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

• Cabiralizumab (Biological): Specified dose on specified days
• Nivolumab (Biological), also known as Opdivo: Specified dose on specified days

Primary outcomes

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

Secondary outcomes

• Number of Participants With Adverse Events (AEs) - Carbiralizumab and Nivolumab Combo Therapy [From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months]: The number of participants that experienced an AE during the course of the study while participating in cabiralizumab and nivolumab combination therapy.
• Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab and Nivolumab Combo Therapy [From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months]: The number of participants that experienced an SAE during the course of the study while participating in cabiralizumab and nivolumab combination therapy.
• Number of Participants With AEs Leading to Discontinuation - Carbiralizumab and Nivolumab Combo Therapy [From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months]: 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.
• Number of Participants Who Died - Carbiralizumab and Nivolumab Combo Therapy [From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months]: The number of participants that died during the course of the study while participating in cabiralizumab and nivolumab combination therapy.
• Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy [From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months]: The number of participants that experienced a laboratory abnormality during the course of the study while participating in carbiralizumab and nivolumab combination therapy
• AI_Ctrough [Cycle 2 (pre-dose), Cycle 8 (pre-dose)]: 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
• AUC(0-T) [Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)]: 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.
• AUC(TAU) [Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)]: 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.
• Cmax [Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)]: 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.
• Ctrough [Cycles 1, 2, 3, 4, 5, 6, 7, 8, 9]: 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.
• T-HALFeff_Ctrough [Cycle 2 (pre-dose), Cycle 8 (pre-dose)]: 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.
• Tmax [Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)]: 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.
• Incidence of Anti-drug Antibodies (ADA) [Day 1 pre-dose for cycles 2, 3, 5, 9, 13, 21]: 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.
• Best Overall Response (BOR) [From first dose to end of follow-up, assessed up to July 2019, approximately 24 months]: 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) [From first dose to end of follow-up]: 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).

Sex: All, ages: 20 Years to any

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

Participant flow

Outcome results

• Number of Participants With Adverse Events (AEs) - Carbiralizumab Monotherapy (Primary), Number, Number of participants: M1 Cohort 3; M2 Cohort 4
• Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab Monotherapy (Primary), Number, Number of participants: M1 Cohort 1; M2 Cohort 2
• Number of Participants With AEs Meeting Protocol-defined Dose-Limiting Toxicity (DLT) Criteria - Carbiralizumab Monotherapy (Primary), Number, Number of participants: M1 Cohort 0; M2 Cohort 0
• Number of Participants With AEs Leading to Discontinuation - Carbiralizumab Monotherapy (Primary), Number, Number of participants: M1 Cohort 0; M2 Cohort 1
• Number of Participants Who Died - Carbiralizumab Monotherapy (Primary), Number, Number of participants: M1 Cohort 0; M2 Cohort 0
• Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy (Primary), Number, Number of participants: M1 Cohort 3; M2 Cohort 4
• Number of Participants With Adverse Events (AEs) - Carbiralizumab and Nivolumab Combo Therapy (Secondary), Number, Number of participants: C1 Cohort 6; C2 Cohort 5
• Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab and Nivolumab Combo Therapy (Secondary), Number, Number of participants: C1 Cohort 1; C2 Cohort 1
• Number of Participants With AEs Leading to Discontinuation - Carbiralizumab and Nivolumab Combo Therapy (Secondary), Number, Number of participants: C1 Cohort 1; C2 Cohort 1
• Number of Participants Who Died - Carbiralizumab and Nivolumab Combo Therapy (Secondary), Number, Number of participants: C1 Cohort 1; C2 Cohort 0
• Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy (Secondary), Number, Number of participants: C1 Cohort 6; C2 Cohort 6
• AI_Ctrough (Secondary), Geometric mean, Ratio of Ctrough: cycle 8 to cycle 2: M1 Cohort NA +/- NA; M2 Cohort ; C1 Cohort NA +/- NA; C2 Cohort
• AUC(0-T) (Secondary), Geometric mean, h*µg/mL: M1 Cohort 4992 +/- 16; M2 Cohort 11668 +/- 14; C1 Cohort 9969 +/- 30; C2 Cohort 8723 +/- 26
• AUC(TAU) (Secondary), Geometric mean, h*µg/mL: M1 Cohort 4992 +/- 16; M2 Cohort 12499 +/- 2; C1 Cohort 9969 +/- 30; C2 Cohort 10590 +/- 6
• Cmax (Secondary), Geometric mean, µg/mL: M1 Cohort 43.7 +/- 20; M2 Cohort 91.4 +/- 7; C1 Cohort 84.8 +/- 19; C2 Cohort 76.2 +/- 15
• Ctrough (Secondary), Geometric mean, µg/mL: M1 Cohort 2.44 +/- 105; M2 Cohort 18.5 +/- 1; C1 Cohort 10.1 +/- 50; C2 Cohort 16.5 +/- 14
• T-HALFeff_Ctrough (Secondary), Median, hour: M1 Cohort NA (NA to NA); M2 Cohort ; C1 Cohort NA (NA to NA); C2 Cohort
• Tmax (Secondary), Median, h (Hour): M1 Cohort 3.18 (0.533 to 4.62); M2 Cohort 0.546 (0.500 to 0.633); C1 Cohort 1.14 (0.517 to 4.00); C2 Cohort 1.32 (0.550 to 4.25)
• Incidence of Anti-drug Antibodies (ADA) (Secondary), Number, Number of participants: M1 Cohort 1; M2 Cohort 0; C1 Cohort 2; C2 Cohort 0
• Best Overall Response (BOR) (Secondary), Number, Number of participants: M1 Cohort 2; M2 Cohort 0; C1 Cohort 3; C2 Cohort 0
• 1 more outcome measures not shown.

Adverse events

Time frame: From first dose to 100 days post last dose for SAEs and AEs, assessed up to July 2019, approximately 24 months. Note: Specifically for mortality data, assessment was performed up to end of study (Apr2020 data base lock).

Serious adverse events by term

Other adverse events by term

7 more terms not shown.

• Statistical Analysis Plan (PDF, 2019-09-10)
• Study Protocol (PDF, 2018-03-22)

• Bristol-Myers Squibb, Study director, Bristol-Myers Squibb