Description:
The purpose of this study is to investigate experimental medication BMS-986277 given alone
and in combination with Nivolumab in patients with epithelial cancers.
Title
- Brief Title: An Investigational Immuno-Therapy Study of Experimental Medication BMS-986277 Given Alone and in Combination With Nivolumab in Epithelial Cancers
- Official Title: Phase 1/2a First in Human Study of BMS-986277 Administered Alone and in Combination With Nivolumab in Advanced Epithelial Tumors
Clinical Trial IDs
- ORG STUDY ID:
CA034-001
- SECONDARY ID:
2017-002199-24
- NCT ID:
NCT03363776
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| BMS-986277 | | Combination Dose Escalation Therapy |
| Nivolumab | Opdivo, BMS-963558 | Combination Dose Escalation Therapy |
Purpose
The purpose of this study is to investigate experimental medication BMS-986277 given alone
and in combination with Nivolumab in patients with epithelial cancers.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Monotherapy | Experimental | BMS-986277 administered alone | |
| Combination Dose Escalation Therapy | Experimental | BMS-986277 administered in combination with Nivolumab | |
| Combination Expansion Therapy | Experimental | BMS-986277 monotherapy with option for subsequent Nivolumab therapy | |
Eligibility 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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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) |
| Safety Issue: | |
| Description: | Number of participants who experienced an AE during the course of the study. |
Secondary Outcome Measures
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | at Weeks 8, 16 and 24 |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Disease Control Rate (DCR) |
| Time Frame: | at Weeks 8, 16 and 24 |
| Safety Issue: | |
| Description: | 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 |
| Measure: | Median Duration of Response (mDOR) |
| Time Frame: | at Weeks 8, 16 and 24 |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Median Progression-Free Survival (mPFS) |
| Time Frame: | at Weeks 8, 16 and 24, to progression |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Progression-Free Survival Rate (PFSR) |
| Time Frame: | at Weeks 8, 16 and 24 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
Cmax is defined as the maximum observed blood concentration. |
| Measure: | Tmax |
| 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
Tmax is defined as the time of maximum observed blood concentration. |
| Measure: | AUC(0-T) |
| 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | AUC(INF) |
| 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 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | T-HALF |
| 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
T-HALF is defined as the apparent terminal half-life. |
| Measure: | CLT |
| 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
CLT is defined as the total body clearance. |
| Measure: | Vss |
| 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
Vss is defined as the volume of distribution at steady-state. |
| Measure: | Vz |
| 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
Vz is defined as the volume of distribution of the elimination phase. |
| Measure: | AUC(0-48) |
| Time Frame: | Cycle 1 (from time zero to 48 hours postdose) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | AUC(0-8) |
| Time Frame: | Cycle 1 (from time zero to 8 hours postdose) |
| Safety Issue: | |
| Description: | 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 |
| Measure: | C48 |
| Time Frame: | Cycle 1 at 48 hours postdose |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
C48 is defined as the blood concentration at 48 hours postdose. |
| Measure: | Css-avg |
| Time Frame: | Cycle 1 (from time zero to 48 hours postdose) |
| Safety Issue: | |
| Description: | 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). |
| Measure: | AI_AUC |
| Time Frame: | Cycle 1 (Day 19, Day 15) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | AI_Cmax |
| Time Frame: | Cycle 1 (Day 19, Day 15) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | T-HALFeff |
| 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 |
| Safety Issue: | |
| Description: | 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) |
| Measure: | Ctrough |
| 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 |
| Safety Issue: | |
| Description: | Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data.
Ctrough is defined as the trough observed blood concentration. |
| Measure: | Number of Participants With a Positive Antibody-Drug-Antibody (ADA) Response |
| 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 |
| Safety Issue: | |
| Description: | 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 |
Details
| Phase: | Phase 1/Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Terminated |
| Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
December 19, 2020
