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

NCT04885998 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 202004392020-005957-26
• Study Type: interventional
• Target: 23
• Locations: 6 countries
• Sites: 17

Brief Summary

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.

Conditions

Small Cell Lung Cancer

Keywords

Small Cell Lung Cancer; SCLC; Lung Cancer; AMG 757; AMG 404; Tarlatamab

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (8)

• Objective Response Rate Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

  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

  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

  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

  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

  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

Study Arms (2)

Phase 1: Dose Exploration

EXPERIMENTAL

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: Tarlatamab; Drug: AMG 404

Phase 2: Dose Expansion

EXPERIMENTAL

Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study.

Drug: Tarlatamab; Drug: AMG 404

Interventions

Tarlatamab DRUG

Tarlatamab will be administered as an intravenous (IV) infusion.

Also known as: AMG 757

Phase 1: Dose Exploration; Phase 2: Dose Expansion

AMG 404 DRUG

AMG 404 will be administered as an intravenous (IV) infusion.

Phase 1: Dose Exploration; Phase 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (17)

Northwestern University, Robert H Lurie Comprehensive Cancer Center

Chicago, Illinois, 60611, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Wake Forest Baptist Comprehensive Cancer Research Center

Winston-Salem, North Carolina, 27157, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Tennessee Oncology, PLLC

Nashville, Tennessee, 37203, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Medizinische Universitaet Innsbruck

Innsbruck, 6020, Austria

Location

Universitaetsklinikum Allgemeines Krankenhaus Wien

Vienna, 1090, Austria

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

National University Hospital

Singapore, 119074, Singapore

Location

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

Chung Shan Medical University Hospital

Taichung, 40201, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Small Cell Lung Carcinoma; Lung Neoplasms

Interventions

AMG 757

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 10, 2021
• First Posted: May 13, 2021
• Study Start: September 27, 2021
• Primary Completion: July 12, 2023
• Study Completion: September 11, 2024
• Last Updated: September 29, 2025
• Results First Posted: October 15, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

TW (2); AU (2); US (7); JP (2); SG (2); BE (2)