AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)

A Phase 1b Study Evaluating the Safety and Efficacy of AMG 757 in Combination With AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)

The main purpose of this study is to evaluate the safety, tolerability, and recommended phase 2 target dose of tarlatamab in combination with AMG 404.

Study Overview

• Status: Completed
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: AMG 404; Drug: Tarlatamab

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 1

Expanded Access

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Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Vienna, Austria, 1090
    • Universitaetsklinikum Allgemeines Krankenhaus Wien
• Belgium
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Leuven, Belgium, 3000
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
• Japan
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
  • Singapore, Singapore, 169610
    • National Cancer Centre Singapore
• Taiwan
  • Taichung, Taiwan, 40201
    • Chung Shan Medical University Hospital
  • Taipei, Taiwan, 11217
    • Taipei Veterans General Hospital
• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University, Robert H Lurie Comprehensive Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • University Of Kentucky
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest Baptist Comprehensive Cancer Research Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology, PLLC
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures
• Age greater than or equal to 18 years old at the same time of signing the informed consent
• Participants with histologically or cytologically confirmed Small Cell Lung Cancer (SCLC) who progressed or recurred following at least 1 platinum-based regimen
• Eastern Cooperative Oncology Group (ECOG) 0 to 1
• Participants with treated brain metastases are eligible provided they meet defined criteria
• Adequate organ function as defined in protocol

Exclusion Criteria:

• History of other malignancy within the past 2 years with exceptions
• Major surgery within 28 days of first dose of tarlatamab
• Untreated or symptomatic brain metastases and leptomeningeal disease
• Prior anti-cancer therapy, including anti-PD1 or anti-PDL1 antibody therapy: at least 28 days must have elapsed between any prior anti-cancer therapy and the first planned dose of tarlatamab

Exceptions:

• Participants who received prior chemotherapy must have completed at least 14 days before the first dose of tarlatamab and all treatment-related toxicity resolved to grade ≤ 1.

• Participants who received prior palliative radiotherapy must have completed at least 7 days before the first dose of tarlatamab

  • Participants who received prior tarlatamab therapy or prior delta-like ligand 3 (DLL3) x cluster of differentiation 3 (CD3) bispecific therapy are not eligible
  • Participants who experienced recurrent grade 2 pneumonitis or severe or life-threatening immune-mediated adverse events or infusion-related reactions including those that lead to permanent discontinuation while on treatment with immuno-oncology agents
  • History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis
  • Participants with evidence of interstitial lung disease or active, non-infectious pneumonitis
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of tarlatamab
  • History of solid organ transplantation
  • History of hypophysitis or pituitary dysfunction
  • 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. Participants with Type I diabetes, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Dose Exploration; The recommended phase 2 target dose (RP2D) of tarlatamab in combination with AMG 404 will be estimated using a modified toxicity probability interval (mTPI-2) design. A combination RP2D may be identified based on emerging safety, efficacy, and pharmacodynamic data prior to reaching an maximum tolerated dose (MTD).	Drug: AMG 404; AMG 404 will be administered as an intravenous (IV) infusion.; Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757
Experimental: Phase 2: Dose Expansion; Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.	Drug: AMG 404; AMG 404 will be administered as an intravenous (IV) infusion.; Drug: Tarlatamab; Tarlatamab will be administered as an intravenous (IV) infusion.; Other Names: AMG 757

