD-1/PD-(L)1]) and at least 1 other prior line of therapy (re-treatment with a 
platinum-based regimen is considered a second-line of therapy).   
A detailed description of the chemistry, pharmacology, efficacy, and safety of tarlatamab 
is provided in the investigator’s brochure. 
2.2 
Background  
2.2.1 
Disease  
Small cell lung cancer accounts for 10 to 15% of lung cancer (Rudin et al, 2015), 
presenting as an aggressive subtype with neuroendocrine differentiation, strongly linked 
to smoking (Koinis et al, 2016).  It exhibits distinct characteristics, including a high 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273  
Date:  06 September 2024 
Page 27 of 137 
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growth rate, rapid doubling time, and early widespread metastasis 
(Gustafsson et al, 2008). 
Approximately 30 of patients have limited disease (LD) confined to one hemithorax, 
while the majority have extensive disease (ED).  Small cell lung cancer is highly 
responsive to first-line chemotherapy (60 to 70 response rates) and radiation, but 
resistance rapidly develops for second-line and subsequent therapies after disease 
recurrence (Byers and Rudin, 2015). 
Patients with ED face drug resistance and typically succumb to the disease within a 
median time of 10 to 12 months from diagnosis (Rudin et al, 2015).  First-line treatment 
for ED-SCLC involves platinum-based chemotherapy, such as platinum etoposide (EP) 
or platinum irinotecan.  Anlotinib is an orally administered tyrosine kinase inhibitor that 
targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor 
receptor (FGFR), platelet-derived growth factor receptors (PDGFR), and c-kit.  It is used 
in China as the current recommended treatment in third or later line treatment in 
advanced SCLC, based on the evidence in ALTER1202.  This study demonstrates a 
significant improvement in median progression-free survival (PFS) and a consistent 
trend in overall survival (OS) (4.0 vs 0.7 months, P  0.0001)/(7.3 vs 4.4 months, 
P  0.006, respectively) compared with placebo (Shi et al, 2020).  However, it shows 
numerically limited improvements in response rate (objective response rate [ORR] of 
4.9).  A median OS of 6.86 months was observed through a real-world study which 
includes 13 studies, involving 779 patients with SCLC (Xu et al, 2023).  There are no 
approved third-line therapies for relapsed ED-SCLC outside of China, and existing 
options offer limited OS benefits, with a median OS of 4.4 months (Coutinho et al, 2019).  
Therefore, there remains a critical medical need for new therapies in third and later-line 
settings. 
2.2.2 
Amgen Investigational Product Background:  Tarlatamab  
BiTE molecules guide T effector memory cells toward target cells, closely mimicking 
cytotoxic T lymphocyte activation.  Tarlatamab, an HLE BiTE, combines binding 
specificities for DLL3 and CD3, genetically fused to the N terminus of the 
immunoglobulin G scFc region.  It is being developed to treat SCLC patients, with its 
activity dependent on binding to both target cells and T cells.  Tarlatamab redirects 
primed cytotoxic CD8 or CD4 T lymphocytes to eliminate DLL3 cells. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273  
Date:  06 September 2024 
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In the phase 1 first in human study (Study 20160323) evaluating the safety, 
tolerability, and antitumor activity of tarlatamab in SCLC, the available data 
demonstrate that tarlatamab shows a manageable safety profile and signs of 
preliminary efficacy.   
The pivotal phase 2 study of tarlatamab in patients with relapsed SCLC after 
2 lines of prior therapy has confirmed efficacy and benefit/risk ratio 
(Study 20200491; Ahn et al, 2023).  Based on a pre-specified interim analysis in 
part 1 of the phase 2 Study 20200491, the regimen using a 10 mg target dose Q2W 
with a 1 mg step-dose was selected as the monotherapy recommended phase 2 
dose regimen to balance the efficacy/safety of tarlatamab and to be further 
evaluated in part 2 and part 3 of the phase 2 Study 20200491, and any subsequent 
studies for tarlatamab.  The primary analysis for the phase 2 Study 20200491 
reinforced the selection of 10 mg target dose for tarlatamab studies. 
Tarlatamab received accelerated approval from the United States FDA for the 
treatment of adult patients with extensive-stage SCLC with disease progression 
on or after platinum-based chemotherapy; please refer to the United States 
Prescribing Information. 
A detailed description of the chemistry, pharmacology, efficacy, and safety of tarlatamab 
is provided in the investigator’s brochure.  
2.2.3 
Non-Amgen Investigational Product Background  
No non-Amgen investigational products will be used in this study. 
2.3 
Benefit/Risk Assessment  
Delta-like ligand 3 is a promising T-cell therapy target is highly expressed in SCLC and 
other neuroendocrine tumors but minimally expressed in normal tissues.  Tarlatamab 
demonstrated potent T-cell recruitment against DLL3-expressing SCLC cells in vitro and 
effectively suppressed tumor growth in systemically treated mice.  Tarlatamab is 
expected to offer deeper and more durable responses compared to current and 
emerging treatments for SCLC. 
As of 27 June 2023 (Study 20200491), among patients evaluated for antitumor activity 
and survival, the median follow-up was 10.6 months in the 10 mg group.  An objective 
response occurred in 40% (97.5% CI, 29 to 52) of the patients.  Among patients with an 
objective response, the duration of response was at least 6 months in 59% (40 of 
68 patients).  Objective responses at the time of data cutoff were ongoing in 22 of 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273  
Date:  06 September 2024 
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40 patients (55%) and the median progression-free survival was 4.9 months (95% CI, 
2.9 to 6.7); the estimates of OS at 9 months were 68% (Ahn et al, 2023). 
Key Safety Information 
Based on tarlatamab's ongoing clinical study experience, the key safety information 
includes the adverse drug reactions of cytokine release syndrome (CRS), immune 
effector cell-associated neurotoxicity syndrome (ICANS), and neutropenia.  Additionally, 
potential safety issues includes pituitary dysfunction, other neurological events, and 
tumor lysis syndrome (TLS) which stem from Tarlatamab’s mechanism of action and 
experience with BiTE molecules.  For complete details, consult the investigator’s 
brochure. 
A comprehensive safety strategy, focusing on CRS, ICANS, neutropenia, other 
neurological toxicities, pituitary dysfunction, and TLS will be implemented in this study.  
This includes prevention, continuous monitoring, early recognition, and prompt 
management.  See Section 6.2.2 and Table 6-2 for detailed management 
recommendations of the key adverse drug reactions and potential safety concerns 
of tarlatamab. 
The above benefit-risk assessment supports the conduct of this clinical study.   
For additional details on the safety risks, refer to the investigator’s brochure. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273  
Date:  06 September 2024 
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3. 
Objective(s) and Endpoint(s)/Estimand(s)  
 
Objectives 
Endpoints 
Primary 
 
Evaluate efficacy of tarlatamab as 
assessed by objective response rate 
(ORR) based on blinded independent 
central review (BICR) per Response 
Evaluation Criteria in Solid Tumors 
version 1.1 (RECIST 1.1) 
 
ORR BICR, defined as proportion with 
best overall response (BOR) of 
complete response (CR) plus partial 
response (PR) 
 
Secondary 
 
Evaluate efficacy of Tarlatamab as 
assessed by duration of response 
(DOR), disease control (DC), and 
progression-free survival (PFS) based 
on BICR per RECIST 1.1 
 
DOR, defined as time from the first 
documentation of objective response 
(OR) until the first documentation of 
disease progression or death due to 
any cause, whichever occurs first.  
Only subjects who have achieved OR 
will be evaluated for DOR  
 
DC, defined as CR + PR + stable 
disease (SD) 
 
Duration of DC, defined as time from 
the first documentation of CR, PR, or 
SD until the first documentation of 
disease progression or death due to 
any cause, whichever occurs first.  
Only subjects who have achieved CR, 
PR, or SD will be evaluated for 
Duration of DC 
 
PFS, defined as time from enrollment 
until disease progression or death 
from any cause, whichever occurs 
first.  Progression will be based on 
RECIST 1.1. 
 
Evaluate efficacy of Tarlatamab as 
assessed by ORR, DOR, DC, and 
PFS based on investigator 
assessment per RECIST 1.1 
 
ORR (Investigator) 
 
DOR  
 
DC 
 
Duration of DC 
 
PFS 
 
Evaluate efficacy of Tarlatamab as 
assessed by overall survival (OS) 
 
OS, defined as time from enrollment 
until death from any cause 
 
Evaluate safety and tolerability 
 
Incidence of treatment-emergent 
adverse events  
 
Characterize the pharmacokinetics of 
tarlatamab 
 
Serum concentration of tarlatamab  

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273  
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 
Evaluate the immunogenicity of 
tarlatamab 
 
Incidence of anti-tarlatamab antibody 
formation 
Estimand(s) for Primary Objective(s) 
Objective response rate (ORR) by blinded independent central review (BICR) per 
RECIST 1.1 in Chinese subjects with advanced SCLC who have progressed on or 
recurred following 1 platinum-based regimen as 1L therapy (including a PD-1/ PD [L]1) 
and at least 1 other prior line of therapy (re treatment with a platinum-based regimen is 
considered a second line of therapy) prior to start of new cancer therapy 
(while-on-treatment strategy). 
4. 
Study Design  
4.1 
Overall Design  
This is a phase 2a, multicenter, single arm, open-label study in Chinese subjects with 
advanced SCLC who have progressed on or recurred following 1 platinum-based 
regimen as 1L therapy (including a PD-1/PD-[L]1) and at least 1 other prior line of 
therapy (re-treatment with a platinum-based regimen is considered a second-line of 
therapy).   
Approximately 30 Chinese subjects are planned to be enrolled in the study.  
The study consists of a 21-day screening period, a treatment period, a safety follow-up 
(SFU) period, and a long-term follow-up (LTFU) period. 
Study treatment will be administered as follows: 
 
Tarlatamab will be administered as a 60-minute ( 10 minutes) intravenous (IV) 
infusion with 1 mg step dose on cycle 1 day 1 (C1D1) followed by a 10 mg target 
dose on cycle 1 day 8 (C1D8), and cycle 1 day 15 (C1D15) in a 28-day cycle.  
Subsequent doses (10 mg) will be administered every 2 weeks (Q2W) (ie, cycle 2 
day 1/day 15 dosing) in a 28-day cycle. 
 
Monitoring during cycle 1: 
o Monitoring – cycle 1:  Monitoring required for 6 to 8 hours post-infusion at C1D1 
and C1D8.   
- Cohabitant (caregiver) support for 24 hours post-infusion and the ability to 
stay within 1 hour of a hospital for 24 hours is required.   
- Counseling the subject and caregiver on signs and symptoms of CRS, 
and ICANS by a health care provider is required prior to discharge.   
- Subjects return to site on cycle 1 day 2 (C1D2) and cycle 1 day 9 (C1D9) 
for vital signs and physical examination.  
- At subsequent visits, additional monitoring may be required post-infusion.  
Refer to Section 6.1.1 (Table 6-1).   
 
Pre- and Post-infusion medication requirements: 

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o Dexamethasone:  8 mg IV (or equivalent dose of other corticosteroids) will be 
administered within 1 hour prior to tarlatamab infusion on C1D1 and C1D8. 
o Intravenous Hydration:  1 L normal saline over 2 to 4 hours following tarlatamab 
administration on C1D1 and C1D8. 
Subjects will receive study treatment until BICR-confirmed disease progression per 
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1), death, 
withdrawal of consent, start of new anticancer therapy, unacceptable toxicity, or end of 
study as determined by the sponsor (whichever occurs first).  Following documented 
radiographic progression, the subject may remain on study treatment provided criteria 
are met.  Refer to Section 6.1.7.  Any subsequent (investigator determined) progressive 
disease per RECIST 1.1 from a new baseline set at initial progression will result in 
permanent discontinuation of study treatment. 
The site principal investigator will make final treatment and subject management 
decisions.  Subjects who discontinue study treatment for reasons other than 
BICR-confirmed disease progression will continue to have tumor assessments (if 
clinically feasible) until disease progression is confirmed by BICR. 
A SFU visit will occur 60 (5) days after the last dose of tarlatamab regardless of 
initiation of subsequent anticancer therapy within that period.  After the SFU visit, 
subjects will be followed in LTFU for survival every 12 weeks ( 14 days) for up to 1 year 
after the last subject’s last dose of tarlatamab or 5 years from first subject enrolled, 
whichever is first. 
The overall study design is described by a study schema in Section 1.2.  The endpoints 
are defined in Section 3. 
Participants in this clinical investigation shall be referred to as “subjects”.  For the 
sample size justification, see Section 9.2. 
4.2 
Patient Input into the Study Design  
Patient input was not obtained for this study. 
4.3 
Justification for Dose  
4.3.1 
Justification for Investigational Product Dose  
The study will evaluate tarlatamab at a 10 mg target dose on a Q2W regimen which is 
the recommended Phase 2 dose of tarlatamab and for all ongoing studies and is an 
approved regimen in the United States, under an accelerated approval by the FDA.  
To mitigate CRS risk, treatment will begin with a 1 mg step dose on C1D1, followed by 
the 10 mg target dose on C1D8, C1D15, and Q2W thereafter, each infusion 

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administered over 60 minutes.  This regimen was selected based on data from the first-
in-human Study 20160323, which explored a target dose range of 0.003 to 100 mg on a 
Q2W regimen in SCLC patients, as well as findings from the ongoing phase 2 
Study 20200491, which evaluated active dose levels of 10 and 100 mg on a Q2W 
schedule using a 1 mg step dose.  
The planned dosing regimen of 10 mg Q2W exhibited near maximal efficacy and 
favorable benefit-risk profile in SCLC patient population (Ahn et al, 2023; 
Paz-Ares et al, 2023). 
For the latest efficacy and safety data from ongoing studies, please refer to the 
investigator’s brochure.   
4.4 
Justification for Monitoring 
Safety data from clinical Study 20200491 has confirmed that the most common adverse 
event with tarlatamab is CRS (Ahn et al, 2023).  Cytokine release syndrome most 
frequently occurs after the first two infusions of tarlatamab (cycle 1 day 1 and cycle 1 
day 8), is mostly grade 1 to 2 in nature and rarely develops rapidly.  The subject 
incidence of CRS at the 10 mg dose in Study 20200491 was 30.1 (40/133) grade 1, 
20.3 (27/133) grade 2 and 0.8 (1/133) grade 3.  There were no grade 4 or 5 CRS 
events in this study.  This profile enables 6 to 8 hours monitoring following the first two 
tarlatamab doses (cycle 1 day 1 and day 8) and leveraging additional risk mitigation 
measures:  mandatory counseling on signs and symptoms of CRS at time of discharge, 
a cohabitant for first 24 hours after cycle 1 day 1 and day 8 infusions, and remaining 
within 1 hour of an appropriate healthcare setting after cycle 1 day 1 and day 8 infusions.  
Importantly, patients will return to study sites on the day following these infusions for 
clinical evaluation (ie, cycle 1 day 2 and cycle 1 day 9).  Additional detailed guidance for 
CRS monitoring and mitigation during and following these treatment visits is outlined in 
protocol Schedule of Activities (Section 1.3) and Section 6.1.   
4.5 
End of Study  
Individual subject study completion is determined by completing the last visit in the 
Schedule of Activities (See Section 1.3).  The study duration for each subject includes 
up to 21 days for screening, followed by a variable treatment period, and there is a SFU 
of 60 ( 5) days after the last tarlatamab dose, and a LTFU that spans up to 1 year after 
the last subject’s last dose of tarlatamab or 5 years from first subject enrolled, whichever 
is first.  The study duration for subjects will be approximately up to 24 months, 
however, this duration will be extended as needed to ensure all subjects have the 

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opportunity to be followed in LTFU for at least 1 year after the last subject’s last 
dose of tarlatamab. 
5. 
Study Population  
Investigators will be expected to maintain a screening log to record details of all subjects 
screened that includes limited information about the screened subject (eg, date of 
screening).  This log may be completed and updated via an Interactive Response 
Technology (IRT). 
Eligibility criteria will be evaluated during screening. 
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 the following criteria apply: 
101 
Subject has provided informed consent prior to initiation of any study specific 
activities/procedures. 
102 
 Subjects must be a resident in China, and of Chinese ancestry  18 years of age 
(or legal adult age within country) at the time of signing the informed consent. 
103 
 Histologically or cytologically confirmed SCLC.  
104 
 Extensive-stage SCLC subjects who progressed on or recurred following 1 
platinum-based regimen as 1L therapy (including a PD-1/ PD-[L]1) and at least 
1 other prior line of therapy. 
Note:  (1) re-treatment with a platinum-based regimen is considered a 
second-line of therapy; (2) platinum-based regimen followed by checkpoint 
inhibitor/anti-PD-L1 as maintenance therapy is considered 1 line of therapy. 
105 
 Measurable lesions as defined per RECIST 1.1 within 21 days prior to the first 
dose of tarlatamab. 
 
Screening scans performed as standard of care (SOC) and prior to informed 
consent, may be used to confirm subject eligibility if completed within the 
21-day screening period, provided that informed consent for the use of 
these scans is obtained prior to any transfer of data. 

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106 
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.  
107 
 Minimum life expectancy of 12 weeks. 
108 
Adequate organ function, defined as follows: 
 
hematological function: 
- absolute neutrophil count  1 x 109/L 
- platelet count  100 x 109/L 
- hemoglobin > 9 g/dL (90 g/L) 
 
coagulation function: 
- prothrombin time (PT)/international normalized ratio (INR) and partial 
thromboplastin time (PTT) or activated partial thromboplastin time (APTT) 
 1.5 x institutional upper limit of normal (ULN) except for subjects 
undergoing new class anticoagulant therapy (eg, Edoxaban), stable dose 
for 2 weeks required.  Subjects on chronic anticoagulation therapy who 
do not meet the criteria above may be eligible to enroll after discussion 
with the medical monitor. 
 
renal function: 
- estimated glomerular filtration rate (eGFR) based on Modification of Diet 
in Renal Disease (MDRD) calculation > 30 mL/min/1.73 m2 
 
hepatic function: 
- aspartate aminotransferase (AST), alanine aminotransferase (ALT), and 
alkaline phosphatase (ALP) < 3 x ULN (or < 5 x ULN for subjects with 
liver involvement) 
- total bilirubin < 1.5 x ULN (or < 2 x ULN for subjects with liver 
metastases) 
 
pulmonary function: 
- no clinically significant pleural effusion.  Pleural effusion managed with 
indwelling pleural catheter (eg, PleurX) are allowed 
- baseline oxygen saturation > 90% on room air 
 
cardiac function: 
- cardiac ejection fraction  50%, no clinically significant pericardial effusion 
as determined by an echocardiogram (ECHO) or multigated acquisition 
(MUGA) scan, and no clinically significant electrocardiogram (ECG) 
findings 
5.2 
Exclusion Criteria  
Subjects are excluded from the study if any of the following criteria apply: 
Disease Related 
201 
Any previous diagnosis of transformed non-small cell lung cancer (NSCLC), 
epidermal growth factor receptor (EGFR) activating mutation positive NSCLC that 
has transformed to SCLC. 
 
Subjects with mixed histology tumors with predominant SCLC histology are 
allowed. 

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202 
Symptomatic CNS metastases: 
 
Subjects with treated brain metastases are eligible provided the following 
criteria are met: 
 
Subject with untreated brain metastasis that are asymptomatic and do not 
require corticosteroids, nor local therapy per investigators standard of 
practice are allowed 
203 
Diagnosis or evidence of leptomeningeal disease. 
204 
Prior history of immune checkpoint inhibitors resulting in: 
 
Any severe or life-threatening immune-mediated adverse event 
 
History of immune-mediated encephalitis or other immune-mediated CNS 
event (any grade) 
 
Grade ≥ 2 immune-mediated recurrent pneumonitis 
 
Infusion-related reactions leading to permanent discontinuation of 
immunotherapy agent 
Exception:  Subjects with a history of immune checkpoint inhibitor-induced 
endocrinopathy which is clinically stable on replacement therapy. 
Other Medical Conditions 
205 
Active autoimmune disease that has required systemic treatment (except 
replacement therapy) within the past 2 years or any other diseases requiring 
immunosuppressive therapy while on study. 
206 
History of solid organ transplantation. 
207 
Evidence of interstitial lung disease or active, non-infectious pneumonitis. 
208 
History of other malignancy within the past 2 years, with the following exceptions: 

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 
malignancy treated with curative intent and with no known active disease 
present for  1 year before enrollment and believed to be at low risk for 
recurrence by the treating physician 
 
adequately treated non-melanoma skin cancer or lentigo maligna without 
evidence of disease 
 
adequately treated cervical carcinoma in situ without evidence of disease 
 
adequately treated breast ductal carcinoma in situ without evidence of 
disease 
 
prostatic intraepithelial neoplasia without evidence of prostate cancer 
 
adequately treated urothelial papillary noninvasive carcinoma or carcinoma in 
situ 
209 
Myocardial infarction and/or symptomatic congestive heart failure (New York 
Heart Association > class II) within 12 months of first dose of tarlatamab 
(Section 11.9). 
210 
History of arterial thrombosis (eg, stroke or transient ischemic attack) within 
12 months of first dose of tarlatamab. 
211 
Subject with symptoms and/or clinical signs and/or radiographic signs that 
indicate an acute and/or uncontrolled active systemic infection within 7 days prior 
to the first dose of tarlatamab.   
 
