Trial Outcomes & Findings for A Study of Nivolumab in Combination With Ipilimumab in Chinese Participants With Previously Treated Advanced or Recurrent Solid Tumors (NCT NCT03195478)

NCT ID: NCT03195478

Last Updated: 2025-09-15

Results Overview

Number of participants with Adverse events

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

37 participants

Primary outcome timeframe

From first dose to 100 days post last dose (Approximately on average Arm A: 8.77 Months, Arm B 20.4 Months, Arm C 24.1 Months)

Results posted on

2025-09-15

Participant Flow

Participant milestones

Participant milestones
Measure	Part 1: Arm A NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3	Part 2: Arm D NIVO 3 mg/kg Q3 + IPI 1mg/kg Q3
Overall Study STARTED	9	9	9	9
Overall Study COMPLETED	1	4	1	7
Overall Study NOT COMPLETED	8	5	8	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1: Arm A NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3	Part 2: Arm D NIVO 3 mg/kg Q3 + IPI 1mg/kg Q3
Overall Study Disease Progression	5	4	6	1
Overall Study Study Drug Toxicity	2	0	0	1
Overall Study Participant requested to discontinue study treatment	0	1	0	0
Overall Study Participant Withdrew Consent	1	0	0	0
Overall Study Maximum Clinical benefit	0	0	1	0
Overall Study Other Reasons	0	0	1	0

Baseline Characteristics

A Study of Nivolumab in Combination With Ipilimumab in Chinese Participants With Previously Treated Advanced or Recurrent Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3	Part 2: Arm D n=9 Participants NIVO 3 mg/kg Q3 + IPI 1mg/kg Q3	Total n=36 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Age, Categorical Between 18 and 65 years	7 Participants n=99 Participants	8 Participants n=107 Participants	8 Participants n=206 Participants	6 Participants n=7 Participants	29 Participants n=31 Participants
Age, Categorical >=65 years	2 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	3 Participants n=7 Participants	7 Participants n=31 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	3 Participants n=107 Participants	4 Participants n=206 Participants	5 Participants n=7 Participants	13 Participants n=31 Participants
Sex: Female, Male Male	8 Participants n=99 Participants	6 Participants n=107 Participants	5 Participants n=206 Participants	4 Participants n=7 Participants	23 Participants n=31 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	9 Participants n=99 Participants	9 Participants n=107 Participants	9 Participants n=206 Participants	9 Participants n=7 Participants	36 Participants n=31 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Asian	9 Participants n=99 Participants	9 Participants n=107 Participants	9 Participants n=206 Participants	9 Participants n=7 Participants	36 Participants n=31 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) White	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days post last dose (Approximately on average Arm A: 8.77 Months, Arm B 20.4 Months, Arm C 24.1 Months)

Population: All treated participants in Part 1

Number of participants with Adverse events

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Adverse Events (AEs) in Part 1.	7 Participants	9 Participants	9 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days post last dose (Approximately on average Arm A: 8.77 Months, Arm B 20.4 Months, Arm C 24.1 Months)

Population: All treated participants in Part 1

Number of participants with Adverse events

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Serious Adverse Events (SAEs) in Part 1.	4 Participants	3 Participants	3 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days post last dose (Approximately on average Arm A: 8.77 Months, Arm B 20.4 Months, Arm C 24.1 Months)

Population: All treated participants in Part 1

Number of participants with Adverse events

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Adverse Events Leading to Discontinuation in Part 1.	3 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days post last dose (Approximately on average Arm A: 8.77 Months, Arm B 20.4 Months, Arm C 24.1 Months)

Population: All treated participants in Part 1

Number of participants with Adverse Events leading to death.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Adverse Events Leading to Death in Part 1.	1 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose to 100 days post last dose (Approximately on average Arm A: 8.77 Months, Arm B 20.4 Months, Arm C 24.1 Months)

Population: All treated participants in Part 1

Number of participants with clinical laboratory abnormalities.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Clinical Laboratory Abnormalities in Part 1. Any Grade	5 Participants	9 Participants	7 Participants
Number of Participants With Clinical Laboratory Abnormalities in Part 1. Grade 3-4	1 Participants	4 Participants	1 Participants

PRIMARY outcome

Timeframe: between the date of first dose and the date of initial objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first as assessed by BICR. (Approximately on average 3.21 Months)

Population: All treated participants in Part 2

ORR is defined as the number of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by BICR, according to RECIST v1.1 criteria, divided by the number of treated subjects. The BOR is defined as the best response designation recorded between the date of first dose and the date of initial objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR determination. For purposes of analysis, if a subject receives one dose and discontinues the study without assessment or receives subsequent therapy prior to assessment, this participant will be counted in the denominator (as nonrespondent).

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
BICR-Assessed ORR in Part 2	77.8 Percentage of Participants Interval 40.0 to 97.2	—	—

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1

Cmax - Maximum observed serum concentration in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Cmax - Maximum Observed Serum Concentration in Part 1. Nivo Cycle 3	122 ug/mL Geometric Coefficient of Variation 21	—	—
Cmax - Maximum Observed Serum Concentration in Part 1. Ipi Cycle 1	18.9 ug/mL Geometric Coefficient of Variation 18	16.8 ug/mL Geometric Coefficient of Variation 43	55.0 ug/mL Geometric Coefficient of Variation 33
Cmax - Maximum Observed Serum Concentration in Part 1. Ipi Cycle 2	—	22.0 ug/mL Geometric Coefficient of Variation 16	64.1 ug/mL Geometric Coefficient of Variation 29
Cmax - Maximum Observed Serum Concentration in Part 1. Ipi Cycle 3	20.1 ug/mL Geometric Coefficient of Variation 17	—	—
Cmax - Maximum Observed Serum Concentration in Part 1. Nivo Cycle 1	59.7 ug/mL Geometric Coefficient of Variation 19	69.5 ug/mL Geometric Coefficient of Variation 19	22.5 ug/mL Geometric Coefficient of Variation 14
Cmax - Maximum Observed Serum Concentration in Part 1. Nivo Cycle 2	—	104 ug/mL Geometric Coefficient of Variation 12	27.2 ug/mL Geometric Coefficient of Variation 21

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1

Tmax - Time of maximum observed serum concentration in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Tmax - Time of Maximum Observed Serum Concentration in Part 1. Nivo Cycle 1	1.68 Hours Interval 1.6 to 8.0	1.62 Hours Interval 1.5 to 48.0	1.59 Hours Interval 1.5 to 1.6
Tmax - Time of Maximum Observed Serum Concentration in Part 1. Nivo Cycle 2	—	1.55 Hours Interval 1.5 to 47.9	4.78 Hours Interval 1.6 to 8.0
Tmax - Time of Maximum Observed Serum Concentration in Part 1. Nivo Cycle 3	1.65 Hours Interval 1.6 to 8.0	—	—
Tmax - Time of Maximum Observed Serum Concentration in Part 1. Ipi Cycle 1	0.617 Hours Interval 0.5 to 7.0	6.83 Hours Interval 0.5 to 46.9	0.517 Hours Interval 0.5 to 6.8
Tmax - Time of Maximum Observed Serum Concentration in Part 1. Ipi Cycle 2	—	6.98 Hours Interval 0.5 to 7.0	0.542 Hours Interval 0.5 to 6.9
Tmax - Time of Maximum Observed Serum Concentration in Part 1. Ipi Cycle 3	6.78 Hours Interval 0.5 to 6.9	—	—

