A Study of Nivolumab in Combination With Ipilimumab in Chinese Participants With Previously Treated Advanced or Recurrent Solid Tumors
- Registration Number
- NCT03195478
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
The purpose of this study is to evaluate the safety and effectiveness of Nivolumab in combination with Ipilimumab in Chinese participants with previously treated late stage cancer.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 37
- Mainland Chinese participants with advanced or recurrent solid tumors
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- One prior anti-cancer therapy that did not work or documented refusal to receive chemotherapy or biological therapy
- Cancer that has spread to the brain or central nervous system unless it has been adequately treated . In addition, either no longer receiving corticosteroids, or on a stable or decreasing dose of no more than 10 mg daily prednisone (or equivalent)
- Active, known or suspected autoimmune disease or infection
- Positive blood screen for chronic infection of hepatitis B or hepatitis C (HCV antibody positive unless HCV RNA is negative)
- Prior immuno-oncology therapy
Other protocol-defined inclusion/exclusion criteria apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Nivo/Ipi Combination Therapy B Ipilimumab - Nivo/Ipi Combination Therapy A Nivolumab - Nivo/Ipi Combination Therapy A Ipilimumab - Nivo/Ipi Combination Therapy B Nivolumab - Nivo/Ipi Combination Therapy C Nivolumab - Nivo/Ipi Combination Therapy C Ipilimumab - Nivo/Ipi Combination Arm D Nivolumab - Nivo/Ipi Combination Arm D Ipilimumab -
- Primary Outcome Measures
Name Time Method Number of Participants With Adverse Events (AEs) in Part 1. 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) Number of participants with Adverse events
Number of Participants With Serious Adverse Events (SAEs) in Part 1. 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) Number of participants with Adverse events
Number of Participants With Adverse Events Leading to Discontinuation in Part 1. 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) Number of participants with Adverse events
Number of Participants With Adverse Events Leading to Death in Part 1. 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) Number of participants with Adverse Events leading to death.
Number of Participants With Clinical Laboratory Abnormalities in Part 1. 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) Number of participants with clinical laboratory abnormalities.
BICR-Assessed ORR in Part 2 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) 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).
- Secondary Outcome Measures
Name Time Method Cmax - Maximum Observed Serum Concentration in Part 1. 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) Cmax - Maximum observed serum concentration in Part 1.
Tmax - Time of Maximum Observed Serum Concentration in Part 1. 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) Tmax - Time of maximum observed serum concentration in Part 1.
AUC(0-T) - Area Under the Plasma Concentration-time Curve in Part 1. 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) 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.
AUC(TAU) - Area Under the Concentration-time Curve in One Dosing Interval in Part 1. 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) AUC(TAU) - Area under the concentration-time curve in one dosing interval in Part 1.
Ceoinf - Serum Concentration Achieved at the End of Study Drug Infusion in Part 1. 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) Ceoinf - Serum concentration achieved at the end of study drug infusion in Part 1.
Ctau - Concentration at the End of Dosing Interval in Part 1. 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) Ctau - Concentration at the end of dosing interval in Part 1. The Ctau is equivilant to the CTrough at these time points.
CLT - Total Body Clearance in Part 1. At Cycle 3 Day 1 for Arm A, Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days) CLT - Total body clearance in Part 1.
Css-avg - Average Concentration Over a Dosing Interval (AUC(TAU)/Tau) in Part 1. 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) Css-avg - Average concentration over a dosing interval (AUC(TAU)/tau) in Part 1.
AI - Accumulation Index in Part 1. At Cycle 3 Day 1 for Arm A, Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days) 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 DoseT-HALFeff - Effective Elimination Half-life in Part 1. At Cycle 3 Day 1 for Arm A, Cycle 2 Day 1 for Arm B and C (1 cycle = 42 days) 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.
Number of Participants With Nivolumab Anti Drug Antibodies in Part 1. 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) Number of participants with nivolumab Anti Drug Antibodies in Part 1.
Number of Participants With Ipilimumab Anti Drug Antibodies in Part 1. 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) Number of participants with Ipilimumab Anti Drug Antibodies in Part 1.
Investigator-Assessed ORR in Part 2 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 the Investigator. (Approximately on average 2 Months) 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).BICR-Assessed Duration of Response (DOR) in Part 2 From first dose to 100 days post last dose (approximately 102 weeks) 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.
Investigator-Assessed Disease Control Rate (DCR) in Part 2 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) The percentage of participants whose BOR is confirmed CR or confirmed PR or stable disease (SD) for at least 12 weeks as per investigator.
BICR-Assessed Disease Control Rate (DCR) in Part 2 Approximately 5.92 Months The percentage of participants whose BOR is confirmed CR or confirmed PR or stable disease (SD) for at least 12 weeks as per BICR.
BICR-Assessed Progression Free Survival (PFS) in Part 2 From first dose to 100 days post last dose (approximately 102 weeks) 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.
Investigator-Assessed Progression Free Survival (PFS) in Part 2 From first dose to 100 days post last dose (approximately 102 weeks) 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.
Investigator-Assessed Duration of Response (DOR) in Part 2 From first dose to 100 days post last dose (approximately 102 weeks) 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.
Trial Locations
- Locations (11)
Local Institution - 0015
🇨🇳Beijing, Beijing Municipality, China
Local Institution - 0001
🇨🇳Beijing, Beijing Municipality, China
Local Institution
🇨🇳Zhengzhou, Henan, China
Local Institution - 0012
🇨🇳Guangzhou, Guangdong, China
Local Institution - 0011
🇨🇳Harbin, Heilongjiang, China
Local Institution - 0021
🇨🇳Wuhan, Hubei, China
Local Institution - 0020
🇨🇳Xi'an, Shan1xi, China
Local Institution - 0016
🇨🇳Shanghai, Shanghai Municipality, China
Local Institution - 0018
🇨🇳Chengdu, Sichuan, China
Local Institution - 0004
🇨🇳Tianjin, Tianjin Municipality, China
Scroll for more (1 remaining)Local Institution - 0015🇨🇳Beijing, Beijing Municipality, China