An Investigational Immuno-Therapy Study of Experimental Medication BMS-986242 Given in Combination With Nivolumab in Patients With Advanced Cancer

Study Overview
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Brief Summary
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The purpose of this study is to investigate safety of experimental medication BMS-986242 and Nivolumab in patients with advanced cancers.

Official Title
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A Phase 1/2a Study of BMS-986242 Administered in Combination With Nivolumab (BMS-936558, Anti-PD-1) in Advanced Malignant Tumors

Conditions
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Cancer

Intervention / Treatment
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* Drug: BMS-986242
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Histologic or cytological confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease per RECIST v1.1 Participants must have received and then progressed or been intolerant to at least 1 standard treatment regimen in the advanced or metastatic setting if such a therapy exists Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 Ability to swallow tablets Adequate bone marrow and organ function, as defined by the protocol Exclusion Criteria: Participants with known or suspected CNS metastases, untreated CNS metastases, or with the CNS as the only site of disease (patients with controlled brain metastasis allowed to enroll) Ocular melanoma Any significant acute or chronic medical illness Prior malignancy Other active malignancy requiring concurrent intervention Prior organ allograft or allogeneic bone marrow transplantation Participants with active, known, or suspected autoimmune disease Requirement for daily supplemental oxygen Uncontrolled or significant cardiovascular disease Pre-existing liver disease Gastrointestinal disease known to interfere with absorption Other protocol defined inclusion/exclusion criteria could 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>BMS-986242 administered in combination with Nivolumab | Drug: BMS-986242<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Anti-PD-1;|
| Experimental: Dose Expansion<br>BMS-986242 administered in combination with Nivolumab | Drug: BMS-986242<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Anti-PD-1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AE) | The primary objective to establish safety to be measured by the primary endpoint of AEs | From initiation of study treatment until 100 days after discontinuation of study treatment | 
| Number of Participants With Serious Adverse Events (SAE) | The primary objective to establish safety to be measured by the primary endpoint of SAEs | From the date of participant's written consent until 100 days after discontinuation of nivolumab or participation in the study | 
| Number of Participants With Dose Limiting Toxicities (DLT) | The primary objective to establish safety to be measured by the primary endpoint of dose limiting toxicities | Approximately 2 years | 
| Number of Participants With AEs Leading to Discontinuation | The primary objective to establish safety to be measured by the primary endpoint of AEs leading to discontinuation | Approximately 2 years | 
| Number of Deaths | The primary objective to establish safety to be measured by the primary endpoint of deaths | Approximately 2 years | 
| Number of Participants With Laboratory Abnormalities | The primary objective to establish safety to be measured by the primary endpoint of clinical laboratory test abnormalities | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Plasma Concentration (Cmax) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Time of Maximum Observed Plasma Concentration (Tmax) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Area Under the Concentration-time Curve in 1 Dosing Interval [AUC(TAU)] | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Area Under the Concentration-time Curve From Time Zero to Infinity [AUC(INF)] | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Trough Observed Plasma Concentration at the End of the Dosing Interval (Ctrough) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Apparent Elimination Half-life (T-HALF) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Apparent Total Body Clearance (CLT/F) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Apparent Volume of Distribution at Steady State (Vss/F) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Accumulation Index (AI) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0. Accumulation index, calculated based on ratio of area under the curve (AUC) and Cmax at steady state to after the first dose. | Approximately 2 years | 
| Percent Urinary Recovery Over 24 Hours (%UR24) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Percent Urinary Recovery Over 72 Hours (%UR72) | The Pharmacokinetic (PK) parameters are assessed for BMS-986242 and selected metabolites following single-dose administration in Cycle 00 and multiple-dose administration in Cycle 0 | Approximately 2 years | 
| Incidence of Anti-drug Antibody (ADA) to Nivolumab in Combination With BMS-986242 | Baseline ADA-positive participant is defined as a participant who has a ADA detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment. | Approximately 2 years | 
| Overall Response Rate (ORR) | ORR in participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for solid tumors | Approximately 2 years |