A Study of BMS-986249 Alone and in Combination With Nivolumab in Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine whether BMS-986249 both by itself and in combination with Nivolumab is safe and tolerable in the treatment of advanced solid tumors

Official Title
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A Phase 1/2 First-in-Human Study of BMS-986249 Alone and in Combination With Nivolumab in Advanced Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Biological: BMS-986249
* Biological: Nivolumab
* Biological: Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent, and/or unresectable) with measurable disease or metastatic disease documented by either bone lesions on radionuclide bone scan and/or soft tissue lesions on CT/MRI for prostate cancer and have at least 1 lesion accessible for biopsy. For Part 2B participants with HCC, intermediate disease is allowed. Eastern Cooperative Oncology Group Performance Status of 0 or 1 Must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to tumor type, if such a therapy exists Prior anti-cancer treatments such as chemotherapy, radiotherapy, or hormonal are permitted for some participants Willing and able to comply with all study procedures Exclusion Criteria: Primary central nervous system (CNS) malignancies, tumors with CNS metastases as the only site of disease or active brain metastases will be excluded Other active malignancy requiring concurrent intervention Prior organ allograft Active, known, or suspected autoimmune disease 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: Part 1A: BMS-986249<br> | Biological: BMS-986249<br>* Specified dose on specified days<br>|
| Experimental: Part 1B: BMS-986249 + nivolumab (nivo)<br> | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2A Arm C: BMS-986249 + nivo<br>Previously untreated unresectable stage III-IV melanoma | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2A Arm D: ipilimumab + nivo then nivo<br>Previously untreated unresectable stage III-IV melanoma | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: BMS-734016;|
| Experimental: Part 2A Arm F: BMS-986249 + nivo<br>Previously untreated unresectable stage III-IV melanoma | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2B Cohort 1: BMS-986249 + nivo<br>Advanced or intermediate hepatocellular carcinoma (HCC) | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2B Cohort 2: BMS-986249 + nivo<br>Metastatic castration-resistant prostate cancer (CRPC) | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2B Cohort 3: BMS-986249 + nivo<br>Unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2A Arm A: BMS-986249 + nivo then nivo<br>Previously untreated unresectable stage III-IV melanoma Enrollment is closed for this Arm | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2A Arm B: BMS-986249 + nivo<br>Previously untreated unresectable stage III-IV melanoma Enrollment is closed for this Arm | Biological: BMS-986249<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Part 2A Arm E: Nivo<br>Previously untreated unresectable stage III-IV melanoma Enrollment is closed for this Arm | 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 2.5 years | 
| Incidence of Serious Adverse Events (SAEs) |  | Up to 2.5 years | 
| Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria |  | Up to 2.5 years | 
| Incidence of AEs leading to discontinuation |  | Up to 2.5 years | 
| Incidence of death |  | Up to 4 years | 
| Number of participants with laboratory abnormalities |  | Up to 2.5 years | 
| Incidence of treatment-related Grade 3-5 AEs |  | Within 24 weeks | 
| Objective Response Rate (ORR) as assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 |  | Up to 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax (Maximum observed serum concentration) |  | Up to 2 years | 
| Tmax (Time of maximum observed concentration) |  | Up to 2 years | 
| AUC(0-T) (Area under the serum concentration-time curve from time zero to time of last quantifiable concentration) |  | Up to 2 years | 
| ORR as assessed by investigator using RECIST v1.1 or Prostate Cancer Working Group 3 (PCWG3) (for prostate cancer) |  | Up to 4 years | 
| Duration of response (DOR) as assessed by investigator using RECIST v1.1 or PCWG3 (for prostate cancer) |  | Up to 4 years | 
| Progression-Free survival (PFS) as assessed by investigator using RECIST v1.1 or PCWG3 (for prostate cancer) |  | Up to 4 years | 
| Time to response (TTR) as assessed by investigator using RECIST v1.1 or PCWG3 (for prostate cancer) |  | Up to 4 years | 
| Incidence of AEs in Part 2 of Study |  | Up to 2.5 years | 
| Incidence of SAEs in Part 2 of Study |  | Up to 2.5 years | 
| Incidence of AEs leading to discontinuation in Part 2 of study |  | Up to 2.5 years | 
| Incidence of death in Part 2 of study |  | Up to 4 years | 
| Number of participants with clinical laboratory abnormalities Part 2 of study |  | Up to 2.5 years | 
| Time to Deterioration (TTD) in Part 2 of study |  | Up to 4 Years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antibodies, Antineoplastic Agents, Immunologic Factors, Nivolumab, Antibodies, Monoclonal, Physiological Effects of Drugs