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.
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
Interventions
Drug | Synonyms | Arms |
---|
BMS-986178 | | Part 1: Dose Escalation |
Nivolumab | BMS-936558, Opdivo | Part 2: Dose Escalation and Expansion |
Ipilimumab | BMS-734016, Yervoy | Part 3: Dose Escalation and Expansion |
Tetanus vaccine | | Part 8: Dose Exploration |
DPV-001 vaccine | | Part 9: Dose Exploration |
Cyclophosphamide | | Part 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
Name | Type | Description | Interventions |
---|
Part 1: Dose Escalation | Experimental | BMS-986178 at specified doses at specified intervals
Enrollment is closed for this arm | |
Part 2: Dose Escalation and Expansion | Experimental | BMS-986178 in combination with Nivolumab at specified doses at specified intervals
Enrollment is closed for this arm | |
Part 3: Dose Escalation and Expansion | Experimental | BMS-986178 in combination with Ipilimumab at specified doses at specified intervals
Enrollment is closed for this arm | |
Part 4: Dose Schedule and Exploration | Experimental | BMS-986178/Nivolumab at specified doses at specified intervals
Enrollment is closed for this arm | |
Part 5: Dose Schedule and Exploration | Experimental | BMS-986178/Ipilimumab at specified doses at specified intervals
Enrollment is closed for this arm | |
Part 6: Dose Safety and Expansion | Experimental | BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
Enrollment is closed for this arm | - BMS-986178
- Nivolumab
- Ipilimumab
|
Part 7: Dose Safety and Expansion | Experimental | BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
Enrollment is closed for this arm | - BMS-986178
- Nivolumab
- Ipilimumab
|
Part 8: Dose Exploration | Experimental | BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
Enrollment is closed for this arm | - BMS-986178
- Nivolumab
- Tetanus vaccine
|
Part 9: Dose Exploration | Experimental | 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)] | - 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: | Completed |
Lead Sponsor: | Bristol-Myers Squibb |
Last Updated
August 2, 2021