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

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

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03363776

Enrollment

Registered

2017-12-06

Start date

2017-12-06

Completion date

2019-11-22

Last updated

2020-12-19

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cancer

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.

Interventions

BIOLOGICALBMS-986277

Specified dose on specified days

BIOLOGICALNivolumab

Specified dose on specified days

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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/

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With a Serious Adverse Event (SAE)	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) Meeting Protocol-defined Dose Limiting Toxicity (DLT) Criteria	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.
Number of Participants With an Adverse Event (AE) Leading to Discontinuation	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)	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 Death	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	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	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.

Secondary

Measure	Time frame	Description
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	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.
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	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.
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. T-HALF is defined as the apparent terminal half-life.
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. CLT is defined as the total body clearance.
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vss is defined as the volume of distribution at steady-state.
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vz is defined as the volume of distribution of the elimination phase.
AUC(0-48)	Cycle 1 (from time zero to 48 hours postdose)	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
Objective Response Rate (ORR)	at Weeks 8, 16 and 24	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
C48	Cycle 1 at 48 hours postdose	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. C48 is defined as the blood concentration at 48 hours postdose.
Css-avg	Cycle 1 (from time zero to 48 hours postdose)	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).
AI_AUC	Cycle 1 (Day 19, Day 15)	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.
AI_Cmax	Cycle 1 (Day 19, Day 15)	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.
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	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)
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Ctrough is defined as the trough observed blood concentration.
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	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
AUC(0-8)	Cycle 1 (from time zero to 8 hours postdose)	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
Disease Control Rate (DCR)	at Weeks 8, 16 and 24	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
Median Duration of Response (mDOR)	at Weeks 8, 16 and 24	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)
Median Progression-Free Survival (mPFS)	at Weeks 8, 16 and 24, to progression	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.
Progression-Free Survival Rate (PFSR)	at Weeks 8, 16 and 24	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.
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Cmax is defined as the maximum observed blood concentration.
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	Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Tmax is defined as the time of maximum observed blood concentration.

Countries

Canada, United States

Participant flow

Pre-assignment details

10 participants randomized and treated

Participants by arm

Arm	Count
Arm A (Part 1) BMS-986277 IV 3 X 10\^10 Cycle 1 of BMS-986277 will be administered as a single IV infusion (D1) before proceeding to sequential dosing (consisting of 3 doses administered on Days 15, 17, and 19). A minimum of 24 hours is required between doses of BMS-986277.	4
Arm B (Part 1) BMS-986277 IV 3 X 10\^11 Cycle 1 of BMS-986277 will be administered as a single IV infusion (D1) before proceeding to sequential dosing (consisting of 3 doses administered on Days 15, 17, and 19). A minimum of 24 hours is required between doses of BMS-986277.	3
Arm C (Part 1) BMS-986277 IV 1 X 10\^12 Cycle 1 of BMS-986277 will be administered as a single IV infusion (D1) before proceeding to sequential dosing (consisting of 3 doses administered on Days 15, 17, and 19). A minimum of 24 hours is required between doses of BMS-986277.	3
Total	10

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Death	1	0	0
Overall Study	Progressive disease	2	3	1
Overall Study	Study drug toxicity	0	0	1

Baseline characteristics

Characteristic	Arm A (Part 1)	Arm B (Part 1)	Arm C (Part 1)	Total
Age, Continuous	61 Years STANDARD_DEVIATION 2.4	59 Years STANDARD_DEVIATION 10.4	47 Years STANDARD_DEVIATION 12.1	57 Years STANDARD_DEVIATION 9.9
Age, Customized <= 65 years	4 Participants	2 Participants	3 Participants	9 Participants
Age, Customized > 65 years	0 Participants	1 Participants	0 Participants	1 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants	0 Participants	1 Participants	2 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants	3 Participants	2 Participants	8 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	4 Participants	3 Participants	3 Participants	10 Participants
Sex: Female, Male Female	2 Participants	1 Participants	2 Participants	5 Participants
Sex: Female, Male Male	2 Participants	2 Participants	1 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	2 / 4	2 / 3	2 / 3
other Total, other adverse events	4 / 4	3 / 3	3 / 3
serious Total, serious adverse events	1 / 4	0 / 3	2 / 3

Outcome results

Primary

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)