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

Advanced Malignancies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03158272
• Other study ID #: CA025-001
• Status: Completed
• Phase: Phase 1
• Start date: May 25, 2017
• Est. completion date: October 23, 2019

Study information

• Verified date: November 2020
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: October 23, 2019
• Est. primary completion date: October 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Malignancies
• Neoplasms

Intervention

Biological:
• Cabiralizumab
Specified dose on specified days
• Nivolumab
Specified dose on specified days

Locations

Country	Name	City	State
Japan	Local Institution	Chuo-ku	Tokyo
Japan	Local Institution	Kamogawa-shi	Chiba
Japan	Local Institution	Kashiwa-shi	Chiba
Japan	Local Institution	Nagoya-shi	Aichi

Sponsors (2)

Lead Sponsor	Collaborator
Bristol-Myers Squibb	Ono Pharmaceutical Co. Ltd

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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)
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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

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