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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

NCT02737475

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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: A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination With Nivolumab and/or Ipilimumab in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CA012-004
  • SECONDARY ID: 2015-004816-39
  • NCT ID: NCT02737475

Conditions

  • Advanced Cancer

Interventions

DrugSynonymsArms
BMS-986178Part 1: Dose Escalation
NivolumabBMS-936558, OpdivoPart 2: Dose Escalation and Expansion
IpilimumabBMS-734016, YervoyPart 3: Dose Escalation and Expansion
Tetanus vaccinePart 8: Dose Exploration
DPV-001 vaccinePart 9: Dose Exploration
CyclophosphamidePart 9: Dose Exploration

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalBMS-986178 at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
Part 2: Dose Escalation and ExpansionExperimentalBMS-986178 in combination with Nivolumab at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
  • Nivolumab
Part 3: Dose Escalation and ExpansionExperimentalBMS-986178 in combination with Ipilimumab at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
  • Ipilimumab
Part 4: Dose Schedule and ExplorationExperimentalBMS-986178/Nivolumab at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
  • Nivolumab
Part 5: Dose Schedule and ExplorationExperimentalBMS-986178/Ipilimumab at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
  • Ipilimumab
Part 6: Dose Safety and ExpansionExperimentalBMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
  • Nivolumab
  • Ipilimumab
Part 7: Dose Safety and ExpansionExperimentalBMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals Enrollment is closed for this arm
  • BMS-986178
  • Nivolumab
  • Ipilimumab
Part 8: Dose ExplorationExperimentalBMS-986178/Nivolumab with tetanus vaccine at specified doses and interval Enrollment is closed for this arm
  • BMS-986178
  • Nivolumab
  • Tetanus vaccine
Part 9: Dose ExplorationExperimentalBMS-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)]
  • BMS-986178
  • Nivolumab
  • DPV-001 vaccine
  • Cyclophosphamide

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of AEs (adverse events)
Time Frame:Approximately 4 years.
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:Approximately 2 years
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:nivo (nivolumab)

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Bristol-Myers Squibb

Last Updated

October 6, 2020