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1

AUC(0-T) - Area under the plasma concentration-time curve from time zero to the last time of the last quantifiable concentration. in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. Ipi Cycle 2	—	4959 h*ug/mL Geometric Coefficient of Variation 28	11388 h*ug/mL Geometric Coefficient of Variation 34
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. Ipi Cycle 3	3480 h*ug/mL Geometric Coefficient of Variation 18	—	—
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. Nivo Cycle 1	10329 h*ug/mL Geometric Coefficient of Variation 21	14141 h*ug/mL Geometric Coefficient of Variation 26	4056 h*ug/mL Geometric Coefficient of Variation 25
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. Nivo Cycle 2	—	23348 h*ug/mL Geometric Coefficient of Variation 28	4323 h*ug/mL Geometric Coefficient of Variation 39
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. Nivo Cycle 3	23147 h*ug/mL Geometric Coefficient of Variation 31	—	—
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. Ipi Cycle 1	2847 h*ug/mL Geometric Coefficient of Variation 18	3377 h*ug/mL Geometric Coefficient of Variation 27	9893 h*ug/mL Geometric Coefficient of Variation 21

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1. Inadequate PK Sampling for arm A ipilimumab treatment, so no data was collected

AUC(TAU) - Area under the concentration-time curve in one dosing interval in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
AUC(TAU) - Area Under the Concentration-time Curve in One Dosing Interval in Part 1. Nivo Cycle 1	10333 h*ug/mL Geometric Coefficient of Variation 21	13919 h*ug/mL Geometric Coefficient of Variation 26	4002 h*ug/mL Geometric Coefficient of Variation 19
AUC(TAU) - Area Under the Concentration-time Curve in One Dosing Interval in Part 1. Nivo Cycle 2	—	24467 h*ug/mL Geometric Coefficient of Variation 23	4647 h*ug/mL Geometric Coefficient of Variation 48
AUC(TAU) - Area Under the Concentration-time Curve in One Dosing Interval in Part 1. Nivo Cycle 3	28098 h*ug/mL Geometric Coefficient of Variation 18	—	—
AUC(TAU) - Area Under the Concentration-time Curve in One Dosing Interval in Part 1. Ipi Cycle 1	—	3339 h*ug/mL Geometric Coefficient of Variation 27	9808 h*ug/mL Geometric Coefficient of Variation 17
AUC(TAU) - Area Under the Concentration-time Curve in One Dosing Interval in Part 1. Ipi Cycle 2	—	5377 h*ug/mL Geometric Coefficient of Variation 20	12206 h*ug/mL Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1

Ceoinf - Serum concentration achieved at the end of study drug infusion in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. Nivo Cycle 1	59.4 ug/mL Geometric Coefficient of Variation 19	68.4 ug/mL Geometric Coefficient of Variation 21	22.5 ug/mL Geometric Coefficient of Variation 14
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. Nivo Cycle 2	—	99.5 ug/mL Geometric Coefficient of Variation 15	25.4 ug/mL Geometric Coefficient of Variation 24
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. Nivo Cycle 3	120 ug/mL Geometric Coefficient of Variation 21	—	—
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. Ipi Cycle 1	17.7 ug/mL Geometric Coefficient of Variation 26	14.0 ug/mL Geometric Coefficient of Variation 50	54.8 ug/mL Geometric Coefficient of Variation 33
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. Ipi Cycle 2	—	16.3 ug/mL Geometric Coefficient of Variation 39	62.7 ug/mL Geometric Coefficient of Variation 27
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. Ipi Cycle 3	17.1 ug/mL Geometric Coefficient of Variation 33	—	—

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1

Ctau - Concentration at the end of dosing interval in Part 1. The Ctau is equivilant to the CTrough at these time points.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Ctau - Concentration at the End of Dosing Interval in Part 1. Nivo Cycle 1	19.7 ug/mL Geometric Coefficient of Variation 24	16.0 ug/mL Geometric Coefficient of Variation 32	3.46 ug/mL Geometric Coefficient of Variation 32
Ctau - Concentration at the End of Dosing Interval in Part 1. Nivo Cycle 2	—	40.6 ug/mL Geometric Coefficient of Variation 30	3.32 ug/mL Geometric Coefficient of Variation 70
Ctau - Concentration at the End of Dosing Interval in Part 1. Nivo Cycle 3	63.2 ug/mL Geometric Coefficient of Variation 24	—	—
Ctau - Concentration at the End of Dosing Interval in Part 1. Ipi Cycle 1	4.85 ug/mL Geometric Coefficient of Variation 25	3.22 ug/mL Geometric Coefficient of Variation 34	8.72 ug/mL Geometric Coefficient of Variation 33
Ctau - Concentration at the End of Dosing Interval in Part 1. Ipi Cycle 2	—	6.74 ug/mL Geometric Coefficient of Variation 24	15.4 ug/mL Geometric Coefficient of Variation 27
Ctau - Concentration at the End of Dosing Interval in Part 1. Ipi Cycle 3	6.07 ug/mL Geometric Coefficient of Variation 20	—	—

SECONDARY outcome

Timeframe: At Cycle 3 Day 1 for Arm A, Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1 with CLT data collected, Inadequate PK Sampling for arm A nivo/ipilimumab treatment, so no data was collected

CLT - Total body clearance in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=3 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
CLT - Total Body Clearance in Part 1. Nivo Cycle 2	—	8.56 mL/h Geometric Coefficient of Variation 37	13.1 mL/h Geometric Coefficient of Variation 51
CLT - Total Body Clearance in Part 1. Nivo Cycle 3	6.99 mL/h Geometric Coefficient of Variation 16	—	—
CLT - Total Body Clearance in Part 1. Ipi Cycle 2	—	13.0 mL/h Geometric Coefficient of Variation 36	15.0 mL/h Geometric Coefficient of Variation 55
CLT - Total Body Clearance in Part 1. Ipi Cycle 3	NA mL/h Geometric Coefficient of Variation NA insufficient number of events to produce quantifiable data	—	—

SECONDARY outcome

Timeframe: At Cycle 1 Day 1 and Cycle 3 Day 1 for Arm A, Cycle 1 and Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1. Inadequate PK Sampling for arm A ipilimumab treatment, so no data was collected

Css-avg - Average concentration over a dosing interval (AUC(TAU)/tau) in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Css-avg - Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) in Part 1. Nivo Cycle 1	30.8 ug/mL Geometric Coefficient of Variation 21	27.6 ug/mL Geometric Coefficient of Variation 26	7.94 ug/mL Geometric Coefficient of Variation 19
Css-avg - Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) in Part 1. Nivo Cycle 2	—	48.5 ug/mL Geometric Coefficient of Variation 23	9.22 ug/mL Geometric Coefficient of Variation 48
Css-avg - Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) in Part 1. Nivo Cycle 3	83.6 ug/mL Geometric Coefficient of Variation 18	—	—
Css-avg - Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) in Part 1. Ipi Cycle 1	—	6.63 ug/mL Geometric Coefficient of Variation 27	19.5 ug/mL Geometric Coefficient of Variation 17
Css-avg - Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) in Part 1. Ipi Cycle 2	—	10.7 ug/mL Geometric Coefficient of Variation 20	24.2 ug/mL Geometric Coefficient of Variation 36

SECONDARY outcome

Timeframe: At Cycle 3 Day 1 for Arm A, Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1. Inadequate PK Sampling for arm A nivo/ipilimumab treatment, so no data was collected

AI - Accumulation index; ratio of an exposure measure at steady-state to that after the first dose (exposure measure includes AUC (TAU) in Part 1. Here SS = Steady State Here FD = First Dose

