Solid Tumors
Conditions
Brief summary
The purpose of this study is to determine whether nivolumab is safe and effective in the treatment of advanced or recurrent solid tumors in Chinese subjects.
Interventions
DRUGNivolumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chinese subjects with advanced or recurrent solid tumors
Exclusion criteria
* Subjects with brain metastases are excluded unless clinically stable for more than 2 weeks at the time of enrollment as determined by the investigator * Subjects with carcinomatous meningitis are excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs) | From first dose to 100 days after last dose (up to approximately 28 months) | A drug related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug that has a causal relationship with the treatment. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening. |
| The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs) | From first dose to 100 days after last dose (up to approximately 28 months) | A drug related serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event that has a casual relationship with the treatment. SAEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening. |
| The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | From first dose to 100 days after last dose (up to approximately 28 months) | The number of participants with the following laboratory abnormalities from the following on-treatment evaluations: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN |
| The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | From first dose to 100 days after last dose (up to approximately 28 months) | The number of participants with Grade 3-4 laboratory results according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Note: Grade 4 Toxicities not included in the below table if there were no participants that experienced Grade 4 in that category. Grade 3: prolonged recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae \[e.g., renal impairment, pulmonary infiltrates\]. Grade 4: Life-threatening; pressor or ventilatory support indicated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) at 24 Weeks | Week 24 | Disease control rate (DCR) at 24 weeks is defined as the percentage of all treated participants who have CR, PR or SD by 24 weeks. Complete Response (CR) is defined as a disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Other tumor types include: gastric, melanoma, neuroblastoma, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma. |
| The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | From pre-dose on day 1 Cycle 1 up to participants end of study (up to approximately 28 months) | The number of participants with the following anti-drug responses: 1. Baseline ADA positive: all participants with baseline ADA positive samples. 2. ADA Positive: participants that have at least one ADA positive sample relative to baseline at any time after initiation of treatment. 3. ADA negative: participants that have no ADA positive samples after the initiation of treatment. |
| Cmax - Maximum Observed Serum Concentration | Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Cmax is the maximum observed serum concentration over time. |
| Tmax - Time of Maximum Observed Serum Concentration | Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Tmax is the time of maximum observed serum concentration. |
| AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AUC (0-T) is the area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration. |
| AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AUC (TAU) is the area under the plasma concentration-time curve in one dosing interval. |
| Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | End of infusion on Day 1 of Cycle 1, 3, 5, 6 | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ceoinf is the serum concentration achieved at the end of study drug infusion. |
| Best Overall Response (BOR) | From first dose up to approximately 28 months | Best overall response (BOR) was assessed by the investigator using Response Evaluation Criteria in Solid Tumor (RECIST v1.1). Complete Response (CR) is defined as a disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). |
| Ctau - Concentration at the End of Dosing Interval | Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ctau is the concentration at the end of dosing interval. |
| T-HALFeff - Effective Elimination Half-Life | Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. T-HALFeff is the effective elimination half-life that explains the degree of observed AUC accumulation calculated based on ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC(TAU), Cmax and Ctau). |
| CLT - Total Body Clearance | Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. CLT is the total body clearance. |
| AI - Accumulation Index (Cmax) | Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of Cmax refers to the accumulation index calculated based on ratio of an exposure measure of Cmax at steady state to that after the first dose. |
| AI - Accumulation Index (Ctau) | Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of Ctau refers to the accumulation index calculated based on ratio of an exposure measure of Ctau at steady state to that after the first dose. |
| AI - Accumulation Index (AUC) | Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of AUC refers to the accumulation index calculated based on ratio of an exposure measure of AUC at steady state to that after the first dose. |
| Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval | Day 1 Cycle 3, 5, 6 (168 hours post dose [Cohort A-B], 336 hours post dose [Cohort C-D]) | Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ctrough is the trough observed serum concentration at the end of dosing interval. |
| Duration of Response (DOR) | From the date of first response (CR or PR) to the date of the first documented tumor progression or death due to any cause, whichever occurs first. (Up to approximately 28 months) | Duration of response is defined as the time from the date of first response (CR or PR) to the date of the first documented tumor progression as determined using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who remain alive and have not progressed will be censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma. |
| Objective Response Rate (ORR) | From first dose up to approximately 28 months | Objective response rate (ORR) is defined as the percentage of all treated participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) by investigator using Response Evaluation Criteria in Solid Tumor (RECIST v1.1). Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma. |
| Response Rate at 24 Weeks | Week 24 | Response rate at 24 weeks is defined as the percentage of all treated participants who have CR or PR by 24 weeks. Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W Participants receive nivolumab (3 mg/kg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43. | 15 |
| Cohort B: Nivolumab 240 mg Q2W Participants receive a flat dose of nivolumab (240 mg) administered as 4 doses in each 8-week treatment cycle at Days 1, 15, 29 and 43. | 20 |
| Cohort C: Nivolumab 360 mg Q3W Participants receive a flat dose of nivolumab (360 mg) administered as one dose in each 3-week treatment cycle. | 11 |
| Cohort D: Nivolumab 480 mg Q4W Participants receive a flat dose of nivolumab (480 mg) administered as one dose in each 4-week treatment cycle | 12 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse event unrelated to study drug | 1 | 1 | 1 | 0 |
| Overall Study | Disease progression | 12 | 16 | 10 | 7 |
| Overall Study | Other reasons | 1 | 1 | 0 | 5 |
| Overall Study | Participant request to discontinue study therapy | 0 | 2 | 0 | 0 |
| Overall Study | Study drug toxicity | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Cohort A: Nivolumab 3 mg/kg Q2W | Cohort B: Nivolumab 240 mg Q2W | Cohort C: Nivolumab 360 mg Q3W | Cohort D: Nivolumab 480 mg Q4W |
|---|---|---|---|---|---|
| Age, Customized >= 65 | 4 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Age, Customized > 65 | 54 Participants | 15 Participants | 20 Participants | 10 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 58 Participants | 15 Participants | 20 Participants | 11 Participants | 12 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 | 20 Participants | 4 Participants | 7 Participants | 4 Participants | 5 Participants |
| Sex: Female, Male Male | 38 Participants | 11 Participants | 13 Participants | 7 Participants | 7 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 | 4 / 15 | 7 / 20 | 0 / 11 | 1 / 12 |
| other Total, other adverse events | 14 / 15 | 20 / 20 | 11 / 11 | 12 / 12 |
| serious Total, serious adverse events | 6 / 15 | 8 / 20 | 2 / 11 | 7 / 12 |
Outcome results
Primary
The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results
The number of participants with the following laboratory abnormalities from the following on-treatment evaluations: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN
Time frame: From first dose to 100 days after last dose (up to approximately 28 months)
Population: All treated participants with least one on-treatment measurement of the corresponding laboratory parameter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 10XULN | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 3XULN | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 20XULN | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 5XULN | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 20XULN | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | TOTAL BILIRUBIN > 2XULN | 3 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 3 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 3 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 3XULN | 3 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 5XULN | 2 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 10XULN | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 3XULN | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | TOTAL BILIRUBIN > 2XULN | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 20XULN | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 5XULN | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 10XULN | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 30 DAYS | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 10XULN | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 3XULN | 1 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST> 5XULN | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT OR AST > 20XULN | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Abnormal Hepatic Laboratory Test Results | ALT/AST ELEV>3XULN;TOTAL BILIRUBIN>2XULN IN 1 DAY | 0 Participants |
Primary
The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs)
A drug related adverse event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug that has a causal relationship with the treatment. AEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening.
Time frame: From first dose to 100 days after last dose (up to approximately 28 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs) | 1 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs) | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Drug-Related Grade 3-4 Adverse Events (AEs) | 0 Participants |
Primary
The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs)
A drug related serious adverse event (SAE) is any untoward medical occurrence that at any dose: results in death; is life-threatening; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; or is an important medical event that has a casual relationship with the treatment. SAEs are graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (Version 4.03) (NCI CTCAE) guidelines where Grade 3= Severe and Grade 4= Life-threatening.
Time frame: From first dose to 100 days after last dose (up to approximately 28 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs) | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs) | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Drug-Related Grade 3-4 Serious Adverse Events (SAEs) | 0 Participants |
Primary
The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results
The number of participants with Grade 3-4 laboratory results according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0. Note: Grade 4 Toxicities not included in the below table if there were no participants that experienced Grade 4 in that category. Grade 3: prolonged recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae \[e.g., renal impairment, pulmonary infiltrates\]. Grade 4: Life-threatening; pressor or ventilatory support indicated.