Subject has known active infection requiring parenteral antibiotic treatment.  
Upon completion of parenteral antibiotics and resolution of symptoms, the 
subject may be considered eligible for the study from an infection standpoint. 
NOTE:  Simple urinary tract infection and uncomplicated bacterial pharyngitis are 
permitted if responding to active treatment.  Subjects requiring oral antibiotics 
who have been afebrile for  24 hours, have no leukocytosis, nor clinical signs of 
infection are eligible.  Screening for chronic infectious conditions are not required 
unless otherwise noted as exclusion criteria.  
212 
HIV, Hepatitis B, and Hepatitis C. 
Human immunodeficiency virus (HIV) infection  
 
Subjects with HIV infection on antiviral therapy and undetectable viral load 
are permitted with a requirement for regular monitoring for reactivation for the 
duration of treatment on study per local or institutional guidelines. 
Active hepatitis C infection (subjects with detectable hepatitis C antibody [HCV 
Ab] and HCV RNA viral load above the limit of quantification). 
 
Subjects with presence of HCV antibody [HCV Ab positive] and HCV RNA 
viral load below the limit of quantification [HCV RNA negative] with or without 
prior treatment are allowed.  
Active hepatitis B infection (presence of hepatitis B surface antigen 
[HBsAg-positive] and HBV DNA viral load above the limit of quantification [HBV 
DNA positive]). 
 
Subjects with resolved hepatitis B virus (HBV) infection, defined as absence 
of HBV surface antigen [HBsAg-negative] and presence of HBV core 
antibody [anti-HBc positive] followed by an HBV DNA viral load below the 
limit of quantification [HBV DNA negative], are allowed with a requirement for 

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regular monitoring for reactivation for the duration of treatment on the study 
and assessing the need for HBV prophylaxis therapy per local or institutional 
guidelines.  
Subjects with chronic hepatitis B virus (HBV) infection inactive carrier state, 
defined as presence of HBV surface antigen [HBsAg-positive] and HBV DNA 
viral load below the limit of quantification [HBV DNA negative], are allowed 
with a requirement for regular monitoring for reactivation for the duration of 
treatment on the study and assessing the need for HBV prophylaxis therapy 
per local or institutional guidelines.   
213 
Major surgery within 28 days of first dose tarlatamab. 
Prior/Concomitant Therapy 
214 
Currently or previously enrolled in a tarlatamab study. 
215 
Prior therapy with any selective inhibitor of the DLL3 pathway. 
216 
Prior anti-cancer therapy within 21 days prior to first dose of study treatment. 
Exceptions: 
 
Subjects who received conventional chemotherapy are eligible if at least 
14 days have elapsed and if all treatment-related toxicity has been resolved 
to grade  1 or to levels dictated in the eligibility criteria, before first dose of 
study treatment, with the exception of alopecia or toxicities considered 
irreversible (defined as having been present and stable for  30 days) which 
are not otherwise described in the exclusion criteria. 
 
Prior palliative radiotherapy must have been completed at least 7 days before 
the first dose of tarlatamab. 
217 
Receiving systemic steroid therapy or any other form of immunosuppressive 
therapy within 7 days prior to the first dose of tarlatamab. 
 
Prophylactic dexamethasone required by the protocol and any anti-emetic 
therapies are allowed 
 
Low-dose corticosteroids (prednisone  10 mg per day or equivalent is 
permitted during the trial) 
218 
Treatment with live virus, including live-attenuated vaccination, within 14 days 
prior to the first dose of tarlatamab.  Inactive vaccines (eg, non-live or 
non-replicating agent) and live viral non-replicating vaccines (eg, Jynneos for 
mpox infection) within 3 days prior to first dose of tarlatamab. 
Prior/Concurrent Clinical Study Experience 
219 
Currently receiving treatment in another investigational device or drug study, or 
less than 30 days since ending treatment on another investigational device or 
drug study(ies).  Other investigational procedures while participating in this study 
are excluded. 
Other Exclusions 
220 
Female subjects of childbearing potential unwilling to use protocol-specified 
method of contraception (see Section 11.5) during treatment and for an 
additional 60 days after the last dose of tarlatamab. 

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221 
Female subjects who are breastfeeding or who plan to breastfeed while on study 
through 60 days after the last dose of tarlatamab. 
222 
Female subjects planning to become pregnant or donate eggs while on study 
through 60 days after the last dose of tarlatamab. 
223 
Female subjects of childbearing potential with a positive pregnancy test 
assessed at screening by a highly sensitive serum pregnancy test. 
224 
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 60 days after the last dose 
of tarlatamab.  Refer to Section 11.5 for additional contraceptive information.  
225 
Male subjects with a pregnant partner who are unwilling to practice abstinence or 
use a condom during treatment and for an additional 60 days after the last dose 
of tarlatamab. 
226 
Male subjects unwilling to abstain from donating sperm during treatment and for 
an additional 60 days after the last dose of tarlatamab. 
227 
Subject has known sensitivity to any of the products or components to be 
administered during dosing. 
228 
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. 
229 
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 medical monitor if consulted, would pose a risk to subject safety or 
interfere with the study evaluation, procedures, or completion.  
5.3 
Lifestyle Considerations  
No lifestyle considerations are applicable to the conduct of this study. 
5.4 
Subject Enrollment  
Before subjects begin participation in any study-specific activities/procedures, Amgen 
requires a copy of the site’s written external review bodies (eg, the institutional review 
board [IRB]/independent ethics committee[IEC]/regulatory authorities) approval of the 
protocol, informed consent form (ICF), and all other subject information and/or 
recruitment material, if applicable (see Section 11.3). 
The subject or the subject’s legally authorized representative and the investigator or 
authorized delegate must personally sign and date the external review body informed 
consent before commencement of study-specific procedures. 
Each subject who enters the screening period for the study (defined as the point at 
which 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 using IRT.  This number will be used to identify the 

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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.   
Subjects are eligible to be enrolled in the study when the investigator confirms that the 
subject has met all eligibility criteria.  Subjects are considered enrolled at the time of first 
dose of investigational product administration.  The investigator is to document 
enrollment decision and date, in the subject’s medical record and in/on the Subject 
Enrollment Case Report Form (CRF) via IRT. 
Sites that do not enroll subjects within 6 months of site activation may be closed. 
5.5 
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) may 
be rescreened.  Refer to Section 8.1.1. 
6. 
Study Intervention  
Study intervention is defined as any investigational product(s), noninvestigational 
product(s)/auxiliary medicinal product(s), or medical device(s) intended to be 
administered to a study subject according to the study protocol. 
Note that according to local regulations in some countries, investigational product(s) 
described in Section 6.1.1 are referred to as investigational medicinal product(s) and 
noninvestigational product(s)/auxiliary medicinal product(s) described in Section 6.1.2 
are referred to as noninvestigational medicinal product(s). 
A summary of the dosing and administration of each treatment is shown in Table 6-1 
below. 
6.1 
Study Interventions Administered  
6.1.1 
Investigational Products  

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Table 6-1.  Investigational Products  
Study Treatment Name 
Amgen Investigational Product:a 
Tarlatamab (AMG 757) 
Dosage Formulation 
Tarlatamab is supplied as a sterile, single-use, preservative-free lyophilized drug 
product containing 1 or 10 mg of tarlatamab per vial.  Tarlatamab is intended for 
reconstitution with sterile water for injection and dilution in an IV bag with normal 
saline (0.9% sodium chloride) and an IV solution stabilizer.  The drug product is 
formulated with L-glutamic acid, sucrose, polysorbate 80, pH 4.2.  
 
 
Dosage Level(s) 
1 mg step dose on C1D1 
10 mg target dose starting C1D8, C1D15, and Q2W thereafter 
 
 
Route of Administration 
IV infusion 
 
 
Accountability 
Product administration information is to be recorded on each subject's eCRF(s). 
 
 
Dosing Instructions 
Tarlatamab will be administered as an IV infusion for 60 minutes (± 10 minutes) 
followed by a slow bolus flush.  Investigational products will be administered at 
the study center by a qualified staff member.  A physician must be available at 
the time of administration of investigational products.  
 
 
Page 1 of 2 
Footnotes defined on last page of this table. 

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Table 6-1.  Investigational Products  
Monitoring Guidance 
 
Cycle 1 Day 1 and Cycle 1 Day 8: 
o 
Subject will remain at study site for 6 to 8 hours post-infusion at C1D1 and C1D8.  Cohabitant (caregiver) 
support for 24 hours post-infusion and the ability to stay within 1 hour of a hospital for 24 hours is 
required. 
o 
Subjects may be discharged after the required monitoring period if there are no signs and symptoms of 
CRS, ICANS, or other acute toxicities according to the discretion of the treating physician.  Counseling 
the subject and caregiver on the signs and symptoms of CRS and ICANS by a healthcare provider is 
required prior to discharge.   
 
Subjects return to site on cycle 1 day 2 and cycle 1 and day 9 for vital signs and physical examination.   
 
Monitoring for subsequent treatment visits is at the discretion of the investigator if asymptomatic and clinically 
stable.  Consider monitoring if the subject experiences a grade  2 CRS, any grade ICANS, or any grade 
ICANS-related neurologicb adverse events at the immediate prior treatment (ie, following the dose given at 
the prior visit). 
- 
Refer to the C1D1 requirements above.   
In the event of an extended study treatment interruption (see Table 6-3), subjects are required to be monitored 
according to cycle 1 monitoring guidance.   
Page 2 of 2 
C1D1  cycle 1 day 1; C1D8  cycle 1 day 8; C1D15  cycle 1 day 15; CRS  cytokine release syndrome; eCRF  electronic case report form; 
ICANS  immune effector cell-associated neurotoxicity syndrome; IV = intravenous; Q2W = every 2 weeks 
a Tarlatamab will be manufactured and packaged by Amgen and distributed using Amgen clinical study drug distribution procedures. 
b ICANS-related neurologic adverse events per discretion of investigator, which may include, but are not limited to confusion, delirium, encephalopathy, apraxia, ataxia, 
neurotoxicity, seizure, tremor, dysgraphia, expressive aphasia, depressed level of consciousness, or impaired attention. 

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6.1.2 
Noninvestigational Products/Auxiliary Medicinal Products  
After the occurrence of an event that, in the opinion of the investigator, warrants other 
treatment, supportive care should be provided including, but not limited to, the guidance 
in Table 6-2 for Dose Modification Guidelines for Adverse Events. 
6.1.2.1 
Pre- and Post-infusion Medications  
Dexamethasone 
Dexamethasone 8 mg IV (or equivalent dose of other corticosteroids) will be 
administered within 1 hour prior to tarlatamab infusion on C1D1 and C1D8. 
IV Hydration 
Intravenous hydration (1 L normal saline) over 2 to 4 hours following tarlatamab 
administration on C1D1 and C1D8.   
6.1.2.2 
Cytokine Release Syndrome Rescue Medication  
All sites will ensure that CRS rescue medications are available on-site, including 
corticosteroids and sites are required to have tocilizumab or siltuximab (if tocilizumab is 
not available) on site for potential treatment of CRS. 
6.1.3 
Medical Devices  
Non-investigational medical devices may be used in the conduct of this study as part of 
standard care. 
Non-Amgen noninvestigational 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 Intervention Procedures  
There are no other intervention procedures in this study.  
6.1.5 
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, combination product, 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. 

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This includes any investigational product and/or other non-investigational 
product(s)/auxiliary medicinal product(s)provisioned and/or repackaged/modified by 
Amgen: 
 
tarlatamab 
Any product complaint(s) associated with an investigational product and/or 
noninvestigational product(s)/auxiliary medicinal product(s) supplied by Amgen are to be 
reported. 
6.1.6 
Excluded Treatments, Medical Devices, and/or Procedures During 
Study Period  
The following treatments and/or procedures are excluded within the timeframes specified 
during the study: 
 
Other investigational agents, devices (other than those specified in the protocol) and 
procedures are prohibited while on study treatment. 
 
Anticancer therapies other than those specified in the protocol are prohibited while 
on study treatment. 
 
Radiation therapy 
- Exception:  Radiation therapy for symptom control (eg, bone metastasis) or brain 
metastasis treatment may be allowed after discussion with the medical monitor.  
The radiation therapy should not include the thoracic field and must have been 
completed at least 7 days before the subsequent dose of tarlatamab. 
 
Immunosuppressive agents with the exception of those required by protocol, 
treatment for adverse events, CNS metastases, corticosteroid replacement therapy, 
or unless agreed upon by the investigator and medical monitor. 
 
During tarlatamab treatment:  Live and live-attenuated vaccines are prohibited for the 
duration of tarlatamab treatment. 
- Live viral non-replicating vaccine (eg, Jynneos for mpox infection) is allowed 
when administered  3 days before or  3 days after a tarlatamab infusion. 
- Seasonal influenza vaccines for injection are generally killed virus vaccines and 
are allowed when administered  3 days before or  3 days after a tarlatamab 
infusion.  However, intranasal influenza vaccines (eg, Flu - Mist) are 
live-attenuated vaccines, and are not allowed at any time during tarlatamab 
treatment. 
- Vaccinations for coronavirus disease 2019 ([COVID-19], severe acute respiratory 
syndrome coronavirus 2 [SARS-CoV-2] vaccination) are generally not live or 
live-attenuated and are allowed when administered  3 days before or  3 days 
after a tarlatamab infusion. 
- After completion of tarlatamab treatment:  live and live-attenuated vaccines are 
prohibited for a further 60 (5) days after the last dose of tarlatamab. 
 
Subjects must not schedule any major elective surgery during the treatment period 
and for at least 30 days after the last administration of study treatment.  If a subject 
undergoes any unexpected surgery during the course of the study, all study 

Product:  Tarlatamab (AMG 757)  
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Date:  06 September 2024 
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treatments must be withheld, and the investigator or designee should notify the 
sponsor’s medical monitor as soon as possible.  A subject may be allowed to resume 
study drugs if both the investigator and sponsor’s medical monitor agree to restart 
study therapy. 
6.1.7 
Continuation on Investigational Product Treatment After First 
Radiologic Disease Progression  
This section details the conditions necessary to allow continued study treatment after 
first disease progression in subjects that, in the investigator’s judgment, continue to have 
clinical benefit.  All of the following criteria must be met: 
 
Subject continues to have clinical benefit per the investigator’s judgment. 
 
Subject has stable ECOG PS. 
 
Absence of threat to vital organs or critical anatomical sites (eg, respiratory 
failure due to tumor compression, spinal cord compression) requiring urgent 
alternative medical intervention with persistent immediate threat to vital organs 
after intervention.  The presence of brain metastases is allowed provided the 
lesions are amenable to radiation therapy or dexamethasone (or corticosteroid 
equivalent), and the subject is clinically stable in the investigator’s judgment. 
 
Subject continues to tolerate study drug. 
 
No other treatment discontinuation criteria are met (Table 6-2 and 
Section 11.7.1). 
 
No significant, unacceptable, or irreversible toxicities related to any dose of the 
study treatment or treatment-related adverse events of Common Terminology 
Criteria for Adverse Events (CTCAE) grade 3 at the current dose at the time of 
progression. 
 
Radiation therapy is permitted after discussion with the medical monitor.  
Palliative radiation and/or surgery for new, progressive, or symptomatic lesions is 
permitted.  Study treatment must be held during either treatment (radiation and/or 
surgery) and the treatment must be completed at least 7 days before the 
subsequent dose of study treatment. 
Subjects should continue to perform all protocol-required procedures as noted in the 
Schedule of Activities (Section 1.3; imaging, labs, and clinic visits). 
Any subsequent (investigator determined) progressive disease per RECIST 1.1 from a 
new baseline set at initial progression will result in permanent discontinuation of study 
treatment. 
6.2 
Dose Modification  
6.2.1 
Dose-group Study Escalation/De-escalation and Stopping Rules  
Not applicable. 

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6.2.2 
Dosage Adjustments, Delays, Rules for Withholding or Restarting, 
Permanent Discontinuation  
6.2.2.1 
Amgen Investigational Product:  Tarlatamab  
The reason for dose change of tarlatamab is to be recorded on each subject’s CRF(s). 
Tarlatamab will be discontinued or temporarily delayed in the event of a toxicity that, in 
the opinion of the investigator, warrants the discontinuation or dose delay.  For treatment 
interruptions, delays, and discontinuations, refer to tarlatamab guidance in Table 6-2.   

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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events 
Grade 
Description of 
Severity 
Interruption/Delay 
Specific Management 
Restart guidance 
Permanent Discontinuation 
Neurologic Events 
1 
Reference 
Section 11.11.2 
for grading and 
management 
guidelines 
No additional 
guidance  
Follow institutional guidelines for management and per 
local practice: 
 Consider diagnostic workup for alternate diagnosisa 
 Supportive Care 
No additional 
guidance 
No additional guidance 
2 
No additional 
guidance 
Follow institutional guidelines for management and 
administer corticosteroids per local practice: 
 Consider diagnostic workup for alternate diagnosisa 
Reference dose of corticosteroids for grade 2 ICANSa: 
 Dexamethasone 8 mg to 10 mg IV every 12 hours or 
methylprednisolone equivalent.  Once ICANS 
improves to grade 1 or less, taper and/or stop 
corticosteroids depending on clinical situation 
No additional 
guidance 
No additional guidance 
3 
Delay tarlatamab 
until the event 
improves to 
grade  1  
Follow institutional guidelines for management and 
administer corticosteroids per local practice: 
 Consider diagnostic workup for alternate diagnosisa 
 Consider ICU transfer 
Reference dose of corticosteroids for grade 3 ICANSa: 
 Dexamethasone 10 mg IV every 6 hours or 
methylprednisolone equivalent (1 mg/kg IV every 
12 hours).  Once ICANS improves to grade 1 or less, 
taper and/or stop corticosteroids depending on clinical 
situation 
Resume 
tarlatamab no less 
than 72 hours 
after the initial 
observation of the 
grade 3 adverse 
event 
 
Initial grade 3 neurologic 
event does not improve 
to grade  1 within 
7 days, OR 
 
Grade 3 neurologic event 
reoccurs within 7 days of 
resuming tarlatamab 
Page 1 of 12 
Abbreviations and footnotes defined on last page of table. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
 
Grade 
Description of 
Severity 
Interruption/Delay 
Specific Management 
Restart guidance 
Permanent Discontinuation 
Neurologic Events (continued) 
4 
Reference 
Section 11.11.2 
for grading and 
management 
guidelines 
Immediately stop 
any ongoing 
infusion 
Follow institutional guidelines for management and 
administer corticosteroids per local practice: 
 Consider diagnostic workup for alternate diagnosisa 
 Transfer to ICU 
Reference dose of corticosteroids for grade 4 ICANSa: 
 Methylprednisolone 1000 mg/day in divided doses IV 
for 3 days followed by taper as clinically indicated.  
Consider additional therapies per guidelines 
Permanently 
discontinue 
Permanently discontinue 
Seizure 
Delay tarlatamab 
until the event 
improves to 
grade  1 
Administration of corticosteroids and anti-seizure 
medication is permissible based on investigator 
judgment and local practice. 
Do not resume 
tarlatamab until 
7 days after the 
last seizure and 
after therapeutic 
levels of 
anti-seizure 
medication are 
likely to have 
been achieved. 
If a second seizure occurs 
after resuming tarlatamab 
Page 2 of 12 
Abbreviations and footnotes defined on last page of table. 

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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Description of 
Severityb 
Interruption/Delay Specific Management 
Restart guidance 
Permanent 
Discontinuation 
Cytokine Release Syndrome (see Section 11.11.1 for additional guidance and grading scale details) 
1 
Symptoms are not 
life-threatening and 
require 
symptomatic 
treatment only 
 Feverc:   38C 
 Hypotension:  
none 
 Hypoxia:  none 
No action required Administer: 
 Symptomatic treatment (eg, paracetamol/acetaminophen) for fever 
 Consider a single dose of dexamethasone (or equivalent) ranging from 
4 mg to 10 mg 
Monitor: 
 CRS symptoms including temperature, blood pressure, and pulse 
oximetry 
 Fluid status, maintain IVF as needed 
 Consider chest X-ray and obtaining appropriate cultures to rule out 
infection 
For subjects with rapid onset ( 4 hours from start of infusion), extensive 
co-morbidities or poor PS, strong suggestion to manage per grade 3 CRS 
guidance below. 
No additional guidance  No additional 
guidance  
Page 3 of 12 
Abbreviations and footnotes defined on last page of table. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Description of 
Severityb 
Interruption/Delay Specific Management 
Restart guidance 
Permanent 
Discontinuation 
Cytokine Release Syndrome continued (see Section 11.11.1 for additional guidance and grading scale details) 
2 
 Feverc:   38C 
WITH 
 Hypotension:  not 
requiring 
vasopressors 
AND/ORd 
 Hypoxia:  
requiring low-flow 
nasal cannulae or 
blow-by 
Delay tarlatamab 
until event 
improves to CRS 
grade  1. 
 
