Advanced Malignancies
Conditions
Brief 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.
Interventions
BIOLOGICALCabiralizumab
Specified dose on specified days
BIOLOGICALNivolumab
Specified dose on specified days
Sponsors
Ono Pharmaceutical Co. Ltd
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel assignment will only in combination therapy arm.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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). |
| 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. |
| 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 |
Countries
Japan
Participant flow
Pre-assignment details
19 participants entered the treatment period, and 19 were treated.
Participants by arm
| Arm | Count |
|---|---|
| M1 Cohort 2 mg/kg cabiralizumab monotherapy | 3 |
| M2 Cohort 4 mg/kg cabiralizumab monotherapy | 4 |
| C1 Cohort Cabiralizumab in combination with nivolumab: 4 mg/kg cabiralizumab and 3 mg/kg nivolumab in participants with solid tumor | 6 |
| C2 Cohort Cabiralizumab in combination with nivolumab: 4 mg/kg cabiralizumab and 3 mg/kg nivolumab in participants with hematologic malignancies | 6 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse event unrelated to the drug | 0 | 1 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 1 | 0 |
| Overall Study | Disease progression | 3 | 3 | 4 | 6 |
| Overall Study | Other reasons | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | M1 Cohort | M2 Cohort | C1 Cohort | C2 Cohort | Total |
|---|---|---|---|---|---|
| Age, Continuous | 66.7 Years STANDARD_DEVIATION 5.1 | 63.8 Years STANDARD_DEVIATION 7.6 | 67.0 Years STANDARD_DEVIATION 6.2 | 64.5 Years STANDARD_DEVIATION 9.4 | 65.5 Years STANDARD_DEVIATION 7.1 |
| Age, Customized <65 | 1 Participants | 2 Participants | 1 Participants | 3 Participants | 7 Participants |
| Age, Customized >=65 | 2 Participants | 2 Participants | 5 Participants | 3 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants | 4 Participants | 6 Participants | 6 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 4 Participants | 4 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 3 | 1 / 4 | 2 / 6 | 2 / 6 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 6 / 6 | 6 / 6 |
| serious Total, serious adverse events | 2 / 3 | 3 / 4 | 2 / 6 | 3 / 6 |
Outcome results
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab monotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants Who Died - Carbiralizumab Monotherapy | 0 Number of participants |
| M2 Cohort | Number of Participants Who Died - Carbiralizumab Monotherapy | 0 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab monotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With Adverse Events (AEs) - Carbiralizumab Monotherapy | 3 Number of participants |
| M2 Cohort | Number of Participants With Adverse Events (AEs) - Carbiralizumab Monotherapy | 4 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab monotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With AEs Leading to Discontinuation - Carbiralizumab Monotherapy | 0 Number of participants |
| M2 Cohort | Number of Participants With AEs Leading to Discontinuation - Carbiralizumab Monotherapy | 1 Number of participants |
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.
