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Completed

NCT Number: NCT02658890

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

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.

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Key information

Conditions

Advanced Cancer Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Lung Diseases Lung Neoplasms Melanoma Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neuroectodermal Tumors Neuroendocrine Tumors Nevi and Melanomas Non-small Cell Lung Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases Thoracic Neoplasms

Age range

18 year–100 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Local Institution - 0045, North Sydney, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

BMS-986205

Drug

Nivolumab

Drug

Other names: BMS-936558, ANTI-PD1

Ipilimumab

Drug

Other names: BMS-734016, ANTI-CTLA-4

Primary outcomes

  1. Number of Participants With AEs, SAEs, AEs Leading to Discontinuation and Deaths

    Time frame: 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.

  2. Number of Treated Participant With Laboratory Abnormalities - Thyroid

    Time frame: 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)

  3. Number of Treated Participant With Laboratory Abnormalities - Liver

    Time frame: 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)

  4. Number of Participants With a Best Overall Response (BOR) - Parts 2 and 3

    Time frame: 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.

  5. Percentage of Participants With an Objective Response Rate (ORR)- Parts 2 and 3

    Time frame: 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.

  6. Median Duration of Response (DoR) - Parts 2 and 3

    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)

    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.

  7. Progression Free Survival Rate (PFSR) at 24 Weeks - Parts 2 and 3

    Time frame: 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.

  8. Progression Free Survival Rate (PFSR) at 1 Year - Parts 2 and 3

    Time frame: 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.

  9. Progression Free Survival Rate (PFSR) at 2 Years - Parts 2 and 3

    Time frame: 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 outcomes

  1. Cmax

    Time frame: 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.

  2. Tmax

    Time frame: 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.

  3. AUC(TAU)

    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)

    AUC(TAU) is defined as the area under the concentration-time curve in 1 dosing interval. Pharmacokinetic parameters measured here are for BMS-986205.

  4. Ctrough

    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]

    Ctrough is defined as the trough observed plasma concentration at the end of the dosing interval.

  5. CLT/F

    Time frame: 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.

  6. Accumulation Index (AI) - AUC(TAU)

    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) 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.

  7. Accumulation Index (AI) - Cmax

    Time frame: 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.

  8. Change From Baseline in Serum Kynurenine

    Time frame: 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.

  9. Percent Change From Baseline in Serum Kynurenine

    Time frame: 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.

  10. Number of Participants With a Best Overall Response (BOR) - Part 1 and Clinical Pharmacology Substudies

    Time frame: 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.

  11. Percentage of Participants With an Objective Response Rate (ORR) - Part 1 and Clinical Pharmacology Substudies

    Time frame: 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.

  12. Median Duration of Response (DoR) - Part 1 and Clinical Pharmacology Substudies

    Time frame: 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.

  13. Progression Free Survival Rate (PFSR) at 24 Weeks - Part 1 and Clinical Pharmacology Substudies

    Time frame: 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.

  14. Progression Free Survival Rate (PFSR) at 1 Year - Part 1 and Clinical Pharmacology Substudies

    Time frame: 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.

  15. Progression Free Survival Rate (PFSR) at 2 Years - Part 1 and Clinical Pharmacology Substudies

    Time frame: 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.

  16. Number of Participants With a Positive Anti-Drug Antibody (ADA) Test

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Bristol-Myers Squibb

Industry

Registry information

Official study 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

Important dates

Study start
2016
Primary completion
2021
Study completion
2021
First posted
Jan 20, 2016
Registry last updated
Aug 28, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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