A Study of Cabiralzumab Given by Itself or With Nivolumab in Advanced Cancer or Cancer That Has Spread

Study Overview
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Brief Summary
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The purpose of this study is to determine whether an investigational immuno-therapy, cabiralizumab in combination with nivolumab, is safe and tolerable in the treatment of advanced malignancies.

Official Title
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A Phase 1 Study of Cabiralizumab (BMS-986227, FPA008) Administered Alone or in Combination With Nivolumab (BMS-936558) in Advanced Malignancies

Conditions
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Advanced Malignancies

Intervention / Treatment
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* Biological: Cabiralizumab
* Biological: Nivolumab


Participation Criteria
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Eligibility Criteria
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For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Performance status 0-1 Adequate organ function Cohort M1, 2 and C1: Measurable disease Cohort M1, M2 and C1: Subjects must have histologic or cytologic confirmation of an advanced (metastatic and/or unresectable) malignant solid tumor Cohort C2: Documented refractory or relapsed multiple myeloma Subjects must be refractory to or have relapsed after standard therapies, or have no known effective treatment Exclusion Criteria: Cohort M1, M2, and C1: Untreated or active central nervous system (CNS) or leptomeningeal metastases Cohort M1, M2, and C1: Subjects with hepatocellular carcinoma (HCC) Cohort C2: Subjects with solitary bone or extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel assignment will only in combination therapy arm.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Monotherapy<br>Cabiralizumab administered as a single agent intravenous formulation | Biological: Cabiralizumab<br>* Specified dose on specified days<br>|
| Experimental: Combination Therapy<br>Cabiralizumab will be administered in combination with Nivolumab as an intravenous formulation | Biological: Cabiralizumab<br>* Specified dose on specified days<br>Biological: Nivolumab<br>* Specified dose on specified days<br>* Other names: Opdivo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) - Carbiralizumab Monotherapy | The number of participants that experienced an AE during the course of the study while participating in cabiralizumab monotherapy treatment. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab Monotherapy | The number of participants that experienced a SAE during the course of the study while participating in cabiralizumab monotherapy treatment. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants With AEs Meeting Protocol-defined Dose-Limiting Toxicity (DLT) Criteria - Carbiralizumab Monotherapy | The number of participants that experienced an AE meeting protocol-defined DLT criteria during the course of the study while participating in cabiralizumab monotherapy treatment. | 28 days (from first day of treatment) | 
| Number of Participants With AEs Leading to Discontinuation - Carbiralizumab Monotherapy | The number of participants that experienced an AE leading to discontinuation during the course of the study while participating in cabiralizumab monotherapy treatment. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants Who Died - Carbiralizumab Monotherapy | The number of participants that died during the course of the study while participating in cabiralizumab monotherapy treatment. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | The number of participants that experienced a laboratory abnormality during the course of the study while participating in cabiralizumab monotherapy treatment. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Adverse Events (AEs) - Carbiralizumab and Nivolumab Combo Therapy | The number of participants that experienced an AE during the course of the study while participating in cabiralizumab and nivolumab combination therapy. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab and Nivolumab Combo Therapy | The number of participants that experienced an SAE during the course of the study while participating in cabiralizumab and nivolumab combination therapy. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants With AEs Leading to Discontinuation - Carbiralizumab and Nivolumab Combo Therapy | The number of participants that experienced an AE leading to discontinuation during the course of the study while participating in cabiralizumab and nivolumab combination therapy. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants Who Died - Carbiralizumab and Nivolumab Combo Therapy | The number of participants that died during the course of the study while participating in cabiralizumab and nivolumab combination therapy. | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | The number of participants that experienced a laboratory abnormality during the course of the study while participating in carbiralizumab and nivolumab combination therapy | From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months | 
| AI_Ctrough | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. Ctrough Accumulation Index; ratio of Ctrough at steady-state (i.e. Cycle 8) to Ctrough after the first dose Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. AI = Ctrough on cycle 8 / Ctrough on Cycle 2 | Cycle 2 (pre-dose), Cycle 8 (pre-dose) | 
| AUC(0-T) | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. AUC(0-T) is defined as the area under the serum concentration-time curve from time zero to time of last quantifiable concentration after the first dose. Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour) | 
| AUC(TAU) | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. AUC(TAU) is defined as the area under the serum concentration-time curve in one dosing interval. Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour) | 
| Cmax | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. Cmax is defined as the maximum observed serum concentration. Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour) | 
| Ctrough | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. Ctrough is defined as the Trough observed serum concentration (predose at each cycle). Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Cycles 1, 2, 3, 4, 5, 6, 7, 8, 9 | 
| T-HALFeff_Ctrough | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. T-HALFeff_Ctrough is defined as the effective elimination half-life that explains the degree of Ctrough accumulation observed. Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Cycle 2 (pre-dose), Cycle 8 (pre-dose) | 
| Tmax | Pharmacokinetics of cabiralizumab and nivolumab were derived from serum concentration versus time data. Tmax is defined as the time of maximum observed serum concentration. Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour) | 
| Incidence of Anti-drug Antibodies (ADA) | To characterize the immunogenicity of cabiralizumab and nivolumab. Baseline ADA-positive participant is defined as a participant who has a 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. Data collected from participants participating in cabiralizumab monotherapy, as well as cabiralizumab and nivolumab combination therapy. | Day 1 pre-dose for cycles 2, 3, 5, 9, 13, 21 | 
| Best Overall Response (BOR) | To assess the preliminary anti-tumor activity of cabiralizumab administered alone and in combination with nivolumab per RECIST 1.1 (M1, M2, C1 cohorts: participants with advanced solid tumors) and per IMWG criteria (Cohort C2: participants with hematologic malignancies). IMWG: International Myeloma Working Group RECIST: Response Evaluation Criteria in Solid Tumors | From first dose to end of follow-up, assessed up to July 2019, approximately 24 months | 
| Duration of Response (DOR) | To assess the preliminary anti-tumor activity of cabiralizumab administered alone and in combination with nivolumab per RECIST 1.1 (M1, M2, C1 cohorts: participants with advanced solid tumors) and per IMWG criteria (Cohort C2: participants with hematologic malignancies). IMWG: International Myeloma Working Group RECIST: Response Evaluation Criteria in Solid Tumors Duration of response (DOR) was listed for participants with a BOR of complete response (CR) or partial response (PR). | From first dose to end of follow-up |