Time frame: 28 days (from first day of treatment)
Population: All treated participants participating in carbiralizumab monotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With AEs Meeting Protocol-defined Dose-Limiting Toxicity (DLT) Criteria - Carbiralizumab Monotherapy | 0 Number of participants |
| M2 Cohort | Number of Participants With AEs Meeting Protocol-defined Dose-Limiting Toxicity (DLT) Criteria - Carbiralizumab Monotherapy | 0 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab monotherapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPONATREMIA - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LYMPHOCYTES (ABSOLUTE) - grade 2 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOCALCEMIA - grade 1 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LYMPHOCYTES (ABSOLUTE) - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HEMOGLOBIN - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | NEUTROPHILS (ABSOLUTE) - grade 0 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERNATREMIA - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | NEUTROPHILS (ABSOLUTE) - grade 1 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HEMOGLOBIN - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | NEUTROPHILS (ABSOLUTE) - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOKALEMIA - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | CREATININE - grade 0 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | PLATELET COUNT - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | CREATININE - grade 1 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERKALEMIA - grade 1 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALKALINE PHOSPHATASE (ALP) - grade 0 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LEUKOCYTES - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALKALINE PHOSPHATASE (ALP) - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOKALEMIA -grade 1 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALKALINE PHOSPHATASE (ALP) - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LEUKOCYTES - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALANINE AMINOTRANSFERASE (ALT) - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOCALCEMIA - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALANINE AMINOTRANSFERASE (ALT) - grade 1 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ABSOLUTE NEUTROPHIL COUNT - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 0 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPONATREMIA - grade 0 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ABSOLUTE NEUTROPHIL COUNT - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERKALEMIA - grade 0 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LYMPHOCYTES (ABSOLUTE) - grade 0 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | BILIRUBIN, TOTAL - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERCALCEMIA - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | BILIRUBIN, TOTAL - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERCALCEMIA - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERKALEMIA - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERKALEMIA - grade 1 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPERNATREMIA - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOCALCEMIA - grade 0 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOCALCEMIA - grade 1 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOKALEMIA - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPOKALEMIA -grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPONATREMIA - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HYPONATREMIA - grade 1 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HEMOGLOBIN - grade 1 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | HEMOGLOBIN - grade 2 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | PLATELET COUNT - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LEUKOCYTES - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LEUKOCYTES - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ABSOLUTE NEUTROPHIL COUNT - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ABSOLUTE NEUTROPHIL COUNT - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LYMPHOCYTES (ABSOLUTE) - grade 0 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LYMPHOCYTES (ABSOLUTE) - grade 2 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | LYMPHOCYTES (ABSOLUTE) - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | NEUTROPHILS (ABSOLUTE) - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | NEUTROPHILS (ABSOLUTE) - grade 1 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | NEUTROPHILS (ABSOLUTE) - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | CREATININE - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | CREATININE - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALKALINE PHOSPHATASE (ALP) - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALKALINE PHOSPHATASE (ALP) - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALKALINE PHOSPHATASE (ALP) - grade 2 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALANINE AMINOTRANSFERASE (ALT) - grade 0 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ALANINE AMINOTRANSFERASE (ALT) - grade 1 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 0 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab Monotherapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 3 | 1 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab monotherapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab Monotherapy | 1 Number of participants |
| M2 Cohort | Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab Monotherapy | 2 Number of participants |
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
Time frame: Cycle 2 (pre-dose), Cycle 8 (pre-dose)
Population: All treated participants who completed through cycle 8 visit
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| M1 Cohort | AI_Ctrough | NA Ratio of Ctrough: cycle 8 to cycle 2 |
| C1 Cohort | AI_Ctrough | NA Ratio of Ctrough: cycle 8 to cycle 2 |
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.
Time frame: Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)
Population: All treated participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| M1 Cohort | AUC(0-T) | 4992 h*µg/mL | Geometric Coefficient of Variation 16 |
| M2 Cohort | AUC(0-T) | 11668 h*µg/mL | Geometric Coefficient of Variation 14 |
| C1 Cohort | AUC(0-T) | 9969 h*µg/mL | Geometric Coefficient of Variation 30 |
| C2 Cohort | AUC(0-T) | 8723 h*µg/mL | Geometric Coefficient of Variation 26 |
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.