Time frame: From first dose to 100 days after last dose (up to approximately 28 months)
Population: All treated participants with least one on-treatment measurement of the corresponding laboratory parameter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALKALINE PHOSPHATASE (Grade 3) | 2 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ABSOLUTE NEUTROPHIL COUNT (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LEUKOCYTES (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LYMPHOCYTES (ABSOLUTE) (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | HEMOGLOBIN (Grade 3) | 1 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALANINE AMINOTRANSFERASE (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ASPARTATE AMINOTRANSFERASE (Grade 3) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 4) | 0 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 4) | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 4) | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | HEMOGLOBIN (Grade 3) | 2 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 3) | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 3) | 1 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LEUKOCYTES (Grade 3) | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LYMPHOCYTES (ABSOLUTE) (Grade 3) | 2 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ABSOLUTE NEUTROPHIL COUNT (Grade 3) | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALKALINE PHOSPHATASE (Grade 3) | 3 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ASPARTATE AMINOTRANSFERASE (Grade 3) | 2 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALANINE AMINOTRANSFERASE (Grade 3) | 2 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 4) | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 3) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 4) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALANINE AMINOTRANSFERASE (Grade 3) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ABSOLUTE NEUTROPHIL COUNT (Grade 3) | 2 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 4) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | HEMOGLOBIN (Grade 3) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LEUKOCYTES (Grade 3) | 2 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 3) | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LYMPHOCYTES (ABSOLUTE) (Grade 3) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ASPARTATE AMINOTRANSFERASE (Grade 3) | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALKALINE PHOSPHATASE (Grade 3) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 4) | 1 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ABSOLUTE NEUTROPHIL COUNT (Grade 3) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALKALINE PHOSPHATASE (Grade 3) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | PLATELET COUNT (Grade 3) | 1 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 4) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ASPARTATE AMINOTRANSFERASE (Grade 3) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | ALANINE AMINOTRANSFERASE (Grade 3) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | HEMOGLOBIN (Grade 3) | 1 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LEUKOCYTES (Grade 3) | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | LYMPHOCYTES (ABSOLUTE) (Grade 3) | 1 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants Experiencing Toxicity Grade 3-4 Laboratory Test Results | BILIRUBIN, TOTAL (Grade 3) | 0 Participants |
Secondary
AI - Accumulation Index (AUC)
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of AUC refers to the accumulation index calculated based on ratio of an exposure measure of AUC at steady state to that after the first dose.
Time frame: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | AI - Accumulation Index (AUC) | Cycle 3 Day 1 | 2.942 (hr*ug/mL)/(hr*ug/mL) |
| Cohort B: Nivolumab 240 mg Q2W | AI - Accumulation Index (AUC) | Cycle 3 Day 1 | 2.707 (hr*ug/mL)/(hr*ug/mL) |
| Cohort C: Nivolumab 360 mg Q3W | AI - Accumulation Index (AUC) | Cycle 6 Day 1 | 2.389 (hr*ug/mL)/(hr*ug/mL) |
| Cohort D: Nivolumab 480 mg Q4W | AI - Accumulation Index (AUC) | Cycle 5 Day 1 | 2.033 (hr*ug/mL)/(hr*ug/mL) |
Secondary
AI - Accumulation Index (Cmax)
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of Cmax refers to the accumulation index calculated based on ratio of an exposure measure of Cmax at steady state to that after the first dose.
Time frame: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | AI - Accumulation Index (Cmax) | Cycle 3 Day 1 | 2.150 (ug/mL)/(ug/mL) |
| Cohort B: Nivolumab 240 mg Q2W | AI - Accumulation Index (Cmax) | Cycle 3 Day 1 | 2.034 (ug/mL)/(ug/mL) |
| Cohort C: Nivolumab 360 mg Q3W | AI - Accumulation Index (Cmax) | Cycle 6 Day 1 | 1.613 (ug/mL)/(ug/mL) |
| Cohort D: Nivolumab 480 mg Q4W | AI - Accumulation Index (Cmax) | Cycle 5 Day 1 | 1.255 (ug/mL)/(ug/mL) |
Secondary
AI - Accumulation Index (Ctau)
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AI of Ctau refers to the accumulation index calculated based on ratio of an exposure measure of Ctau at steady state to that after the first dose.
