An Investigational Immuno-therapy Study of Experimental Medication BMS-986179 Given Alone and in Combination With Nivolumab

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tumor-shrinking ability of experimental medication BMS-986179 alone and when combined with Nivolumab, in patients with solid cancers that are advanced or have spread.

Official Title
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A Phase 1/2a Study of BMS-986179 Administered Alone and in Combination With Nivolumab (BMS-936558) in Subjects With Advanced Solid Tumors

Conditions
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Malignant Solid Tumor

Intervention / Treatment
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* Biological: BMS-986179
* Biological: Nivolumab
* Biological: rHuPH20


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: Solid cancers that are advanced or have spread (for which alternative therapies were deemed not effective) Eastern Cooperative Oncology Group (ECOG) 0-1 Acceptable lab testing results Allow biopsies Exclusion Criteria: Central nervous system (CNS) tumors Uncontrolled or significant cardiovascular diseases Active or known autoimmune disease Organ transplant 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A-Monotherapy<br>BMS-986179, dose as specified | Biological: BMS-986179<br>* Specified dose on specified days<br>|
| Experimental: Arm B- Combination Therapy<br>BMS-986179 + nivolumab, dose as specified | Biological: BMS-986179<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|
| Experimental: Arm C-Combination Therapy<br>BMS-986179 + rHuPH20, dose as specified | Biological: BMS-986179<br>* Specified dose on specified days<br>Biological: rHuPH20<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 Drug Related AEs, SAEs, AEs Leading to Discontinuation and Deaths. | Number of participants with drug related adverse events (AE), drug related serious adverse events (SAE), drug related AEs Leading to discontinuation and drug related deaths | From first dose to 100 days post last dose: Part 1 up to 25.1 months, Part 2 SC up to 17.5 months, RCC Mono up to 28.1 months, Part 2 up to 27.2 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With a Best Overall Response (BOR) at Week 24 | Best overall response (BOR) is defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy. CR or PR determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met. | from initial treatment to week 24 | 
| Percentage of Participants With an Objective Response Rate (ORR) at Week 24 | ORR is defined as the percentage of all treated participants whose BOR is either a CR or PR. | from initial treatment to week 24 | 
| Progression Free Survival Rate (PFSR) at Week 24 | PFSR at 24 weeks is defined as the percentage of treated participants remaining progression free and surviving at 24 weeks. | from initial treatment to week 24 | 
| Median Duration of Response (DOR) | DOR (computed for all treated subjects with a BOR of CR or PR) is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. | from first measure response approximately up to 25 months | 
| Cmax | Cmax is defined as maximum plasma concentration of the drug | Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days | 
| Tmax | Tmax is defined is the time to maximum plasma concentration | Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days | 
| AUC (0-T) | Area under the plasma concentration time-curve. AUC from time 0 to the last time of quantifiable concentration | Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days | 
| AUC (Tau) | Area under the plasma concentration time-curve. AUC over the dosing interval. | Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days | 
| Ctau | Ctau is defined as the concentration of study drug at the end of the dosing interval | Part 1A Cycle 0 = 14 days Cycle 1 = 28 days Part 1B and Part 2 Q2W regimen Cycle 0 = 14 days Cycle 1 = 28 days Cycle 2 = 28 days Part 1B and 2 Q4W Regimen Cycle 1= 28 days Cycle 2 = 28 days Cycle 4 = 28 days | 
| Mean Change From Baseline in CD73 Assays | Mean change from baseline in CD73 assays at the end of Part 1A treatment period Assays Measured: EHC CD73 H-score IHC CD73 Cytoplasm H-Score IHC CDS73 Membrane H-Score The H-score is given by the ratio of the weighted sum of the number of positive cells to the total number of detected cells. The H-score captures both the intensity and the proportion of the biomarker of interest from the IHC image and comprises values between 0 and 300. The lower the number equals a better prognosis. | approximately up to 95 weeks | 
| Number of Participants With a Positive Anti-drug Antibody (ADA) Test. | A participant with at least one ADA-positive sample relative to baseline at any time after initiation of treatment with BMS-986179 and nivolumab. | From first dose to last dose: Part 1: up to 95 weeks, Part 2 SC: up to 62 weeks, RCC Mono: up to 108 weeks, Part 2: up to 104 weeks |