Phase 1/2a First in Human Study of BMS-986277 Administered Alone and in Combination With Nivolumab in Advanced Epithelial Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 10
- Locations
- 3
- Primary Endpoint
- Number of Participants With an Adverse Event (AE) Leading to Death
Study Overview
Brief Summary
The purpose of this study is to investigate experimental medication BMS-986277 given alone and in combination with Nivolumab in patients with epithelial cancers.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
Arms & Interventions
Combination Expansion Therapy
BMS-986277 monotherapy with option for subsequent Nivolumab therapy
Intervention: BMS-986277 (Biological)
Combination Expansion Therapy
BMS-986277 monotherapy with option for subsequent Nivolumab therapy
Intervention: Nivolumab (Biological)
Combination Dose Escalation Therapy
BMS-986277 administered in combination with Nivolumab
Intervention: Nivolumab (Biological)
Combination Dose Escalation Therapy
BMS-986277 administered in combination with Nivolumab
Intervention: BMS-986277 (Biological)
Monotherapy
BMS-986277 administered alone
Intervention: BMS-986277 (Biological)
Outcomes
Primary Outcomes
Number of Participants With an Adverse Event (AE) Leading to Death
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced an AE leading to death during the course of the study.
Number of Participants With a Clinical Laboratory Test Abnormality
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced a clinical laboratory test abnormality during the course of the study.
Number of Participants With a Vital Sign Abnormality or Other Safety Biomarkers
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced a vital sign abnormality or other safety biomarkers during the course of the study.
Number of Participants With a Serious Adverse Event (SAE)
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced a SAE during the course of the study.
Number of Participants With an Adverse Event (AE)
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced an AE during the course of the study.
Number of Participants With an Adverse Event (AE) Leading to Discontinuation
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced an AE leading to discontinuation during the course of the study.
Number of Participants With an Adverse Event (AE) Meeting Protocol-defined Dose Limiting Toxicity (DLT) Criteria
Time Frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Number of participants who experienced an AE meeting protocol-defined DLT criteria during the course of the study.
Secondary Outcomes
- C48(Cycle 1 at 48 hours postdose)
- Disease Control Rate (DCR)(at Weeks 8, 16 and 24)
- 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)
- AUC(0-T)(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)
- Objective Response Rate (ORR)(at Weeks 8, 16 and 24)
- Median Duration of Response (mDOR)(at Weeks 8, 16 and 24)
- Median Progression-Free Survival (mPFS)(at Weeks 8, 16 and 24, to progression)
- AUC(INF)(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(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)
- Progression-Free Survival Rate (PFSR)(at Weeks 8, 16 and 24)
- Tmax(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(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(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)(Cycle 1 (from time zero to 48 hours postdose))
- AUC(0-8)(Cycle 1 (from time zero to 8 hours postdose))
- Css-avg(Cycle 1 (from time zero to 48 hours postdose))
- Vz(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)
- AI_AUC(Cycle 1 (Day 19, Day 15))
- AI_Cmax(Cycle 1 (Day 19, Day 15))
- T-HALFeff(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(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(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)