 
Administer:  
 Symptomatic treatment (eg, paracetamol/acetaminophen) for fever 
 Consider a single dose of dexamethasone (or equivalent) ranging from 
4 mg to 10 mg 
 Supplemental oxygen when oxygen saturation is  90 on room air 
(low-flow [ 6 L/minute] nasal cannula or blow-by) 
 Intravenous fluids when systolic blood pressure is  85 mmHg.  
Persistent tachycardia (eg,  120 bpm) may also indicate the need for 
intervention for hypotension 
Monitor: 
 CRS symptoms including temperature, blood pressure, and pulse 
oximetry  
 Fluid status, maintain IVF as needed 
 Cardiac and other organ function 
 Consider chest X-ray and obtaining appropriate cultures to rule out 
infection 
For subjects with rapid onset (4 hours from start of infusion), extensive 
co-morbidities or poor performance status, strong suggestion to manage 
per grade 3 CRS guidance below. 
 The next infusion may 
be administered if the 
event has resolved to 
grade  1 prior to 
resuming treatment  
 In case of infusion 
interruption, continue 
treatment with next 
scheduled infusion.  
Do not resume prior 
infusion or administer 
delayed infusion.   
If there is no 
improvement to 
CRS  grade 1 
within 7 days 
Page 4 of 12 
Abbreviations and footnotes defined on last page of table. 

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Protocol Number:  20230273 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Description of 
Severityb 
Interruption/
Delay 
Specific Management 
Restart guidance 
Permanent 
Discontinuation 
Cytokine Release Syndrome continued (see Section 11.11.1 for additional guidance and grading scale details) 
3  
 Feverc:  38C 
WITH 
 Hypotension:  
requiring a single 
vasopressor 
(excluding 
vasopressin) 
AND/ORd 
 Hypoxia:  requiring 
high-flow nasal 
cannulae, facemask, 
nonrebreather mask, 
or Venturi mask 
Delay 
tarlatamab 
until event 
improves to 
CRS 
grade  1. 
Administer: 
 Symptomatic treatment (eg, paracetamol/acetaminophen) for fever 
 Supplemental oxygen (high-flow nasal cannula [> 6 L/min]), facemask, 
non-rebreather mask, or Venturi mask), as needed 
 A vasopressor  vasopressin, as needed  
 Dexamethasone (or equivalent) IV at a dose maximum of 3 doses of 
8 mg (24 mg/d).  The dose should then be reduced step-wise. 
AND/OR 
 Consider use of tocilizumab (in countries where available) as an 
additional therapy in this setting at a dose of 4 to 8 mg/kg as a single 
dose.  The maximum dose per infusion for tocilizumab is 800 mg.  
Tocilizumab can be repeated for an additional 3 doses with at least an 
8-hour interval between doses. 
 If tocilizumab is not available, siltuximab (an anti-IL-6 monoclonal 
antibody) may be used in the management of CRS, following the 
criteria outlined in this table.  The recommended dose of siltuximab is 
11 mg/kg administered over 1 hour as an IV infusion, consistent with 
the prescribing information for the treatment of multicentric Castleman’s 
disease (Sylvant Prescribing Information), and the CARTOX Working 
Group Guidelines for CRS management (Neelapu et al, 2018).  
Siltuximab may be repeated if needed, in the event that CRS recurs 
after a subsequent infusion of tarlatamab.  Siltuximab may not be 
repeated in an individual subject who develops anaphylaxis to 
siltuximab, or gastrointestinal perforation after siltuximab.  
 As per local institutional guidelines. 
The next infusion may be 
administered if all of the 
following criteria are met: 
 The medical monitor 
must be consulted 
prior to resuming 
treatment 
 The event has 
resolved to grade  1 
prior to resuming 
treatment 
In case of infusion 
interruption, continue 
treatment with next 
scheduled infusion.  Do 
not resume prior infusion 
or administer delayed 
infusion. 
If there is no 
improvement to 
CRS  grade 2 
within 5 days 
and CRS 
 grade 1 within 
7 days. 
OR 
If CRS grade 3 
occurs at the 
step dose. 
OR 
In the case of 
2 separate 
grade 3 CRS 
events. 
Page 5 of 12 
Abbreviations and footnotes defined on last page of table. 

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Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade Description of Severityb 
Interruption/Delay Specific Management 
Restart guidance 
Permanent 
Discontinuation 
Cytokine Release Syndrome continued (see Section 11.11.1 for additional guidance and grading scale details) 
3 
(cont.) 
 
 
Monitor: 
 CRS symptoms including temperature, blood pressure, 
and pulse oximetry 
 Fluid status, maintain IVF as needed 
 Consider chest X-ray and obtaining appropriate cultures 
to rule out infection 
 If refractory hypotension (after 2 fluid boluses), consider 
ECHO 
Admit to intensive care unit for close clinical and vital sign 
monitoring per institutional guidelines 
 
 
4 
Life-threatening symptoms 
 Feverc:   38C 
WITH 
 Hypotension:  requiring 
multiple vasopressors 
(excluding vasopressin) 
AND/ORd 
 Hypoxia:  requiring 
positive pressure (eg, 
CPAP, BiPAP, intubation, 
and mechanical 
ventilation) 
Immediately stop 
any ongoing 
infusion  
Administer: 
 Symptomatic treatment (eg, paracetamol/acetaminophen) 
for fever 
 Supplemental oxygen (positive pressure [eg, CPAP, 
BiPAP, intubation, and mechanical ventilation], as 
needed) 
 Multiple vasopressors, as needed 
 Dexamethasone (or equivalent) IV at a dose maximum of 
3 doses of 8 mg (24 mg/d).  Further corticosteroid use 
should be discussed with the medical monitor. 
 Tocilizumab should be administered at a dose of 
4 to 8 mg/kg as a single dose.  Tocilizumab can be 
repeated for an additional 3 doses with at least an 8-hour 
interval between doses.  
Do not resume tarlatamab 
Permanently 
discontinue 
tarlatamab 
Page 6 of 12 
Abbreviations and footnotes defined on last page of table. 

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Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade Description of Severityb 
Interruption/Delay Specific Management 
Restart guidance 
Permanent 
Discontinuation 
Cytokine Release Syndrome continued (see Section 11.11.1 for additional guidance and grading scale details) 
4 
(cont.) 
 
 
 If tocilizumab is not available, siltuximab (an anti-IL-6 
monoclonal antibody) may be used in the management of 
CRS, following the criteria outlined in this table.  The 
recommended dose of siltuximab is 11 mg/kg 
administered over 1 hour as an IV infusion, consistent 
with the prescribing information for the treatment of 
multicentric Castleman’s disease (Sylvant Prescribing 
Information), and the CARTOX Working Group Guidelines 
for CRS management (Neelapu et al, 2018).  Siltuximab 
may be repeated if needed, in the event that CRS recurs 
after a subsequent infusion of tarlatamab.  Siltuximab may 
not be repeated in an individual subject who develops 
anaphylaxis to siltuximab, or gastrointestinal perforation 
after siltuximab. 
Monitor: 
 CRS symptoms including temperature, blood pressure, 
and pulse oximetry 
 Fluid status, maintain IVF as needed 
 Consider chest X-ray and obtaining appropriate cultures 
to rule out infection 
 If refractory hypotension (after 2 fluid boluses), consider 
ECHO 
Admit to intensive care unit for close clinical and vital sign 
monitoring per institutional guidelines. 
 
 
Page 7 of 12 
Abbreviations and footnotes defined on last page of table.

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Interruption/Delay 
Specific Management 
Restart guidance 
Permanent Discontinuation 
Tumor Lysis Syndrome (TLS) (see Section 11.11.3) 
Present 
Immediate interruption/delay 
until event has resolved 
TLS should be managed 
according to the local 
standard of care and 
institutional guidelines. 
 
Resume only if TLS is successfully managed and 
resolved in  14 days 
 
Consult with medical monitor first. 
 
In case of infusion interruption, continue treatment 
with next scheduled infusion.  Do not resume prior 
infusion or administer delayed infusion. 
 
Monitoring:  per Monitoring Guidance for first 
tarlatamab administration (Section 6.1)  
If subject missed more than 
2 consecutive doses of 
tarlatamab 
OR 
In case of repeat TLS event, 
or life-threatening 
TLS, permanently discontinue 
tarlatamab  
Page 8 of 12 
Abbreviations and footnotes defined on last page of table.

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Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Interruption/Delay 
Specific Management 
Restart guidance 
Permanent Discontinuation 
Non-febrile Neutropenia 
3f 
Delay tarlatamab until the 
event improves to grade  2 
 
Assess for other potential etiologies of 
neutropenia, including concomitant 
medications and underlying infection 
 
Consider bone marrow biopsy, 
anti-neutrophil antibodies  
 
Granulocyte colony-stimulating factor 
(G-CSF) administration is permitted 
Resume tarlatamab no less than 
72 hours after the initial 
observation of the grade 3 
adverse event   
No additional guidance  
4f 
Delay tarlatamab until the 
event improves to grade  2 
 
Assess for other potential etiologies of 
neutropenia, including concomitant 
medications and underlying infection 
 
Consider bone marrow biopsy, 
anti-neutrophil antibodies 
 
Consider G-CSF administration 
Resume tarlatamab no less than 
72 hours after the initial 
observation of the grade 4 
adverse event   
Initial grade 4 nonfebrile 
neutropenia event 
lasts  7 days 
OR  
Grade 4 event reoccurs  
Page 9 of 12 
Abbreviations and footnotes defined on last page of table. 

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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Description of 
Severity 
Interruption/Delay 
Specific Management 
Restart Guidance 
Permanent 
Discontinuation 
Hypersensitivity (Allergic Reactions) 
1 
Systemic 
intervention not 
indicated  
No additional guidance 
Follow institutional guidelines for 
management 
No additional guidance  
No additional 
guidance 
2 
Oral intervention 
indicated  
Immediately pause any ongoing 
infusion 
Follow institutional guidelines for 
management and administer oral 
antihistamines and/or 
corticosteroids per local practice. 
Restart current infusion 
of remaining dose at 
lower rate per local 
practice if event has 
resolved 
No additional 
guidance 
3 
Bronchospasm, 
hospitalization 
indicated for 
clinical sequelae; 
intravenous 
intervention 
indicated  
Immediately stop any ongoing 
infusion and do not resume the 
current infusion.  
 
Delay next tarlatamab 
administration until the event 
improves to grade  1 
Follow institutional guidelines for 
management and administer IV 
corticosteroids, antihistamines, IV 
fluids, supplemental oxygen, and 
consider epinephrine per local 
practice  
Close monitoring  
and 
Consider ICU transfer 
The next infusion may 
be administered if  
all the following criteria 
are met: 
 
The Amgen 
medical monitor 
must be consulted 
prior to resuming 
treatment 
 
The event has 
resolved to 
grade  1 prior to 
resuming treatment 
 
Consider 
premedication (ie, 
antihistamine, 
corticosteroid) 
prior to the next 
infusion 
Discontinue 
tarlatamab if:  
there is no 
improvement to  
≤ grade 1 within 
5 days 
OR 
if grade 3 occurs at 
the step dose 
OR 
in the case of 2 
separate grade 3 
events. 
Page 10 of 12 
Abbreviations and footnotes defined on last page of table. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Grade 
Description of 
Severity 
Interruption/Delay 
Specific Management 
Restart Guidance 
Permanent 
Discontinuation 
Hypersensitivity (Allergic Reactions) continued 
4 
Life-threatening 
consequences, 
urgent intervention 
indicated 
Immediately stop any ongoing 
infusion and do not resume the 
current infusion. 
Follow institutional guidelines for 
management and administer 
epinephrine, IV corticosteroids, 
antihistamines, IV fluids, and 
supplemental oxygen per local 
practice. 
Immediate medical attention, ICU 
care, intubation as clinically 
indicated. 
Do not resume 
tarlatamab. 
Permanently 
discontinue 
tarlatamab 
Page 11 of 12 
Abbreviations and footnotes defined on last page of table. 
 

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Protocol Number:  20230273 
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Table 6-2.  Tarlatamab Dose Modification Guidelines for Adverse Events  
Pituitary Gland Dysfunction (González-Rodríguez and Rodríguez-Abreu, 2016) 
 
Monitor for signs and symptoms of pituitary gland dysfunction.  Consider the following studies as indicated:  TSH, FSH, LH, cortisol, FT4, testosterone/estradiol 
ACTH, prolactin, and IGF-1 
- 
Abnormal hormone monitoring result or clinical suspicion of pituitary gland dysfunction (headache, fatigue, asthenia, impaired vision, vomiting, hypotension, 
amenorrhea, impotence) 
- 
Diagnostic tests:  brain MRI (if clinically indicated), blood pressure, glycemia, plasma and urine osmolarity, electrolytes, laboratory values (ACTH, TSH, 
FSH, LH, IGF-1, plasma cortisol, FT4, prolactin, testosterone/estradiol) 
 
Urgent endocrinology consultation to guide management of the event 
 
Once pituitary gland dysfunction is confirmed, delay scheduled dose of tarlatamab 
 
Once residual related toxicity  grade 2, clinically stable on replacement therapy and  10 mg prednisone or equivalent, resume tarlatamab 
 
Continue endocrinological surveillance 
Hepatotoxicity 
For Stopping and Rechallenge Rules, please refer to Section 11.7. 
Page 12 of 12 
ACTH  adrenocorticotropic hormone; BiPAP  bi-level positive airway pressure; CARTOX  CAR-T-cell therapy-associated TOXicity; CRS  cytokine release 
syndrome; CPAP  continuous positive airway pressure; ECHO  echocardiogram; FSH  follicle-stimulating hormone; FT4  free T4; G-CSF  granulocyte 
colony-stimulating factor; ICANS  immune effector cell-associated neurologic syndrome; IGF-1  insulin-like growth factor 1; IL-6  interleukin 6; IV  intravenous; 
IVF  intravenous fluid(s); LH  luteinizing hormone; MRI  magnetic resonance imaging; OS  overall survival; PS  performance status; TLS  tumor lysis syndrome; 
TSH  thyroid-stimulating hormone 
a Based on Immune Effector Cells Therapy Toxicity Assessment and Management (also known as CARTOX) https://www.mdanderson.org/documents/for-
physicians/algorithms/clinical-management/clin-management-cytokine-release-web-algorithm.pdf 
b American Society for Transplantation and Cellular Therapy (ASTCT) grading system for CRS (Lee et al, 2019). 
c Fever is defined as temperature  38C not attributable to any other cause.  In subjects who have CRS then receive antipyretic or anticytokine therapy such as 
tocilizumab, siltuximab, or steroids, fever is no longer required to grade subsequent CRS severity.  In this case, CRS grading is driven by hypotension and/or 
hypoxia. 
d CRS grade is determined by the more severe event:  hypotension or hypoxia not attributable to any other cause.  For example, a subject with temperature of 39.5C, 
hypotension requiring 1 vasopressor, and hypoxia requiring low-flow nasal cannula is classified as grade 3 CRS. 
e Low-flow nasal cannula is defined as oxygen delivered at  6 L/minute.  Low-flow also includes blow-by oxygen delivery, sometimes used in pediatrics.  High-flow 
nasal cannula is defined as oxygen delivered at  6 L/minute. 
f For neutropenia adverse events grade  2, please follow institutional guidelines for management.

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
Page 59 of 137 
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For all other treatment interruptions or delays, restart tarlatamab in accordance with the following guidelines in Table 6-3: 
Table 6-3.  Step dose Rechallenge Requirement After Tarlatamab Delay  
Last Dose Administered 
Duration of Delay from the Last Dose 
Administered 
Action 
Step dose (1 mg) 
 14 days 
Proceed with tarlatamab 10 mg target dose and then continue 
treatment Q2W. 
 14 days 
Repeat tarlatamab 1 mg step dose per cycle 1 guidelines, including 
pre-medication and monitoring requirements (refer to Table 6-1). 
First target dose (10 mg) 
 21 days 
Proceed with tarlatamab 10 mg target dose and then continue 
treatment Q2W. 
 21 days 
Repeat tarlatamab 1 mg step dose schedule per cycle 1 guidelines, 
including pre-medication and monitoring requirements (refer to ). 
Any subsequent target dose 
(10 mg) 
 28 days 
Proceed with tarlatamab 10 mg target dose and then continue 
treatment Q2W. 
 28 days 
Repeat tarlatamab 1 mg step dose per cycle 1 guidelines, including 
pre-medication and monitoring requirements (refer to Table 6-1). 
Q2W  every 2 weeks. 

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6.2.3 
Hepatotoxicity Stopping and Rechallenge Rules  
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.   
6.3 
Preparation/Handling/Storage/Accountability  
Guidance and information on drug preparation, handling, storage, and accountability for 
the investigational product, and noninvestigational product(s)/auxiliary medicinal 
product(s) will be provided to the site. 
6.4 
Method of Treatment Assignment  
Subjects who meet eligibility criteria and enroll in the study will be assigned to treatment 
with tarlatamab. 
6.5 
Blinding  
This is an open-label study; procedures to blind treatment assignment are not 
applicable. 
6.6 
Treatment Compliance  
When subjects are dosed at the site, they will receive tarlatamab directly from the 
investigator or designee, under medical supervision.  The date and time of each dose 
administered in the clinic will be recorded in the source documents and recorded on the 
CRF. 
6.7 
Treatment of Overdose  
The effects of overdose of tarlatamab are not known. 
For this study, any dose of tarlatamab greater than 10% of intended dose will be 
considered an overdose.  A dose of greater than 10% higher than the intended 
tarlatamab dose will be considered clinically important and classified as a serious 
adverse event under the criterion of “other medically important serious event”.  
In the event of an overdose, the investigator/treating physician should: 
1. Contact the medical monitor immediately for prompt reporting of clinically 
apparent or laboratory adverse events possibly related to overdosage.  
Consultation with the medical monitor is also required even if there are no 
adverse events, to discuss further management of the subject. 
2. If the overdose results in clinically apparent or symptomatic adverse events, 
closely monitor the subjects until all signs or toxicity are resolved or returned to 

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baseline and the adverse event(s) should be recorded/reported (refer to 
Section 11.4, Appendix 4). 
3. 
Document the quantity of the excess dose in the CRF. 
6.8 
Prior and Concomitant Treatment  
6.8.1 
Prior Treatment  
Prior therapies (including prescription and non-prescription, herbal, and alternative 
therapies) that were being taken/used from 21 days prior to first dose of study treatment 
through the end of SFU period will be collected on each subject’s CRF. 
6.8.2 
Concomitant Treatment  
Throughout the study, investigators may prescribe any concomitant medications or 
treatments deemed necessary to provide adequate supportive care except for those 
listed in Section 6.1.6. 
Concomitant therapies (including prescription and non-prescription, herbal, and 
alternative therapies) are to be collected from main study informed consent through the 
end of the SFU period. 
Vaccines 
Refer to Section 6.1.6 for details on the use of vaccines.   
7. 
Discontinuation of Study Treatment and Subject 
Discontinuation/Withdrawal  
Subjects have the right to withdraw from investigational product(s), noninvestigational 
product(s)/auxiliary medicinal product(s), and/or 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(s), noninvestigational product(s)/auxiliary medicinal product(s), device, and/or 
protocol procedures, or the study as a whole at any time before study completion for the 
reasons listed in Section 7.1 and Section 7.2.1. 
7.1 
Discontinuation of Study Treatment  
Subjects (or a legally authorized representative) can decline to continue receiving 
investigational product(s) and/or noninvestigational product(s)/auxiliary medicinal 
product(s) and/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(s) and/or noninvestigational 
product(s)/auxiliary medicinal product(s) and must discuss with the subject the 

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possibilities for continuation of the Schedule of Activities (see Section 1.3) including 
different options of follow-up (eg, in person, by phone/mail, through family/friends, in 
correspondence/communication with other treating physicians, from the review of 
medical records) and collection of data, including endpoints, adverse events, and 
product complaints (including device-related adverse events, as applicable) and must 
document this decision in the subject’s medical records.  Subjects who have 
discontinued investigational product(s) and/or noninvestigational product(s)/auxiliary 
medicinal product(s) and/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.  Continuation on 
investigational product treatment may be allowed after first radiologic disease 
progression, see Section 6.1.7. 
Reasons for early removal from investigational product(s), noninvestigational 
product(s)/auxiliary medicinal product(s) and/or procedures 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 (see Section 6.1.7) 
 
requirement for alternative therapy 
 
pregnancy 
7.2 
Subject Discontinuation/Withdrawal From the Study  
Withdrawal of consent for a study means that the subject does not wish to, or is unable 
to continue further study participation.  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.  Subjects who are withdrawn or 
removed from treatment or the study will not be replaced. 

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If a subject withdraws from the study, they 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 (Section 1.3) 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 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 they repeatedly fail 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 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, where permitted per local 
regulation, 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 [contact the 
patient’s family or direct assigned contact]).  These contact attempts are to be 
documented in the subject’s medical record. 
 
If the subject continues to be unreachable, they 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 should 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 Section 1.3).  
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. 
8.1 
General Study Periods  
8.1.1 
Screening and Enrollment  
Informed consent must be obtained before completing any screening procedure.  After 
the subject has signed the informed consent form, the site will register the subject in IRT 
and screen the subject to assess eligibility for participation.  The screening window is up 
to 21 days. 
All screening evaluations must be completed and reviewed to confirm that potential 
subjects meet all eligibility criteria.  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 5.5) 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 up to 2 additional times.  
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 21-day 
screening window will begin.  Subjects will retain the same subject identification number 
assigned at the original screening.  If the rescreening period begins more than 21 days 
after the original signing of the informed consent form, all screening procedures, 
including informed consent, must be repeated. 
8.1.2 
Treatment Period  
Visits will occur per the Schedule of Activities (Section 1.3).  The date of the first dose of 
tarlatamab is defined as day 1.  All subsequent doses and study visits will be scheduled 
based on the day 1 date.  On-study cycle 1 day 8 and day 15 visits have a  1 day 
window and all subsequent visits beginning from cycle 2 have a  3 day window, unless 
otherwise specified.  Administration of tarlatamab is to be administered last during each 
visit that it is required.  Subjects will receive study treatment until BICR-confirmed 
disease progression per RECIST 1.1, death, withdrawal of consent, start of new 
anticancer therapy, unacceptable toxicity, or end of study as determined by the 
sponsor (whichever occurs first).  Following documented radiographic 
progression, the subject may remain on study treatment provided criteria are met.  
Refer to Section 6.1.7.  Any subsequent (investigator-determined) progressive 

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disease per RECIST 1.1 from a new baseline set at initial progression will result in 
permanent discontinuation of study treatment.   
The site principal investigator will make final treatment and subject management 
decisions.  Subjects who discontinue study treatment for reasons other than 
BICR-confirmed disease progression will continue to have tumor assessments (if 
clinically feasible) until disease progression is confirmed by BICR. 
8.1.3 
End of Treatment 
Upon permanent discontinuation from study treatment for any reason, an end of 
treatment visit will be performed at the time the decision is made to discontinue 
study treatment (preferably within 14 days after last dose of study treatment) and 
prior to the start of subsequent anti-cancer therapy. 
8.1.4 
Safety Follow-up  
Upon permanent discontinuation from the study treatment for any reason, a safety 
follow-up visit will be performed approximately 60 (+5) days after the end of the last dose 
of tarlatamab, regardless of initiation of subsequent anticancer therapy within that 
period. 
8.1.5 
Long-term Follow-up  
Following the SFU visit (60 [5] days), subjects will enter the LTFU period for clinical 
evaluation of disease status and survival.  Subjects will be followed via telephone, clinic 
visit, or chart review to assess for survival and/or the commencement of subsequent 
cancer therapy every 12 weeks ( 14 days) from the SFU visit or last imaging visit, 
whichever is later, for up to 1 year after the last subject’s last dose of tarlatamab or 
5 years from first subject enrolled, whichever occurs first.  Radiological imaging and 
pregnancy testing may also be collected during the LTFU period, if applicable.  The 
assessments that will be collected during the LTFU are designated in the Schedule of 
Activities (Section 1.3). 
8.1.6 
End of Study  
Refer to Section 4.5 for the end of study definition.  The end of study visit will occur 
during the LTFU. 
All end of study procedures should be performed at the final visit for subjects who 
discontinue study before the defined end of study visit.  Amgen will not continue 
provision of investigational product for subjects after their study participation ends unless 
it is a legal requirement. 

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8.2 
General Assessments  
8.2.1 
Informed Consent  
All subjects or their legally authorized representative must sign and personally date the 
external review body approved informed consent before any study-specific procedures 
are performed. 
8.2.2 
Demographics  
Demographic data collection including sex, age, race, and ethnicity will be collected to 
study their possible association with subject safety and treatment effectiveness.  
Additionally, demographic data will be used to study the impact on the PK of tarlatamab. 
8.2.3 
Medical History  
The investigator or designee will collect a complete medical and surgical history that 
started prior to enrollment through the time of first dose.  Medical history will include 
information on the subject's concurrent medical conditions.  Record all findings on the 
medical history CRF.  In addition to the medical history above, SCLC history must date 
back to the original diagnosis.   
8.2.4 
Physical Examination  
Physical examination will be performed as per SOC.  Physical examination findings 
should be recorded on the appropriate CRF (eg, Medical History, Event). 
At minimum, the examination should include assessments of the head and neck, skin, 
neurological, lungs, cardiovascular, abdomen (liver and spleen), thyroid, lymph nodes, 
and extremities. 
8.2.5 
Neurological Examination  
Subjects will be specifically queried for neurological symptoms observed in the interval 
since the last extended neurological examination.  Abnormalities of the following should 
be recorded:  level of consciousness, orientation, vision, cranial nerves and brain stem 
functions, pyramidal and extra pyramidal motor system, reflexes, muscle tone and 
trophic findings, coordination, sensory system, neuropsychological findings (eg, speech, 
cognition, and emotion). 
The individual performing the neurological examination will characterize the findings as 
either normal or abnormal.  Abnormal findings found predose will be reported on the 
medical history page of the electronic Case Report Form (eCRF).  Abnormal findings 
found after the subject is dosed will be reported on the Event page of the eCRF. 

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8.2.6 
Physical Measurements  
Height (in centimeters) and weight (in kilograms) should be measured without shoes.  
8.2.7 
Performance Status  
The subject’s performance status will be assessed using the ECOG performance scale 
(see Section 11.9). 
8.3 
Efficacy Assessments  
8.3.1 
Radiological Imaging Assessment  
The extent of disease will be evaluated by contrast-enhanced computed tomography 
(CT)/magnetic resonance imaging (MRI) according to RECIST 1.1 (Section 11.10).  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. 
Screening scans: 
The screening scans must be performed within 21 days prior to enrollment.  If there are 
multiple screening scans, the one closest to the enrollment will be used as baseline.  
Assessments that were performed as SOC prior to signature of informed consent, but 
within 21 days prior to first dose of tarlatamab can be used as screening assessments 
and do not need to be repeated to confirm subject eligibility. 
Radiological assessment must include CT/MRI of the chest, abdomen, and pelvis, as 
well as assessment of all other known sites of disease (as detailed within the Site 
Imaging Manual). 
All subjects must have imaging of the brain performed within 21 days prior to the first 
dose of tarlatamab.  All brain scans for subjects are required to be MRI unless MRI is 
contraindicated, and then CT with contrast is acceptable. 
Subsequent scans: 
All subsequent scans should be performed in the same manner (eg, with the same 
contrast, MRI field strength) as at screening preferably on the same scanner.  If the 
imaging modality must be altered (eg, unscheduled assessment), consultation with the 
medical monitor is recommended. 
Subsequent brain MRI/CT scans may be performed at any time, if in the judgement of 
the managing physician, the subject displays signs, or symptoms of CNS metastasis. 

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During treatment and follow-up, radiological imaging of the chest, abdomen, pelvis, as 
well as all other known sites of disease, will be performed independent of treatment 
cycle as specified in the Schedule of Activities (Section 1.3).  Imaging may also be 
performed more frequently if clinically necessitated at the discretion of the managing 
physician.  Confirmed radiographic response (CR, PR) requires confirmation by a repeat 
scan at least 4 weeks after the first documentation of response, but may be performed 
later at the next scheduled scan, see Section 11.10.  Radiologic imaging and tumor 
assessment will be performed until BICR-confirmed disease progression per 
RECIST 1.1, death, withdrawal of consent, start of new anticancer therapy, or end of 
study, whichever occurs first.  Any unscheduled scans should be submitted to the 
central imaging core laboratory. 
Scans will be submitted to a central imaging core laboratory for archival, response 
assessment by BICR including RECIST 1.1, and/or 
 
.  Detailed information regarding submission of images 
to the central imaging core laboratory is found in the Site Imaging Manual. 
The site principal investigator will make final treatment and subject management 
decisions.  Subjects who discontinue study treatment for reasons other than 
BICR-confirmed disease progression will continue to have tumor assessments (if 
clinically feasible) until disease progression is confirmed by BICR. 
8.3.2 
Blinded Independent Central Review (BICR) 
All scheduled images for all study subjects from the sites will be submitted to the central 
imaging vendor for BICR.  In addition, images (including Imaging Manual-defined 
acceptable modalities) that are obtained at an unscheduled time point to determine 
disease progression, as well as imaging obtained for other reasons, but captures 
radiologic progression based on investigator assessment should also be submitted to 
the central imaging vendor.   
When the investigator identifies radiographic progression per RECIST 1.1, the current 
imaging and all images to date must be immediately sent to the central imaging vendor.  
An expedited review of progression will be performed by central vendor, as detailed in 
the Site Imaging Manual, to inform real-time patient treatment decisions.  
Treatment will continue until BICR-confirmed disease progression per RECIST 1.1, 
death, withdrawal of consent, start of new anticancer therapy, or end of study, whichever 
occurs first. 

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The site principal investigator will make final treatment and subject management 
decisions (refer to Section 6.1.7).  Subjects who discontinue study treatment for 
reasons other than BICR-confirmed disease progression will continue to have 
tumor assessments (if clinically feasible) until disease progression is confirmed 
by BICR. 
Following documented radiographic progression, the subject may remain on study 
treatment provided criteria are met.  Refer to Section 6.1.7.  Any subsequent 
(investigator determined) progressive disease per RECIST 1.1 from a new baseline 
set at initial progression will result in permanent discontinuation of study 
treatment. 
8.4 
Safety Assessments  
Planned time points for all safety assessments are listed in the Schedule of Activities 
see (Section 1.3). 
8.4.1 
Vital Signs  
The following measurements must be performed:  systolic/diastolic blood pressure, heart 
rate, respiratory rate, pulse oximetry, and temperature.  Subject must be in a supine 
position in a rested and calm state for at least 5 minutes before blood pressure and 
pulse oximetry 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.  Oxygen saturation will be measured using a 
standard pulse oximeter.  The temperature location selected for a subject should be the 
same that is used throughout the study and documented on the vital signs CRF.  Record 
all measurements on the vital signs CRF. 
Table 8-1.  Vital Signs for Subjects Receiving Tarlatamab 
Cycle 1 
Day 1 and Day 8 
 
Pre-infusion  5 minutes  
 
EOI  5 minutes  
 
1 hour post-EOI  10 minutes  
For subjects that require monitoring for restarting due to delays between doses (refer to 
Table 6-3); collect vital signs according to the timepoints in cycle 1 day 1 and day 8 guidance.  
Vital signs thereafter will be collected as indicated in the Schedule of assessments (see 
Section 1.3), including scheduled visits on cycle 1 day 2 and cycle 1 day 9. 
EOI  end of infusion 

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8.4.2 
Electrocardiograms  
Electrocardiograms will be performed as indicated in the Schedule of Activities (see 
Section 1.3). 
Single ECGs 
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 P-R intervals.  The 
investigator 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. 
8.4.3 
Clinical Laboratory Assessments  
Refer to Section 11.2 for the list of clinical laboratory tests to be performed and to the 
Schedule of Activities (Section 1.3) for the timing and frequency.  
The investigator is responsible for reviewing laboratory test results and recording any 
clinically relevant changes occurring during the study in the Events 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. 
All protocol-required laboratory assessments, as defined in Section 11.2, must be 
conducted in accordance with the laboratory manual and the Schedule of Activities 
(Section 1.3).  
8.4.4 
Vital Status (Survival Status) 
Vital status (survival 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 
and legally permissible.  If deceased, the date and reported cause of death should be 
obtained. 

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8.4.5 
Other Safety  
8.4.5.1 
Echocardiogram (ECHO)/Multigated Acquisition (MUGA) Scan  
Echocardiogram or MUGA will be performed to assess cardiac ejection fraction and will 
occur at time points specified in the Schedule of Activities (see Section 1.3).  
Echocardiogram/MUGA should include an evaluation from left ventricular ejection 
fraction.  Additional ECHO/MUGA assessments may be performed as clinically 
indicated. 
8.4.5.2 
Cytokine Release Syndrome  
Cytokine release syndrome is defined a supraphysiologic response following any 
immune therapy that results in the activation or engagement of endogenous or infused 
T cells and/or other immune effector cells.  Symptoms can be progressive, must include 
fever at the onset, and may include hypotension, capillary leak (hypoxia), and end organ 
dysfunction. 
Refer to Section 11.11.1 for details on specific guidance for CRS. 
8.4.5.3 
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)  
For this study, ICANS will be defined according to the criteria referenced in the 
publication by Lee et al (2019).  While the grading system has been developed in large 
part from chimeric antigen receptor T cells therapies, symptoms of ICANS may be 
shared among immune effector cell-associated therapies such as BiTE® molecules. 
Refer to Section 11.11.2 for details on specific guidance for ICANS. 
8.4.5.4 
Hepatitis B  
Subjects with resolved HBV infection, defined as absence of HBV surface antigen 
[HBsAg-negative] and presence of HBV core antibody [anti-HBc positive]; and subjects 
with chronic HBV infection inactive carrier state, defined as presence of HBV surface 
antigen [HBsAg-positive] and HBV DNA viral load below the limit of quantification [HBV 
DNA negative], should undergo consultation with a specialist in HBV and have HBV 
DNA testing and monitoring of HBV DNA every 12 weeks ( 2 weeks) or more 
frequently, if clinically indicated, through SFU.  
Subjects with chronic HBV infection inactive carrier state should be evaluated for HBV 
reactivation prophylaxis treatment as per a specialist in hepatitis B following local or 
institutional practice guidelines.  Subjects with resolved Hepatitis B are at lower risk of 
HBV reactivation with anticancer therapies, however, they should also be potentially 

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evaluated for HBV prophylaxis as per an HBV specialist following local or institutional 
guidelines.  
Any subject in which HBV DNA viral load becomes positive or develops reactivation of 
HBV will have study treatment interrupted and receive appropriate antiviral treatment as 
per a specialist in hepatitis B.  Resumption of clinical study therapy may be considered 
in subjects whose HBV reactivation is controlled and where the benefits of clinical study 
therapy outweigh the risks.  After cessation of study therapy for any reason, any ongoing 
monitoring and antiviral treatment should be under the guidance of a specialist in HBV. 
Subjects that have received hepatitis B vaccination with only anti-HBs positivity and no 
clinical signs of hepatitis do not require HBV DNA monitoring. 
8.4.5.5 
Hypersensitivity 
Hypersensitivity reactions have been reported in subjects treated with tarlatamab 
including rare severe events.  Clinical signs and symptoms of hypersensitivity may 
include but are not limited to rash and bronchospasm.  Monitor subjects for signs and 
symptoms of hypersensitivity during treatment with tarlatamab and manage as clinically 
indicated.  Withhold or consider permanent discontinuation of tarlatamab based on 
severity. 
8.4.6 
Adverse Events and Serious Adverse Events  
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. 
8.4.6.1 
Time Period and Frequency for Collecting and Reporting Safety 
Event Information  
8.4.6.1.1 
Adverse Events  
The adverse event grading scale to be used for this study will be the CTCAE v5.0 and is 
described in Section 11.4, with the following exceptions:  CRS and ICANS will be graded 
according to American Society for Transplantation and Cellular Therapy (Lee et al, 2019) 
as described in Table 6-2.  Tumor lysis syndrome will be graded based on CTCAE v5.0 
but will be managed based on Cairo Bishop criteria (Coiffier et al, 2008). 
The investigator is responsible for ensuring that all adverse events observed by the 
investigator or reported by the subject that occur after first dose of investigational 
product(s) or noninvestigational product(s)/auxiliary medicinal product(s) through the 

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SFU visit or 60 days after the last dose of the study treatment, whichever is later, 
are reported using the Events CRF. 
Disease progression is an efficacy endpoint.  Disease progression of SCLC is not 
considered an adverse event and should not be reported as an adverse event unless 
there is evidence as suggesting a causal relationship between the investigational 
product(s) and/or noninvestigational product(s)/auxiliary medicinal product(s) and 
progression or symptom/sign of progression of the SCLC as indicated in 
Section 11.4.  Progression of the subject's underlying malignancy will be recorded in the 
Tumor Response CRF page as part of efficacy data collection and not on the Events 
CRF.   
8.4.6.1.2 
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 SFU visit or 60 days after the last dose of study treatment, 
whichever is later, are recorded in the subject’s medical record and are submitted to 
Amgen or its designee using the Events CRF. 
Disease progression and death due to disease progression of SCLC are not considered 
serious adverse events and will not be reported as serious adverse event unless there 
is evidence as suggesting a causal relationship between the investigational 
product(s) and/or noninvestigational product(s)/auxiliary medicinal product(s) and 
progression or symptom/sign of progression of the SCLC as indicated in 
Section 11.4.  Progression of the subject's underlying malignancy will be recorded in the 
Tumor Response CRF page as part of efficacy data collection and not on the Events 
CRF.  Death due to disease progression is to be recorded in the End of Study CRF page 
and not on the Events CRF. 
All serious adverse events will be collected, recorded, and reported to the sponsor or 
designee immediately and no later than 24 hours of the investigator’s awareness of the 
event, as indicated in Section 11.4.  The investigator will submit any updated serious 
adverse event data to the sponsor immediately and no later than 24 hours of it being 
available. 
Since the criteria of the CTCAE grading scale differs from the regulatory criteria for 
serious adverse events, if adverse events correspond to grade 4 CTCAE toxicity grading 
scale criteria (eg, laboratory abnormality reported as grade 4 without manifestation of 

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life-threatening status), it will be left to the investigator’s judgment to also report these 
abnormalities as serious adverse events.  For any adverse event that applies to this 
situation, comprehensive documentation of the event’s severity must be recorded in the 
subject medical records. 
8.4.6.1.3 
Serious Adverse Events After the Protocol-required Reporting 
Period  
During the long-term follow-up period, if the investigator becomes aware of serious 
adverse event suspected to be related to tarlatamab after the protocol-required reporting 
period (as defined in Section 8.4.6.1.2) is complete, then these serious adverse events 
will be reported to Amgen.  The investigator will report serious adverse events to Amgen 
immediately and no later 24 hours after the investigator’s awareness of the event on the 
Events CRF. 
Disease progression and death due to disease progression of SCLC are not considered 
serious adverse events and will not be reported as serious adverse events unless there 
is evidence as suggesting a causal relationship between the investigational 
product(s) and/or noninvestigational product(s)/auxiliary medicinal product(s) and 
progression or symptom/sign of progression of the SCLC as indicated in 
Section 11.4.  Progression of the subject's underlying malignancy will be recorded in the 
Tumor Response CRF page as part of the efficacy data collection and not on the Events 
CRF.  Death due to disease progression is to be recorded in the End of Study CRF and 
not on the Events CRF. 
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 
product, then these serious adverse events will be reported to Amgen immediately and 
no later than 24 hours after the investigator’s awareness of the event. 
Serious adverse events reported after the end of the study will be captured within the 
safety database as clinical study 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 records after the subject ends the study. 

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8.4.6.2 
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 nonleading verbal questioning of the subject is the 
preferred method to inquire about adverse event occurrence. 
8.4.6.3 
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 immediately and no later than 24 hours after investigator’s 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.   
8.4.6.4 
Regulatory Reporting Requirements for Safety Information  
If subject is permanently withdrawn from investigational product(s), and/or 
noninvestigational product(s)/auxiliary medicinal product(s) 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 external review body and investigators. 
Individual safety reports must be prepared for suspected unexpected serious adverse 
reactions will be reported by the sponsor according to local regulatory requirements 
as well as 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 

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events) from the sponsor will file it along with the investigator’s brochure and will notify 
the external review body, if appropriate according to local requirements. 
For studies in which the treatment assignment is blinded, to comply with worldwide 
reporting regulations for serious adverse events, the treatment assignment of subjects 
who develop serious, unexpected, and related adverse events may be unblinded by 
Amgen before submission to regulatory authorities.  Aggregate analyses may also be 
unblinded by the Safety Assessment Team, as appropriate.  Investigators will receive 
notification of related serious adverse events reports sent to regulatory authorities in 
accordance with local requirements.   
Amgen will prepare a single Development Safety Update Report (DSUR) (also referred 
to as Annual Safety Report in the European Union) for the Amgen Investigational 
Product.  To ensure that consolidated safety information for the study is provided, this 
single DSUR will also include appropriate information on any other investigational 
products used in the clinical study, if applicable.   
8.4.6.5 
Safety Monitoring Plan  
Subject safety will be routinely monitored as defined in Amgen’s safety surveillance and 
signal management processes. 
8.4.6.6 
Other Safety Findings/Special Situations  
All medication errors, misuse or abuse of the investigational product when associated 
with a serious adverse event must be reported to Amgen or designee immediately and 
no later than 24 hours of the investigator’s awareness by collecting and recording the 
Other Safety Findings (OSF)/Special Situations (SS) event on the paper-based 
electronic Serious Adverse Event (eSAE) Contingency Report Form. 
Further details and definitions regarding OSF/SS - medication errors, misuse, and 
abuse, can be found in Section 11.4. 
8.4.6.7 
Pregnancy and Lactation  
Details of all pregnancies and/or lactation in female subjects and, if indicated, female 
partners of male subjects will be collected after the start of study treatment and until 
60 days after last dose of investigational product/noninvestigational product(s)/auxiliary 
medicinal product(s). 
If a pregnancy is reported, the investigator is to inform Amgen immediately and no later 
than 24 hours of learning of the pregnancy and/or lactation and is to follow the 

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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, and ectopic pregnancy) are considered serious adverse events. 
Further details regarding pregnancy and lactation are provided in Section 11.5. 
Pregnancy Testing 
A highly sensitive serum pregnancy test should be completed at screening and  7 days 
prior to initiation of investigational product and serum or urine test completed on day 
1 of each cycle, at end of treatment, and at SFU for females of childbearing potential 
(Section 1.3). 
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 (serum or urine) should be performed on day 1 of each 
cycle, at end of treatment, at SFU and 60 days after last dose of tarlatamab 
(Section 1.3).   
Additional on-treatment pregnancy testing may be performed at the investigator’s 
discretion or as required per local laws and regulations. 
8.5 
Pharmacokinetic Assessments  
Blood samples will be collected for measurement of serum concentrations of tarlatamab 
as specified in the Schedule of Activities (Section 1.3).  Blood must not be drawn from 
a port catheter during investigational product infusion.  If a permanent central line 
with more than 1 lumen is used, blood draws can be done via the lumen that is not 
used for drug administration.  However, the preference is for PK samples to be 
drawn peripherally.  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 collection for each sample will be recorded.  In case the PK sample is not 
collected within the scheduled window, it will not be considered a protocol 
deviation.   
8.6 
Pharmacogenetic Assessments  
There are no pharmacogenetic assessments in this study. 

