An Investigational Immuno-therapy Study of BMS-986205 Given in Combination With Nivolumab and in Combination With Both Nivolumab and Ipilimumab in Cancers That Are Advanced or Have Spread
- Conditions
- MelanomaNon-Small Cell Lung CancerAdvanced Cancer
- Interventions
- Registration Number
- NCT02658890
- Lead Sponsor
- Bristol-Myers Squibb
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 627
- During dose escalation, subjects with advanced solid tumors that have progressed following at least one standard regimen
- During cohort expansion, subjects with advanced cancer that either have received at least one prior therapy or are treatment naive, depending on the specified tumor type
- Subjects must have measurable disease
- Subject must consent to provide previously collected tumor tissue and a tumor biopsy during screening.
- At least 4 weeks since any previous treatment for cancer
- Must be able to swallow pills or capsules
- Eastern Cooperative Oncology Group(ECOG) Performance Status 0-1
- Active or chronic autoimmune diseases
- Uncontrolled or significant cardiovascular disease
- History of any chronic Hepatitis, active Hepatitis B or C, human immunodeficiency virus (HIV), or acquired immune deficiency syndrome (AIDS)
- Chronic hepatitis: Positive test for Hepatitis B virus surface antigen or Hepatitis C antibody (except for subjects with hepatocellular carcinoma)
- Active central nervous system (CNS) metastases and CNS metastases as the only sites of disease
- Active infection
Other protocol defined inclusion/exclusion criteria could apply
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Combination Therapy (Dose Escalation) BMS-986205 BMS 986205 + Nivolumab specified dose at specified intervals. Combination Therapy (Dose Escalation) Nivolumab BMS 986205 + Nivolumab specified dose at specified intervals. Combination Therapy 2 (Dose Expansion) Ipilimumab BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals Combination Therapy 2 (Dose Expansion) BMS-986205 BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals Combination Therapy 2 (Dose Expansion) Nivolumab BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals Combination Therapy (Dose Expansion) BMS-986205 BMS 986205 + Nivolumab specified dose at specified intervals. Combination Therapy (Dose Expansion) Nivolumab BMS 986205 + Nivolumab specified dose at specified intervals.
- Primary Outcome Measures
Name Time Method Number of Treated Participant With Laboratory Abnormalities - Liver From first dose to 100 days after last dose (up to 15 months) 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)Number of Participants With AEs, SAEs, AEs Leading to Discontinuation and Deaths From first dose to 100 days after last dose (up to 15 months) Number of participants with adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuation and deaths.
Number of Treated Participant With Laboratory Abnormalities - Thyroid From first dose to 100 days after last dose (up to 15 months) 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)Percentage of Participants With an Objective Response Rate (ORR)- Parts 2 and 3 From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks) 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.
Progression Free Survival Rate (PFSR) at 24 Weeks - Parts 2 and 3 At 24 weeks after first dose 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.
Progression Free Survival Rate (PFSR) at 1 Year - Parts 2 and 3 At 1 year 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.
Number of Participants With a Best Overall Response (BOR) - Parts 2 and 3 From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks) 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.
Median Duration of Response (DoR) - Parts 2 and 3 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) 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.
Progression Free Survival Rate (PFSR) at 2 Years - Parts 2 and 3 At 2 years 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.
- Secondary Outcome Measures
Name Time Method CLT/F At Cycle 0 Day 14 [cycle 0 = up to 2 weeks] CLT/F is defined as the apparent total body clearance. Pharmacokinetic parameters measured here are for BMS-986205.
Percent Change From Baseline in Serum Kynurenine At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks] 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.
Cmax At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks] Cmax is defined as the maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.
Accumulation Index (AI) - AUC(TAU) 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) 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.
Accumulation Index (AI) - Cmax At Cycle 0 Day 14 [cycle 0 = up to 2 weeks] 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.
Tmax At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks] Tmax is defined as the time of maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.
Progression Free Survival Rate (PFSR) at 24 Weeks - Part 1 and Clinical Pharmacology Substudies At 24 weeks after first dose 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.
Ctrough At cycles 0 [up to 2 weeks] and at cycles 3, 5, 7, 10, 11, 13, 15 [each cycle is up to 4 weeks] Ctrough is defined as the trough observed plasma concentration at the end of the dosing interval.
