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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 Patients With Solid Cancers That Are Advanced or Have Spread

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ClinicalTrials.gov Identifier: NCT02737475
Recruitment Status : Active, not recruiting
First Posted : April 14, 2016
Last Update Posted : June 17, 2020
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 170 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 : May 13, 2021
Estimated Study Completion Date : August 15, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
BMS-986178 at specified doses at specified intervals
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
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
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
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
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
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
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
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
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




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 - Blood [ Time Frame: Approximately 4 years. ]
  6. Incidence of clinical laboratory test abnormalities - Blood Serum [ 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 combo with nivolumab or nivolumab alone (Part 8) and sustained T cell expansion with DPV-001 in combo with nivolumab or nivolumab alone (Part 9) [ Time Frame: Up to 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  • Participants must have at least 1 standard treatment regimen in the advanced, recurrent or metastatic setting
  • ECOG (Eastern Cooperative Oncology Group) 0-1
  • Men and women 18 years old or older
  • At least one measurable lesion at baseline by CT (computed tomography) or MRI (magnetic resonance imaging) as per RECIST (Response Evaluation Criteria In Solid Tumors) v1.1
  • All participants must have a fresh tumor biopsy

Exclusion Criteria:

  • Known central nervous system metastases or central nervous system as the only source of disease
  • Concomitant malignancies
  • Active known or suspected autoimmune disease
  • Uncontrolled or significant cardiovascular disease
  • Major surgery less than 4 weeks before the start of the study
  • Participants with known allergies to egg products, neomycin, or tetanus toxoid
  • Prior adverse reaction to tetanus toxoid-containing vaccines

Other protocol defined inclusion/exclusion criteria could apply


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


Locations
Show Show 22 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
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Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
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: June 17, 2020
Last Verified: June 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