A Study of BMS-986207 Given Alone and in Combination With Nivolumab or With Nivolumab and Ipilimumab in Advanced Solid Tumors
Phase 1/2a First-In-Human Study of BMS-986207 Monoclonal Antibody Alone and in Combination With Nivolumab or With Nivolumab and Ipilimumab in Advanced Solid Tumors
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Ciudad Autónoma De Buenos Aires
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Caba, Ciudad Autónoma De Buenos Aires, Argentina, C1430EGF
- Local Institution - 0023
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Cordoba
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Córdoba, Cordoba, Argentina, X5002HWE
- Local Institution - 0019
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Distrito Federal
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Buenos Aires, Distrito Federal, Argentina, C1093AAS
- Local Institution - 0022
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Local Institution - 0006
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Ontario
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Ottawa, Ontario, Canada, K1H 8L6
- Local Institution - 0008
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Toronto, Ontario, Canada, M5G 2M9
- Local Institution - 0007
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Metropolitana
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Santiago, Metropolitana, Chile, 8420383
- Local Institution - 0021
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Chiba
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Kashiwa-shi, Chiba, Japan, 2778577
- Local Institution - 0004
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Tokyo
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Chuo-ku, Tokyo, Japan, 1040045
- Local Institution - 0005
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Bucharest, Romania, 022328
- Local Institution - 0017
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Cluj, Romania, 400015
- Local Institution - 0016
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Craiova, Romania, 200542
- Local Institution - 0018
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Florești, Romania, 407280
- Local Institution - 0015
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Singapore, Singapore, 119074
- Local Institution - 0020
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New Jersey
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Hackensack, New Jersey, United States, 07601
- Local Institution - 0001
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New York
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New York, New York, United States, 10032
- Local Institution - 0003
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- Local Institution - 0012
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Philadelphia, Pennsylvania, United States, 19111
- Local Institution - 0002
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Pittsburgh, Pennsylvania, United States, 15213
- Local Institution - 0009
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Utah
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Salt Lake City, Utah, United States, 84112
- Local Institution - 0010
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must have pre-existing or prior programmed death-ligand 1 (PD-L1) immunohistochemistry (IHC) results within 3 months of enrollment from testing of tumor tissue; PD-L1 expression must be tumor cell positive ≥ 1% for a participant to be eligible for enrollment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria; radiographic tumor assessment performed within 28 days before randomization
Exclusion Criteria:
- Primary central nervous system (CNS) disease, or tumors with CNS metastases as the only site of disease. Controlled brain metastases will be allowed to enroll
- Other active malignancy requiring concurrent intervention
- Uncontrolled or significant cardiovascular disease
- Active, known, or suspected autoimmune disease
- NSCLC without prior treatment in the advanced or metastatic setting (Part 2C)
Other protocol-defined inclusion/exclusion criteria apply
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Part 1A: Dose Escalation Monotherapy
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Specified dose on specified days
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Experimental: Part 1B: Dose Escalation Combination Therapy
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Specified dose on specified days
Other Names:
Specified dose on specified days
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Experimental: Part 2A: Expansion Monotherapy
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Specified dose on specified days
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Experimental: Part 2B: Expansion Combination Therapy
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Specified dose on specified days
Other Names:
Specified dose on specified days
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Experimental: Part 1C: Triplet Cohort
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Specified dose on specified days
Other Names:
Specified dose on specified days
Other Names:
Specified dose on specified days
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Experimental: Part 2C: Triplet Expansion
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Specified dose on specified days
Other Names:
Specified dose on specified days
Other Names:
Specified dose on specified days
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Number of Participants With Adverse Events
Time Frame: From first dose (Day 1) untill 100 days after last dose (Up to approximately 27 months)
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An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization.
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From first dose (Day 1) untill 100 days after last dose (Up to approximately 27 months)
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Number of Participants Who Died
Time Frame: From first dose (Day 1) untill 100 days after last dose (Up to approximately 27 months)
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Participants who died with any cause are considered in the analysis.
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From first dose (Day 1) untill 100 days after last dose (Up to approximately 27 months)
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Part 1A, 1B and 1C and 2A: Number of Participants With Dose Limiting Toxicities
Time Frame: From first dose (Day 1) and up to 6 weeks
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Criteria for Dose-Limiting Toxicities (DLTs): Hepatic DLTs (excluding HCC): Grade (Gr) 4 elevations in AST, ALT, ALP, or total bilirubin.
Gr 3 elevations in AST, ALT, or ALP >5 days, with symptoms, or bilirubin >2xULN without cholestasis.
Gr 2 AST or ALT with symptomatic liver inflammation.
AST or ALT >3xULN and bilirubin >2xULN without cholestasis.
Hepatic DLTs for HCC: AST or ALT >10xULN for >2 weeks.