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Number of Participants Who Experienced Dose-limiting Toxicity (DLT)	A DLT was any of the following during the DLT window, assessed by Common Terminology Criteria for Adverse Events v4.0: Grade 3 adverse event (AE) except for fatigue lasting < 7 days, Grade 3 nonfebrile neutropenia that improved to ≤ Grade 1 within 3 weeks, endocrinopathies if managed with replacement therapy, Grade 3 nausea/vomiting or diarrhea for < 72 hours, Grade 3 amylase or lipase values not associated with pancreatitis, Grade 3 hematologic laboratory abnormalities not clinically relevant, or Grade 3 electrolyte abnormality up to 72 hours.; Grade 4 AE except for Grade 4 nonfebrile neutropenia lasting ≤ 7 days, Grade 4 electrolyte abnormality lasting up to 72 hours, Grade 4 amylase or lipase values not associated with pancreatitis, or Grade 4 hematologic laboratory abnormalities no clinically relevant.; Grade 5 AE; Recurrent Grade ≥ 2 pneumonitis; Any other toxicity requiring permanent discontinuation of AMG 404.	First dose of tarlatamab up to 28 days
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An AE was defined as any untoward medical occurrence in a clinical trial participant. A TEAE was an AE that started on or after the first dose of investigational product (IP; tarlatamab) up to 65 days after the last dose of tarlatamab or AMG 404 or the end of study (EOS), whichever was earlier. A TEAE for the EP was an AE that occurred after the 65th day after the last dose of tarlatamab or AMG 404 up to 145 days after the last dose of tarlatamab or AMG 404 or end of study, whichever was later. A treatment-related AE was any TEAE where there was a reasonable possibility that the TEAE could have been caused by tarlatamab or AMG 404. Any clinically significant changes in vital signs, physical examinations, electrocardiograms, and clinical laboratory tests were included as TEAEs.	Any TEAEs: From first IP dose up to last dose + 65 days or EOS, median duration was 4.2 months; TEAEs for EP: From last dose + 65 days up to snapshot date (15 November 2024), death, or last dose + 145 days or EOS, median duration was 2.6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	The objective response rate was defined as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) based on the modified RECIST v1.1. CR: complete disappearance of all lesions and pathologic lymph nodes reduced in short axis to < 10 mm. PR: decrease in tumor burden of ≥ 30% relative to baseline, or complete disappearance of all index lesions with the presence of non-index lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR. Exact 95% confidence intervals (CIs) were calculated using the Clopper-Pearson method.	From first dose of IP up to a minimum of last dose date + 65 days or EOS; median (min, max) duration was 4.2 (0.4, 25.4) months
Duration of Response Per Modified RECIST v1.1	The duration of response was defined as the time from first evidence of CR or PR to progressive disease (PD) or death due to any cause, whichever occurred first, estimated via Kaplan-Meier methods. CR: complete disappearance of all lesions and pathologic lymph nodes reduced in short axis to < 10 mm. PR: decrease in tumor burden of ≥ 30% relative to baseline, or complete disappearance of all index lesions with the presence of non-index lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR. PD: radiologic detection of ≥ 20% increase in tumor burden relative to nadir and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or presence of new lesions. 95% CIs were calculated using the Brookmeyer and Crowley method.	From first dose of IP up to a minimum of last dose date + 65 days or EOS; median (min, max) duration was 4.2 (0.4, 25.4) months
Disease Control Rate Per Modified RECIST v1.1	The disease control rate was defined as the percentage of participants with a best overall response of a confirmed response (CR/PR) or stable disease (SD) while on the study as defined by modified RECIST v1.1. CR: complete disappearance of all lesions and pathologic lymph nodes reduced in short axis to < 10 mm. PR: decrease in tumor burden of ≥ 30% relative to baseline, or complete disappearance of all index lesions with the presence of non-index lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR SD: Index lesions not meeting the criteria for CR, PR, or PD or the persistence of one or more non-index lesions. Exact 95% CIs were calculated using the Clopper-Pearson method.	From first dose of IP up to a minimum of last dose date + 65 days or EOS; median (min, max) duration was 4.2 (0.4, 25.4) months
Progression-free Survival Per Modified RECIST v1.1	Progression-free survival was defined as the interval from the earlier date of the first dose of IP to the earlier of PD per modified RECIST v1.1 or death due to any cause, estimated via Kaplan-Meier methods. PD: radiologic detection of ≥ 20% increase in tumor burden to nadir and ≥ 5 mm absolute increase, or unequivocal progression of non-index lesions, or the presence of new lesions. Confirmation scans were required within 4 weeks of the first documented response of CR or PR, and 4-6 weeks for PD. 95% CIs were calculated using the Brookmeyer and Crowley method.	From first dose of IP up to a minimum of EOS or death; median (min, max) time was 9.4 (0.4, 25.5) months
Overall Survival	Overall survival was defined as the interval from the earlier date of the first dose of IP to the event of death due to any cause, estimated via Kaplan-Meier methods. Participants who were still alive were censored at the date last known to be alive. If the date last known to be alive was after the data cutoff date, the participant was censored at the analysis trigger date. 95% CIs were calculated using the Brookmeyer and Crowley method.	From first dose of IP up to a minimum of EOS or death; median (min, max) time was 9.4 (0.4, 25.5) months
Maximum Observed Concentration (Cmax) of Tarlatamab in Combination With AMG 404	Cmax was obtained using noncompartmental analysis, which was performed for tarlatamab PK parameter estimation. PK analysis is presented per dose received as pre-specified.	Cycle 2 Day 1 (pre-dose up to 7 days post-dose); Cycle 2 Day 15 (pre-dose up to 14 days post-dose)
Trough Concentration (Ctrough) of Tarlatamab in Combination With AMG 404	Ctrough was obtained at the end of a dosing interval or just before the administration of the next planned dose using noncompartmental analysis, which was performed for tarlatamab PK parameter estimation. PK analysis is presented per dose received as pre-specified.	Cycle 2 Day 15 (pre-dose)
Area Under the Concentration-time Curve From Time 0 to 336 Hours (AUC0-336) of Tarlatamab in Combination With AMG 404	AUC0-336 was defined as the actual body exposure to the drug over time following administration of a dose, calculated from time zero to 336 hours post-dose using noncompartmental analysis, which was performed for tarlatamab PK parameter estimation. PK analysis is presented per dose received as pre-specified.	Cycle 2 Day 1 (pre-dose up to 7 days post-dose); Cycle 2 Day 15 (pre-dose up to 14 days post-dose)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2021
• Primary Completion (Actual): July 12, 2023
• Study Completion (Actual): September 11, 2024

Study Registration Dates

• First Submitted: May 10, 2021
• First Submitted That Met QC Criteria: May 10, 2021
• First Posted (Actual): May 13, 2021

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 4, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Lung Cancer; Small Cell Lung Cancer; SCLC; AMG 757; AMG 404; Tarlatamab
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Antineoplastic Agents; AMG 757
• Other Study ID Numbers: 20200439; 2020-005957-26 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No