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8.7 
Antibody Testing Procedures  
Blood sample(s) for antibody testing are to be collected according to the time points 
specified in the Schedule of Activities (Section 1.3) for the measurement of 
anti-tarlatamab binding antibodies.  Samples testing positive for binding antibodies will 
be evaluated for anti-tarlatamab neutralizing antibodies. 
Refer to the laboratory manual for detailed collection and handling instructions.  More 
frequent antibody testing or testing for a longer period of time may be requested in the 
event of safety-related concerns. 
8.8 
Medical Resource Utilization and Health Economics  
Medical resource utilization data, associated with medical encounters (including but not 
limited to CRS, ICANS, etc) will be collected on the CRF by the investigator and 
study-site personnel for all subjects throughout the study.  Protocol-required procedures, 
tests, and encounters are excluded from the analysis of medical resource utilization and 
health economics. 
The data collected may be used to conduct medical resource use analyses and may 
include: 
 
Number and duration of hospitalization (total days or length of stay, including 
duration by wards; eg, intensive care unit) 
 
Number and type of diagnostic and therapeutic tests and surgical and nonsurgical 
procedures 
 
Reason for hospitalization (eg, adverse event such as CRS/ICANS or other). 
Cytokine Release Syndrome 
Medical resource utilization and health economics data, related to CRS, will be collected 
in the eCRF by the investigator and study-site personnel for all subjects throughout the 
study.  Protocol-mandated procedures, tests, and encounters are excluded from the 
analysis of health resource utilization and health economics.  
The data collected may be used to conduct exploratory economic analyses and may 
include hospitalizations (by ward), concomitant medications, diagnostic and therapeutic 
tests and procedures related to CRS. 
9. 
Statistical Considerations  
9.1 
Statistical Hypotheses  
No statistical hypotheses will be tested. 

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9.2 
Sample Size Determination  
Approximately 30 subjects will be enrolled in the study.  With 30 subjects enrolled at the 
target dose, the probability that the observed ORR will be greater than different 
thresholds are presented in Table 9-1. 
Table 9-1.  Probabilities of Observed ORR Greater Than Thresholds With Sample 
Size of 30 
True ORR 
Probability of Observed 
ORR  25 % 
Probability of Observed 
ORR  30% 
0.35 
88% 
64% 
0.4 
96% 
82% 
ORR = overall response rate 
With 30 subjects, there is a 79% to 96% probability of observing at least 1 adverse event 
if the true event rate is 5% to 10%. 
9.3 
Populations for Analysis  
The following populations are defined: 
Population 
Description 
Safety analysis set 
The Safety Analysis Set will consist of all subjects who 
receive at least 1 dose of tarlatamab.  The analysis of all 
safety endpoints, unless noted otherwise, will be conducted 
on the Safety Analysis Set. 
Note:  Additional populations for efficacy analyses will be defined in the SAP. 
9.3.1 
Covariates  
The relationship of covariates to efficacy endpoints will be explored if appropriate. 
9.4 
Statistical Analyses  
The statistical analysis plan will be developed and finalized before database lock.  Below 
is a summary of the timing and methods for the planned statistical analyses. 
9.4.1 
Planned Analyses  
9.4.1.1 
Primary Analysis  
The primary analysis is planned after all subjects have been enrolled and have had 
opportunity to confirm an objective response after the first post-treatment scan or up 
to 13 weeks of follow-up, whichever occurs first.  
The data will be subject to ongoing checks for integrity, completeness, and accuracy in 
accordance with the Data Management Plan.  The data supporting the primary analysis 

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will be locked.  It is expected that outstanding data issues are resolved ahead of the lock 
to the extent possible. 
9.4.1.2 
Final Analysis  
The final analysis will occur when enrollment is complete and each subject completes 
the study, including long-term follow-up. 
The data will be subject to ongoing checks for integrity, completeness, and accuracy in 
accordance with the Data Management Plan.  The data supporting the final analysis will 
be locked to prevent future changes.  It is expected that all outstanding data issues are 
resolved ahead of the final lock. 
9.4.2 
Methods of Analyses  
9.4.2.1 
General Considerations  
Descriptive statistics will be provided for selected demographics, safety, and PK.   
Descriptive statistics on continuous data will include means, medians, standard 
deviations, and ranges, while categorical data will be summarized using frequency 
counts and percentages.  Graphical summaries of the data may also be presented. 
Ninety-five percent CI for proportions will be estimated using an exact method proposed 
by Clopper-Pearson (Clopper and Pearson, 1934).  Kaplan-Meier methods will be used 
to estimate the median and percentiles for time-to-event endpoints with CI calculated 
using the Brookmeyer and Crowley (Brookmeyer and Crowley, 1982) method.  
Kaplan-Meier methods will be used to estimate landmarks for time-to-event endpoints 
(eg, 1-year OS) with the Greenwood formula (Kalbfleisch and Prentice, 1980) used to 
estimate the standard error used in CI calculation.  Kaplan-Meier curves will be 
constructed for time-to-event endpoints. 

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9.4.2.2 
Efficacy Analyses  
 
Endpoint/Estimand 
Statistical Analysis Methods 
Primary 
Objective Response Rate (ORR) 
Summarized along with a Clopper-Pearson exact 
binomial CI.  Subjects without a post-baseline 
tumor assessment will be considered non-
responders. 
Duration of Response (DOR) 
Summarized with Kaplan-Meier estimate and 95% 
CI for quartiles and rates for select durations 
Disease Control Rate (DCR) 
Analyzed by the same methods used to analyze 
ORR.  The summary of clinical benefit (ie, 
percentages of subjects with duration of disease 
control ≥ 4 months) will be provided.  The percent 
change from baseline in target lesion sum of 
diameters will be plotted. 
Progression-free survival (PFS) 
Analyzed by the same methods used to analyze 
DOR 
Overall Survival (OS) 
Analyzed by the same methods used to analyze 
DOR 
 
9.4.2.3 
Safety Analyses  
9.4.2.3.1 
Adverse Events  
Subject incidence of all treatment-emergent adverse events will be tabulated by system 
organ class and preferred term and coded using Medical Dictionary for Regulatory 
Activities (MedDRA).  Tables of grade 3 or higher treatment-emergent adverse events, 
fatal treatment-emergent adverse events, serious treatment-emergent adverse events, 
treatment-emergent adverse events leading to discontinuation from investigational 
product and treatment-related adverse events will also be provided.   
9.4.2.3.2 
Laboratory Test Results  
The analyses of safety laboratory endpoints will include summary statistics over time.  
Shifts in grades of safety laboratory values between the baseline and the worst on-study 
value will be tabulated. 
9.4.2.3.3 
Vital Signs  
The analyses of vital signs will include summary statistics over time.  The incidence and 
percentage of abnormal changes in vital signs will be tabulated. 
9.4.2.3.4 
Physical Measurements  
The analyses of physical measurements will include summary statistics at baseline. 

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9.4.2.3.5 
Electrocardiogram  
Single ECGs 
The single ECG measurements from this clinical study were performed as per SOC 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 statistical 
analyses of single ECG measurements are not planned, and these data would not be 
expected to be useful for meta-analysis with data from other trials. 
9.4.2.3.6 
Antibody Formation  
The incidence and percentage of subjects who develop anti-tarlatamab antibodies at any 
time will be tabulated.  
9.4.2.3.7 
Exposure to Investigational Product  
Subject exposure to investigational product will be summarized using descriptive 
statistics.  The number of doses, duration of therapy, the cumulative dose, and the 
average dose per administration and relative dose intensity will be summarized.  The 
number and percent of subjects with dose modifications (eg, dose reductions, dose 
interruptions) and reason for modification will be summarized as well.  Subject-level data 
may be provided instead of the summary if the subject incidence is low or single dose is 
given. 
9.4.2.3.8 
Exposure to Concomitant Medication  
Number and proportion of subjects receiving therapies of interest will be summarized by 
preferred term as coded by the World Health Organization Drug dictionary. 
9.4.2.4 
Other Analyses  
Pharmacokinetic data from this study may be pooled with other studies and may be 
analyzed using a population PK approach.  The observed PK parameter values from 
non-compartmental analysis or model-predicted Bayesian estimates will be utilized to 
drive the qualitative (graphical) and quantitative relationship of tarlatamab exposures 
with relevant efficacy or safety variables.  The efficacy/safety variables will be aligned 
with primary and secondary endpoints.  Relevant covariates may also be explored to 
assess the impact on exposure-response relationships.  The selection of safety variables 
will be primarily driven by frequency of events and clinical relevance.  Additional 
pharmacodynamic variables may also be explored if deemed clinically relevant.  These 
analyses will not be part of the clinical study report. 

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10. 
References  
Ahn MJ, Cho BC, Felip E, Korantzis I, et al.  Tarlatamab for Patients with Previously 
Treated Small-Cell Lung Cancer.  N Engl J Med.  2023 doi:  10.1056/NEJMoa2307980. 
Brookmeyer R, Crowley J.  A confidence interval for the median survival time.  
Biometrics.  1982;38:29-41. 
Byers LA, Rudin CM.  Small cell lung cancer:  where do we go from here?  
Cancer.  2015;121:664-672. 
Clopper CJ, Pearson ES.  The use of confidence or fiducial limits illustrated in the case 
of the binomial.  Biometricka.  1934;26:404-413. 
Coiffier B, Altman A, Pui CH, Younes A, Cairo MS.  Guidelines for the management of 
pediatric and adult tumor lysis syndrome:  an evidence-based review.  J Clin Oncol.  
2008;26:2767-2778. 
Coutinho AD, Shah M, Lunacsek OE, Eaddy M, Willey JP.  Real-world treatment 
patterns and outcomes of patients with small cell lung cancer progressing after 2 lines of 
therapy.  Lung Cancer.  2019;127:53-58. 
Eisenhauer EA, Therasse P, Bogaerts J, et al.  New response evaluation criteria in solid 
tumours:  Revised RECIST guideline (version 1.1).  Eur J Cancer.  2009;45(2):228-247. 
González-Rodríguez E, Rodríguez-Abreu D.  Spanish Group for Cancer Immuno 
Biotherapy (GETICA).  Immune Checkpoint Inhibitors:  Review and Management of 
Endocrine Adverse Events.  Oncologist.  2016;21(7):804-816. 
Gustafsson BI, Kidd M, Chan A, Malfertheiner MV, Modlin IM.  Bronchopulmonary 
neuroendocrine tumors.  Cancer.  2008;113:5-21.  
Kalbfleisch JD, Prentice RL.  The statistical analysis of failure time data.  John Wiley & 
Sons, Inc., New York, 1980. 
Koinis F, Kotsakis A, Georgoulias V.  Small cell lung cancer (SCLC):  no treatment 
advances in recent years.  Transl Lung Cancer Res.  2016;5:39-50. 
Lee DW, Santomasso BD, Locke FL, et al.  ASTCT Consensus Grading for Cytokine 
Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells.  
Biol Blood Marrow Transplant.  2019;25:625-638. 
Neelapu SS, Tummala S, Kebriaei P, et al.  Chimeric antigen receptor T-cell 
therapy - assessment and management of toxicities.  Nat Rev Clin Oncol.  
2018;15(1):47-62. 
Paz-Ares L, Champiat S, Lai WV, Izumi H, et al.  Tarlatamab, a First-in-Class 
DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer:  An 
Open-Label, Phase I Study.  J Clin Oncol.  2023;41(16):2893-2903. 
Rudin CM, Ismaila N, Hann CL, et al.  Treatment of small-cell lung cancer:  American 
Society of Clinical Oncology endorsement of the American College of Chest Physicians 
guideline.  J Clin Oncol.  2015;33:4106-4111. 
Saunders LR, Bankovich AJ, Anderson WC, et al.  A DLL3-targeted antibody-drug 
conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo.  
Sci Transl Med.  2015;7:302ra136. 
Shi J, Cheng Y, Wang Q, Li K, Wu L, et al.  Effect of anlotinib in advanced small cell lung 
cancer (SCLC) patients relapsed within three months after second-line treatment:  A 

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subgroup analysis from a randomized, double-blind phase II trial (ALTER 1202).  
J Clin Oncol.  2020;38(15).  2020 ASCO Annual Meeting I.  Abstract 9063 
United States Food and Drug Administration.  Guidance for Industry Drug-Induced Liver 
Injury:  Premarketing Clinical Evaluation, July 2009. 
Xu H, Cao D, Jie F, He A, Ge W.  The efficacy and safety of anlotinib for subsequent line 
treatment of small cell lung cancer: a systematic review and meta-analysis.  
Tumori.  2023;109(2):203-214. 

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11. 
Appendices  

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11.1 
Appendix 1.  List of Abbreviations  
Abbreviation 
Explanation 
1L 
first-line 
Ab 
antibody 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
BICR 
blinded independent central review 
BIL 
bilirubin 
BiTE 
bispecific T-cell engager 
BOR 
overall response 
C1D1 
cycle 1 day 1 
C1D8 
cycle 1 day 8 
C1D15 
cycle 1 day 15 
CFR 
U.S. Code of Federal Regulations 
CNS 
central nervous system 
CR 
complete response 
CRF 
Case Report Form 
CRS 
cytokine release syndrome 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DC 
disease control 
DILI 
drug-induced liver injury 
DOR 
duration of response 
DLL3 
Delta-like ligand 3 
DMC 
data monitoring committee 
DRT 
data review team 
DSUR 
Development Safety Update Report 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eCRF 
electronic case report form 
ED 
extensive disease 
EDC 
electronic data capture 
eSAE 
electronic Serious Adverse Event 
FDA 
Food and Drug Administration 
FDG-PET 
fluorodeoxyglucose-positron emission tomography 
FSH 
follicle-stimulating hormone 

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GCP 
Good Clinical Practice 
HLE 
extended half-life 
HBV 
hepatitis B virus 
HBsAg 
hepatitis B virus surface antigen 
HCV 
hepatitis C virus 
ICE 
Immune-effector cell-associated encephalopathy 
ICF 
informed consent form 
ICANS 
Immune effector cell-associated neurotoxicity syndrome 
ICH 
International Council for Harmonisation 
INR 
international normalized ratio 
IRT 
interactive response technology 
IV 
intravenous  
LTFU 
long-term follow-up 
MRI 
magnetic resonance imaging  
NCT 
National Clinical Trials 
NE 
not evaluable 
NSCLC 
non-small cell lung cancer 
ORR 
objective response rate 
OS 
overall survival 
OSF 
other safety finding 
PCR 
polymerase chain reaction 
PD 
progressive disease 
PD-1 
Programmed Cell Death Protein 1  
PD-(L)1 
Programmed Cell Death Ligand 1  
PET-CT 
positron emission tomography–computed tomography 
PFS 
progression-free survival 
PK 
pharmacokinetic  
PR 
partial response 
QTc 
corrected QT interval 
QTL 
quality tolerance limit 
RECIST 1.1 
Response Evaluation Criteria in Solid Tumors Version 1.1 
scFc 
single-chain fragment crystallizable 
SCLC 
small cell lung cancer 
SD 
stable disease 
SFU 
Safety follow-up 
SOC 
standard of care 
SS 
special situations 
TBL 
total bilirubin 

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TLS 
tumor lysis syndrome 
ULN 
upper limit of normal 
US 
United States 
 

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11.2 
Appendix 2.  Clinical Laboratory Tests  
The tests detailed in Table 11-1 will be performed by the central laboratory and/or by the 
local laboratory.  Additional analyte test results may be reported by the local or central 
laboratory, in accordance with standard laboratory procedures (eg, components of a 
hematology panel). 
Protocol-specific requirements for inclusion or exclusion of subjects are detailed in 
Sections 5.1 to 5.2 of the protocol. 
Additional 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: 
Chemistry 
Local 
Laboratory: 
Coagulation 
Local Laboratory: 
Urinalysis 
Local Laboratory: 
Hematology 
Other Lab 
Analytes 
Sodium 
Potassium 
Chloride 
Bicarbonate or 
CO2 
Total protein 
Albumin 
Calcium 
Magnesium 
Phosphorus 
Glucose 
BUN or serum 
urea 
Creatinine 
Creatine Kinase 
Uric acid 
Total bilirubin 
Direct bilirubin 
ALP 
LDH 
AST (SGOT) 
ALT (SGPT) 
 
 
PT/INR 
PTT/APTT 
 
 
Blood 
Protein 
Glucose 
Bilirubin 
 
RBC 
Hemoglobin 
MCV  
 
Platelets 
WBC 
Differentials: 
5-part 
differential: 
• Lymphocytes 
• Monocytes  
• Eosinophils 
• Basophils 
• Total 
Neutrophils or 
(Segmented 
Neutrophils and 
bands/stabs 
3-part differential 
if unable to 
perform 5-part: 
• Lymphocytes 
• Granulocytes 
• Monocytes 
OR 
• Lymphocytes 
• Neutrophils 
• Mid-cell fraction 
Central 
Laboratory:  
Anti-tarlatamab 
antibodies 
Tarlatamab PK 
 
Local 
Laboratory: 
Serum or Urine 
Pregnancy 
HIV Antibody 
testing 
Hepatitis 
serology 
testing 
(DNA/RNA by 
PCR as 
needed) 
Hep B surface 
antigen 
Hep B core 
antibody 
Hep C virus 
antibody  
Amylase 
Lipase 
TSH 
FT4 
  
ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; 
APTT  activated partial thromboplastin time; BUN = blood urea nitrogen; CO2 = carbon dioxide; DNA = 
deoxyribonucleic acid; FT4 = free T4 Hep = hepatitis; HIV = human immunodeficiency virus;  
INR = international normalized ratio; LDH = lactate dehydrogenase; MCV  mean corpuscular volume; PCR 
= polymerase chain reaction; PK = pharmacokinetics; PT = prothrombin time; PTT = partial thromboplastin 
time; RBC = red blood cell count; RNA = ribonucleic acid; SGOT = serum glutamic-oxaloacetic 
transaminase; SGPT = serum glutamic-pyruvic transaminase; TSH = thyroid-stimulating hormone; 
WBC = white blood cell count 
If the subject is being followed for possible drug-induced liver injury (DILI), the following 
analytes may be tested at the local laboratory depending on the clinical situation (see 
Section 11.7). 