Time frame: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | AI - Accumulation Index (Ctau) | Cycle 3 Day 1 | 3.333 (ug/mL)/(ug/mL) |
| Cohort B: Nivolumab 240 mg Q2W | AI - Accumulation Index (Ctau) | Cycle 3 Day 1 | 3.215 (ug/mL)/(ug/mL) |
| Cohort C: Nivolumab 360 mg Q3W | AI - Accumulation Index (Ctau) | Cycle 6 Day 1 | 2.675 (ug/mL)/(ug/mL) |
| Cohort D: Nivolumab 480 mg Q4W | AI - Accumulation Index (Ctau) | Cycle 5 Day 1 | 2.053 (ug/mL)/(ug/mL) |
Secondary
AUC (0-T)-Area Under the Plasma Concentration-Time Curve
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AUC (0-T) is the area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration.
Time frame: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 1 Day 1 | 8353.429 h*ug/mL |
| Cohort A: Nivolumab 3 mg/kg Q2W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 3 Day 1 | 28442.153 h*ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 3 Day 1 | 35649.049 h*ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 1 Day 1 | 11646.854 h*ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 1 Day 1 | 23567.315 h*ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 6 Day 1 | 51087.588 h*ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 1 Day 1 | 49115.208 h*ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | AUC (0-T)-Area Under the Plasma Concentration-Time Curve | Cycle 5 Day 1 | 91967.438 h*ug/mL |
Secondary
AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. AUC (TAU) is the area under the plasma concentration-time curve in one dosing interval.
Time frame: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 1 Day 1 | 8732.232 h*ug/mL |
| Cohort A: Nivolumab 3 mg/kg Q2W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 3 Day 1 | 30823.993 h*ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 3 Day 1 | 37794.083 h*ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 1 Day 1 | 12112.137 h*ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 1 Day 1 | 23567.315 h*ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 6 Day 1 | 53162.102 h*ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 1 Day 1 | 49115.208 h*ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | AUC(TAU) - Area Under the Concentration-Time Curve in One Dosing Interval | Cycle 5 Day 1 | 100655.626 h*ug/mL |
Secondary
Best Overall Response (BOR)
Best overall response (BOR) was assessed by the investigator using Response Evaluation Criteria in Solid Tumor (RECIST v1.1). Complete Response (CR) is defined as a disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study).
Time frame: From first dose up to approximately 28 months
Population: All treated participants
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Best Overall Response (BOR) | Progressive Disease | 9 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Best Overall Response (BOR) | Partial Response | 3 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Best Overall Response (BOR) | Unable to Determine | 1 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Best Overall Response (BOR) | Stable Disease | 2 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort B: Nivolumab 240 mg Q2W | Best Overall Response (BOR) | Stable Disease | 12 Participants |
| Cohort B: Nivolumab 240 mg Q2W | Best Overall Response (BOR) | Progressive Disease | 5 Participants |
| Cohort B: Nivolumab 240 mg Q2W | Best Overall Response (BOR) | Unable to Determine | 1 Participants |
| Cohort B: Nivolumab 240 mg Q2W | Best Overall Response (BOR) | Partial Response | 2 Participants |
| Cohort B: Nivolumab 240 mg Q2W | Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | Best Overall Response (BOR) | Stable Disease | 6 Participants |
| Cohort C: Nivolumab 360 mg Q3W | Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | Best Overall Response (BOR) | Partial Response | 1 Participants |
| Cohort C: Nivolumab 360 mg Q3W | Best Overall Response (BOR) | Progressive Disease | 4 Participants |
| Cohort C: Nivolumab 360 mg Q3W | Best Overall Response (BOR) | Unable to Determine | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | Best Overall Response (BOR) | Progressive Disease | 4 Participants |
| Cohort D: Nivolumab 480 mg Q4W | Best Overall Response (BOR) | Partial Response | 2 Participants |
| Cohort D: Nivolumab 480 mg Q4W | Best Overall Response (BOR) | Complete Response | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | Best Overall Response (BOR) | Stable Disease | 6 Participants |
| Cohort D: Nivolumab 480 mg Q4W | Best Overall Response (BOR) | Unable to Determine | 0 Participants |
Secondary
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ceoinf is the serum concentration achieved at the end of study drug infusion.
