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: Active, not recruiting
• Conditions: Small Cell Lung Cancer
• Intervention / Treatment: Drug: AMG 404; Drug: Tarlatamab

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

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Austria
  • Innsbruck, Austria, 6020
    • Medizinische Universitaet Innsbruck
  • Wien, 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	Time Frame
Number of Participants with a Dose Limiting Toxicity (DLT)	28 days
Number of Participants with a Treatment-emergent Adverse Event (TEAE)	24 months
Number of Participants with a Treatment-related Adverse Event	24 months
Number of Participants with a Clinically Significant Change from Baseline in Vital Signs	Baseline to Month 24
Number of Participants with a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements	Baseline to Month 24
Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests	Baseline to Month 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	24 months
Duration of Response (DOR)	24 months
Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1	24 months
Disease Control Rate (DCR)	24 months
Progression-free Survival (PFS)	24 months
Maximum Observed Concentration (Cmax) of Tarlatamab in Combination with AMG 404	24 months
Minimum Observed Concentration (Cmin) of Tarlatamab in Combination with AMG 404	24 months
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of Tarlatamab in Combination with AMG 404	24 months

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 (Estimated): January 11, 2025

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 (Actual): October 13, 2023
• Last Update Submitted That Met QC Criteria: October 12, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Lung Cancer; Small Cell Lung Cancer; SCLC; AMG 757; AMG 404; Tarlatamab
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; 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