AST or ALT >15xULN.
Total bilirubin >8xULN (elevated at entry) or >5xULN (normal at entry).
ALT ≥10xULN and bilirubin ≥2xULN or baseline, without other causes.
Hematologic DLTs: Gr 4 neutropenia ≥7 days.
Gr 4 thrombocytopenia.
Gr 3 thrombocytopenia with bleeding or platelet transfusion.
Febrile neutropenia.
Gr 3 hemolysis requiring intervention.
Gr 4 anemia not due to underlying disease.
Dermatologic DLTs: Gr 4 rash.
Gr 3 rash not improving to ≤Gr 1 after 1-2 week delay.
Other DLTs: Gr 2-4 eye issues, Gr 3-4 toxicities, excluding specific Gr 3 events like nausea, fever.
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From first dose (Day 1) and up to 6 weeks
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Part 1A, 1B and 1C and 2A: Number of Participants With Grade 3/Grade 4 Laboratory Abnormalities
Time Frame: From first dose (Day 1) till 100 days after last dose (Up to approximately 27 months)
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Blood samples were collected to assess the abnormalities in laboratory parameters.
The laboratory parameters were graded by Common Terminology Criteria for Adverse Events (CTCAE).
Grade 3=Severe; Grade 4=Life-threatening.
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From first dose (Day 1) till 100 days after last dose (Up to approximately 27 months)
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Part 2C: Objective Response Rate (ORR)
Time Frame: From first dose (Day 1) and up to 24 weeks
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ORR is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
From first dose (Day 1) and up to 24 weeks
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Part 2C: Duration of Response (DOR)
Time Frame: From first dose (Day 1) and up to 24 weeks
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DOR is defined for participants who have a confirmed CR or PR as the date from first documented CR or PR per RECIST v1.1 to the date of the documentation of disease progression or death due to any cause, whichever is earlier. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
From first dose (Day 1) and up to 24 weeks
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Part 2C: Progression Free Survival Rate at Week 24
Time Frame: Week 24
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Progression Free Survival Rates at 24 weeks is defined as the percentage of participants who achieve PFS at 24 weeks. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Objective Response Rate (ORR)
Time Frame: From first dose (Day 1) and up to 24 weeks
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ORR is defined as the percentage of participants with a confirmed Best overall response of Complete Response (CR) or Partial Response (PR) by RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters |
From first dose (Day 1) and up to 24 weeks
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Duration of Response
Time Frame: From first dose (Day 1) and up to 24 weeks
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DOR is defined for participants who have a confirmed CR or PR as the date from first documented CR or PR per RECIST v1.1 to the date of the documentation of disease progression or death due to any cause, whichever is earlier. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
From first dose (Day 1) and up to 24 weeks
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Progression Free Survival Rate at Week 24
Time Frame: Week 24
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Progression Free Survival Rates at 24 weeks is defined as the percentage of participants who achieve PFS at 24 weeks. PFS for a participant is defined as the time from randomization date to the date of first objectively documented disease progression by investigator per response evaluation criteria in solid tumors (RECIST) v1.1 or death due to any cause, whichever occurs first. Based on Kaplan-Meier Estimates. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum during the study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. |
Week 24
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Maximum Observed Concentration (Cmax) of BMS-986207
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Cmax is defined as maximum plasma concentration of the drug.
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Time to Maximum Concentration (Tmax)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Time to observed maximum concentration (Tmax) is defined as the amount of time in hours for a drug to reach the maximum concentration after administration.
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T))
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC (0-T)).
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Blood samples were collected for assessing AUC (TAU).
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Observed Serum Concentration at the End of a Dosing Interval (Ctau)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Blood samples were collected for assessing Ctau.
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Total Body Clearance (CLT)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Blood samples were collected for assessing CLT.
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Average Concentration Over a Dosing Interval (Css-avg)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Blood samples were collected for assessing Css-avg.
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Ratio of an Exposure Measure at Steady State to That After the First Dose (AI_TAU)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Blood samples were collected for assessing AI_TAU.
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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BMS-986207 Effective Elimination Half-life That Explains the Degree of Accumulation Observed for a Specific Exposure Measure (T-HALFeff)
Time Frame: Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Blood samples were collected for assessing T-HALFeff.
Exposure measure includes AUC[TAU].
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Day 1 of Cycle 1, Cycle 2 and Cycle 3 (Each cycle is of 8 weeks)
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Number of Participants With Positive Anti-BMS-986207-Antibodies Results
Time Frame: From first dose (Day 1) till 100 days after last dose (Up to approximately 27 months)
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Participants who were treated with BMS-986207 and at least one post-baseline evaluable ADA assessment were considered in the analysis
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From first dose (Day 1) till 100 days after last dose (Up to approximately 27 months)
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CA020-002
- 2016-002263-34 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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