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

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

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.

Study Overview

• Status: Completed
• Conditions: Advanced Malignancies
• Intervention / Treatment: Biological: Nivolumab; Biological: Cabiralizumab

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Aichi
    • Nagoya-shi, Aichi, Japan, 4678602
      • Local Institution
  • Chiba
    • Kamogawa-shi, Chiba, Japan, 2968602
      • Local Institution
    • Kashiwa-shi, Chiba, Japan, 2778577
      • Local Institution
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 1040045
      • Local Institution

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb
• Collaborators: Ono Pharmaceutical Co. Ltd

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2017
• Primary Completion (Actual): October 23, 2019
• Study Completion (Actual): October 23, 2019

Study Registration Dates

• First Submitted: May 16, 2017
• First Submitted That Met QC Criteria: May 16, 2017
• First Posted (Actual): May 18, 2017

Study Record Updates

• Last Update Posted (Actual): December 21, 2020
• Last Update Submitted That Met QC Criteria: November 24, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: CA025-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes