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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03363776




Registration number
NCT03363776
Ethics application status
Date submitted
1/12/2017
Date registered
6/12/2017
Date last updated
19/12/2020

Titles & IDs
Public title
An Investigational Immuno-Therapy Study of Experimental Medication BMS-986277 Given Alone and in Combination With Nivolumab in Epithelial Cancers
Scientific title
Phase 1/2a First in Human Study of BMS-986277 Administered Alone and in Combination With Nivolumab in Advanced Epithelial Tumors
Secondary ID [1] 0 0
2017-002199-24
Secondary ID [2] 0 0
CA034-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cancer 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - BMS-986277
Treatment: Other - Nivolumab

Experimental: Monotherapy - BMS-986277 administered alone

Experimental: Combination Dose Escalation Therapy - BMS-986277 administered in combination with Nivolumab

Experimental: Combination Expansion Therapy - BMS-986277 monotherapy with option for subsequent Nivolumab therapy


Treatment: Other: BMS-986277
Specified dose on specified days

Treatment: Other: Nivolumab
Specified dose on specified days
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With an Adverse Event (AE)
Assessment method [1] 0 0
Number of participants who experienced an AE during the course of the study.
Timepoint [1] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Primary outcome [2] 0 0
Number of Participants With a Serious Adverse Event (SAE)
Assessment method [2] 0 0
Number of participants who experienced a SAE during the course of the study.
Timepoint [2] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Primary outcome [3] 0 0
Number of Participants With an Adverse Event (AE) Meeting Protocol-defined Dose Limiting Toxicity (DLT) Criteria
Assessment method [3] 0 0
Number of participants who experienced an AE meeting protocol-defined DLT criteria during the course of the study.
Timepoint [3] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Primary outcome [4] 0 0
Number of Participants With an Adverse Event (AE) Leading to Discontinuation
Assessment method [4] 0 0
Number of participants who experienced an AE leading to discontinuation during the course of the study.
Timepoint [4] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Primary outcome [5] 0 0
Number of Participants With an Adverse Event (AE) Leading to Death
Assessment method [5] 0 0
Number of participants who experienced an AE leading to death during the course of the study.
Timepoint [5] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Primary outcome [6] 0 0
Number of Participants With a Clinical Laboratory Test Abnormality
Assessment method [6] 0 0
Number of participants who experienced a clinical laboratory test abnormality during the course of the study.
Timepoint [6] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Primary outcome [7] 0 0
Number of Participants With a Vital Sign Abnormality or Other Safety Biomarkers
Assessment method [7] 0 0
Number of participants who experienced a vital sign abnormality or other safety biomarkers during the course of the study.
Timepoint [7] 0 0
from first dose to 60 days post last dose, assessed up to February 2020 (approx. 26 months)
Secondary outcome [1] 0 0
Objective Response Rate (ORR)
Assessment method [1] 0 0
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
Timepoint [1] 0 0
at Weeks 8, 16 and 24
Secondary outcome [2] 0 0
Disease Control Rate (DCR)
Assessment method [2] 0 0
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
Timepoint [2] 0 0
at Weeks 8, 16 and 24
Secondary outcome [3] 0 0
Median Duration of Response (mDOR)
Assessment method [3] 0 0
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)
Timepoint [3] 0 0
at Weeks 8, 16 and 24
Secondary outcome [4] 0 0
Median Progression-Free Survival (mPFS)
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
at Weeks 8, 16 and 24, to progression
Secondary outcome [5] 0 0
Progression-Free Survival Rate (PFSR)
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
at Weeks 8, 16 and 24
Secondary outcome [6] 0 0
Cmax
Assessment method [6] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Cmax is defined as the maximum observed blood concentration.
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Tmax
Assessment method [7] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Tmax is defined as the time of maximum observed blood concentration.
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
AUC(0-T)
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
AUC(INF)
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
T-HALF
Assessment method [10] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. T-HALF is defined as the apparent terminal half-life.
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
CLT
Assessment method [11] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. CLT is defined as the total body clearance.
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
Vss
Assessment method [12] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vss is defined as the volume of distribution at steady-state.
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
Vz
Assessment method [13] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Vz is defined as the volume of distribution of the elimination phase.
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
AUC(0-48)
Assessment method [14] 0 0
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
Timepoint [14] 0 0
Cycle 1 (from time zero to 48 hours postdose)
Secondary outcome [15] 0 0
AUC(0-8)
Assessment method [15] 0 0
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
Timepoint [15] 0 0
Cycle 1 (from time zero to 8 hours postdose)
Secondary outcome [16] 0 0
C48
Assessment method [16] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. C48 is defined as the blood concentration at 48 hours postdose.
Timepoint [16] 0 0
Cycle 1 at 48 hours postdose
Secondary outcome [17] 0 0
Css-avg
Assessment method [17] 0 0
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).
Timepoint [17] 0 0
Cycle 1 (from time zero to 48 hours postdose)
Secondary outcome [18] 0 0
AI_AUC
Assessment method [18] 0 0
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.
Timepoint [18] 0 0
Cycle 1 (Day 19, Day 15)
Secondary outcome [19] 0 0
AI_Cmax
Assessment method [19] 0 0
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.
Timepoint [19] 0 0
Cycle 1 (Day 19, Day 15)
Secondary outcome [20] 0 0
T-HALFeff
Assessment method [20] 0 0
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)
Timepoint [20] 0 0
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
Secondary outcome [21] 0 0
Ctrough
Assessment method [21] 0 0
Pharmacokinetics of BMS-986277 were derived from blood concentration versus time data. Ctrough is defined as the trough observed blood concentration.
Timepoint [21] 0 0
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
Secondary outcome [22] 0 0
Number of Participants With a Positive Antibody-Drug-Antibody (ADA) Response
Assessment method [22] 0 0
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
Timepoint [22] 0 0
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

Eligibility
Key inclusion criteria
For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com



* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
6/12/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/11/2019
Sample size
Target
Accrual to date
Final
10
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
South Dakota
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bristol-Myers Squibb
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Bristol-Myers Squibb
Address 0 0
Bristol-Myers Squibb
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol
Statistical analysis plan



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT03363776