Time frame: End of infusion on Day 1 of Cycle 1, 3, 5, 6
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 1 Day 1 | 55.020 ug/mL |
| Cohort A: Nivolumab 3 mg/kg Q2W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 3 Day 1 | 122.051 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 3 Day 1 | 152.058 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 1 Day 1 | 66.746 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 1 Day 1 | 93.168 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 6 Day 1 | 155.811 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 1 Day 1 | 171.494 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion | Cycle 5 Day 1 | 254.704 ug/mL |
Secondary
CLT - Total Body Clearance
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. CLT is the total body clearance.
Time frame: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | CLT - Total Body Clearance | Cycle 3 Day 1 | 5.732 mL/hr |
| Cohort B: Nivolumab 240 mg Q2W | CLT - Total Body Clearance | Cycle 3 Day 1 | 6.350 mL/hr |
| Cohort C: Nivolumab 360 mg Q3W | CLT - Total Body Clearance | Cycle 6 Day 1 | 6.772 mL/hr |
| Cohort D: Nivolumab 480 mg Q4W | CLT - Total Body Clearance | Cycle 5 Day 1 | 4.769 mL/hr |
Secondary
Cmax - Maximum Observed Serum Concentration
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Cmax is the maximum observed serum concentration over time.
Time frame: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Cmax - Maximum Observed Serum Concentration | Cycle 1 Day 1 | 57.025 ug/mL |
| Cohort A: Nivolumab 3 mg/kg Q2W | Cmax - Maximum Observed Serum Concentration | Cycle 3 Day 1 | 132.222 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Cmax - Maximum Observed Serum Concentration | Cycle 3 Day 1 | 171.604 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Cmax - Maximum Observed Serum Concentration | Cycle 1 Day 1 | 77.674 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Cmax - Maximum Observed Serum Concentration | Cycle 1 Day 1 | 108.455 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Cmax - Maximum Observed Serum Concentration | Cycle 6 Day 1 | 165.369 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Cmax - Maximum Observed Serum Concentration | Cycle 1 Day 1 | 206.630 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Cmax - Maximum Observed Serum Concentration | Cycle 5 Day 1 | 265.550 ug/mL |
Secondary
Ctau - Concentration at the End of Dosing Interval
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ctau is the concentration at the end of dosing interval.
Time frame: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Ctau - Concentration at the End of Dosing Interval | Cycle 1 Day 1 | 16.430 ug/mL |
| Cohort A: Nivolumab 3 mg/kg Q2W | Ctau - Concentration at the End of Dosing Interval | Cycle 3 Day 1 | 65.286 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Ctau - Concentration at the End of Dosing Interval | Cycle 3 Day 1 | 78.278 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Ctau - Concentration at the End of Dosing Interval | Cycle 1 Day 1 | 20.788 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Ctau - Concentration at the End of Dosing Interval | Cycle 1 Day 1 | 26.143 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Ctau - Concentration at the End of Dosing Interval | Cycle 6 Day 1 | 65.762 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Ctau - Concentration at the End of Dosing Interval | Cycle 1 Day 1 | 40.910 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Ctau - Concentration at the End of Dosing Interval | Cycle 5 Day 1 | 90.201 ug/mL |
Secondary
Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Ctrough is the trough observed serum concentration at the end of dosing interval.