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Table 11-2.  DILI Potential Analyte Listing  
Chemistry 
Total bilirubin, direct bilirubin, ALP, LDH, AST (SGOT), ALT (SGPT), 
creatine kinase, ferritin, gamma-glutamyl transferase, haptoglobin 
Hematology 
Hemoglobin, Platelets, RBC Morphology, RBC Count, WBC Count, WBC 
Differential 
Coagulation 
PT, INR, APTT 
Immunology 
5 Prime Nucleotidase, Alpha-1 Antitrypsin, Antinuclear Antibodies, 
Anti-Smooth Muscle Antibody, Anti-Soluble Liver Ag/Liver-Pancreas Ag, 
Cytomegalovirus IgG Antibody, Cytomegalovirus IgM Antibody, Endomysial 
IgA Antibody, Epstein-Barr Virus EDA IgG Antibody, Epstein-Barr Virus NA 
IgG Antibody, Epstein-Barr Virus VCA IgG Antibody, Epstein-Barr Virus 
VCA IgM Antibody, Hepatitis A Virus IgG Antibody, Hepatitis A Virus IgM 
Antibody, Hepatitis B Core Antibodies, Hepatitis B Core IgM Antibody, 
Hepatitis B Surface Antigen, Hepatitis B Virus DNA Genotyping, Hepatitis B 
Virus Surface Antibody, Hepatitis C Antibodies, Hepatitis C Virus RNA 
Genotyping, Hepatitis D Virus Antibody, Hepatitis D RNA, Hepatitis E RNA, 
Hepatitis E IgG Antibody, Hepatitis E IgM Antibody, Herpes Simplex Virus 
Type 1_2 IgG AB, Herpes Simplex Virus Type 1_2 IgM AB, Human Herpes 
Virus 6 DNA, Human Herpes Virus 7 DNA, Human Herpes Virus 8 DNA, 
Immunoglobulin G, Liver Kidney AB 1,  
Parvovirus IgM/IgG Antibody, Serum Caeruloplasmin, Tissue 
Transglutaminase IgA Antibody, Toxoplasma IgM/IgG, Varicella Zoster 
Virus Antibody 
Toxicology 
Acetaminophen 
AB  antibody; ALP = alkaline phosphatase; ALT = alanine aminotransferase; AST = aspartate 
aminotransferase; APTT  activated partial thromboplastin time; DILI = drug-induced liver injury; EDA = 
early antigen; Ig = immunoglobulin; INR = international normalized ratio; LDH = lactate dehydrogenase; 
NA = nuclear antigen; PT = prothrombin time; RBC = red blood cell; RNA = ribonucleic acid; SGOT = serum 
glutamic-oxaloacetic transaminase; SGPT = serum glutamic pyruvic transaminase; VCA = viral capsid 
antigen; WBC = white blood cell 

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11.3 
Appendix 3.  Study Governance Considerations  
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 International Council for Harmonisation (ICH) Good Clinical Practice 
(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 external review body (eg, institutional review board 
[IRB]/Independent ethics committee [IEC]/regulatory authorities) by the investigator and 
reviewed and approved by the external review body.  A copy of the written approval of 
the protocol and informed consent form 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 external review body for all protocol amendments 
and changes to the informed consent document that Amgen distributes to the site.  The 
investigator must send a copy of the approval letter, if applicable, from the external 
review body and amended protocol investigator’s Signature page to Amgen before 
implementation of the protocol amendment at their site. 
During the course of the study, if new information becomes available that alters the 
benefit-risk of the study or the study drug, Amgen will follow applicable regulations to 
notify investigators, the external review body, as appropriate. 
The investigator will be responsible for the following: 
 
Providing written summaries of the status of the study to the external review body 
annually or more frequently in accordance with the requirements, policies, and 
procedures established by the external review body. 
 
Obtaining, if applicable, annual external review body approval/renewal throughout 
the duration of the study.  Copies of the investigator’s reports and the external review 
body continuance of approval must be sent to Amgen. 
 
Notifying the external review body 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. 

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 
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 external review 
body, and all other applicable local regulations. 
Informed Consent Process 
An initial sample informed consent form is provided for the investigator to prepare the 
informed consent document to be used at their site.  Updates to the sample informed 
consent form are to be communicated formally in writing from the Amgen Study Manager 
to the investigator.  The written informed consent form is to be prepared in the 
language(s) of the potential patient population. 
The investigator or their delegated representative will explain to the subject, or their 
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 external review body 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 person who conducted the informed consent discussion (investigator or 
their delegated representative) must also sign the informed consent form. 
The investigator is also responsible for asking the subject if the subject has a primary 
care physician and if the subject agrees to have their primary care physician informed of 
the subject’s participation in the clinical study.  If the subject agrees to such notification, 
(or it is a local requirement) 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 their 
notification of the primary care physician is to be documented in the subject’s medical 

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records, and the informed consent form is to be signed and personally dated by the 
subject or a legally authorized 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. 
If important new information becomes available that may be relevant to the subject’s 
consent during their participation in the study, subjects will be reconsented.  
The original signed informed consent form is to be retained in accordance with 
institutional policy, and a copy of the informed consent form(s) must be provided to the 
subject or the subject’s legally authorized representative.  
If a potential subject is illiterate or visually impaired and does not have a legally 
authorized representative, the investigator must provide an impartial witness to read the 
ICF to the subject and must allow for questions.  Thereafter, both the subject and the 
witness must sign the ICF to attest that informed consent was freely given and 
understood.  (Refer to ICH GCP guideline, Section 4.8.9.) 
A subject who is rescreened is not required to sign another ICF if the rescreening occurs 
within 21 days from the previous ICF signature date. 
Data Protection/Subject Confidentiality 
The investigator must ensure that the subject’s confidentiality is maintained for 
documents submitted to Amgen. 
The 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 informed consent forms) are to 
be kept in confidence by the investigator, except as described below. 

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Subject data should be kept in a secure location.  Access to subject data will be limited 
to authorized individuals, as described below. 
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 external review body 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 their study-related records, including personal 
information. 
Amgen complies with all relevant and applicable laws and regulations that protect 
personal information to ensure subject confidentiality and privacy.  Subjects are 
designated by a unique subject identification number in the sponsor’s systems.  The 
sponsor uses access-controlled systems to house, review and analyze subject data.  
These systems are backed-up regularly to minimize the risk of loss of subject data; 
procedures are also defined for data recovery in the event of data loss.  The sponsor 
has standard operating procedures in place that restrict access to subject data to those 
who require access to this data based on their role and have also completed the 
required training.  These procedures also outline the process for revoking access to 
such data when it is no longer needed.  In the event of a security breach, the sponsor 
has procedures in place for notification of privacy incidents and to address these 
incidents, via its Business Conduct Hotline. 
Serious Breach 
Suspected Serious Breaches must be reported to the study team or the Clinical Out-of-
Hours Support Program:   https://wwwext.amgen.com/science/clinical-trials/clinical-out-
of-hours-support-program immediately and no later than 1 calendar day from the time of 
awareness. 
A Serious Breach is a breach of any of the following: 
 
Good Clinical Practice (GCP) 
 
the clinical trial protocol 
 
an applicable regulation 
That is likely to impact to a significant degree either of the following: 

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 
the safety, physical, or mental integrity and the rights of the subject  
 
the reliability and robustness of the data and the scientific value of the trial 
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. 
All publications (eg, manuscripts, abstracts, oral/slide presentations, book chapters) 
based on this study must be prepared in accordance with Amgen’s publications policy 
and submitted to Amgen for review.  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, or the acquisition, analysis, or 
interpretation of data for the work; (2) drafting the work 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 
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, 

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investigator, and Amgen will detail the procedures for, and timing of, Amgen’s review of 
publications.  
Results Reporting 
Results will be reported to clinical study registries in accordance with applicable 
regulatory requirements.  The final summary results will be reported after the global end 
of study (as defined in Section 4.5) to ensure data from all sites globally are included in 
the reported results.  
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 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 on the CRF.  
The investigator must permit study-related monitoring, audits, external review body 
review, 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. 
The sponsor or designee will perform ongoing source data verification to confirm that 
data entered on 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 

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approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements per the sponsor’s monitoring plan. 
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 Compliance and Audit function (or 
designees).  Inspection of site facilities (eg, pharmacy, investigational product(s), and/or 
noninvestigational product(s)/auxiliary medicinal product(s) 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. 
Quality tolerance limit parameters (QTLs) will be predefined in the QTL definitions table 
to identify possible systematic issues that can impact participant safety and/or reliability 
of the study results.  These predefined parameters will be monitored during the study.  
Important deviations from the QTL threshold limits for these parameters and remedial 
actions taken will be summarized in the clinical study report. 
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. 
Source Documents 
The investigator is to maintain a list of appropriately qualified persons to whom they 
have 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. 

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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 system (if used, such as subject ID 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 or certain demographic information, such as gender, race, and ethnicity). 
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, informed consent forms, 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 external 
review body 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 
 
Noninvestigational product(s)/auxiliary medicinal 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. 
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.  

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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 external review body 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 a separate 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. 
Events Meeting the Adverse Event Definition 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) 
or other safety assessments (eg, electrocardiogram [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 preexisting 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 intentional overdose of 
either study treatment or a concomitant medication.   
 
Intentional overdose will be reported as an adverse event/serious adverse event 
when it is taken with possible suicidal/self-harming intent.  Such intentional 
overdoses are to be reported regardless of sequelae on the Events CRF.  
 
Accidental/unintentional overdose will be captured as a medication error.   
 
Disease progression is an efficacy endpoint.  Progression or symptom/sign of the 
small cell lung cancer (SCLC) should ONLY be reported as an adverse event or 
serious adverse event if there is evidence suggesting a causal relationship 
between the investigational product(s) and/or noninvestigational 
product(s)/auxiliary medicinal product(s) and progression or symptom/sign of 
progression of the SCLC.  The event should be recorded on the Events CRF. 
 
“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.   
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. 

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 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
 
Anticipated day-to-day fluctuations of preexisting disease(s) or condition(s) present 
or detected at the start of the study that do not worsen. 
 
Progression of the SCLC should be considered disease progression and not 
considered an adverse event or serious adverse event.  Progression of the 
subject's underlying malignancy will be recorded in the Tumor Response CRF as 
part of efficacy data collection and not on the Events CRF.  Death due to disease 
progression is to be recorded on the End of Study CRF page and not on the 
Events form. 
The following are not considered adverse events or serious adverse events: 
o Progression of SCLC (Progressive disease):  If progressive disease is 
consistent with progression of the underlying malignancy as defined by 
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 
(See Section 11.10)  
o Clinical symptoms or signs that meet the expected pattern of disease 
progression of the SCLC in the presence of documented evidence of 
progression underlying malignancy as defined by RECIST 1.1 
(See Section 11.10) 
o Deaths that are attributed by the investigator to progression of SCLC 
 
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 

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treatment of a preexisting 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. 
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. 
 

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Other Safety Findings/Special Situations:  Medication Errors, Misuse or Abuse 
All medication errors, misuse or abuse of the investigational product when 
associated with a serious adverse event, the OSF/SS must be reported to Amgen or 
designee immediately and no later than 24 hours of investigator’s awareness by 
submitting the paper-based electronic Serious Adverse Event (eSAE) Contingency 
Report Form.  
 
 
 
 
 
Definitions 
Medication Error:  A medication error is an unintended failure in the 
drug treatment process that leads to, or has the potential to lead to 
harm to the participant (eg, mistake in the process of prescribing, 
storing, dispensing, preparing, or administering medicinal products 
in clinical practice.   
Misuse:  A misuse refers to situations where the medicinal  
product, combination product, or medical device is intentionally 
and inappropriately used not in accordance or outside what is  
foreseen in the protocol.   
  
Abuse:  An abuse corresponds to the persistent or sporadic, 
intentional excessive use of a medicinal product, combination 
product, or medical device, which is accompanied by harmful 
physical or psychological effects.  

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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 CRF. 
 
The investigator must assign the following mandatory adverse event attributes: 
- Adverse event diagnosis or syndrome(s), if known (if not known, signs or 
symptoms) 
- Dates of onset and resolution (if resolved) 
- Did the event start before first dose of investigational product 
- Assessment of seriousness 
- Severity (or toxicity defined below) 
- Assessment of relatedness to investigational product(s), noninvestigational 
product(s)/auxiliary medicinal product(s) 
- Assessment of relatedness to study-required activity and/or procedures is only 
required for Serious Adverse Events 
- Action taken 
- Outcome of event 
 
It is not acceptable for the investigator to send photocopies of the subject’s 
medical records to sponsor in lieu of completion of the Events CRF. 
 
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, except for the subject number, 
will be blinded on the copies of the medical records before submission to Amgen. 
 
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 assess 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 (CTCAE), version 5.0 which is 
available at the following location:  
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 

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CTCAE will be used with the following exceptions:  Cytokine release syndrome (CRS) 
and immune-effector cell associated neurologic syndrome (ICANS) will be graded 
according to American Society for Transplantation and Cellular Therapy (ASTCT) 
(Lee et al, 2019) as described in Section 11.11.  Tumor lysis syndrome (TLS) will be 
graded based on CTCAE v5.0 but will be managed based on Cairo Bishop criteria 
(Coiffier et al, 2008). 
Assessment of Causality 
 
The investigator is obligated to assess the relationship between investigational 
product(s) investigational product(s), noninvestigational product(s)/auxiliary 
medicinal product(s), and each occurrence of each adverse event. 
 
The investigator is obligated to assess the relationship between investigational 
product(s) investigational product(s), noninvestigational product(s)/auxiliary 
medicinal product(s), study-required activity and/or procedure(s) and each 
occurrence of each 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 their assessment. 
 
For each adverse event/serious adverse event, the investigator must document in 
the medical notes that they have reviewed the adverse event/serious adverse 
event and has provided an assessment of causality.  For sites reporting serious 
adverse events via electronic data capture (EDC), the investigator or 
sub-investigator must confirm causality in EDC within 72 hours of the serious 
adverse event being entered on the Events CRF. 
 
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 assess causality for every event before 
the initial transmission of the serious adverse event data. 
 
The investigator may change their opinion of causality in light of follow-up 
information and send a serious adverse event follow-up report with the updated 
causality assessment.  In this case, for sites reporting serious adverse events via 
EDC, the investigator or sub-investigator must reconfirm causality in the EDC 
system within 72 hours of the serious adverse event being entered on the Events 
CRF. 
 
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 
healthcare professionals. 
 
If a subject is permanently withdrawn from investigational product(s) and/or 
noninvestigational product(s)/auxiliary medicinal product(s) 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 will provide Amgen with a copy of any postmortem findings 
including histopathology. 
 
New or updated information will be recorded in the originally completed Events 
CRF. 
 
The investigator will submit any updated serious adverse event data to Amgen 
immediately and no later than 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 EDC 
system. 
 
If the EDC system is unavailable, then the site will report the information to Amgen 
using a paper-based Serious Adverse Event Contingency Report Form (also 
referred to as the eSAE Contingency Report Form) (see Figure 11-1) immediately 
and no later than 24 hours of the investigator’s awareness of the event. 
 
If the event is a serious adverse event associated with the Other Safety 
Finding/Special Situation (medication error, misuse or abuse) then the site must 
complete/submit the paper-based eSAE Contingency Report Form (see Figure 
11-1) for the associated Other Safety Finding/Special Situation (medication error, 
misuse or abuse) and this is the primary reporting method. 
 
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 system has been taken off-line, then the site can report this information on 
the 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 product will be reported to Amgen immediately and no later than 
24 hours of the investigator’s awareness of the event.  The investigator should use 
the paper-based Serious Adverse Event Contingency Report Form (see 
Figure 11-1) to report the event. 

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Figure 11-1.  Sample Electronic Serious Adverse Event Contingency Report Form 
(Paper-based 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 females of childbearing potential 
are outlined in Section 5.2.  Contraceptive use and methods should be consistent with 
local regulations for subjects participating in clinical studies. 
Male and female subjects of childbearing potential OR for pediatric studies:  who have 
reached puberty should be advised of the pregnancy prevention requirements and the 
potential risk to the fetus if they become pregnant or father a child during treatment and 
for an additional 60 days after the last dose of tarlatamab.  Note:  contraception 
requirements for noninvestigational medicinal product(s)/auxiliary medicinal 
product(s) including auxiliary medicinal products are based on regional/local 
prescribing information. 
Definition of Females of Childbearing Potential 
A female is considered fertile after menarche and until becoming postmenopausal 
unless permanently sterile.  Permanent sterilization methods include documented 
hysterectomy, bilateral salpingectomy, and bilateral oophorectomy.  Females with 
documented permanent infertility due to an alternate medical cause (eg, Mullerian 
agenesis, androgen insensitivity, gonadal dysgenesis), can be considered not of 
childbearing potential. 
Note:  Bilateral tubal ligation/occlusion is not considered a permanent sterilization 
method. 
Note:  Documentation from the following sources is acceptable to provide confirmation of 
each sterilization method:  (1) review of subject’s medical records; (2) subject’s medical 
examination; or (3) subject’s medical history interview. 
A postmenopausal female is defined as: 
 
A woman of ≥ 55 years with no menses for 12 months without an alternative medical 
cause. 
 
A woman age < 55 years with no menses for at least 12 months and with a 
follicle-stimulating hormone (FSH) level within the definition of “postmenopausal 
range” for the laboratory involved.  In the absence of 12 months of amenorrhea, 
confirmation with more than 1 FSH measurement is required. 

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Contraception Methods for Female Subjects 
Highly Effective Contraceptive Methods 
 
Combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal, or transdermal) 
 
Progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable, or implantable) 
 
Intrauterine device  
 
Intrauterine hormonal-releasing system  
 
Bilateral tubal ligation/occlusion 
 
Vasectomized partner (if 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 study 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 investigational product(s) and/or noninvestigational 
product(s)/auxiliary medicinal product(s); the reliability of sexual abstinence must be 
evaluated in relation to the duration of the study and the preferred and usual lifestyle of 
the subject)  
 
Use a condom during treatment and for an additional 60 days after the last dose of 
tarlatamab 
Note:  contraception requirements for noninvestigational medicinal 
product(s)/auxiliary medicinal product(s) including auxiliary medicinal 
products are based on regional/local prescribing information. 
The female partner should consider using a method of contraception for female subjects 
stated above (a female condom should not be used because there is a risk of tearing 
when both partners use a condom). 
Note:  If the male’s sole female partner is of nonchildbearing potential or has had a 
bilateral tubal ligation/occlusion or if the male has had a vasectomy and testing confirms 
there is no sperm in the semen, he is not required to use additional forms of 
contraception during the study. 

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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 investigational product(s) and/or noninvestigational 
product(s)/auxiliary medicinal product(s) through 60 days after the last dose of 
tarlatamab. 
 
Information will be recorded on the Pregnancy Notification Form (see Figure 11-2).  
The form must be submitted to Amgen Global Patient Safety immediately and no 
later than 24 hours of the site’s awareness 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 consent 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 investigational product(s) and/or noninvestigational 
product(s)/auxiliary medicinal product(s) through 60 days after the last dose of 
tarlatamab.  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 elective termination of a pregnancy for medical 
reasons will be reported as an adverse event or serious adverse event.  Abnormal 
pregnancy outcomes (eg, spontaneous abortions, stillbirth, fetal death, congenital 
anomalies) 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. 
 
Any serious adverse event occurring as a result of a poststudy 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 while pregnant (see Section 7.1 for details). 
Male Subjects With Partners Who Become Pregnant or Were Pregnant at the Time of 
Enrollment 
 
In the event a male subject fathers a child during treatment, and for an additional 
60 days after the last dose of tarlatamab.  The information will be recorded on the 
Pregnancy Notification Form.  The form (see Figure 11-2) must be submitted to 
Amgen Global Patient Safety immediately and no later than 24 hours of the site’s 
awareness of the pregnancy.  (Note:  Sites are not required to provide any 

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information on the Pregnancy Notification Form that violates the country or regions 
local privacy laws). 
 
Males with pregnant partners or whose partners become pregnant during treatment 
and for an additional 60 days after the last dose of tarlatamab must practice sexual 
abstinence or use a condom through 60 days after the last dose of tarlatamab. 
 
The investigator will attempt to obtain a signed consent 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 consent 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 investigational product(s) and/or noninvestigational product(s)/auxiliary 
medicinal product(s) through 60 days after the last dose of tarlatamab. 
 
Information will be recorded on the Lactation Notification Form (see below) and 
submitted to Amgen Global Patient Safety immediately and no later than 24 hours of 
the investigator’s awareness of the event. 
 
Study treatment will be discontinued if female subject breastfeeds during the study 
as described in the exclusion criteria (see Section 5.2). 
 
With the female subjects signed consent 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 tarlatamab through 60 days after the last dose of tarlatamab. 

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Figure 11-2.  Pregnancy and Lactation Notification Forms (Paper-based Form)  
 

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11.6 
Appendix 6.  Sample Storage and Destruction  
When permitted by local regulations, any blood, pharmacokinetic (PK) samples collected 
according to the Schedule of Activities (Section 1.3) 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.  
All samples and associated results will be coded before 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.  
When permitted by local regulations and if informed consent is provided by the subject, 
Amgen can do additional testing on remaining samples (ie, residual and back-up) to 
investigate and better understand the SCLC, the dose response and/or prediction of 
response to tarlatamab, 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 5 years after the study is finished.   
Since the evaluations are not expected to benefit the subject directly or to alter the 
treatment course, the results of pharmacogenetic, 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.  After 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 
completed and according to the approval of local laws and regulations.  However, 
information collected from samples before the request for destruction, will be retained by 
Amgen. 

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All rights in inventions and discoveries that are made or developed by Institution, 
Investigator and/or Study Personnel as a result of the conduct of the Study, other than 
Registrational Research Inventions, (“Exploratory Research Inventions”) shall be owned 
by both Institution and Sponsor equally.  

