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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1/2a Study of BMS-986205 Administered in Combination With Nivolumab (Anti-PD-1 Monoclonal Antibody) and in Combination With Both Nivolumab and Ipilimumab (Anti-CTLA-4 Monoclonal Antibody) in Advanced Malignant Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02658890
• Other study ID #: CA017-003
• Secondary ID: 2015-004914-79
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 14, 2016
• Est. completion date: October 26, 2021

Study information

• Verified date: August 2023
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 627
• Est. completion date: October 26, 2021
• Est. primary completion date: October 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

For more information regarding Bristol-Myers Squibb (BMS) Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Advanced Cancer
• Carcinoma, Non-Small-Cell Lung
• Melanoma
• Non-Small Cell Lung Cancer

Intervention

Drug:
• BMS-986205

• Nivolumab

• Ipilimumab

Locations

Country	Name	City	State
Australia	Local Institution - 0044	Brisbane	Queensland
Australia	Local Institution - 0008	Clayton	Victoria
Australia	Local Institution - 0004	Melbourne	Victoria
Australia	Local Institution - 0047	Nedlands	Western Australia
Australia	Local Institution - 0045	North Sydney	New South Wales
Australia	Local Institution - 0029	Sydney	New South Wales
Australia	Local Institution - 0046	Westmead	New South Wales
Canada	Local Institution - 0003	Edmonton	Alberta
Canada	Local Institution	Greenfield Park	Quebec
Canada	Local Institution - 0036	Montreal	Quebec
Canada	Local Institution - 0001	Toronto	Ontario
Canada	Local Institution - 0002	Vancouver	British Columbia
Finland	Local Institution - 0059	Helsinki
France	Local Institution - 0040	Lille CEDEX
France	Local Institution - 0024	Lyon Cedex 08
France	Local Institution - 0053	Marseille Cedex 5
France	Local Institution - 0052	Nantes Cedex 01
France	Local Institution - 0025	Paris
France	Local Institution - 0023	Toulouse
France	Local Institution - 0022	Villejuif
Germany	Local Institution - 0019	Essen
Germany	Local Institution - 0013	Heilbronn
Italy	Local Institution - 0010	Milano
Italy	Local Institution - 0011	Milano
Italy	Local Institution - 0012	Milano
Italy	Local Institution - 0009	Rozzano MI
Norway	Local Institution - 0054	Oslo
Poland	Local Institution - 0042	Warszawa	Mazowieckie
Spain	Local Institution - 0017	Barcelona
Spain	Local Institution - 0016	Madrid
Spain	Local Institution - 0018	Madrid
Sweden	Local Institution - 0055	Solna
United States	Local Institution - 0005	Atlanta	Georgia
United States	Local Institution - 0048	Atlanta	Georgia
United States	Local Institution - 0027	Chicago	Illinois
United States	Local Institution - 0030	Cleveland	Ohio
United States	Local Institution - 0049	Detroit	Michigan
United States	Local Institution - 0033	Hackensack	New Jersey
United States	Local Institution - 0026	La Jolla	California
United States	Local Institution - 0051	Lutherville	Maryland
United States	Local Institution - 0043	Nashville	Tennessee
United States	Local Institution - 0041	New York	New York
United States	Local Institution - 0034	Philadelphia	Pennsylvania
United States	Local Institution - 0057	Pittsburgh	Pennsylvania
United States	Local Institution - 0006	Saint Louis	Missouri
United States	Local Institution - 0035	Tampa	Florida
United States	Local Institution - 0028	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  France,  Germany,  Italy,  Norway,  Poland,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From first dose to 100 days after last dose (up to 15 months)
Primary	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)	From first dose to 100 days after last dose (up to 15 months)
Primary	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)	From first dose to 100 days after last dose (up to 15 months)
Primary	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.	From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Primary	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.	From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Primary	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.	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)
Primary	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.	At 24 weeks after first dose
Primary	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.	At 1 year
Primary	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.	At 2 years
Secondary	Cmax	Cmax is defined as the maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.	At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks]
Secondary	Tmax	Tmax is defined as the time of maximum observed plasma concentration. Pharmacokinetic parameters measured here are for BMS-986205.	At cycle 0 day 1 and day 14 [cycle 0= up to 2 weeks]
Secondary	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.	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)
Secondary	Ctrough	Ctrough is defined as the trough observed plasma concentration at the end of the dosing interval.	At cycles 0 [up to 2 weeks] and at cycles 3, 5, 7, 10, 11, 13, 15 [each cycle is up to 4 weeks]
Secondary	CLT/F	CLT/F is defined as the apparent total body clearance. Pharmacokinetic parameters measured here are for BMS-986205.	At Cycle 0 Day 14 [cycle 0 = up to 2 weeks]
Secondary	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.	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)
Secondary	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.	At Cycle 0 Day 14 [cycle 0 = up to 2 weeks]
Secondary	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.	At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks]
Secondary	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.	At baseline (cycle 1, day 1) and at cycle 1, day 15 [cycle 1 = up to 4 weeks]
Secondary	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.	From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Secondary	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.	From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Secondary	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.	From first dose to the last tumor assessment prior to subsequent therapy (up to a maximum of 185 weeks)
Secondary	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.	At 24 weeks after first dose
Secondary	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.	At 1 year
Secondary	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.	At 2 years
Secondary	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.	From first dose to last dose (up to approximately 48 weeks)

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