The purpose of the study is to determine safety and effectiveness of experimental medication BMS-986205 when combined with Nivolumab and in combination with both Nivolumab and Ipilimumab in patients with cancers that are advanced or have spread. Pharmacokinetics and pharmacodynamics of BMS-986205 when combined with Nivolumab and in combination with Nivolumab and Ipilimumab in this patient population will also be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
627
Local Institution - 0028
Tucson, Arizona, United States
Local Institution - 0026
La Jolla, California, United States
Local Institution - 0035
Tampa, Florida, United States
Local Institution - 0005
Atlanta, Georgia, United States
Local Institution - 0048
Atlanta, Georgia, United States
Local Institution - 0027
Number of Participants With AEs, SAEs, AEs Leading to Discontinuation and Deaths
Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation and deaths.
Time frame: From first dose to 100 days after last dose (up to 15 months)
Number of Treated Participant With Laboratory Abnormalities - Thyroid
The number of treated participants who experienced a laboratory abnormality of the thyroid during the course of the study. Free T3 (FT3) Free T4 (FT4) Thyroid stimulating hormone (TSH) Lower Limit of Normal (LLN) Upper limit of normal (ULN) Results reported in International System of Units (SI)
Time frame: From first dose to 100 days after last dose (up to 15 months)
Number of Treated Participant With Laboratory Abnormalities - Liver
The number of treated participants who experienced a laboratory abnormality of the liver during the course of the study. Aspartate aminotransferase (AST) Alanine aminotransferase (ALT) Upper Limit of Normal (ULN) Results reported in International System of Units (SI)
Time frame: From first dose to 100 days after last dose (up to 15 months)
Number of Participants With a Best Overall Response (BOR) - Parts 2 and 3
Best overall response (BOR) is defined as the best response designation over the study as a whole. Complete response (CR) or partial response (PR) determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met. For those participants who have surgical resection, only pre-surgical tumor assessments will be considered in the determination of BOR. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease. (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Appearance of 1 or more new lesions is also considered progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Percentage of Participants With an Objective Response Rate (ORR)- Parts 2 and 3
Objective response rate (ORR) is defined as the percentage of all treated participants whose BOR is either a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Time frame: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Median Duration of Response (DoR) - Parts 2 and 3
Duration of response (DoR) was computed for all treated subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Time frame: From first dose to the date of disease progression, death, or until participants withdraw from the study, whichever occurs first (up to a maximum of 185 weeks)
Progression Free Survival Rate (PFSR) at 24 Weeks - Parts 2 and 3
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 24 weeks. Reported values are estimates derived from Kaplan-Meier analyses.
Time frame: At 24 weeks after first dose
Progression Free Survival Rate (PFSR) at 1 Year - Parts 2 and 3
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 1 year. Reported values are estimates derived from Kaplan-Meier analyses.
Time frame: At 1 year
Progression Free Survival Rate (PFSR) at 2 Years - Parts 2 and 3
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 2 years. Reported values are estimates derived from Kaplan-Meier analyses.
Time frame: At 2 years
Cmax
Cmax is defined as the maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.
Time frame: At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks]
Tmax
Tmax is defined as the time of maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.
Time frame: At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks]
AUC(TAU)
AUC(TAU) is defined as the area under the concentration-time curve in 1 dosing interval. Pharmacokinetic parameters measured here are for BMS-986205.
Time frame: Cycle 0 Day 1 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 0 Day 14 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose)
Ctrough
Ctrough is defined as the trough observed plasma concentration at the end of the dosing interval.
Time frame: At cycles 0 [up to 2 weeks] and at cycles 3, 5, 7, 10, 11, 13, 15 [each cycle is up to 4 weeks]
CLT/F
CLT/F is defined as the apparent total body clearance. Pharmacokinetic parameters measured here are for BMS-986205.
Time frame: At Cycle 0 Day 14 [cycle 0 = up to 2 weeks]
Accumulation Index (AI) - AUC(TAU)
Accumulation index (AI) of AUC(TAU) is calculated based on the ratio of AUC(TAU) at steady state to after the first dose. Pharmacokinetic parameters measured here are for BMS-986205.
