A Study of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that treatment with BMS-986012 in combination with carboplatin, etoposide, and nivolumab will have acceptable safety and tolerability and will improve progression-free survival compared with carboplatin, etoposide, and nivolumab alone in newly diagnosed participants with extensive-stage small cell lung cancer (ES-SCLC).

Official Title
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A Randomized, Open-label Phase 2 Clinical Trial of BMS-986012 in Combination With Carboplatin, Etoposide, and Nivolumab as First-line Therapy in Extensive-stage Small Cell Lung Cancer

Conditions
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Extensive-stage Small Cell Lung Cancer

Intervention / Treatment
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* Biological: BMS-986012
* Drug: Carboplatin
* Drug: Etoposide
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented extensive-stage small cell lung cancer (ES-SCLC) and extensive-stage disease (American Joint Committee on Cancer, 8th edition, Stage IV [T any, N any, M1a, M1b, or M1c], or T3-4 due to multiple lung nodules that are too extensive or tumor or nodal volume that is too large to be encompassed in a tolerable radiation plan) Participants taking part in the separate PET tracer sub-study must provide a fresh tumor biopsy from any disease site (primary or metastatic) Archived tumor specimens, in the form of blocks or sectioned slides, are mandatory for all participants except those participating in the separate PET tracer sub-study for whom the archived tumor specimen is optional Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1 At least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) criteria Adequate hematologic and end organ function Must agree to follow specific methods of contraception, if applicable Exclusion Criteria: Women who are pregnant or breastfeeding. Japan only: participation in the study is not allowed even if breastfeeding is suspended Prior chemotherapy, radiation therapy, or biologic therapy for SCLC. Previously treated limited stage SCLC (LS-SCLC) participants are also excluded Symptomatic brain or other central nervous system (CNS) metastases Paraneoplastic autoimmune syndrome requiring systemic treatment History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, idiopathic pneumonitis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan Grade ≥ 2 peripheral sensory neuropathy at study entry Significant uncontrolled cardiovascular disease Active, known or suspected autoimmune disease or inflammatory disorder Other protocol-defined inclusion/exclusion criteria apply

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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Carboplatin + Etoposide + Nivolumab + BMS-986012<br> | Biological: BMS-986012<br>* Specified dose on specified days<br>* Other names: Fucosyl-GM1 Antibody;Drug: Carboplatin<br>* Specified dose on specified days<br>Drug: Etoposide<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Arm B: Carboplatin + Etoposide + Nivolumab<br> | Drug: Carboplatin<br>* Specified dose on specified days<br>Drug: Etoposide<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AEs) |  | Up to 2 years and 100 days | 
| Incidence of serious adverse events (SAEs) |  | Up to 2 years and 128 days | 
| Incidence of AEs leading to discontinuation |  | Up to 2 years and 128 days | 
| Incidence of deaths |  | Up to 2 years and 128 days | 
| Progression-free survival (PFS) by blinded independent central review (BICR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria |  | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival rate (PFSR) | PFS by BICR based on RECIST v1.1 criteria | 6 and 12 months | 
| PFS by investigator based on RECIST v1.1 criteria |  | Up to 2 years | 
| PFSR | PFS by investigator based on RECIST v1.1 criteria | 6 and 12 months | 
| Objective response rate (ORR) based on RECIST v1.1 criteria |  | Up to 2 years | 
| Time to response (TTR) based on RECIST v1.1 criteria |  | Up to 2 years | 
| Duration of response (DOR) based on RECIST v1.1 criteria |  | Up to 2 years | 
| Overall survival (OS) | By arm | Up to 3 years | 
| Overall survival rate (OSR) | By arm | Up to 3 years | 
| Immunogenicity of BMS-986012 measured by assessment of the presence of specific anti-drug antibodies (ADAs) to BMS-986012 (i.e. incidence of positive ADAs) |  | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BMS-986012, Carboplatin, Etoposide, Extensive-stage small cell lung cancer, Fucosyl, Nivolumab, Targeted SCLC therapy