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

Phase 2TerminatedNCT03363776

Bristol-Myers Squibb10 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cancer

Interventions

BMS-986277BIOLOGICAL

Specified dose on specified days

NivolumabBIOLOGICAL

Specified dose on specified days

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Sanford Research

Sioux Falls, South Dakota, United States

Local Institution

Ottawa, Ontario, Canada

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Outcomes

Primary Outcomes

Number of Participants With an Adverse Event (AE)

Number of participants who experienced an AE during the course of the study.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

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

Time frame: 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

Time frame: 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)

Time frame: 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.

Time frame: at Weeks 8, 16 and 24, to progression

Progression-Free Survival Rate (PFSR)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vz is defined as the volume of distribution of the elimination phase.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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.

Time frame: 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

Time frame: 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