Time frame: Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)
Population: All treated participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| M1 Cohort | AUC(TAU) | 4992 h*µg/mL | Geometric Coefficient of Variation 16 |
| M2 Cohort | AUC(TAU) | 12499 h*µg/mL | Geometric Coefficient of Variation 2 |
| C1 Cohort | AUC(TAU) | 9969 h*µg/mL | Geometric Coefficient of Variation 30 |
| C2 Cohort | AUC(TAU) | 10590 h*µg/mL | Geometric Coefficient of Variation 6 |
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
Time frame: From first dose to end of follow-up, assessed up to July 2019, approximately 24 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1 Cohort | Best Overall Response (BOR) | Not evaluable | 0 Number of participants |
| M1 Cohort | Best Overall Response (BOR) | Progression | 1 Number of participants |
| M1 Cohort | Best Overall Response (BOR) | Stable disease | 2 Number of participants |
| M2 Cohort | Best Overall Response (BOR) | Progression | 3 Number of participants |
| M2 Cohort | Best Overall Response (BOR) | Stable disease | 0 Number of participants |
| M2 Cohort | Best Overall Response (BOR) | Not evaluable | 1 Number of participants |
| C1 Cohort | Best Overall Response (BOR) | Stable disease | 3 Number of participants |
| C1 Cohort | Best Overall Response (BOR) | Progression | 3 Number of participants |
| C1 Cohort | Best Overall Response (BOR) | Not evaluable | 3 Number of participants |
| C2 Cohort | Best Overall Response (BOR) | Progression | 6 Number of participants |
| C2 Cohort | Best Overall Response (BOR) | Not evaluable | 0 Number of participants |
| C2 Cohort | Best Overall Response (BOR) | Stable disease | 0 Number of participants |
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.
Time frame: Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)
Population: All treated participants
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| M1 Cohort | Cmax | 43.7 µg/mL | Geometric Coefficient of Variation 20 |
| M2 Cohort | Cmax | 91.4 µg/mL | Geometric Coefficient of Variation 7 |
| C1 Cohort | Cmax | 84.8 µg/mL | Geometric Coefficient of Variation 19 |
| C2 Cohort | Cmax | 76.2 µg/mL | Geometric Coefficient of Variation 15 |
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.
Time frame: Cycles 1, 2, 3, 4, 5, 6, 7, 8, 9
Population: All treated participants for all cohorts for Cabiralizumab;~All treated participants for Cohorts C1 and C2 for Nivolumab.~Note: Data reported for the cycles that were reached.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| M1 Cohort | Ctrough | Cabiralizumab cycle 5 | 1.43 µg/mL | Geometric Coefficient of Variation 64 |
| M1 Cohort | Ctrough | Cabiralizumab cycle 9 | 0.304 µg/mL | — |
| M1 Cohort | Ctrough | Cabiralizumab cycle 6 | 1.49 µg/mL | Geometric Coefficient of Variation 88 |
| M1 Cohort | Ctrough | Cabiralizumab cycle 3 | 4.70 µg/mL | Geometric Coefficient of Variation 95 |
| M1 Cohort | Ctrough | Cabiralizumab cycle 7 | 1.52 µg/mL | Geometric Coefficient of Variation 108 |
| M1 Cohort | Ctrough | Cabiralizumab cycle 8 | 1.53 µg/mL | Geometric Coefficient of Variation 124 |
| M1 Cohort | Ctrough | Cabiralizumab cycle 4 | 2.27 µg/mL | Geometric Coefficient of Variation 46 |
| M1 Cohort | Ctrough | Cabiralizumab cycle 2 | 2.44 µg/mL | Geometric Coefficient of Variation 105 |
| M2 Cohort | Ctrough | Cabiralizumab cycle 3 | 39.8 µg/mL | Geometric Coefficient of Variation 25 |
| M2 Cohort | Ctrough | Cabiralizumab cycle 4 | 45.8 µg/mL | Geometric Coefficient of Variation 20 |
| M2 Cohort | Ctrough | Cabiralizumab cycle 2 | 18.5 µg/mL | Geometric Coefficient of Variation 1 |
| C1 Cohort | Ctrough | Nivolumab cycle 9 | 49.2 µg/mL | — |
| C1 Cohort | Ctrough | Cabiralizumab cycle 2 | 10.1 µg/mL | Geometric Coefficient of Variation 50 |
| C1 Cohort | Ctrough | Cabiralizumab cycle 3 | 18.8 µg/mL | Geometric Coefficient of Variation 53 |
| C1 Cohort | Ctrough | Cabiralizumab cycle 4 | 24.5 µg/mL | Geometric Coefficient of Variation 48 |
| C1 Cohort | Ctrough | Cabiralizumab cycle 5 | 53.3 µg/mL | — |
| C1 Cohort | Ctrough | Cabiralizumab cycle 6 | 55.8 µg/mL | — |
| C1 Cohort | Ctrough | Cabiralizumab cycle 7 | 14.0 µg/mL | Geometric Coefficient of Variation 110 |
| C1 Cohort | Ctrough | Cabiralizumab cycle 8 | 37.7 µg/mL | Geometric Coefficient of Variation 29 |
| C1 Cohort | Ctrough | Nivolumab cycle 5 | 42.1 µg/mL | — |
| C1 Cohort | Ctrough | Cabiralizumab cycle 9 | 30.5 µg/mL | — |
| C1 Cohort | Ctrough | Nivolumab cycle 2 | 16.4 µg/mL | Geometric Coefficient of Variation 12 |
| C1 Cohort | Ctrough | Nivolumab cycle 3 | 25.8 µg/mL | Geometric Coefficient of Variation 14 |
| C2 Cohort | Ctrough | Cabiralizumab cycle 2 | 16.5 µg/mL | Geometric Coefficient of Variation 14 |
| C2 Cohort | Ctrough | Nivolumab cycle 2 | 17.5 µg/mL | Geometric Coefficient of Variation 8 |
