An Investigational Immunotherapy Study of BMS-986310 Administered Alone and in Combination With Nivolumab in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to determine if BMS-986310 administered in combination with nivolumab, will demonstrate adequate safety and tolerability, as well as a favorable risk/benefit profile, to support further clinical testing.

Official Title
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Phase 1/2 Study of BMS-986310 Administered Alone and in Combination With Nivolumab in Participants With Advanced Solid Tumors

Conditions
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Advanced Cancer

Intervention / Treatment
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* Drug: BMS-986310
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with measurable disease per RECIST v1.1 and have at least one lesion accessible for biopsy. ECOG performance status less than or equal to 1 Part 1 and Sub-study B: i) Part 1 participants must have advanced or metastatic disease where no other standard of care treatment option is possible. ii) Sub-study B participants must have advanced or metastatic disease where no other standard of care treatment is possible, in one of the following tumor types: Renal cell carcinoma, Melanoma, colorectal cancer (CRC) microsatellite instability (MSI)-High (determined by Clinical Laboratory Improvement Amendments (CLIA) validated assay, testing methodology must be provided), Bladder cancer, Squamous Cell Carcinoma of the Head and Neck (SCCHN), and they must have had disease progression on an anti-PD-(L)1 based regimen as their most recent prior therapy Sub-study A: i) Participants must be newly diagnosed, no prior history of treatment for bladder cancer ii) Participants must not meet criteria for standard of care neoadjuvant therapy and must be candidates for SOC surgical resection of primary tumor. iii) Histologically confirmed muscle-Invasive bladder cancer (MIBC) pure or mixed histology urothelial carcinoma Part 2 - Patients with relapsed / refractory solid tumors where no other standard of care treatment option is available. Exclusion Criteria: History of severe adverse drug reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) or Cyclooxygenase-2 (COX-2) inhibitors. Participants with an active, known or suspected autoimmune disease. Evidence of organ dysfunction or any clinically significant deviation from normal in physical examination, vital signs, ECG or clinical laboratory determinations beyond what is consistent with the target population

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: Dose Escalation<br>Part 1: BMS-986310 + Nivolumab Combination Dose Escalation Sub-Study A: A cohort of Cisplatin Ineligible Muscle Invasive Bladder Cancer patients will receive either monotherapy BMS-986310, or BMS-986310 + Nivolumab, or Nivolumab monotherapy. Sub-Study B: A cohort of PD[L]1 relapsed / refractory tumor cancer patients will be treated with monotherapy BMS-986310 followed by BMS-986310 + nivolumab | Drug: BMS-986310<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-936558;|
| Experimental: Cohort Expansion<br>Part 2: Cohort Expansion will initiate upon consideration of the totality of data from Part 1. BMS-986310 + Nivolumab combination will be administered in specific patient populations. | Drug: BMS-986310<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 (AE) |  | up to 3 years | 
| Incidence of Serious Adverse Events (SAE) |  | up to 3 years | 
| Incidence of AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria |  | up to 3 years | 
| Incidence of AEs leading to dose delays and discontinuation or delay in radical cystectomy (RC) |  | up to 3 years | 
| Incidence of Laboratory abnormalities |  | up to 3 years | 
| Incidence of death |  | up to 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) |  | up to 3 years | 
| Median duration of response (mDOR) |  | up to 3 years | 
| Progression free survival rate (PFSR) |  | up to 24 months | 
| Maximum observed serum concentration (Cmax) |  | up to 3 years | 
| Observed serum concentration at the end of a dosing interval (Ctau) |  | up to 3 years | 
| Area under the serum concentration-time curve from time zero to time of last quantifiable concentration [AUC(0-T)] |  | up to 3 years | 
| Apparent total body clearance (CLT/F) |  | up to 3 years | 
| Area under the serum concentration-time curve in 1 dosing interval [AUC(TAU)] |  | up to 3 years | 
| AUC accumulation index (AI_AUC) |  | up to 3 years | 
| Cmax accumulation index (AI_Cmax) |  | up to 3 years | 
| Summary changes of prostaglandin E metabolite (PGEM) in urine |  | up to 3 years | 
| Summary changes of tumor necrosis factor (TNFa) in blood |  | up to 3 years | 
| Summary of PK parameters at T-HALF |  | up to 3 years | 
| Summary of PK parameter AUC(INF) after single dose |  | up to 3 years |