Percentage of Participants With an Objective Response Rate (ORR) - Part 1 and Clinical Pharmacology Substudies From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks) 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.
AUC(TAU) 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) AUC(TAU) is defined as the area under the concentration-time curve in 1 dosing interval. Pharmacokinetic parameters measured here are for BMS-986205.
Change From Baseline in Serum Kynurenine At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks] 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.
Number of Participants With a Best Overall Response (BOR) - Part 1 and Clinical Pharmacology Substudies From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks) 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.
Progression Free Survival Rate (PFSR) at 1 Year - Part 1 and Clinical Pharmacology Substudies At 1 year 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.
Median Duration of Response (DoR) - Part 1 and Clinical Pharmacology Substudies From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks) 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.
Progression Free Survival Rate (PFSR) at 2 Years - Part 1 and Clinical Pharmacology Substudies At 2 years 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.
Number of Participants With a Positive Anti-Drug Antibody (ADA) Test From first dose to last dose (up to approximately 48 weeks) 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.
Trial Locations
- Locations (47)
Local Institution - 0057
🇺🇸Pittsburgh, Pennsylvania, United States
Local Institution - 0022
🇫🇷Villejuif, France
Local Institution - 0033
🇺🇸Hackensack, New Jersey, United States
Local Institution - 0051
🇺🇸Lutherville, Maryland, United States
Local Institution - 0026
🇺🇸La Jolla, California, United States
Local Institution - 0044
🇦🇺Brisbane, Queensland, Australia
Local Institution - 0008
🇦🇺Clayton, Victoria, Australia
Local Institution - 0004
🇦🇺Melbourne, Victoria, Australia
Local Institution - 0036
🇨🇦Montreal, Quebec, Canada
Local Institution - 0016
🇪🇸Madrid, Spain
Local Institution - 0053
🇫🇷Marseille Cedex 5, France
Local Institution - 0010
🇮🇹Milano, Italy
Local Institution - 0003
🇨🇦Edmonton, Alberta, Canada
Local Institution - 0045
🇦🇺North Sydney, New South Wales, Australia
Local Institution - 0018
🇪🇸Madrid, Spain
Local Institution - 0046
🇦🇺Westmead, New South Wales, Australia
Local Institution - 0024
🇫🇷Lyon Cedex 08, France
Local Institution - 0055
🇸🇪Solna, Sweden
Local Institution - 0017
🇪🇸Barcelona, Spain
Local Institution - 0001
🇨🇦Toronto, Ontario, Canada
Local Institution - 0052
🇫🇷Nantes Cedex 01, France
Local Institution - 0059
🇫🇮Helsinki, Finland
Local Institution - 0019
🇩🇪Essen, Germany
Local Institution - 0012
🇮🇹Milano, Italy
Local Institution - 0054
🇳🇴Oslo, Norway
Local Institution - 0005
🇺🇸Atlanta, Georgia, United States
Local Institution - 0027
🇺🇸Chicago, Illinois, United States
Local Institution - 0034
🇺🇸Philadelphia, Pennsylvania, United States
Local Institution - 0030
🇺🇸Cleveland, Ohio, United States
Local Institution - 0006
🇺🇸Saint Louis, Missouri, United States
Local Institution - 0047
🇦🇺Nedlands, Western Australia, Australia
Local Institution - 0048
🇺🇸Atlanta, Georgia, United States
Local Institution - 0029
🇦🇺Sydney, New South Wales, Australia
Local Institution - 0041
🇺🇸New York, New York, United States
Local Institution - 0023
🇫🇷Toulouse, France
Local Institution - 0013
🇩🇪Heilbronn, Germany
Local Institution - 0011
🇮🇹Milano, Italy
Local Institution - 0009
🇮🇹Rozzano MI, Italy
Local Institution - 0035
🇺🇸Tampa, Florida, United States
Local Institution - 0049
🇺🇸Detroit, Michigan, United States
Local Institution - 0043
🇺🇸Nashville, Tennessee, United States
Local Institution - 0028
🇺🇸Tucson, Arizona, United States
Local Institution
🇨🇦Greenfield Park, Quebec, Canada
Local Institution - 0042
🇵🇱Warszawa, Mazowieckie, Poland
Local Institution - 0025
🇫🇷Paris, France
Local Institution - 0040
🇫🇷Lille CEDEX, France
Local Institution - 0002
🇨🇦Vancouver, British Columbia, Canada