A Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to investigate experimental medication BMS-986253 in combination with Nivolumab or Nivolumab plus Ipilimumab in participants with advanced cancers.

Official Title
-----------------
A Phase 1/2 Study of BMS-986253 in Combination With Nivolumab or Nivolumab Plus Ipilimumab in Advanced Cancers

Conditions
-----------------
Cancer, Melanoma

Intervention / Treatment
-----------------
* Drug: BMS-986253
* Biological: Nivolumab
* Biological: Ipilimumab
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Histologic or cytologic confirmation of a solid tumor that is advanced (metastatic, recurrent and/or unresectable) with measurable disease per RECIST v1.1 At least 1 lesion accessible for biopsy Eastern Cooperative Oncology Group Performance Status of 0 or 1 Exclusion Criteria: Participants with CNS metastases as the only site of active disease (Participants with controlled brain metastases; however, will be allowed to enroll) Participants with active, known or suspected autoimmune disease Participants with conditions requiring systemic treatment with either corticosteroids (> 10mg prednisone equivalents) or other immunosuppressive medications within 14 days of study treatment administration Participants with a known history of testing positive for Human Immunodeficiency Virus (HIV) or known Acquired Immunodeficiency Syndrome (AIDS) Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A: BMS-986253 + nivolumab<br> | Drug: BMS-986253<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 1B: BMS-986253 + nivolumab<br> | Drug: BMS-986253<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Part 1C: BMS-986253 + nivolumab + ipilimumab<br> | Drug: BMS-986253<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: YERVOY;|
| Experimental: Part 2A: BMS-986253 + nivolumab + ipilimumab<br> | Drug: BMS-986253<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: YERVOY;|
| Placebo Comparator: Part 2B: Placebo + nivolumab + ipilimumab<br> | Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;Biological: Ipilimumab<br>* Specified dose on specified days<br>* Other names: YERVOY;Other: Placebo<br>* Specified dose on specified days<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (AE) | Part 1 | Approximately 5 years | 
| Incidence of serious adverse events (SAE) | Part 1 | Approximately 5 years | 
| Incidence of AEs meeting protocol-defined dose limiting toxicities (DLT) criteria | Part 1 | Approximately 5 years | 
| Incidence of AEs leading to discontinuation | Part 1 | Approximately 5 years | 
| Incidence of deaths | Part 1 | Approximately 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | Part 1 | Approximately 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests | Part 1 | Approximately 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | Part 1 | Approximately 5 years | 
| Progression-free survival (PFS) hazard ratio based on Blinded independent central review (BICR) assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Part 2, participants with advanced melanoma, selected by baseline serum interleukin-8 (IL-8) level using RECIST v1.1 | Approximately 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) based on Blinded independent central review (BICR) assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Part 1 and Part 2 | Approximately 5 years | 
| Median duration of response (mDOR) per response evaluation criteria in solid tumors (RECIST) v1.1 | Part 1 | Approximately 5 years | 
| Incidence of anti-drug antibody (ADA) to BMS-986253 | Part 1 and Part 2 | Approximately 5 years | 
| Serum biomarker concentration | Part 1 | Approximately 5 years | 
| Maximum observed serum concentration (Cmax) | Part 1 and Part 2 | Approximately 5 years | 
| Time of maximum observed serum concentration (Tmax) | Part 1 and Part 2 | Approximately 5 years | 
| Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] | Part 1 and Part 2 | Approximately 5 years | 
| Area under the serum concentration-time curve in 1 dosing interval [AUC(TAU)] | Part 1 and Part 2 | Approximately 5 years | 
| Observed serum concentration at the end of a dosing interval (CTAU) | Part 1 and Part 2 | Approximately 5 years | 
| Trough observed serum concentration at the end of the dosing interval (CTROUGH) | Part 1 and Part 2 | Approximately 5 years | 
| Progression-free survival (PFS) hazard ratio based on Blinded independent central review (BICR) assessments per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Part 2, participants with advanced melanoma, using RECIST v1.1 (regardless of baseline serum IL-8 levels) | Approximately 5 years | 
| Overall Survival (OS) | Part 2 | Approximately 5 years | 
| Incidence of AEs | Part 2 | Approximately 5 years | 
| Incidence of SAEs | Part 2 | Approximately 5 years | 
| Incidence of AEs leading to discontinuation | Part 2 | Approximately 5 years | 
| Incidence of death | Part 2 | Approximately 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Hematology tests | Part 2 | Approximately 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Clinical Chemistry tests | Part 2 | Approximately 5 years | 
| Incidence of clinically significant changes in clinical laboratory results: Urinalysis tests | Part 2 | Approximately 5 years |