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=3 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
AI - Accumulation Index in Part 1. Nivo Cycle 2	—	1.65 ratio of AUC(Tau) at SS vs FD Geometric Coefficient of Variation 22	1.13 ratio of AUC(Tau) at SS vs FD Geometric Coefficient of Variation 30
AI - Accumulation Index in Part 1. Nivo Cycle 3	2.71 ratio of AUC(Tau) at SS vs FD Geometric Coefficient of Variation 4	—	—
AI - Accumulation Index in Part 1. Ipi Cycle 2	—	1.50 ratio of AUC(Tau) at SS vs FD Geometric Coefficient of Variation 20	1.26 ratio of AUC(Tau) at SS vs FD Geometric Coefficient of Variation 22
AI - Accumulation Index in Part 1. Ipi Cycle 3	NA ratio of AUC(Tau) at SS vs FD Geometric Coefficient of Variation NA insufficient number of events to produce quantifiable data	—	—

SECONDARY outcome

Timeframe: At Cycle 3 Day 1 for Arm A, Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days)

Population: PK Evaluable Population in Part 1. Inadequate PK Sampling for arm A nivo/ipilimumab treatment, so no data was collected

T-HALFeff - Effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure (exposure measure includes AUC(TAU), Cmax, or Ctau) in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=3 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=9 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
T-HALFeff - Effective Elimination Half-life in Part 1. Nivo Cycle 2	—	385 Hours Geometric Coefficient of Variation 36	263 Hours Geometric Coefficient of Variation 37
T-HALFeff - Effective Elimination Half-life in Part 1. Nivo Cycle 3	507 Hours Geometric Coefficient of Variation 4	—	—
T-HALFeff - Effective Elimination Half-life in Part 1. Ipi Cycle 2	—	325 Hours Geometric Coefficient of Variation 38	282 Hours Geometric Coefficient of Variation 14
T-HALFeff - Effective Elimination Half-life in Part 1. Ipi Cycle 3	NA Hours Geometric Coefficient of Variation NA insufficient number of events to produce quantifiable data	—	—

SECONDARY outcome

Timeframe: At baseline and from first dose to last dose (Approximately on average of Arm A 24.54 weeks, Arm B 76 weeks, Arm C 92.5 Weeks)

Population: All Treated Subjects with Baseline and at Least One Post-baseline Evaluable ADA Assessment (Part 1)

Number of participants with nivolumab Anti Drug Antibodies in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=7 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Nivolumab Anti Drug Antibodies in Part 1. Neutralizing Positive	0 Participants	0 Participants	1 Participants
Number of Participants With Nivolumab Anti Drug Antibodies in Part 1. ADA Negative	9 Participants	9 Participants	4 Participants
Number of Participants With Nivolumab Anti Drug Antibodies in Part 1. Baseline ADA Positive	0 Participants	2 Participants	0 Participants
Number of Participants With Nivolumab Anti Drug Antibodies in Part 1. ADA Positive	0 Participants	0 Participants	3 Participants

SECONDARY outcome

Timeframe: At baseline and from first dose to last dose (Approximately on average of Arm A 24.54 weeks, Arm B 76 weeks, Arm C 92.5 Weeks)

Population: All Treated Subjects with Baseline and at Least One Post-baseline Evaluable ADA Assessment (Part 1)

Number of participants with Ipilimumab Anti Drug Antibodies in Part 1.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B n=9 Participants NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C n=7 Participants NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Number of Participants With Ipilimumab Anti Drug Antibodies in Part 1. Baseline ADA Positive	1 Participants	0 Participants	2 Participants
Number of Participants With Ipilimumab Anti Drug Antibodies in Part 1. ADA Positive	0 Participants	0 Participants	0 Participants
Number of Participants With Ipilimumab Anti Drug Antibodies in Part 1. Neutralizing Positive	0 Participants	0 Participants	0 Participants
Number of Participants With Ipilimumab Anti Drug Antibodies in Part 1. ADA Negative	9 Participants	9 Participants	7 Participants

SECONDARY outcome

Population: All treated participants in Part 2

ORR is defined as the number of subjects with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) assessed by Investigator, according to RECIST v1.1 criteria, divided by the number of treated subjects. The BOR is defined as the best response designation recorded between the date of first dose and the date of initial objectively documented progression per RECIST v1.1 or the date of subsequent therapy, whichever occurs first. For participants without documented progression or subsequent therapy, all available response designations will contribute to the BOR determination. For purposes of analysis, if a subject receives one dose and discontinues the study without assessment or receives subsequent therapy prior to assessment, this participant will be counted in the denominator (as nonrespondent).