Time frame: Cycle 0 Day 1 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose), Cycle 0 Day 14 (0, 1, 2, 3, 4, 6, 8, 24 hours post-dose)
Accumulation Index (AI) - Cmax
Accumulation index (AI) of Cmax is calculated based on the ratio of Cmax at steady state to after the first dose. Pharmacokinetic parameters measured here are for BMS-986205.
Time frame: At Cycle 0 Day 14 [cycle 0 = up to 2 weeks]
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Chicago, Illinois, United States
Local Institution - 0051
Lutherville, Maryland, United States
Local Institution - 0049
Detroit, Michigan, United States
Local Institution - 0006
St Louis, Missouri, United States
Local Institution - 0033
Hackensack, New Jersey, United States
...and 37 more locations
Change From Baseline in Serum Kynurenine
Pharmacodynamics assessed by change from baseline in serum kynurenine. Changes in kynurenine expression were evaluated in serum samples from participants treated using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Kynurenine is an important metabolite of the IDO-1 Enzyme. Change in Kynurenine levels from baseline is an important indicator of BMS-986205 (IDO1 inhibitor) pharmacodynamic activity.
Time frame: At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks]
Percent Change From Baseline in Serum Kynurenine
Pharmacodynamics assessed by change from baseline in serum kynurenine. Changes in kynurenine expression were evaluated in serum samples from participants treated using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Kynurenine is an important metabolite of the IDO-1 Enzyme. Change in Kynurenine levels from baseline is an important indicator of BMS-986205 (IDO1 inhibitor) pharmacodynamic activity.
Time frame: At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks]
Number of Participants With a Best Overall Response (BOR) - Part 1 and Clinical Pharmacology Substudies
Best overall response (BOR) is defined as the best response designation over the study as a whole. Complete response (CR) or partial response (PR) determinations included in the BOR assessment must be confirmed by a second scan performed no less than 4 weeks after the criteria for response are first met. For those participants who have surgical resection, only pre-surgical tumor assessments will be considered in the determination of BOR. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. Progressive Disease. (PD): At least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. Appearance of 1 or more new lesions is also considered progression. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.
Time frame: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Percentage of Participants With an Objective Response Rate (ORR) - Part 1 and Clinical Pharmacology Substudies
Objective response rate (ORR) is defined as the percentage of all treated participants whose BOR is either a complete response (CR) or partial response (PR). Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions. CR+PR confidence interval based on the Clopper and Pearson method.
Time frame: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Median Duration of Response (DoR) - Part 1 and Clinical Pharmacology Substudies
Duration of response (DoR) was computed for all treated subjects with a best overall response (BOR) of complete response (CR) or partial response (PR) and is defined as the time between the date of first response and the date of disease progression or death, whichever occurs first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Time frame: From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Progression Free Survival Rate (PFSR) at 24 Weeks - Part 1 and Clinical Pharmacology Substudies
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 24 weeks. Reported values are estimates derived from Kaplan-Meier analyses.
Time frame: At 24 weeks after first dose
Progression Free Survival Rate (PFSR) at 1 Year - Part 1 and Clinical Pharmacology Substudies
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 1 year. Reported values are estimates derived from Kaplan-Meier analyses.
Time frame: At 1 year
Progression Free Survival Rate (PFSR) at 2 Years - Part 1 and Clinical Pharmacology Substudies
Progression free survival rate (PFSR) is defined as the percentage of participants who remain progression free and surviving at 2 years. Reported values are estimates derived from Kaplan-Meier analyses.
Time frame: At 2 years
Number of Participants With a Positive Anti-Drug Antibody (ADA) Test
A participant with at least one ADA-positive sample relative to baseline after initiation of treatment with nivolumab or ipilimumab. ADA-Positive after initiation of treatment was defined as (1) an ADA detected (positive seroconversion) sample in a subject for whom ADA is not detected at baseline, or (2) an ADA detected sample with ADA titer to be at least 4-fold or greater (≥) than baseline positive titer.
Time frame: From first dose to last dose (up to approximately 48 weeks)