An Investigational Immuno-Therapy Study of Experimental Medication BMS-986277 Given Alone and in Combination With Nivolumab in Epithelial Cancers

Study Overview
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Brief Summary
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The purpose of this study is to investigate experimental medication BMS-986277 given alone and in combination with Nivolumab in patients with epithelial cancers.

Official Title
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Phase 1/2a First in Human Study of BMS-986277 Administered Alone and in Combination With Nivolumab in Advanced Epithelial Tumors

Conditions
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Cancer

Intervention / Treatment
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* Biological: BMS-986277
* 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: Histological or cytological confirmation of metastatic and/or unresectable metastatic colorectal, prostate, pancreatic, breast, ovarian, or urothelial carcinoma with measureable disease for solid tumors per RECIST v1.1 and for prostate carcinoma per PCWG3 Presence of at least 2 lesions: at least one with measurable disease as defined by RECIST v1.1 for solid tumors and by PCWG3 for prostate carcinoma for response assessment; at least 1 lesion must be accessible for biopsy in addition to the target lesion 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, and have been considered for all other potentially efficacious therapies prior to enrollment ECOG performance status less than or equal to 2 Exclusion Criteria: Participants with active central nervous system (CNS) metastases, untreated CNS metastases, or with the CNS as the only site of disease Participants with carcinomatous meningitis Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study treatment Participants with active, known, or suspected autoimmune disease 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: Monotherapy<br>BMS-986277 administered alone | Biological: BMS-986277<br>* Specified dose on specified days<br>|
| Experimental: Combination Dose Escalation Therapy<br>BMS-986277 administered in combination with Nivolumab | Biological: BMS-986277<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-963558;|
| Experimental: Combination Expansion Therapy<br>BMS-986277 monotherapy with option for subsequent Nivolumab therapy | Biological: BMS-986277<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: BMS-963558;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With an Adverse Event (AE) | Number of participants who experienced an AE during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 
| Number of Participants With a Serious Adverse Event (SAE) | Number of participants who experienced a SAE during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 
| Number of Participants With an Adverse Event (AE) Meeting Protocol-defined Dose Limiting Toxicity (DLT) Criteria | Number of participants who experienced an AE meeting protocol-defined DLT criteria during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 
| Number of Participants With an Adverse Event (AE) Leading to Discontinuation | Number of participants who experienced an AE leading to discontinuation during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 
| Number of Participants With an Adverse Event (AE) Leading to Death | Number of participants who experienced an AE leading to death during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 
| Number of Participants With a Clinical Laboratory Test Abnormality | Number of participants who experienced a clinical laboratory test abnormality during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 
| Number of Participants With a Vital Sign Abnormality or Other Safety Biomarkers | Number of participants who experienced a vital sign abnormality or other safety biomarkers during the course of the study. | from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR is defined as the proportion of all treated participants whose BOR is either CR or PR. BOR was determined by investigators for the reported data. Estimate of ORR and corresponding 2-sided exact 95% CI using the Clopper-Pearson method | at Weeks 8, 16 and 24 | 
| Disease Control Rate (DCR) | DCR includes complete response (CR), partial response (PR), and stable disease (SD). Estimate of DCR and corresponding 2-sided exact 95% CI using the Clopper-Pearson method | at Weeks 8, 16 and 24 | 
| Median Duration of Response (mDOR) | DOR for a participant with a BOR of CR or PR is defined as the time between the date of first response and the date of the first objectively documented tumor progression per RECIST v1.1/PCWG3 or death, whichever occurs first. Estimate by the Kaplan-Meier method and corresponding 2-sided 95% CI using Brookmeyer and Crowley methodology (using log-log transformation) | at Weeks 8, 16 and 24 | 
| Median Progression-Free Survival (mPFS) | PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Estimate by the Kaplan-Meier method and corresponding 2-sided 95% CI using Brookmeyer and Crowley methodology (using log-log transformation) for the median and Greenwood formula for the rate. | at Weeks 8, 16 and 24, to progression | 
| Progression-Free Survival Rate (PFSR) | PFS for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurs first. Estimate by the Kaplan-Meier method and corresponding 2-sided 95% CI using Brookmeyer and Crowley methodology (using log-log transformation) for the median and Greenwood formula for the rate. | at Weeks 8, 16 and 24 | 
| Cmax | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Cmax is defined as the maximum observed blood concentration. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| Tmax | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Tmax is defined as the time of maximum observed blood concentration. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| AUC(0-T) | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. AUC(0-T) is the area under the blood concentration-time curve from time zero to time of last quantifiable concentration. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| AUC(INF) | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. AUC(INF) is the area under the blood concentration-time curve from time zero extrapolated to infinite time. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| T-HALF | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. T-HALF is defined as the apparent terminal half-life. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| CLT | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. CLT is defined as the total body clearance. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| Vss | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vss is defined as the volume of distribution at steady-state. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| Vz | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vz is defined as the volume of distribution of the elimination phase. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| AUC(0-48) | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. AUC(0-T) is the area under the blood concentration-time curve from time zero to 48 hours postdose | Cycle 1 (from time zero to 48 hours postdose) | 
| AUC(0-8) | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. AUC(0-T) is the area under the blood concentration-time curve from time zero to 8 hours postdose | Cycle 1 (from time zero to 8 hours postdose) | 
| C48 | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. C48 is defined as the blood concentration at 48 hours postdose. | Cycle 1 at 48 hours postdose | 
| Css-avg | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Css-avg is defined as the average blood concentration over a dosing interval at steady state (AUC[0-48]/48). | Cycle 1 (from time zero to 48 hours postdose) | 
| AI_AUC | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. AUC accumulation index; ratio of AUC(0-48) on Cycle 1 Day 19 to AUC(0-48) on Cycle 1 Day 15 for monotherapy. | Cycle 1 (Day 19, Day 15) | 
| AI_Cmax | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Cmax accumulation index; ratio of Cmax on Cycle 1 Day 19 to Cmax on Cycle 1 Day 15 for monotherapy. | Cycle 1 (Day 19, Day 15) | 
| T-HALFeff | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. T-HALFeff is defined as effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC, Cmax) | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| Ctrough | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Ctrough is defined as the trough observed blood concentration. | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits | 
| Number of Participants With a Positive Antibody-Drug-Antibody (ADA) Response | Baseline ADA-positive participant is defined as a participant who has an 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. Frequency distribution of baseline ADA-positive participants and ADA-positive participants after initiation of the treatment | Cycle 1 (Day 1 pre-dose through Day 29, 240 hour), Cycle 2 (Day 1 pre-dose through Day 22, 408 hour); through Follow-up visits |