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Investigator-Assessed ORR in Part 2	66.7 Percentage of Participants Interval 29.9 to 92.5	—	—

SECONDARY outcome

Timeframe: between the date of first dose and the date of initial objectively documented progression per RECIST v1.1 as assessed by the Investigator. (Approximately on average 5 Months)

Population: All treated participants in Part 2

The percentage of participants whose BOR is confirmed CR or confirmed PR or stable disease (SD) for at least 12 weeks as per investigator.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Investigator-Assessed Disease Control Rate (DCR) in Part 2	88.9 Percentage of Participants Interval 51.8 to 99.7	—	—

SECONDARY outcome

Timeframe: Approximately 5.92 Months

Population: All treated participants in Part 2

The percentage of participants whose BOR is confirmed CR or confirmed PR or stable disease (SD) for at least 12 weeks as per BICR.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
BICR-Assessed Disease Control Rate (DCR) in Part 2	88.9 Percentage of Participants Interval 51.8 to 99.7	—	—

SECONDARY outcome

Timeframe: From first dose to 100 days post last dose (approximately 102 weeks)

Population: All confirmed responders per BICR in Part 2

The time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first as per BICR.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=7 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
BICR-Assessed Duration of Response (DOR) in Part 2	NA Months Interval 15.21 to Median and ULN were not reached due to insufficient number of events to calculate via KM methodology.	—	—

SECONDARY outcome

Timeframe: From first dose to 100 days post last dose (approximately 102 weeks)

Population: All confirmed responders per investigator in Part 2

The time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first as per investigator.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=6 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Investigator-Assessed Duration of Response (DOR) in Part 2	NA Months Median, LLN and ULN were not reached due to insufficient number of events to calculate via KM methodology.	—	—

SECONDARY outcome

Timeframe: From first dose to 100 days post last dose (approximately 102 weeks)

Population: All Treated participtants in Part 2

The time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first as per BICR.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
BICR-Assessed Progression Free Survival (PFS) in Part 2	NA Months Interval 1.22 to Insufficient number of events to calculate median and ULN using Kaplan-Meier methodology.	—	—

SECONDARY outcome

Timeframe: From first dose to 100 days post last dose (approximately 102 weeks)

Population: All Treated participtants in Part 2

The time between the date of first confirmed response to the date of the first documented tumor progression (per RECIST 1.1), or death due to any cause, whichever occurs first as per investigator.

Outcome measures

Outcome measures
Measure	Part 1: Arm A n=9 Participants NIVO 3 mg/kg Q2 + IPI 1 mg/kg Q6	Part 1: Arm B NIVO 3 mg/kg Q3 + IPI 1 mg/kg Q3	Part 1: Arm C NIVO 1 mg/kg Q3 + IPI 3 mg/kg Q3
Investigator-Assessed Progression Free Survival (PFS) in Part 2	NA Months Interval 1.22 to Insufficient number of events to calculate median and ULN using Kaplan-Meier methodology.	—	—

Adverse Events

Part 1: Arm A

Serious events: 4 serious events

Other events: 7 other events

Deaths: 2 deaths

Part 1: Arm B

Serious events: 3 serious events

Other events: 9 other events

Deaths: 2 deaths

Part 1: Arm C

Serious events: 3 serious events

Other events: 9 other events

Deaths: 1 deaths

Part 2: Arm D

Serious events: 4 serious events

Other events: 9 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Bristol-Myers Squibb Study Directo

Bristol-Myers Squibb

Phone: 1-855-907-3286

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Publication restrictions are in place

Restriction type: OTHER