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

• ClinicalTrials.gov Identifier: NCT04885998
• Recruitment Status: Active, not recruiting
• First Posted: May 13, 2021
• Last Update Posted: October 13, 2023
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: May 10, 2021
• First Posted Date: May 13, 2021
• Last Update Posted Date: October 13, 2023
• Actual Study Start Date: September 27, 2021
• Actual Primary Completion Date: July 12, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 27, 2022)

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

Original Primary Outcome Measures (submitted: May 10, 2021)

• Number of Participants with a Dose Limiting Toxicity (DLT) [ Time Frame: 28 days ]
• Number of Participants with a Treatment-emergent Adverse Event (TEAE) [ Time Frame: 12 months ]
• Number of Participants with a Treatment-related Adverse Event [ Time Frame: 12 months ]
• Number of Participants with a Clinically Significant Change from Baseline in Vital Signs [ Time Frame: Baseline to Month 12 ]
• Number of Participants with a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Measurements [ Time Frame: Baseline to Month 12 ]
• Number of Participants with a Clinically Significant Change from Baseline in Clinical Laboratory Tests [ Time Frame: Baseline to Month 12 ]

Current Secondary Outcome Measures (submitted: May 27, 2022)

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

Original Secondary Outcome Measures (submitted: May 10, 2021)

• Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 [ Time Frame: 12 months ]
• Duration of Response (DOR) [ Time Frame: 12 months ]
• Disease Control Rate (DCR) [ Time Frame: 12 months ]
• Progression-free Survival (PFS) [ Time Frame: 12 months ]
• Overall Survival (OS) [ Time Frame: 12 months ]
• Maximum Observed Concentration (Cmax) of AMG 757 in Combination with AMG 404 [ Time Frame: 12 months ]
• Minimum Observed Concentration (Cmin) of AMG 757 in Combination with AMG 404 [ Time Frame: 12 months ]
• Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 757 in Combination with AMG 404 [ Time Frame: 12 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: AMG 757 and AMG 404 in Subjects With Small Cell Lung Cancer (SCLC)
• Official Title: 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)
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Small Cell Lung Cancer

Intervention

• Drug: Tarlatamab
  Tarlatamab will be administered as an intravenous (IV) infusion.
  Other Name: AMG 757
• Drug: AMG 404
  AMG 404 will be administered as an intravenous (IV) infusion.

Study Arms

• 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).
  Interventions:

  • Drug: Tarlatamab
  • Drug: AMG 404
• 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.
  Interventions:

  • Drug: Tarlatamab
  • Drug: AMG 404

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 24, 2023): 23
• Original Estimated Enrollment (submitted: May 10, 2021): 40
• Estimated Study Completion Date: January 11, 2025
• Actual Primary Completion Date: July 12, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All
• Gender Based Eligibility: Yes

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, Belgium, Japan, Singapore, Taiwan, United States

Administrative Information

• NCT Number: NCT04885998
• Other Study ID Numbers: 20200439; 2020-005957-26 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (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.
• URL: http://www.amgen.com/datasharing

• Current Responsible Party: Amgen
• Original Responsible Party: Same as current
• Current Study Sponsor: Amgen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: October 2023