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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Small Cell Lung Cancer

Intervention / Treatment
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* Drug: Tarlatamab
* Drug: AMG 404


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: Dose Exploration<br>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<br>* Tarlatamab will be administered as an intravenous (IV) infusion.<br>* Other names: AMG 757;Drug: AMG 404<br>* AMG 404 will be administered as an intravenous (IV) infusion.<br>|
| Experimental: Phase 2: Dose Expansion<br>Participants will receive the RP2D of tarlatamab in combination with AMG 404 identified in Phase 1 (dose exploration) of the study. | Drug: Tarlatamab<br>* Tarlatamab will be administered as an intravenous (IV) infusion.<br>* Other names: AMG 757;Drug: AMG 404<br>* AMG 404 will be administered as an intravenous (IV) infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response (OR) per modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 |  | 24 months | 
| Duration of Response (DOR) |  | 24 months | 
| Disease Control Rate (DCR) |  | 24 months | 
| Progression-free Survival (PFS) |  | 24 months | 
| Overall Survival (OS) |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Small Cell Lung Cancer, SCLC, Lung Cancer, AMG 757, AMG 404, Tarlatamab