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 |
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Recruitment Status :
Completed
First Posted : April 14, 2016
Last Update Posted : August 2, 2021
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Sponsor:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Bristol-Myers Squibb
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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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 171 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 17, 2016 |
| Actual Primary Completion Date : | November 2, 2020 |
| Actual Study Completion Date : | November 2, 2020 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
Experimental: Part 1: Dose Escalation
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Drug: BMS-986178
Specified dose on specified days |
Experimental: Part 2: Dose Escalation and Expansion
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Drug: BMS-986178
Specified dose on specified days Drug: Nivolumab Specified dose on specified days
Other Names:
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Experimental: Part 3: Dose Escalation and Expansion
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Drug: BMS-986178
Specified dose on specified days Drug: Ipilimumab Specified dose on specified days
Other Names:
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Experimental: Part 4: Dose Schedule and Exploration
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Drug: BMS-986178
Specified dose on specified days Drug: Nivolumab Specified dose on specified days
Other Names:
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Experimental: Part 5: Dose Schedule and Exploration
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Drug: BMS-986178
Specified dose on specified days Drug: Ipilimumab Specified dose on specified days
Other Names:
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Experimental: Part 6: Dose Safety and Expansion
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Drug: BMS-986178
Specified dose on specified days Drug: Nivolumab Specified dose on specified days
Other Names:
Drug: Ipilimumab Specified dose on specified days
Other Names:
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Experimental: Part 7: Dose Safety and Expansion
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Drug: BMS-986178
Specified dose on specified days Drug: Nivolumab Specified dose on specified days
Other Names:
Drug: Ipilimumab Specified dose on specified days
Other Names:
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Experimental: Part 8: Dose Exploration
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Drug: BMS-986178
Specified dose on specified days Drug: Nivolumab Specified dose on specified days
Other Names:
Biological: Tetanus vaccine Specified dose on specified days |
Experimental: Part 9: Dose Exploration
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Drug: BMS-986178
Specified dose on specified days Drug: Nivolumab Specified dose on specified days
Other Names:
Biological: DPV-001 vaccine DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days Drug: Cyclophosphamide Specified dose on specified days |
Primary Outcome Measures :
- 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. ]
Secondary Outcome Measures :
- 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)
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
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 22 study locations
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
| Study Director: | Bristol-Myers Squibb | Bristol-Myers Squibb |
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| 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: | August 2, 2021 |
| Last Verified: | July 2021 |
| 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 Immune Checkpoint Inhibitors |