Time frame: Day 1 Cycle 3, 5, 6 (168 hours post dose [Cohort A-B], 336 hours post dose [Cohort C-D])
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval | Cycle 3 Day 1 | 62.417 ug/mL |
| Cohort B: Nivolumab 240 mg Q2W | Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval | Cycle 3 Day 1 | 62.115 ug/mL |
| Cohort C: Nivolumab 360 mg Q3W | Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval | Cycle 6 Day 1 | 61.530 ug/mL |
| Cohort D: Nivolumab 480 mg Q4W | Ctrough - Trough Observed Serum Concentration at the End of Dosing Interval | Cycle 5 Day 1 | 92.796 ug/mL |
Secondary
Disease Control Rate (DCR) at 24 Weeks
Disease control rate (DCR) at 24 weeks is defined as the percentage of all treated participants who have CR, PR or SD by 24 weeks. Complete Response (CR) is defined as a disappearance of all target lesions. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. Other tumor types include: gastric, melanoma, neuroblastoma, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Time frame: Week 24
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Disease Control Rate (DCR) at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 11.1 Percent of participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Disease Control Rate (DCR) at 24 Weeks | Nasopharyngeal carcinoma | 33.3 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Disease Control Rate (DCR) at 24 Weeks | Hepatocellular carcinoma | 0 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Disease Control Rate (DCR) at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 0 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Disease Control Rate (DCR) at 24 Weeks | Nasopharyngeal carcinoma | 23.5 Percent of participants |
| Cohort C: Nivolumab 360 mg Q3W | Disease Control Rate (DCR) at 24 Weeks | Nasopharyngeal carcinoma | 20.0 Percent of participants |
| Cohort C: Nivolumab 360 mg Q3W | Disease Control Rate (DCR) at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 100 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Disease Control Rate (DCR) at 24 Weeks | Other tumor types | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Disease Control Rate (DCR) at 24 Weeks | Hepatocellular carcinoma | 100 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Disease Control Rate (DCR) at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 66.7 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Disease Control Rate (DCR) at 24 Weeks | Nasopharyngeal carcinoma | 100 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Disease Control Rate (DCR) at 24 Weeks | Colorectal Cancer | 100 Percent of participants |
Secondary
Duration of Response (DOR)
Duration of response is defined as the time from the date of first response (CR or PR) to the date of the first documented tumor progression as determined using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who remain alive and have not progressed will be censored on the date of their last tumor assessment. Participants who started subsequent therapy without a prior reported progression will be censored at the last tumor assessment prior to initiation of the subsequent anticancer therapy. Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Time frame: From the date of first response (CR or PR) to the date of the first documented tumor progression or death due to any cause, whichever occurs first. (Up to approximately 28 months)
Population: All treated participants with a BOR of CR or PR
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Duration of Response (DOR) | Non-small cell lung carcinoma (NSCLC) | NA Weeks |
| Cohort A: Nivolumab 3 mg/kg Q2W | Duration of Response (DOR) | Nasopharyngeal carcinoma | NA Weeks |
| Cohort B: Nivolumab 240 mg Q2W | Duration of Response (DOR) | Nasopharyngeal carcinoma | NA Weeks |
| Cohort C: Nivolumab 360 mg Q3W | Duration of Response (DOR) | Non-small cell lung carcinoma (NSCLC) | 6.1 Weeks |
| Cohort D: Nivolumab 480 mg Q4W | Duration of Response (DOR) | Hepatocellular carcinoma | NA Weeks |
| Cohort D: Nivolumab 480 mg Q4W | Duration of Response (DOR) | Nasopharyngeal carcinoma | NA Weeks |
Secondary
Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the percentage of all treated participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) by investigator using Response Evaluation Criteria in Solid Tumor (RECIST v1.1). Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Time frame: From first dose up to approximately 28 months
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Objective Response Rate (ORR) | Nasopharyngeal carcinoma | 33.3 Percent of participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Objective Response Rate (ORR) | Non-small cell lung carcinoma (NSCLC) | 11.1 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Objective Response Rate (ORR) | Nasopharyngeal carcinoma | 11.8 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Objective Response Rate (ORR) | Hepatocellular carcinoma | 0 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Objective Response Rate (ORR) | Non-small cell lung carcinoma (NSCLC) | 0 Percent of participants |
| Cohort C: Nivolumab 360 mg Q3W | Objective Response Rate (ORR) | Non-small cell lung carcinoma (NSCLC) | 100 Percent of participants |
| Cohort C: Nivolumab 360 mg Q3W | Objective Response Rate (ORR) | Nasopharyngeal carcinoma | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Objective Response Rate (ORR) | Other tumor types | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Objective Response Rate (ORR) | Hepatocellular carcinoma | 100 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Objective Response Rate (ORR) | Non-small cell lung carcinoma (NSCLC) | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Objective Response Rate (ORR) | Nasopharyngeal carcinoma | 100 Percent of participants |
Secondary
Response Rate at 24 Weeks
Response rate at 24 weeks is defined as the percentage of all treated participants who have CR or PR by 24 weeks. Complete response (CR) is defined as a disappearance of all target lesions and partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Other tumor types include: gastric, melanoma, neuroblastoma, colorectal cancer, cervical cancer, duodenal papillary carcinoma, and gallbladder carcinoma.
