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

• ClinicalTrials.gov Identifier: NCT02658890
• Recruitment Status: Active, not recruiting
• First Posted: January 20, 2016
• Last Update Posted: October 18, 2021
• Sponsor: Bristol-Myers Squibb
• Information provided by (Responsible Party): Bristol-Myers Squibb

Tracking Information

• First Submitted Date: January 14, 2016
• First Posted Date: January 20, 2016
• Last Update Posted Date: October 18, 2021
• Actual Study Start Date: February 22, 2016
• Estimated Primary Completion Date: October 24, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 24, 2017)

• Safety and tolerability of BMS-986205 as measured by a composite of the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities. [ Time Frame: 100 days after the last dose of study therapy ]
  measured by incidence
• Safety of BMS-986205 plus nivolumab as measured by a composite of the incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities. [ Time Frame: 100 days after the last dose of study therapy ]
  measured by incidence
• Safety of BMS-986205 plus both nivolumab and ipilimumab as measured by incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities. [ Time Frame: 100 days after the last dose of study therapy ]
  measured by incidence
• Anti-tumor activity of BMS 986205 administered in combination with nivolumab as measured by the best overall response (BOR) [ Time Frame: Approximately 3 years ]
  measured by CT scan
• Anti-tumor activity of BMS 986205 administered in combination with nivolumab as measured by the duration of response (DOR) [ Time Frame: Approximately 3 years ]
  measured by CT scan
• Anti-tumor activity of BMS 986205 administered in combination with nivolumab as measured by progression-free survival rates (PFSRs) [ Time Frame: Approximately 3 years ]
  measured by CT scan
• Anti-tumor activity of BMS 986205 administered in combination with both nivolumab and ipilimumab as measured by the best overall response (BOR) [ Time Frame: Approximately 3 years ]
  measured by CT scan
• Anti-tumor activity of BMS 986205 administered in combination with both nivolumab and ipilimumab as measured by the duration of response (DOR) [ Time Frame: Approximately 3 years ]
  measured by CT scan
• Anti-tumor activity of BMS 986205 administered in combination with both nivolumab and ipilimumab as measured by progression-free survival rates (PFSRs) [ Time Frame: Approximately 3 years ]
  measured by CT scan

Original Primary Outcome Measures (submitted: January 15, 2016)

• Safety of BMS-986205 as measured by incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities. [ Time Frame: 100 days after the last dose of study therapy ]
• Safety of BMS-986205 plus nivolumab as measured by incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to discontinuation, deaths, and clinical laboratory test abnormalities. [ Time Frame: 100 days after the last dose of study therapy ]

Current Secondary Outcome Measures (submitted: May 24, 2017)

• Maximum observed plasma concentration (Cmax) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Time of maximum observed plasma concentration (Tmax) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Trough observed plasma concentration at the end of the dosing interval (Ctrough) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Observed plasma concentration at 24 hours (C24) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Apparent terminal phase half-life (T-HALF) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Apparent total body clearance (CLT/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Apparent renal clearance (CLR/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Volume of distribution of terminal phase (Vz/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Apparent volume of distribution at steady state (Vss/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Accumulation index (AI) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Percent urinary recovery (%UR) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by urine concentration
• Percent urinary recovery over 24 hours(%UR24) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by urine concentration
• Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight (single dose in clinical pharmacology substudy only) [MR_AUC(0-T)] of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight (single dose in clinical pharmacology substudy only) [MR_AUC(INF)] of BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by plasma concentration
• Anti-drug antibody (ADA) response to Nivolumab in combination with BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by immunoassay and liquid chromatography- mass spectrometry
• Anti-drug antibody (ADA) response to Ipilimumab in combination with BMS-986205 [ Time Frame: Approximately 3 years ]
  measured by immunoassay and liquid chromatography- mass spectrometry

Original Secondary Outcome Measures (submitted: January 15, 2016)

• Maximum observed plasma concentration (Cmax) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Time of maximum observed plasma concentration (Tmax) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Area under the concentration-time curve from time zero extrapolated to infinite time [AUC(INF)] of BMS-986205 [ Time Frame: Approximately 3 years ]
• Area under the concentration-time curve from time zero to the time of the last quantifiable concentration [AUC(0-T)] of BMS-986205 [ Time Frame: Approximately 3 years ]
• Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of BMS-986205 [ Time Frame: Approximately 3 years ]
• Trough observed plasma concentration at the end of the dosing interval (Ctrough) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Observed plasma concentration at 24 hours (C24) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Apparent terminal phase half-life (T-HALF) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Apparent total body clearance (CLT/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Apparent renal clearance (CLR/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Volume of distribution of terminal phase (Vz/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Apparent volume of distribution at steady state (Vss/F) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Accumulation index (AI) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Percent urinary recovery (%UR) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Percent urinary recovery over 24 hours(%UR24) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Ratio of metabolite Cmax to parent Cmax, corrected for molecular weight (MR_Cmax) of BMS-986205 [ Time Frame: Approximately 3 years ]
• Ratio of metabolite AUC(0-T) to parent AUC(0-T), corrected for molecular weight (single dose in clinical pharmacology substudy only) [MR_AUC(0-T)] of BMS-986205 [ Time Frame: Approximately 3 years ]
• Ratio of metabolite AUC(TAU) to parent AUC(TAU), corrected for molecular weight [MR_AUC(TAU)] of BMS-986205 [ Time Frame: Approximately 3 years ]
• Ratio of metabolite AUC(INF) to parent AUC(INF), corrected for molecular weight (single dose in clinical pharmacology substudy only) [MR_AUC(INF)] of BMS-986205 [ Time Frame: Approximately 3 years ]
• Anti-drug antibody (ADA) response to Nivolumab in combination with BMS-986205 [ Time Frame: Approximately 3 years ]
• Objective response rate (ORR) [ Time Frame: Approximately 3 years ]
• Progression free survival rate (PFSR) [ Time Frame: Approximately 3 years ]
• Duration of response(DOR) [ Time Frame: Approximately 3 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

• Drug: BMS-986205
• Drug: Nivolumab
  Other Names:

  • BMS-936558
  • ANTI-PD1
• Drug: Ipilimumab
  Other Names:

  • BMS-734016
  • ANTI-CTLA-4

Study Arms

• Experimental: Combination Therapy (Dose Escalation)
  BMS 986205 + Nivolumab specified dose at specified intervals.
  Interventions:

  • Drug: BMS-986205
  • Drug: Nivolumab
• Experimental: Combination Therapy (Dose Expansion)
  BMS 986205 + Nivolumab specified dose at specified intervals.
  Interventions:

  • Drug: BMS-986205
  • Drug: Nivolumab
• Experimental: Combination Therapy 2 (Dose Expansion)
  BMS 986205 + both Nivolumab and ipilimumab specified dose at specified intervals
  Interventions:

  • Drug: BMS-986205
  • Drug: Nivolumab
  • Drug: Ipilimumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 13, 2021): 630
• Original Estimated Enrollment (submitted: January 15, 2016): 252
• Estimated Study Completion Date: October 25, 2021
• Estimated Primary Completion Date: October 24, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 100 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Canada, Finland, France, Germany, Italy, Norway, Poland, Spain, Sweden, United States

Administrative Information

• NCT Number: NCT02658890
• Other Study ID Numbers: CA017-003; 2015-004914-79 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Bristol-Myers Squibb
• Study Sponsor: Bristol-Myers Squibb
• Collaborators: Not Provided

Investigators

• Study Director: Bristol-Myers Squibb; Bristol-Myers Squibb

• PRS Account: Bristol-Myers Squibb
• Verification Date: October 2021