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).
Time frame: From first dose to end of follow-up
Population: All treated participants Note: there is no DOR data to report as no participant had a BOR of CR or PR or better.
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.
Time frame: Day 1 pre-dose for cycles 2, 3, 5, 9, 13, 21
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1 Cohort | Incidence of Anti-drug Antibodies (ADA) | Nivolumab data | NA Number of participants |
| M1 Cohort | Incidence of Anti-drug Antibodies (ADA) | Cabiralizumab data | 1 Number of participants |
| M2 Cohort | Incidence of Anti-drug Antibodies (ADA) | Cabiralizumab data | 0 Number of participants |
| M2 Cohort | Incidence of Anti-drug Antibodies (ADA) | Nivolumab data | NA Number of participants |
| C1 Cohort | Incidence of Anti-drug Antibodies (ADA) | Cabiralizumab data | 2 Number of participants |
| C1 Cohort | Incidence of Anti-drug Antibodies (ADA) | Nivolumab data | 1 Number of participants |
| C2 Cohort | Incidence of Anti-drug Antibodies (ADA) | Nivolumab data | 0 Number of participants |
| C2 Cohort | Incidence of Anti-drug Antibodies (ADA) | Cabiralizumab data | 0 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab and nivolumab combo therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants Who Died - Carbiralizumab and Nivolumab Combo Therapy | 1 Number of participants |
| M2 Cohort | Number of Participants Who Died - Carbiralizumab and Nivolumab Combo Therapy | 0 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab and nivolumab combo therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With Adverse Events (AEs) - Carbiralizumab and Nivolumab Combo Therapy | 6 Number of participants |
| M2 Cohort | Number of Participants With Adverse Events (AEs) - Carbiralizumab and Nivolumab Combo Therapy | 5 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab and nivolumab combo therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With AEs Leading to Discontinuation - Carbiralizumab and Nivolumab Combo Therapy | 1 Number of participants |
| M2 Cohort | Number of Participants With AEs Leading to Discontinuation - Carbiralizumab and Nivolumab Combo Therapy | 1 Number of participants |
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
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab and nivolumab combo therapy
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERCALCEMIA - grade 0 | 6 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOKALEMIA - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 4 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERNATREMIA - grade 1 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPONATREMIA - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 3 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPONATREMIA - grade 1 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 0 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 4 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HEMOGLOBIN - grade 1 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LYMPHOCYTES (ABSOLUTE) - grade 1 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERKALEMIA - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LYMPHOCYTES (ABSOLUTE) - grade 2 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HEMOGLOBIN - grade 2 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LYMPHOCYTES (ABSOLUTE) - grade 3 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 1 | 4 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HEMOGLOBIN - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | BILIRUBIN, TOTAL - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 0 | 4 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 4 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 1 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERKALEMIA - grade 1 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 3 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 3 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 3 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 0 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | BILIRUBIN, TOTAL - grade 0 | 5 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 1 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 4 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOKALEMIA - grade 0 | 5 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 3 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 0 | 3 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALANINE AMINOTRANSFERASE (ALT) - grade 0 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERNATREMIA - grade 0 | 6 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALANINE AMINOTRANSFERASE (ALT) - grade 1 | 4 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 1 | 2 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALANINE AMINOTRANSFERASE (ALT) - grade 2 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOKALEMIA -grade 1 | 0 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 1 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 2 | 1 Number of participants |
| M1 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 2 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 4 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | BILIRUBIN, TOTAL - grade 0 | 6 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | BILIRUBIN, TOTAL - grade 2 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERCALCEMIA - grade 0 | 6 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERKALEMIA - grade 0 | 5 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERKALEMIA - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERNATREMIA - grade 0 | 5 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPERNATREMIA - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 0 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 1 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOCALCEMIA - grade 3 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOKALEMIA - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOKALEMIA -grade 1 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPOKALEMIA - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPONATREMIA - grade 0 | 5 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HYPONATREMIA - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HEMOGLOBIN - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HEMOGLOBIN - grade 2 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | HEMOGLOBIN - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 0 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 1 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 2 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | PLATELET COUNT - grade 4 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 0 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 1 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LEUKOCYTES - grade 4 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 2 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ABSOLUTE NEUTROPHIL COUNT - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LYMPHOCYTES (ABSOLUTE) - grade 1 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LYMPHOCYTES (ABSOLUTE) - grade 2 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | LYMPHOCYTES (ABSOLUTE) - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 0 | 3 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 2 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 3 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | NEUTROPHILS (ABSOLUTE) - grade 4 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | CREATININE - grade 3 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 1 | 2 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 2 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALKALINE PHOSPHATASE (ALP) - grade 3 | 0 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALANINE AMINOTRANSFERASE (ALT) - grade 0 | 4 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALANINE AMINOTRANSFERASE (ALT) - grade 1 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ALANINE AMINOTRANSFERASE (ALT) - grade 2 | 1 Number of participants |
| M2 Cohort | Number of Participants With Laboratory Abnormalities - Carbiralizumab and Nivolumab Combination Therapy | ASPARTATE AMINOTRANSFERASE (AST) - grade 1 | 4 Number of participants |
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.
Time frame: From first dose to 30 days post last dose, assessed up to July 2019, approximately 24 months
Population: All treated participants participating in carbiralizumab and nivolumab combo therapy
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| M1 Cohort | Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab and Nivolumab Combo Therapy | 1 Number of participants |
| M2 Cohort | Number of Participants With Serious Adverse Events (SAEs) - Carbiralizumab and Nivolumab Combo Therapy | 1 Number of participants |
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.
Time frame: Cycle 2 (pre-dose), Cycle 8 (pre-dose)
Population: All treated participants who completed through cycle 8 visit
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M1 Cohort | T-HALFeff_Ctrough | NA hour |
| C1 Cohort | T-HALFeff_Ctrough | NA hour |
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.
Time frame: Cycle 1 (from Day 1 pre-dose to Day 8, 168 hour)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| M1 Cohort | Tmax | 3.18 h (Hour) |
| M2 Cohort | Tmax | 0.546 h (Hour) |
| C1 Cohort | Tmax | 1.14 h (Hour) |
| C2 Cohort | Tmax | 1.32 h (Hour) |