A Study of Safety, Tolerability and Pharmacokinetics of Nivolumab in Chinese Subjects With Previously Treated Advanced or Recurrent Solid Tumors

Solid Tumors Clinical Trial

— CheckMate 077  

Official title:

A Phase 1/2, Open-Label Study of Nivolumab (BMS-936558) in Chinese Subjects With Previously Treated Advanced or Recurrent Solid Tumors (CheckMate 077: CHECKpoint Pathway and nivoluMAb Clinical Trial Evaluation 077)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02593786
• Other study ID #: CA209-077
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 7, 2016
• Est. completion date: September 27, 2021

Study information

• Verified date: September 2022
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: September 27, 2021
• Est. primary completion date: September 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• Nivolumab

Locations

Country	Name	City	State
China	Local Institution - 0001	Guangzhou	Guangdong
China	Local Institution	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	From first dose to 100 days after last dose (up to approximately 28 months)
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.	From first dose to 100 days after last dose (up to approximately 28 months)
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	From first dose to 100 days after last dose (up to approximately 28 months)
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.	From first dose to 100 days after last dose (up to approximately 28 months)
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).	From first dose up to approximately 28 months
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.	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)
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.	From first dose up to approximately 28 months
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.	Week 24
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.	Week 24
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: Baseline ADA positive: all participants with baseline ADA positive samples.; ADA Positive: participants that have at least one ADA positive sample relative to baseline at any time after initiation of treatment.; ADA negative: participants that have no ADA positive samples after the initiation of treatment.	From pre-dose on day 1 Cycle 1 up to participants end of study (up to approximately 28 months)
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.	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)
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.	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)
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.	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)
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.	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)
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.	End of infusion on Day 1 of Cycle 1, 3, 5, 6
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.	Day 1 Cycle 3, 5, 6 (168 hours post dose [Cohort A-B], 336 hours post dose [Cohort C-D])
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.	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)
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).	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)
Secondary	CLT - Total Body Clearance	Nivolumab pharmacokinetic parameters are derived from serum concentration versus time data. CLT is the 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)
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.	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)
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.	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)
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.	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)

External Links

•   BMS Clinical Trial Information
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