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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 such as alanine aminotransferase 
(ALT), aspartate aminotransferase (AST), total bilirubin (TBL), alkaline phosphatase 
[ALP], and/or international normalized ratio (INR) and/or signs and symptoms of 
hepatotoxicity (as described below) may meet the criteria for interruption or permanent 
discontinuation of study drug(s).  This instruction is based on the FDA Guidance for 
Industry Drug-Induced Liver Injury: Premarketing Clinical Evaluation (US FDA, July 
2009).   
Reporting and management of hepatotoxicity in subjects in clinical trials is 
described below and management is summarized in the flow chart in Figure 11-3. 
11.7.1 
Criteria for Stopping Amgen Investigational Product and 
Noninvestigational Product(s)/Auxiliary Medicinal Product(s) Due to 
Potential Hepatotoxicity  
Stopping rules apply to each of the following criteria in subjects for whom another 
cause for the changes in liver biomarkers (TBL, INR, and transaminases) has not been 
identified: 
 
ALT or AST > 8 x upper limit of normal (ULN) 
 
ALT or AST > 5 x ULN for more than 2 weeks 
 
ALT or AST > 3 x ULN and (TBL >2 x ULN or INR > 1.5)  
 
ALT or AST > 3 x ULN with the appearance of fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(> 5%). 
Of note in subjects with elevated values at baseline (before exposure to the 
investigational medicinal product), fold increases above the baseline values will 
guide the interruption and close observation.   
11.7.2 
Reporting Criteria 
Cases with events of elevation of AST, ALT, TBL, INR, mentioned above require 
the following: 
 
The event is to be reported to Amgen as a serious adverse event immediately and 
no later than 24 hours of discovery or notification of the event (ie, before additional 
etiologic investigations have been concluded). 
 
The appropriate case report form (CRF) (eg, Events electronic case report form 
([eCRF]) that captures information necessary to facilitate the evaluation of treatment-
emergent liver abnormalities is to be completed and sent to Amgen. 

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Other events of potential hepatotoxicity are to be reported as serious adverse events if 
they meet the criteria for a serious adverse event defined in Section 11.4. 
11.7.3 
Follow up Actions 
All subjects in whom investigational product(s) or protocol-required therapies is/are 
interrupted (either permanently or conditionally) due to potential hepatotoxicity should 
undergo a period of “close observation” until elevated laboratory values return to 
normal ranges 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 laboratory values are still elevated perform repeat measurement of 
liver laboratory tests every 2 to 3 days until laboratory abnormalities improve. 
Testing frequency of the above laboratory tests may decrease if the laboratory 
abnormalities stabilize, or the study drug(s) has/have been discontinued AND the 
subject is asymptomatic. 
The “close observation period” is to continue for a minimum of 4 weeks after 
discontinuation of study drug(s). 
The hepatotoxicity events and additional information such as medical history, 
concomitant medications and laboratory results must be captured in the 
corresponding CRFs. 
Initiate investigation of alternative causes for hepatotoxicity (Section 11.7.3.1). 
If laboratory values improve, consider rechallenging with the study drug(s) only if 
the benefit: risk ratio is supportive (and as described in Section 11.7.4).  
Otherwise, discontinue study drug(s) permanently. 
11.7.3.1 
Investigating Alternative Causes of Hepatotoxicity 
 
The following assessments are to be considered depending on the clinical situation: 
 
Blood count with differential to assess for eosinophilia. 
 
Serum total immunoglobulin 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: 
 
prior and/or concurrent diseases or illness 
 
exposure to environmental and/or industrial chemical agents 
 
symptoms (if applicable) including right upper quadrant pain, 
hypersensitivity-type reactions, fatigue, nausea, vomiting, and fever 

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 
prior and/or concurrent use of alcohol, recreational drugs, and special 
diets 
 
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 (appropriate liver biopsy may be considered in consultation with 
a hepatologist). 
11.7.3.1.1 
Important Alternative Causes  
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 
 
NASH (nonalcoholic fatty liver disease aka MASH) including steatohepatitis. 
 
non-hepatic causes (eg, rhabdomyolysis, hemolysis) 
Special consideration is warranted when using products known to cause transient 
elevation of liver enzymes, such as T cell engager molecules.  For example, in the 
instances of cytokine release syndrome (CRS) following exposure to BiTE 
molecules, transient elevations of isolated liver parameters were frequently noted.  
Careful monitoring of laboratory parameters and the clinical status of subjects is 
required, and continuation of the medication may be considered and will be at the 
discretion of the investigators. 

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11.7.4 
Rechallenge and Dose Modification in Patients with Suspected 
Hepatotoxicity in Oncology Trials 
 
The decision to rechallenge the subject is to be discussed and agreed upon 
unanimously by the subject, investigator, and Amgen.  If rechallenge is considered 
appropriate, the subject must be fully informed about the risk and should give 
written consent.  Any rechallenge must be accompanied by close monitoring, 
with at least weekly liver biochemistry until response to the rechallenge is fully 
characterized. 
 
If signs or symptoms recur with rechallenge, then Amgen investigational product and 
noninvestigational product(s)/auxiliary medicinal product(s), as appropriate is to be 
permanently discontinued.  Subjects who clearly meet the criteria for permanent 
discontinuation are never to be rechallenged. 
 
For oncology drugs that demonstrate potential benefit but also potential 
hepatotoxicity, consideration of rechallenge or dose modification (with a 
reduced dose) should be based on benefit: risk and clinical and biochemical 
characteristics of the original liver injury.  
 
Rechallenge is not recommended when there is no evidence of benefit for the 
individual subject, or where alternative treatment options are available.  
 
Rechallenge is generally not recommended for cases of suspected or 
confirmed severe hepatocellular injury (clinical evidence of liver dysfunction 
with jaundice or INR elevation), in the presence of underlying cirrhosis, or 
where there are features of immunologic hepatotoxicity. 
 
Before undertaking a rechallenge, there should be sufficient resolution of liver 
biochemistry abnormalities; although these depend on the patient population, 
reasonable options include ALT reducing to < 3x ULN for those with normal 
baseline ALT or returning to < 4x ULN and < 6x ULN for those with elevated 
baseline ALT of 1.5 to 3x ULN and 3 to 5x ULN respectively. 
11.7.5 
Permanent Discontinuation of Study Drug(s) 
In the absence of acceptable enzyme level decrease or lack of a plausible 
alternative explanation for the elevated laboratory pattern, consider permanent 
discontinuation of study drug treatment. 
11.7.6 
Management Flow Chart 
The following flow chart can be used to manage potential hepatotoxicity cases 
(Figure 11-3). 

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, monitor 
closely and 
i
li
, monitor 
closely and 
review liver 
li i
l
Figure 11-3.  Management of Potential Hepatotoxicity 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Interrupt study drug(s) 
administration, monitor closely and 
review liver clinical laboratory 
parameters 
ALT or AST> 3x ULN 
AND 
 TBL > 2x ULN OR INR > 1.5 
ALT or AST> 8x ULN 
OR 
ALT or AST> 5x ULN for more than 2 weeks 
OR 
ALT or AST> 3x ULN AND (TBL > 2x ULN OR INR >1.5) 
OR 
ALT or AST > 3x ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever, rash, and/or eosinophilia (>5%) 
ALT or AST> 8x ULN 
OR 
ALT or AST> 5x ULN for more 
than 2 weeks 
OR 
ALT or AST > 3x ULN with the 
appearance of fatigue, nausea, 
vomiting, right upper quadrant 
pain or tenderness, fever, rash, 
and/or eosinophilia (>5%) 
rug(
s) 
close
 
Discontinue 
 study  
drug(s) 
permanently. 
Not Improved 
YES 
Rechallenge 
Improved 
rug(s) 
closely 
and
 
Discontinue study 
drug(s) permanently. 
Did signs or symptoms re-occur after 
rechallenge with study drug(s) 
NO 
Continue 
YES 
NO 
The decision to rechallenge 
subject is to be discussed and 
agreed upon unanimously by 
the subject, investigator, and 
Amgen. 
Other reason can be found to explain 
the combination of increased AT and 
TBL, including but not limited to viral 
hepatitis A, B, or C; preexisting or 
acute liver disease; or another drug 
capable of causing the observed injury 
AND 
Initial finding of elevated ALP 
(cholestasis) 
YES 

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11.8 
Appendix 8.  Protocol-specific Anticipated Serious Adverse Events  
Anticipated serious adverse events are events that are anticipated to occur in the study 
population at some frequency independent of investigational product exposure and do 
not need to be reported individually as a United States Food and Drug Administration 
(FDA) Investigational New Drug (IND) safety report by the sponsor.  Identification and 
reporting of anticipated serious adverse events is the responsibility of the sponsor; the 
investigator is responsible for reporting adverse events and serious adverse events as 
described in Section 8.4.6 and Appendix 11.4. 
Anticipated Serious Adverse Events for Study 20230273 
MedDRA Preferred Terma 
cough 
weight loss 
decreased appetite 
anorexia 
hemoptysis 
small cell lung cancer 
metastasis 
chest pain 
fatigue 
anemia 
MedDRA  Medical Dictionary for Regulatory Activities 
a MedDRA Version 24.0 

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11.9 
Appendix 9.  ECOG Performance Status and NYHA Functional 
Classification  
Eastern Cooperative Oncology Group (ECOG) Performance Status 
 
0: Fully active, able to carry out all pre-disease performance without restriction. 
 
1: Restricted in physically strenuous activity, but ambulatory and able to carry out 
work of a light or sedentary nature (eg, light housework, office work). 
 
2: Ambulatory and capable of all self-care, but unable to carry out any work 
activities.  Up and about more than 50 of waking hours. 
 
3: Capable of only limited self-care, confined to bed or chair more than 50 of 
waking hours. 
 
4: Completely disabled.  Cannot carry out any self-care.  Totally confined to bed or 
chair. 
 
5: Dead 
New York Heart Association Functional Classification 
 
Class I: 
No limitation of physical activity.  Ordinary physical activity does not 
cause undue fatigue, palpitation, or dyspnea. 
 
Class II: 
Slight limitation of physical activity.  Comfortable at rest, but ordinary 
physical activity results in fatigue, palpitation or dyspnea.  
 
Class III: Marked limitation of physical activity.  Comfortable at rest, but less than 
ordinary activity causes fatigue, palpitation or dyspnea. 
 
Class IV: Unable to carry out any physical activity without discomfort.  Symptoms of 
cardiac insufficiency may be present even at rest.  If any physical activity is 
undertaken, discomfort is increased. 
 

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11.10 
Appendix 10.  Response Evaluation Criteria in Solid Tumors 
Version 1.1 (RECIST 1.1); Eisenhauer et al, 2009  
11.10.1 
Definitions  
11.10.1.1 
Measurable Disease  
The presence of at least 1 measurable lesion.  If the measurable disease is restricted to 
a solitary lesion, its neoplastic nature should be confirmed by cytology/histology. 
11.10.1.2 
Measurable Lesions  
11.10.1.2.1 
Measurable Non-nodal Tumor Lesions  
Non-nodal lesions with clear borders that can be accurately measured in at least 
1 dimension with longest diameter  10 mm in computed tomography (CT)/ magnetic 
resonance imaging (MRI) scan with slice thickness no greater than 5 mm.  When slice 
thickness is greater than 5 mm, the minimum size of measurable lesion should be twice 
the slice thickness. 
11.10.1.2.2 
Nodal Lesions  
Lymph nodes are to be considered measurable if  15 mm in short axis when assessed 
by CT/MRI (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. 
11.10.1.2.3 
Cystic Lesions  
Cystic lesions thought to represent cystic metastases can be considered as measurable 
lesions, if they meet the definition of measurability described above for non-nodal 
lesions. 
11.10.1.2.4 
Bone lesions with identifiable soft tissue components  
Bone lesions with identifiable soft tissue components, that can be evaluated by cross 
sectional imaging techniques such as CT or MRI can be considered as measurable 
lesions if the soft tissue component meets the definition of measurability described 
above for non-nodal lesions. 
11.10.1.2.5 
Clinically Measured Lesions  
Visible or palpable lesions can be considered measurable if  10 mm in longest diameter 
for non-nodal or  15 mm in shortest diameter for lymph nodes.  Lesions should be 
measured radiologically if more accurate, if not then measured by calipers. 

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11.10.1.2.6 
Irradiated Lesions  
Tumor lesions situated in a previously irradiated area, or in an area subjected to other 
loco-regional therapy, are not measurable unless there has been demonstrated 
progression that is measurable in the lesion prior to enrollment. 
11.10.1.3 
Non-measurable Lesions  
All other lesions, including small lesions (longest diameter  10 mm or pathological 
lymph nodes with  10 mm to  15 mm short axis with CT scan slice thickness no 
greater than 5 mm) are considered non-measurable.  (When slice thickness is greater 
than 5 mm, the minimum size of measurable lesion should be twice the slice thickness). 
Other examples of lesions usually considered to be non-measurable include: 
 
Lesions with prior local treatment:  tumor lesions situated in a previously irradiated 
area, or an area subject to other loco-regional therapy, should not be considered 
measurable unless there has been demonstrated progression in the lesion. 
 
Categorically, clusters of small lesions, bone lesions without a soft tissue component, 
inflammatory breast disease, ascites, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis and leptomeningeal disease are non-measurable. 
11.10.2 
Methods of Measurement  
All measurements should be taken and recorded in metric notation, using a ruler or 
calipers.  The same method of assessment and the same technique should be used to 
characterize each identified and reported lesion at baseline and throughout the trial.  
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 will be 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. 
11.10.2.1 
CT/MRI  
Contrast-enhanced CT or MRI should be used to assess all lesions.  Optimal 
visualization and measurement of metastasis in solid tumors requires consistent 
administration (dose and rate) of intravenous (IV) contrast as well as timing of scanning.  
CT and MRI should be performed with  5 mm thick contiguous slices.  The longest 
diameter of selected lesions should be measured in the plane in which the images were 
acquired.  Ideally, the same scanner or at least type of scanner should be used and the 
image acquisition protocol should be followed as closely as possible to prior scans. 

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11.10.2.2 
PET-CT  
At present, the low dose or attenuation correction CT portion of a combined positron 
emission tomography–computed tomography (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 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. 
11.10.2.3 
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. 
11.10.2.4 
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. 
 
  
 
 
 
11.10.2.6 
Cytology, Histology  
These techniques can be used to differentiate between partial response (PR) and CR in 
rare cases if required by protocol (for example, residual lesions in tumor types such as 
germ cell tumors, where known residual benign tumors can remain). 
When effusions are known to be a potential adverse effect of treatment (eg, with certain 
taxane compounds or angiogenesis inhibitors), the cytological confirmation of the 

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neoplastic origin of any effusion that appears or worsens during treatment can be 
considered if the measurable tumor has met criteria for response or stable disease (SD) 
in order to differentiate between response (or SD) and progressive disease. 
11.10.2.7 
FDG-PET  
While fluorodeoxyglucose-positron emission tomography (FDG-PET) response 
assessments need additional study, it is sometimes reasonable to incorporate the use of 
FDG-PET scanning to complement CT scanning in assessment of progression 
(particularly possible 'new' disease).  New lesions on the basis of FDG-PET imaging can 
be identified according to the following algorithm:  
 
Negative FDG-PET at baseline, with a positive FDG-PET at follow-up is a sign of 
progressive disease (PD) based on a new lesion. 
 
No FDG-PET at baseline and a positive FDG-PET at follow-up:  If the positive 
FDG-PET at follow-up corresponds to a new site of disease confirmed by CT, this is 
PD.  If the positive FDG-PET at follow-up is not confirmed as a new site of disease 
on CT, additional follow-up CT scans are needed to determine if there is truly 
progression occurring at that site (if so, the date of PD will be the date of the initial 
abnormal FDG-PET scan).  If the positive FDG-PET at follow-up corresponds to a 
pre-existing site of disease on CT that is not progressing on the basis of the 
anatomic images, this is not PD. 
11.10.3 
Lesion Evaluation  
11.10.3.1 
Baseline documentation of “Target” and “Non-target” lesions  
11.10.3.1.1 
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) and suitability for accurate repeated measurements.  All other measurable 
lesions will be followed as non-target lesions. 
 
Lymph nodes are considered one organ, thus a maximum of 2 measurable lymph 
nodes may be identified as target lesions.  
 
A sum of the diameters (longest for non-nodal lesions, short axis for nodal lesions) 
for all target lesions will be calculated and reported as the baseline sum of 
diameters.  The baseline sum of diameters will be used as reference by which to 
characterize objective tumor response. 
11.10.3.1.2 
Non-Target Lesions  
 
All other lesions (or sites of disease) including pathological lymph nodes should be 
identified as non-target lesions and should be recorded at baseline.  These lesions 
should be followed as “present”, “absent”, “unequivocal progression”, or “not 
evaluable” throughout the study.  In addition, it is possible to record multiple 
non-target lesions involving the same organ as a single item on the CRF 
(eg, “multiple enlarged pelvic lymph nodes” or “multiple liver metastases”).  

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11.10.4 
Response Criteria  
Table 11-3.  Evaluation of Target Lesions 
Complete 
Response (CR) 
Disappearance of all target non-nodal lesions.  Any target lymph 
node must have reduction in short axis to  10 mm, NOT total 
disappearance. 
Partial 
Response (PR) 
At least a 30 decrease in the sum of the diameters of target 
lesions, taking as reference the baseline sum of 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.  If a subject is missing lesion 
data at a disease assessment and yet progressive disease criteria is 
met despite the missing data, the subject will be classified as PD.  
Stable Disease 
(SD) 
Neither sufficient shrinkage to qualify for PR nor sufficient increase 
to qualify for PD. 
Not Evaluable 
(NE) 
When inadequate or no imaging/measurement is done at a 
particular time point, the subject’s response is not evaluable (NE) at 
that time point.  
Table 11-4.  Evaluation of Non-target Lesions 
Complete 
Response (CR) 
Disappearance of all non-nodal non-target lesions and normalization 
of tumor marker level.  All non-target lymph nodes must be 
non-pathological in size ( 10 mm short axis). 
Non-CR/Non-P
D 
Persistence of one or more non-target lesions(s) and/or 
maintenance of tumor marker level above the normal limits. 
Progressive 
Disease (PD) 
Unequivocal progression of existing non-target lesionsa.  If a subject 
is missing lesion data at a disease assessment and yet unequivocal 
progression is met despite the missing data, the subject will be 
classified as PD. 
Not Evaluable 
(NE) 
When inadequate or no imaging is done at a particular time point, 
the subject’s response is not evaluable (NE) at that time point.  
PR  partial response; SD  stable disease 
a  To achieve “unequivocal progression” on the basis of the non-target disease, there must be an overall 
level of substantial worsening in non-target disease such that, even in presence of SD or PR in target 
disease, the overall tumor burden has increased sufficiently to merit discontinuation of therapy.  A modest 
“increase” in the size of 1 or more non-target lesions is usually not sufficient to qualify for unequivocal 
progression status. 
11.10.5 
Evaluation of Best Overall Response  
The subject's best response assignment will depend on the findings of both target and 
non-target disease and will also take into consideration the appearance of new lesions 
and confirmation of response.  Best overall response (BOR) will be based on all 
post-baseline disease assessments that occur prior to the initiation of subsequent 

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anticancer treatment.  At least 5 weeks from the first dose of tarlatamab must elapse 
without radiological disease progression to meet the minimum criteria for SD duration in 
order to assign a BOR of SD.  In general, subjects not classifiable under the RECIST 1.1 
response categories due to inadequate data or early death will be classified as 
non-evaluable (NE) for BOR but will be counted in the denominator of all response rate 
calculations.  
Table 11-5.  Time Point Overall Response 
Target 
Lesions 
Non-target Lesions 
New 
Lesions 
Overall Response 
Subjects with Target ( Non-target) Disease 
CR 
CR or NA 
No 
CR 
CR 
Non-CR/non-PD or NE 
No 
PR 
PR 
CR or Non-CR/Non-PD or NE 
or NA 
No 
PR 
SD 
CR or Non-CR/Non-PD or NE 
or NA 
No 
SD 
PD 
Any 
Any 
PD 
Any 
PD 
Any 
PD 
Any 
Any 
Yes 
PD 
NE 
CR or Non-CR/Non-PD or NE 
or NA 
No 
NE 
Subjects with Non-target Disease Only 
NA 
CR 
No 
CR 
NA 
Non-CR/Non-PD 
No 
(Non-CR/Non-PD)a 
NA 
CR or Non-CR/Non-PD 
NE 
(Non-CR/Non-PD)a 
NA 
PD 
Any 
PD 
NA 
Any 
Yes 
PD 
NA 
NE 
No 
NE 
CR  complete response; NA  Not applicable; NE  Not evaluable; PD  progressive disease; PR  partial 
response; RECIST  Response Evaluation Criteria in Solid Tumors; SD  stable disease. 
a Per RECIST 1.1, “SD (Non-CR/Non-PD)” is preferred over “SD” for Non-Target disease since SD is 
increasingly used as endpoint for assessment of efﬁcacy in some trials so to assign this category when no 
lesions can be measured is not advised. 

