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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Cancer Drug: BMS-986178 Drug: Nivolumab Drug: Ipilimumab Biological: Tetanus vaccine Biological: DPV-001 vaccine Drug: Cyclophosphamide Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 207 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 16, 2016
Estimated Primary Completion Date : July 11, 2023
Estimated Study Completion Date : October 14, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
  • BMS-986178 at specified doses at specified intervals
  • Enrollment is closed for this arm
 Drug: BMS-986178
Specified dose on specified days
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
 Drug: BMS-986178
Specified dose on specified days

Drug: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
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
 Drug: BMS-986178
Specified dose on specified days

Drug: Ipilimumab
Specified dose on specified days
Other Names:
  • BMS-734016
  • Yervoy
Experimental: Part 4: Dose Schedule and Exploration
  • BMS-986178/Nivolumab at specified doses at specified intervals
  • Enrollment is closed for this arm
 Drug: BMS-986178
Specified dose on specified days

Drug: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo
Experimental: Part 5: Dose Schedule and Exploration
  • BMS-986178/Ipilimumab at specified doses at specified intervals
  • Enrollment is closed for this arm
 Drug: BMS-986178
Specified dose on specified days

Drug: Ipilimumab
Specified dose on specified days
Other Names:
  • BMS-734016
  • Yervoy
Experimental: Part 6: Dose Safety and Expansion
  • BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
  • Enrollment is closed for this arm
 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
Experimental: Part 7: Dose Safety and Expansion
  • BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
  • Enrollment is closed for this arm
 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
Experimental: Part 8: Dose Exploration
  • BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
  • Enrollment is closed for this arm
 Drug: BMS-986178
Specified dose on specified days

Drug: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo

Biological: Tetanus vaccine
Specified dose on specified days
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)]
 Drug: BMS-986178
Specified dose on specified days

Drug: Nivolumab
Specified dose on specified days
Other Names:
  • BMS-936558
  • Opdivo

Biological: DPV-001 vaccine
DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days

Drug: Cyclophosphamide
Specified dose on specified days


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of AEs (adverse events) [ Time Frame: Approximately 4 years. ]
  2. Incidence of SAEs (serious adverse events) [ Time Frame: Approximately 4 years. ]
  3. Incidence of AEs leading to discontinuation [ Time Frame: Approximately 4 years. ]
  4. Incidence of deaths [ Time Frame: Approximately 4 years. ]
  5. Incidence of clinical laboratory test abnormalities - Hematology [ Time Frame: Approximately 4 years. ]
  6. Incidence of clinical laboratory test abnormalities - Chemistry [ Time Frame: Approximately 4 years. ]
  7. Incidence of clinical laboratory test abnormalities - Urinalysis [ Time Frame: Approximately 4 years. ]
  8. Incidence of clinical laboratory test abnormalities - Serology [ Time Frame: Approximately 4 years. ]

Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
  2. 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) ]
  3. 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) ]
  4. 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) ]
  5. 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) ]
  6. 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) ]
  7. 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) ]
  8. 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) ]
  9. 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) ]
  10. 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) ]
  11. 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) ]
  12. 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) ]
  13. 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) ]
  14. 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) ]
  15. 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)


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02737475


Contacts
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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 #.

Locations
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Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
More Information
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Additional Information:

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Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT02737475    
Other Study ID Numbers: CA012-004
2015-004816-39 ( EudraCT Number )
First Posted: April 14, 2016    Key Record Dates
Last Update Posted: October 8, 2020
Last Verified: October 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Cyclophosphamide
Nivolumab
Ipilimumab
Vaccines
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
 Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological