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An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread

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ClinicalTrials.gov Identifier: NCT02737475
Recruitment Status : Recruiting
First Posted : April 14, 2016
Last Update Posted : October 8, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Tracking Information
First Submitted Date  ICMJE April 8, 2016
First Posted Date  ICMJE April 14, 2016
Last Update Posted Date October 8, 2020
Actual Study Start Date  ICMJE June 16, 2016
Estimated Primary Completion Date July 11, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 23, 2020)
  • Incidence of AEs (adverse events) [ Time Frame: Approximately 4 years. ]
  • Incidence of SAEs (serious adverse events) [ Time Frame: Approximately 4 years. ]
  • Incidence of AEs leading to discontinuation [ Time Frame: Approximately 4 years. ]
  • Incidence of deaths [ Time Frame: Approximately 4 years. ]
  • Incidence of clinical laboratory test abnormalities - Hematology [ Time Frame: Approximately 4 years. ]
  • Incidence of clinical laboratory test abnormalities - Chemistry [ Time Frame: Approximately 4 years. ]
  • Incidence of clinical laboratory test abnormalities - Urinalysis [ Time Frame: Approximately 4 years. ]
  • Incidence of clinical laboratory test abnormalities - Serology [ Time Frame: Approximately 4 years. ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 8, 2016)		 Incidence of AE's (adverse events) and SAE's (serious adverse events), AE's leading to discontinuation, deaths and clinical laboratory test abnormalities [ Time Frame: Approximately 4 years. ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2020)
  • Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
  • Cmax (maximum observed serum concentration) for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Tmax (time of maximum observed concentration) for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • AUC(0-t) (area under the concentration-time curve from time zero to the time) for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • AUC(TAU) (area under the concentration-time curve in 1 dosing interval) for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Ctau (the observed concentration at the end of a dosing interval) for BMS- 986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • CLT (total body clearance) for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Css-avg [average concentration over a dosing interval (AUC(TAU)/tau)] for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • AI [ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC(TAU), Cmax and Ctau)] for BMS- 986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • T-HALFeff [effective elimination half-life to explain degree of accumulation for a specific exposure measure (exposure measure includes AUC(TAU), Cmax and Ctau)] for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Ctrough [trough observed plasma concentrations (this includes pre-dose concentrations (C0) and Ctau)] for BMS-986178 alone and in combination with nivolumab and/or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Immunogenicity assessed by number of participants with positive anti-drug antibodies (ADA) to BMS-986178 [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Immunogenicity assessed by number of participants with positive ADA to nivolumab [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Immunogenicity assessed by number of participants with positive ADA to ipilimumab [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Number of participants showing a change in one of the pharmacodynamic biomarkers of BMS-986178 dosed in combination with nivo or nivo alone (Part 8) and sustained T cell expansion with DPV-001 in combination with nivo with or without BMS-986178 (Part 9) [ Time Frame: Up to 2 years ]
    nivo (nivolumab)
Original Secondary Outcome Measures  ICMJE
 (submitted: April 8, 2016)
  • Cmax (maximum observed serum concentration) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Tmax (time of maximum observed concentration) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • AUC(0-t) (area under the concentration-time curve from time zero to the time) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • AUC(TAU) (area under the concentration-time curve in 1 dosing interval) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Ctau (the observed concentration at the end of a dosing interval) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • CLT (total body clearance) for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Css-avg [average concentration over a dosing interval (AUC(TAU)/tau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • AI [ratio of an exposure measure at steady state to that after the first dose (exposure measure includes AUC(TAU), Cmax and Ctau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • T-HALFeff [effective elimination half-life to explain degree of accumulation for a specific exposure measure (exposure measure includes AUC(TAU), Cmax and Ctau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Ctrough [trough observed plasma concentrations (this includes pre-dose concentrations (C0) and Ctau)] for BMS-986178 alone and in combination with nivolumab or ipilimumab, if data permits [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Immunoassay of anti-nivolumab antibody in combination with anti-BMS- 986178 antibody [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Immunoassay of anti-ipilimumab antibody in combination with anti-BMS-986178 antibody [ Time Frame: Approximately 100 days after the final study drug administration (end of treatment) ]
  • Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
  • Progression Free Survival Rate (PFSR) [ Time Frame: Approximately 2 years ]
  • Immunoassay of anti-BMS-986178 antibody alone [ Time Frame: Approximately 100 days after 6 months of treatment ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Investigational Immuno-Therapy Study of Experimental Medication BMS-986178 by Itself or in Combination With Nivolumab and/or Ipilimumab in Participants With Solid Cancers That Are Advanced or Have Spread
Official Title  ICMJE A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination With Nivolumab and/or Ipilimumab in Subjects With Advanced Solid Tumors
Brief Summary The purpose of the study is to determine the safety and tumor-shrinking ability of experimental medication BMS-986178, when given by itself or in combination with Nivolumab and/or Ipilimumab, in participants with solid cancers that are advanced or have spread.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Cancer
Intervention  ICMJE
  • Drug: BMS-986178
    Specified dose on specified days
  • Drug: Nivolumab
    Specified dose on specified days
    Other Names:
    • BMS-936558
    • Opdivo
  • Drug: Ipilimumab
    Specified dose on specified days
    Other Names:
    • BMS-734016
    • Yervoy
  • Biological: Tetanus vaccine
    Specified dose on specified days
  • Biological: DPV-001 vaccine
    DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days
  • Drug: Cyclophosphamide
    Specified dose on specified days
Study Arms  ICMJE
  • Experimental: Part 1: Dose Escalation
    • BMS-986178 at specified doses at specified intervals
    • Enrollment is closed for this arm
    Intervention: Drug: BMS-986178
  • Experimental: Part 2: Dose Escalation and Expansion
    • BMS-986178 in combination with Nivolumab at specified doses at specified intervals
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Nivolumab
  • Experimental: Part 3: Dose Escalation and Expansion
    • BMS-986178 in combination with Ipilimumab at specified doses at specified intervals
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Ipilimumab
  • Experimental: Part 4: Dose Schedule and Exploration
    • BMS-986178/Nivolumab at specified doses at specified intervals
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Nivolumab
  • Experimental: Part 5: Dose Schedule and Exploration
    • BMS-986178/Ipilimumab at specified doses at specified intervals
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Ipilimumab
  • Experimental: Part 6: Dose Safety and Expansion
    • BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Nivolumab
    • Drug: Ipilimumab
  • Experimental: Part 7: Dose Safety and Expansion
    • BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Nivolumab
    • Drug: Ipilimumab
  • Experimental: Part 8: Dose Exploration
    • BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
    • Enrollment is closed for this arm
    Interventions:
    • Drug: BMS-986178
    • Drug: Nivolumab
    • Biological: Tetanus vaccine
  • Experimental: Part 9: Dose Exploration
    • BMS-986178/Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 1) at specified doses at specified intervals OR Nivolumab/DPV-001 vaccine/cyclophosphamide (cohort 2) at specified doses at specified intervals
    • Enrollment is open for this arm [Tumor type triple negative breast cancer (TNBC)]
    Interventions:
    • Drug: BMS-986178
    • Drug: Nivolumab
    • Biological: DPV-001 vaccine
    • Drug: Cyclophosphamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 23, 2020)		 207
Original Estimated Enrollment  ICMJE
 (submitted: April 8, 2016)		 212
Estimated Study Completion Date  ICMJE October 14, 2024
Estimated Primary Completion Date July 11, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Inclusion Criteria:

