A Phase 1/2a Study of BMS-986178 Administered Alone or in Combination With Nivolumab and/or Ipilimumab in Subjects With Advanced Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Enrollment
- 166
- Locations
- 17
- Primary Endpoint
- The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Part 6: Dose Safety and Expansion
- BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 1: Dose Escalation
- BMS-986178 at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 2: Dose Escalation and Expansion
- BMS-986178 in combination with Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 2: Dose Escalation and Expansion
- BMS-986178 in combination with Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Nivolumab (Drug)
Part 6: Dose Safety and Expansion
- BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Nivolumab (Drug)
Part 3: Dose Escalation and Expansion
- BMS-986178 in combination with Ipilimumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 3: Dose Escalation and Expansion
- BMS-986178 in combination with Ipilimumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Ipilimumab (Drug)
Part 4: Dose Schedule and Exploration
- BMS-986178/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 4: Dose Schedule and Exploration
- BMS-986178/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Nivolumab (Drug)
Part 5: Dose Schedule and Exploration
- BMS-986178/Ipilimumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 5: Dose Schedule and Exploration
- BMS-986178/Ipilimumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Ipilimumab (Drug)
Part 6: Dose Safety and Expansion
- BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Ipilimumab (Drug)
Part 7: Dose Safety and Expansion
- BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 7: Dose Safety and Expansion
- BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Nivolumab (Drug)
Part 7: Dose Safety and Expansion
- BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals
- Enrollment is closed for this arm
Intervention: Ipilimumab (Drug)
Part 8: Dose Exploration
- BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
- Enrollment is closed for this arm
Intervention: BMS-986178 (Drug)
Part 8: Dose Exploration
- BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
- Enrollment is closed for this arm
Intervention: Nivolumab (Drug)
Part 8: Dose Exploration
- BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval
- Enrollment is closed for this arm
Intervention: Tetanus vaccine (Biological)
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)]
Intervention: BMS-986178 (Drug)
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)]
Intervention: Nivolumab (Drug)
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)]
Intervention: DPV-001 vaccine (Biological)
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)]
Intervention: Cyclophosphamide (Drug)
Outcomes
Primary Outcomes
The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
Time Frame: From first dose to 28 days after first dose
The number of participants experiencing dose-limiting toxicities (DLTs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. DLTs are defined based on the incidence, severity, and duration of adverse events (AEs) for which no clear alternative cause is identified. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Adverse Events (AEs)
Time Frame: From first dose to 100 days after last dose (up to approximately 2.5 years)
The number of participants experiencing adverse events (AEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
The Number of Participants Experiencing Serious Adverse Events (SAEs)
Time Frame: From first dose to 100 days after last dose (up to approximately 2.5 years)
The number of participants experiencing serious adverse events (SAEs) to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. A SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.
The Number of Participants Experiencing Adverse Events (AEs) Leading to Discontinuation
Time Frame: From first dose to 100 days after last dose (up to approximately 2.5 years)
The number of participants experiencing adverse events (AEs) leading to discontinuation of study drug to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment.
The Number of Participant Deaths
Time Frame: From first dose to study completion (up to approximately 4 years 5 months)
The number of deaths in each arm to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors.
The Number of Participants With Clinical Laboratory Test Abnormalities (Hematology)
Time Frame: From baseline to 100 days after last dose (up to approximately 2.5 years)
The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time
The Number of Participants With Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION)
Time Frame: From baseline to 100 days after last dose (up to approximately 2.5 years)
The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time
The Number of Participants With Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING )
Time Frame: From baseline to 100 days after last dose (up to approximately 2.5 years)
The number of participants with clinical laboratory test abnormalities to assess the overall safety and tolerability of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab in participants with advanced solid tumors. Results will be categorized according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life Threatening Grade 5 = Death Related to AE Baseline is defined as the last non-missing measurement prior to the first dosing date and time
Secondary Outcomes
- Objective Response Rate (ORR)(From baseline up to approximately 2.5 years)
- Duration of Response (DOR)(From baseline up to approximately 2.5 years)
- AUC(TAU): Area Under the Serum Concentration-time Curve in 1 Dosing Interval(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Ctau)(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- Progression Free Survival (PFS) Rate at 24 Weeks(24 weeks after first dose)
- Cmax: Maximum Observed Serum Concentration(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- Tmax: Time of Maximum Observed Serum Concentration(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- AUC(0-t): Area Under the Serum Concentration-time Curve From Time 0 to Time t(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- Ctau: Observed Serum Concentration at the End of a Dosing Interval When Intensive Samples Are Collected(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- CLT: Total Body Clearance(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (Cmax)(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- T-HALFeff: Effective Elimination Half-life That Explains the Degree of Accumulation Observed for a Specific Exposure Measure (Exposure Measure Includes AUC(TAU), Cmax)(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- Ctrough: Trough Observed Plasma Concentration(Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose))
- Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178(Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose))
- The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8(Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose))
- Tumor Pharmacodynamics of BMS-986178 in Combination With Nivolumab or Nivolumab Monotherapy in Part 8(Screening, cycle 1-2 timepoints can include (Pre-dose, 336, 1848 hours post dose))
- Css-avg: Average Concentration Over a Dosing Interval (AUC(TAU)/Tau)(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- AI: Accumulation Index. Ratio of an Exposure Measure at Steady State (AUC)(Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose))
- Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab(Cycle 1-6 timepoints can include (Pre-dose, 336, 696 hours post dose))
- The Number of Participants With Sustained T Cell Expansion With DPV-001 in Combination With Nivolumab or Nivolumab Monotherapy in Part 9(Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose))
- Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab.(Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose))