A Study of BMS-986406 as Monotherapy and Combination Therapies in Participants With Advanced Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability of BMS-986406 administered alone, in combination with nivolumab, or in combination with nivolumab and platinum-doublet chemotherapy (PDCT) in participants with advanced tumors.

Official Title
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A Phase 1 First-in-human Study of BMS-986406 as Monotherapy and Combination Therapies in Participants With Advanced Malignant Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: BMS-986406
* Biological: Nivolumab
* Drug: Carboplatin
* Drug: Pemetrexed
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parts 1A, 1B, 1C: Histologically or cytologically confirmed locally advanced unresectable, metastatic, or recurrent malignant tumor. Eligible tumor types are non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC), pancreatic ductal adenocarcinoma (PDAC), gastric/gastroesophageal junction, castration-resistant prostate cancer (CRPC), ovarian, squamous cell carcinoma of the head and neck (SCCHN), bladder, melanoma, mesothelioma, triple negative breast cancer (TNBC), and soft tissue sarcoma, except for participants with tumors with central nervous system (CNS) metastases as the only site of active disease Part 1D: Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) of non-squamous or squamous histology with Stage IV A/B (as defined by the 8th International Association for the Study of Lung Cancer Classification) or recurrent disease following multi-modal therapy for locally advanced disease, who have not had systemic therapy for metastatic or recurrent disease. All Parts: Measurable disease by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Prostate Cancer Working Group 3 (PCWG3) (for prostate cancer), or modified Response Evaluation Criteria in Solid tumors (mRECIST) (for mesothelioma) Eastern Cooperative Oncology Group Performance Status of 0 or 1 Adequate organ function Exclusion Criteria: Prior organ or tissue allograft Leptomeningeal metastases Untreated CNS metastases Serious or uncontrolled medical disorders 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A: BMS-986406 (Monotherapy Dose Escalation)<br> | Biological: BMS-986406<br>* Specified dose on specified days<br>|
| Experimental: Part 1B: BMS-986406 + Nivolumab (Combination Dose Escalation)<br> | Biological: BMS-986406<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 1C: BMS-986406 + Nivolumab (Indication-Specific Dose Expansion)<br> | Biological: BMS-986406<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 2: BMS-986406 + Nivolumab (Expansion Cohorts)<br> | Biological: BMS-986406<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 1D: BMS-986406 + Nivolumab + Carboplatin with Pemetrexed or Paclitaxel<br> | Biological: BMS-986406<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Drug: Carboplatin<br>* Specified dose on specified days<br>Drug: Pemetrexed<br>* Specified dose on specified days<br>Drug: Paclitaxel<br>* Specified dose on specified days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) |  | Up to 100 days | 
| Number of participants with serious adverse events (SAEs) |  | Up to 100 days | 
| Number of participants with AEs meeting protocol defined dose-limiting toxicity (DLT) criteria |  | Up to 28 days | 
| Number of participants with AEs leading to discontinuation |  | Up to 100 days | 
| Number of participants with death |  | Up to 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) |  | Up to 14 days | 
| Time of maximum observed plasma concentration (Tmax) |  | Up to 14 days | 
| Trough observed plasma concentration (Ctrough) |  | Up to 14 days | 
| Incidence of anti-drug antibody (ADAs) |  | Up to 14 days | 
| Objective response rate (ORR) |  | Up to 24 months | 
| Disease control rate (DCR) |  | Up to 24 months | 
| Duration of response (DOR) per tumor appropriate criteria: Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for mesothelioma |  | Up to 24 months | 
| DOR per tumor appropriate criteria: Prostate Cancer Working Group 3 (PCWG3) for prostate cancer |  | Up to 24 months | 
| DOR per tumor appropriate criteria: Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) for other solid tumor types |  | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opdivo®, Immunotherapy