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Table 11-6.  Best Overall Response When Confirmation of Complete Response 
(CR) and Partial Response (PR) Required 
Overall 
Response First 
Time Point 
Overall Response 
Second Time 
Point 
Best Overall Response 
CR 
CR 
CR 
CR 
PR 
SD, PD or PRa 
CR 
SD 
SD provided minimum criteria for SD duration 
met, otherwise, PD 
CR 
PD 
SD provided minimum criteria for SD duration 
met, otherwise, PD 
CR 
NE 
SD provided minimum criteria for SD duration 
met, otherwise, NE 
PR 
CR 
PR 
PR 
PR 
PR 
PR 
SD 
SD 
PR 
PD 
SD provided minimum criteria for SD duration 
met, otherwise, PD 
PR 
NE 
SD provided minimum criteria for SD duration 
met, otherwise, NE 
NE 
NE 
NE 
CR  complete response; NE  Not evaluable; PD  progressive disease; PR  partial response; SD  stable 
disease. 
a If a CR is truly met at first time point, then any disease at a subsequent time point (see Confirmation 
Section below for timing), even disease meeting PR criteria relative to baseline, makes the disease PD at 
that point (since disease must have reappeared after CR).  Best response would depend on whether 
minimum duration for SD was met.  However, sometimes “CR” may be claimed when subsequent scans 
suggest small lesions were likely still present and in fact that subject had PR, not CR at the first time point.  
Under these circumstances, the original CR should be changed to PR and the best response is PR. 
11.10.6 
Special Notes on Response Assessment  
 
Target lesions that become “too small to measure” – While on study, all lesions 
(nodal and non-nodal) recorded at baseline should have their measurements 
recorded at each subsequent evaluation, even when very small (eg, 2 mm).  
However, sometimes lesions or lymph nodes which are recorded as target lesions at 
baseline become so faint on CT scan that the radiologist may not feel comfortable 
assigning an exact measure and may report them as being ‘too small to measure’.  
When this occurs, it is important that a value be recorded on the case report form.  
If it is the opinion of the radiologist that the non-lymph node lesion has likely 
disappeared, the measurement should be recorded as 0 mm.  If the lesion is 
believed to be present and is faintly seen but too small to measure, a default value of 
5 mm should be assigned (Note:  It is less likely that this rule will be used for lymph 
nodes since they usually have a definable size when normal and are frequently 
surrounded by fat such as in the retroperitoneum; however, if a lymph node is 
believed to be present and is faintly seen but too small to measure, a default value of 
5 mm should be assigned in this circumstance as well).  This default value is derived 
from the 5 mm CT slice thickness (but should not be changed with varying CT slice 

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thickness).  The measurement of these lesions is potentially non-reproducible, 
therefore providing this default value will prevent false responses or progressions 
based upon measurement error.  To reiterate, however, if the radiologist is able to 
provide an accurate measure, that should be recorded, even if it is below 5 mm. 
 
New lesions – The term “new lesion” always refers to the presence of a new finding 
that is definitely tumor.  If a new lesion is identified via a modality other than CT or 
MRI, CT or MRI confirmation is recommended unless the new lesion is deemed 
unequivocally tumor.  New findings that are not definitively tumor but may be benign 
(infection, inflammation, etc.) are not selected as new lesions, until that time when 
the review is certain they represent tumor.   
- If a new lesion is equivocal, for example because of its small size, continued 
therapy and follow-up evaluation will clarify if it represents truly new disease.  
If additional imaging confirms there is definitely a new lesion, then progression 
should be declared using the date of the initial scan. 
- A lesion identified on a follow-up study in an anatomical location that was not 
scanned at baseline is considered a new lesion and will indicate disease 
progression, regardless of any response that may be seen in target or non-target 
lesions present from baseline. 
 
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.  
 
Lesions that split or coalesce on treatment - When non-nodal lesions "fragment", the 
longest diameters of the fragmented portions should be added together to calculate 
the target lesion sum and identified as a fragment of the original lesion.  Similarly, as 
lesions coalesce, a plane between them may be maintained that would aid in 
obtaining maximal diameter measurements of each individual lesion.  If the lesions 
have truly coalesced such that they are no longer separable, the vector of the 
longest diameter in this instance should be the maximal longest diameter for the 
"coalesced lesion". 
 
“Symptomatic deterioration” alone does not qualify as objective progression.  
If objective progression was not previously documented, then every effort should be 
made to document objective progression even after discontinuation of treatment.  
 
In some circumstances it may be difficult to distinguish residual disease from scar or 
normal tissue.  When the evaluation of CR depends on this determination, it is 
recommended that the residual lesion be further investigated by fine needle 
aspirate/biopsy, to confirm the CR status.  
 
If a lesion disappears and reappears at a subsequent time point it should continue to 
be measured.  However, the patient’s response at the point in time when the lesion 
reappears will depend upon the status of his/her other lesions.  For example, if the 
patient’s tumor had reached a CR status and the lesion reappeared, then the patient 
would be considered PD at the time of reappearance.  In contrast, if the tumor status 
was a partial response (PR) or SD and one lesion which had disappeared then 

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reappears, its maximal diameter should be added to the sum of the remaining 
lesions for a calculated response:  in other words, the reappearance of an apparently 
‘disappeared’ single lesion amongst many which remain is not in itself enough to 
qualify for PD:  that requires the sum of all lesions to meet the PD criteria. 
11.10.7 
Confirmation Measurement  
Confirmation of CR and PR is required and must occur no fewer than 4 weeks after 
initial documentation of CR or PR.  If CR is pending confirmation and is designated at an 
assessment followed by 1 or more NE assessments, and/or PR assessments such that 
the Target Lesion Response is CR and the Non-Target Lesion Response is NE, CR may 
be confirmed thereafter if Non-Target Lesion Response returns to CR.  Similarly, if a PR 
is pending confirmation and is designated at an assessment followed by 1 or more NE 
and/or SD assessments, PR may be confirmed thereafter.  Subsequent Target Lesion 
Responses following a CR are limited to CR, PD or NE; PD for target lymph nodes is 
met only if any lymph node target lesion reaches a short axis measurement of  15 mm. 

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11.11 
Appendix 11.  Specific Guidance for Cytokine Release Syndrome, 
Immune-effector Cell-associated Neurologic Syndrome, and Tumor 
Lysis Syndrome  
11.11.1 
Specific Guidance for Cytokine Release Syndrome  
Cytokine release syndrome (CRS) is defined as a supraphysiologic response following 
any immune therapy that results in the activation or engagement of endogenous or 
infused T-cells and/or other immune effector cells.  Symptoms can be progressive, must 
include fever at the onset, and may include hypotension, capillary leak (hypoxia) and 
end organ dysfunction. 
Clinical signs and symptoms of CRS are non-specific and may include a combination of 
the following:  
 
constitutional:  fever  rigors, malaise, fatigue, anorexia, myalgias, arthralgias, 
nausea, vomiting, headache 
 
skin:  rash 
 
gastrointestinal:  nausea, vomiting, diarrhea 
 
respiratory:  tachypnea, hypoxemia 
 
cardiovascular:  tachycardia, widened pulse pressure, hypotension, increased 
cardiac output (early), potentially diminished cardiac output (late) 
 
coagulation:  elevated D-dimer, hypofibrinogenemia  bleeding 
 
renal:  azotemia 
 
hepatic:  transaminitis, hyperbilirubinemia 
The symptoms associated with the CRS event do not meet the definition of an adverse 
event as defined in Section 11.4.  Therefore, the CRS associated event (ie, CRS, 
cytokine storm) should be documented on the Events electronic eCRF as the diagnosis.  
However, since it is important to document all symptoms related to a CRS event, a CRS 
Symptoms eCRF will also be available to record the symptoms associated with each 
CRS event.  
If the severity of a CRS event changes from the date of onset to the date of resolution, 
record a single event for each increased level of severity on the Events eCRF and fill out 
an associated CRS Symptoms eCRF.  If the symptoms worsen enough to impact the 
overall CRS grade, it is important to remember to record a new CRS event on the 
Events eCRF with the appropriate grade. 
Temperature may normalize within a few hours of treatment, whereas the other 
components of CRS take longer to resolve.  Once such therapies are used, the patient is 

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considered to still have CRS, even in the absence of fever, until all signs and symptoms 
leading to the diagnosis of CRS have resolved.  Likewise, CRS can be downgraded in 
an afebrile patient treated with anticytokine therapy as their hemodynamic status and/or 
hypoxia improves.  Typically, a patient with severe CRS in whom fever, oxygen, and 
pressor requirements have resolved may be assumed to have resolved CRS unless 
there are alternative causes for the fever, hypoxia, and/or hypotension. 
Refer to Table 6-2 for details regarding CRS grading and management. 

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11.11.2 
Specific Guidance for Immune-effector Cell-associated Neurologic 
Syndrome  
For this trial, immune-effector cell associated neurologic syndrome (ICANS) will be using 
the criteria referenced in the publication by Lee et al, 2019.  While the grading system 
has been developed in large part from chimeric antigen receptor T-cells (CAR-T) 
therapies, symptoms of ICANS may be shared among immune effector-cell associated 
therapies such as bispecific T-cell engager (BiTE) molecules.  Although there may be a 
wide range of symptoms associated with ICANS, subjects may have a stereotypic 
course of a specific set of symptoms.  The earliest manifestations of ICANS are tremor, 
dysgraphia, mild difficulty with expressive speech (especially in naming objects), 
impaired attention, apraxia, and mild lethargy. 
Immune-effector cell associated neurologic syndrome grade is determined by the most 
severe event (eg, depressed level of consciousness, seizure, motor findings, raised 
intracranial pressure [ICP]/cerebral edema) not attributable to any other cause.  Refer to 
the immune-effector cell-associated encephalopathy (ICE) score below for grading of 
ICANS. 
Immune-effector Cell-associated Encephalopathy (ICE) Assessment Tool 
 
Orientation:  Orientation to year, month, city, hospital:  4 points  
 
Naming:  ability to name 3 objects (eg, point to clock, pen, button):  3 points 
 
Following commands:  ability to follow simple commands (eg, “Show me two fingers” 
or “Close your eyes and stick out your tongue”):  1 point 
 
Writing:  ability to write a standard sentence (eg, “Our national bird is the bald 
eagle”):  1 point 
 
Attention:  ability to count backwards from 100 by 10:  1 point 
ICE scoring 
 
7 to 9, grade 1 
 
3 to 6, grade 2 
 
0 to 2, grade 3 
 
0 due to subject unarousable and unable to perform ICE 
 
Assessment, grade 4 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
Page 136 of 137 
CONFIDENTIAL 
 
Table 11-7.  ASBMT Immune-effector Cell-associated Neurotoxicity Syndrome 
(ICANS) Consensus Grading for Adults 
Neurotoxicity 
Domaina 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
ICE scoreb 
7-9 
3-6 
0-2 
0 (subject is 
unarousable and unable 
and unable to perform 
ICE) 
Depression level of 
consciousnessc 
Awakens 
spontaneously 
Awakens to 
voice 
Awakens only to 
tactile stimulus 
Subject is unarousable 
or requires vigorous or 
repetitive tactile stimuli 
to arouse. 
Stupor or coma  
Seizure 
N/A 
N/A 
Any clinical seizure 
focal or generalized 
that resolves rapidly 
or nonconvulsive 
seizures on EEG that 
resolve with 
intervention 
Life-threatening 
prolonged seizure 
( 5 min); or repetitive 
clinical or electrical 
seizures without return 
to baseline in between 
Motor findingsd 
N/A 
N/A 
N/A 
Deep focal motor 
weakness such as 
hemiparesis or 
paraparesis 
Elevated 
ICP/cerebral 
edema 
N/A 
N/A 
Focal/local edema on 
neuroimaginge 
Diffuse cerebral edema 
on neuroimaging; 
Decerebrate or 
decorticate posturing; or 
Cranial nerve VI palsy; 
or Papilledema; or 
Cushing’s triad 
ASBMT  American Society for Blood and Marrow Transplantation; CTCAE  Common Terminology Criteria 
for Adverse Events; EEG  electroencephalogram; ICANS  immune-effector cell associated neurologic 
syndrome; ICE  immune-effector cell-associated encephalopathy; ICP  intracranial pressure; 
N/A  not applicable 
a Other signs and symptoms such as headache, tremor, myoclonus, asterixis, and hallucinations may occur 
and could be attributable to immune effector-cell engaging therapies.  Although they are not included in 
this grading scale, careful attention and directed therapy may be warranted.  
b A subject with an ICE score of 0 may be classified as grade 3 ICANS if awake with global aphasia, but a 
subject with an ICE score of 0 may be classified as grade 4 ICANS if unarousable. 
c Depressed level of consciousness should be attributable to no other cause (eg, no sedating medication). 
d Tremors and myoclonus associated with immune effector cell therapies may be graded according to 
CTCAE v5.0, but they do not influence ICANS grading.  
e Intracranial hemorrhage with or without associated edema is not considered a neurotoxicity feature and is 
excluded from ICANS grading It may be graded according to CTCAE v5.0. 
Source:  Lee et al, 2019 
Assessment and Supportive Care Recommendations (all grades) 
 
Neurologic assessment and grading at least twice a day to include cognitive 
assessment and motor weakness 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  06 September 2024 
Page 137 of 137 
CONFIDENTIAL 
 
 
MRI of the brain with and without contrast (or brain CT if MRI is not feasible) for 
 grade 2 neurotoxicity 
 
Neurology consultation at first sign of neurotoxicity 
 
Conduct electroencephalogram (EEG) for seizure activity for  grade 2 neurotoxicity 
 
Aspiration precautions; IV hydration 
 
Use caution when prescribing medications that can cause central nervous system 
(CNS) depression (aside from those needed for seizure prophylaxis/treatment) 
11.11.3 
Tumor Lysis Syndrome  
Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 classifies TLS in 
grade 3 (present), grade 4 (life threatening consequences; urgent intervention indicated) 
and grade 5 (death).  Cairo and Bishop developed a system for defining and grading 
TLS based on Hande-Garrow classification of laboratory or clinical TLS 
(Coiffier et al, 2008).  In this trial, the Cairo-Bishop classification will be used to define 
presence of TLS; ie, presence of laboratory TLS (see Table 11-8) and clinical TLS.  Final 
event grade will be assigned according to CTCAE version 5.0. 
Based on the Cairo and Bishop system, laboratory TLS is defined as any 2 or more 
abnormal serum values present within 3 days before or 7 days after initiation of 
treatment in the setting of adequate hydration (with or without alkalinization) and use of a 
hypouricemic agent (Table 11-8). 
Table 11-8.  Cairo-Bishop Definition of Laboratory Tumor Lysis Syndrome 
Element 
Value 
Change from baseline 
Uric acid 
 476 mol/L or 8 mg/dL 
25 increase 
Potassium 
 6.0 mmol/L or 6 mg/L 
25 increase 
Phosphorus 
 2.1 mmol/L for children or 
 1.45 mol/L for adults 
25 increase 
Calcium 
 1.75 mmol/L 
25 decrease 
Note:  Two or more laboratory changes within 3 days before or 7 days after cytotoxic therapy will constitute 
laboratory tumor lysis syndrome. 
Clinical TLS requires the presence of laboratory TLS in addition to 1 or more of the 
following significant complications:  renal insufficiency, cardiac arrhythmias/sudden 
death, and seizures.   

Approval Signatures
Document Name:
Protocol Amendment tarlatamab 20230273 2
Document Description:
Tarlatamab 20230273 PA1- development for a China only study
Document Number:
CLIN-000332994
Approval Date:
06 Sep 2024
Type of Study Protocol:
Amendment
Protocol Amendment No.: 2
Document Approvals
Reason for Signing: Management
Name: 
Date of Signature: 06-Sep-2024 15:25:09 GMT+0000

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  15 May 2024 
Page 1 of 62 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 1  
Protocol Title:  Phase 2a Study Evaluating the Efficacy, Safety, Tolerability, and 
Pharmacokinetics of Tarlatamab in Chinese Subjects with Advanced Small Cell Lung 
Cancer after Two or More Prior Lines of Treatment (DeLLphi-307) 
Amgen Protocol Number:  20230273 
 
Amendment Date: 
15 May 2024 
 
Rationale: 
This protocol is mainly being amended to update the objectives and endpoints to include 
efficacy as a primary endpoint and pharmacokinetics (PK) as secondary endpoint along with 
safety and tolerability.  Changes including, but not limited to, the following were incorporated 
into the protocol:   
 
Updated the phase throughout the protocol from a phase 1b to a phase 2a.  
 
Updated the protocol to replace mention of “preliminary anti-tumor activity” to “efficacy” 
throughout the protocol.  
 
Updated the objectives and endpoint sections to: 
o clarify that the primary objective was to evaluate efficacy of tarlatamab as assessed by 
objective response rate (ORR) based on blinded independent central review (BICR) per 
Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1). 
o Incorporate two new efficacy secondary endpoints to: 
▪ 
evaluate the efficacy of Tarlatamab as assessed by ORR based on investigator 
assessment per RECIST 1.1. 
▪ 
evaluate efficacy of Tarlatamab as assessed by duration of response (DOR), disease 
control (DC), and progression-free survival (PFS), based on BICR and investigator 
assessment per RECIST 1.1. 
▪ 
evaluate efficacy of Tarlatamab as assessed by overall survival (OS) 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  15 May 2024 
Page 2 of 62 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
o include PK and immunogenicity as secondary endpoints  
o include estimand(s) for primary objective(s) 
 
Updated overall design section to clarify that Chinese subjects will include those with 
advanced small cell lung cancer (SCLC) who have progressed on or recurred following 1 
platinum-based regimen as 1L therapy (including a PD-1/PD-[L]1) and at least 1 other prior 
line of therapy (re treatment with a platinum-based regimen is considered a second-line of 
therapy). 
 
Updated the number of Chinese subjects in this study from 15 to 30. 
 
Monitoring guidance for subjects has been updated from a minimum of 24 hours post-
infusion to 6 to 8 hours for cycle 1 day 1 and cycle 1 day 8 throughout the protocol where 
applicable.   
 
Added a new section (Section 4.4) to capture details on the justification for monitoring. 
 
Updated Table 8-1 (Section 8.4.1) to align with Schedule of Activities (Section 1.3).   
 
Updated radiological imaging assessment section (Section 8.3.1) to clarify that scans will be 
submitted to a central imaging core laboratory for archival, response assessment by BICR 
including RECIST 1.1, and/or 
 
.   
 
Incorporated new BICR Section (Section 8.3.2).  
 
Updated antibody testing procedure (Section 8.7) to clarify that samples testing positive for 
binding antibodies will be evaluated for anti-tarlatamab neutralizing antibodies. 
 
Updated statistical consideration section (Section 9) to update the sample size 
determination, planned analyses, population for analysis, and exposure to investigational 
product language.   
 
Updated Appendix 3 (Section 11.3) to incorporate quality tolerance limit parameters (QTLs) 
language. 

Product:  Tarlatamab (AMG 757)  
Protocol Number:  20230273 
Date:  15 May 2024 
Page 3 of 62 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
 
General editorial changes, including administrative, abbreviations, typographical, and 
formatting corrections have been made throughout the protocol for clarification.  

Product:  AMG 757 
Protocol Number:  20230273 
Date:  06 September 2024 
Page 1 of 40 
Amgen Proprietary - Confidential 
FORM-492529,   Effective Date: 02 Mar 2020,  Version:6.0 
Amendment 2 
Phase 2a Study Evaluating the Efficacy, Safety, Tolerability and Pharmacokinetics 
of Tarlatamab in Chinese Subjects with Advanced Small Cell Lung Cancer after 
Two or More Prior Lines of Treatment (DeLLphi-307) 
Amgen Protocol Number AMG 757 20230273 
NCT Number:  NCT06502977 
 
Rationale: 
This protocol has been amended to align with the United States Prescribing information 
for tarlatamab and other clarifications throughout the protocol.  Changes including the 
following were incorporated into the protocol: 
 
Addition of the NCT number 
 
Addition of language regarding the accelerated approval of tarlatamab from the 
United States Food and Drug Administration 
 
Revision of the duration of the safety follow-up visit for alignment with the tarlatamab 
approved label 
 
Revision of disease progression language to specify that subjects will receive study 
treatment until blinded independent central review-confirmed disease progression 
per RECIST 1.1, death, withdrawal of consent, start of new anticancer therapy, 
unacceptable toxicity, or end of study as determined by the sponsor (whichever 
occurs first) 
 
Clarification of the New York Heart Association data collection 
 
Clarification of the timing of screening local laboratory assessments 
 
Clarification of the timing of laboratory assessments prior to cycle 1 day 1 dose 
 
Revision of inclusion criterion to clarify that extensive-stage small cell lung cancer 
could be enrolled 
 
Revision of contraception and lactation language to align the timing with the 
tarlatamab approved label 
 
Addition of dose modification guidance for hypersensitivity (allergic reactions) 
 
Safety language was updated when applicable to align with most recent guidance 
from Amgen safety and pharmacovigilance. 
 
Hepatoxicity guidelines were updated to align with most recent guidance from 
Amgen safety 
 
Addition of End of Treatment section 
Amendment Date: 
06 September 2024