Time frame: Week 24
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Response Rate at 24 Weeks | Nasopharyngeal carcinoma | 33.3 Percent of participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | Response Rate at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 11.1 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Response Rate at 24 Weeks | Nasopharyngeal carcinoma | 5.9 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Response Rate at 24 Weeks | Hepatocellular carcinoma | 0 Percent of participants |
| Cohort B: Nivolumab 240 mg Q2W | Response Rate at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 0 Percent of participants |
| Cohort C: Nivolumab 360 mg Q3W | Response Rate at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 100 Percent of participants |
| Cohort C: Nivolumab 360 mg Q3W | Response Rate at 24 Weeks | Nasopharyngeal carcinoma | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Response Rate at 24 Weeks | Other tumor types | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Response Rate at 24 Weeks | Hepatocellular carcinoma | 100 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Response Rate at 24 Weeks | Non-small cell lung carcinoma (NSCLC) | 0 Percent of participants |
| Cohort D: Nivolumab 480 mg Q4W | Response Rate at 24 Weeks | Nasopharyngeal carcinoma | 100 Percent of participants |
Secondary
T-HALFeff - Effective Elimination Half-Life
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. T-HALFeff is the effective elimination half-life that explains the degree of observed AUC accumulation calculated based on ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC(TAU), Cmax and Ctau).
Time frame: Day 1 Cycle 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | T-HALFeff - Effective Elimination Half-Life | Cycle 3 Day 1 | 551.194 h |
| Cohort B: Nivolumab 240 mg Q2W | T-HALFeff - Effective Elimination Half-Life | Cycle 3 Day 1 | 510.262 h |
| Cohort C: Nivolumab 360 mg Q3W | T-HALFeff - Effective Elimination Half-Life | Cycle 6 Day 1 | 677.642 h |
| Cohort D: Nivolumab 480 mg Q4W | T-HALFeff - Effective Elimination Half-Life | Cycle 5 Day 1 | 732.44 h |
Secondary
The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment
The number of participants with the following anti-drug responses: 1. Baseline ADA positive: all participants with baseline ADA positive samples. 2. ADA Positive: participants that have at least one ADA positive sample relative to baseline at any time after initiation of treatment. 3. ADA negative: participants that have no ADA positive samples after the initiation of treatment.
Time frame: From pre-dose on day 1 Cycle 1 up to participants end of study (up to approximately 28 months)
Population: All Nivolumab Treated Participants with Baseline and at Least One Post-baseline Assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample at baseline | 1 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA Negative sample after initiation of treatment | 12 Participants |
| Cohort A: Nivolumab 3 mg/kg Q2W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample after initiation of treatment | 1 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample at baseline | 4 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA Negative sample after initiation of treatment | 19 Participants |
| Cohort B: Nivolumab 240 mg Q2W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample after initiation of treatment | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample after initiation of treatment | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample at baseline | 0 Participants |
| Cohort C: Nivolumab 360 mg Q3W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA Negative sample after initiation of treatment | 10 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample at baseline | 0 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA Negative sample after initiation of treatment | 10 Participants |
| Cohort D: Nivolumab 480 mg Q4W | The Number of Participants With Positive Anti Drug Antibody (ADA) Assessments at Baseline and Positive or Negative ADA Samples After Treatment | ADA positive sample after initiation of treatment | 2 Participants |
Secondary
Tmax - Time of Maximum Observed Serum Concentration
Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. Tmax is the time of maximum observed serum concentration.
Time frame: Day 1 Cycle 1, 3, 5, 6 (pre-dose, 0.5, 4, 8, 24, 48, 96, 168, hours post dose. Cohort C-D includes also 336 hours post dose)
Population: All treated participants with evaluable serum concentration data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort A: Nivolumab 3 mg/kg Q2W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 1 Day 1 | 4.00 h |
| Cohort A: Nivolumab 3 mg/kg Q2W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 3 Day 1 | 8.00 h |
| Cohort B: Nivolumab 240 mg Q2W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 3 Day 1 | 8.00 h |
| Cohort B: Nivolumab 240 mg Q2W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 1 Day 1 | 4.00 h |
| Cohort C: Nivolumab 360 mg Q3W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 1 Day 1 | 4.0 h |
| Cohort C: Nivolumab 360 mg Q3W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 6 Day 1 | 8.00 h |
| Cohort D: Nivolumab 480 mg Q4W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 1 Day 1 | 4.01 h |
| Cohort D: Nivolumab 480 mg Q4W | Tmax - Time of Maximum Observed Serum Concentration | Cycle 5 Day 1 | 2.26 h |