For Part 9 (only arm open for enrollment):

  • Stage IV metastatic or unresectable triple negative breast cancer (TNBC) with zero or one prior systemic therapies in the advanced metastatic setting
  • Participants with < 12 months from receipt of last curative-intent chemotherapy are allowed; curative chemotherapy will be considered first-line therapy
  • Prior receipt of chemotherapy in the (neo)adjuvant setting is acceptable, as long as completed greater than 6 months from start of treatment
  • Tumor biopsy samples (mandatory pre- and on-treatment biopsies) are required for all participants enrolled
  • Must have histologic or cytologic confirmation of a malignancy that is advanced (metastatic, recurrent, refractory, and/or unresectable) with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
  • Men and women must agree to follow specific methods of contraception, if applicable

Exclusion Criteria:

  • Must be immunotherapy treatment naïve, including no prior therapy with T cell immune checkpoint blocker (anti-PDL1, anti-PD1). Prior receipt of intralymphatic cytokine therapy (IRX-2) is acceptable (Part 9 only)
  • Other active malignancy requiring concurrent intervention
  • Prior therapy with any agent specifically targeting T-cell co-stimulation pathways such as anti-OX40 antibody, anti-CD137, anti- glucocorticoid-induced TNFR-related gene (anti-GITR) antibody, and anti-CD27
  • Known or underlying medical or psychiatric condition and/or social reason that, in the opinion of the investigator or Sponsor, could make the administration of study drug hazardous to the participant or could adversely affect the ability of the participant to comply with or tolerate the study

Other protocol-defined inclusion/exclusion criteria apply
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.
Listed Location Countries  ICMJE Canada,   France,   Israel,   Italy,   Netherlands,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02737475
Other Study ID Numbers  ICMJE CA012-004
2015-004816-39 ( 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  ICMJE Not Provided
Responsible Party Bristol-Myers Squibb
Study Sponsor  ICMJE Bristol-Myers Squibb
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
PRS Account Bristol-Myers Squibb
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP