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
- Conditions
- Advanced Cancer
- Interventions
- Biological: Tetanus vaccineBiological: DPV-001 vaccine
- Registration Number
- NCT02737475
- Lead Sponsor
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 166
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 9: Dose Exploration BMS-986178 * 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 \[Tumor type triple negative breast cancer (TNBC)\] Part 2: Dose Escalation and Expansion BMS-986178 * BMS-986178 in combination with Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 3: Dose Escalation and Expansion BMS-986178 * BMS-986178 in combination with Ipilimumab at specified doses at specified intervals * Enrollment is closed for this arm Part 3: Dose Escalation and Expansion Ipilimumab * BMS-986178 in combination with Ipilimumab at specified doses at specified intervals * Enrollment is closed for this arm Part 2: Dose Escalation and Expansion Nivolumab * BMS-986178 in combination with Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 4: Dose Schedule and Exploration BMS-986178 * BMS-986178/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 5: Dose Schedule and Exploration BMS-986178 * BMS-986178/Ipilimumab at specified doses at specified intervals * Enrollment is closed for this arm Part 6: Dose Safety and Expansion BMS-986178 * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 7: Dose Safety and Expansion BMS-986178 * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 4: Dose Schedule and Exploration Nivolumab * BMS-986178/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 1: Dose Escalation BMS-986178 * BMS-986178 at specified doses at specified intervals * Enrollment is closed for this arm Part 8: Dose Exploration BMS-986178 * BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval * Enrollment is closed for this arm Part 8: Dose Exploration Tetanus vaccine * BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval * Enrollment is closed for this arm Part 7: Dose Safety and Expansion Ipilimumab * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 9: Dose Exploration DPV-001 vaccine * 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 \[Tumor type triple negative breast cancer (TNBC)\] Part 5: Dose Schedule and Exploration Ipilimumab * BMS-986178/Ipilimumab at specified doses at specified intervals * Enrollment is closed for this arm Part 6: Dose Safety and Expansion Nivolumab * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 6: Dose Safety and Expansion Ipilimumab * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 7: Dose Safety and Expansion Nivolumab * BMS-986178/Ipilimumab/Nivolumab at specified doses at specified intervals * Enrollment is closed for this arm Part 8: Dose Exploration Nivolumab * BMS-986178/Nivolumab with tetanus vaccine at specified doses and interval * Enrollment is closed for this arm Part 9: Dose Exploration Nivolumab * 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 \[Tumor type triple negative breast cancer (TNBC)\] Part 9: Dose Exploration Cyclophosphamide * 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 \[Tumor type triple negative breast cancer (TNBC)\]
- Primary Outcome Measures
Name Time Method The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) 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) 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) 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 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 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) 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 timeThe Number of Participants With Clinical Laboratory Test Abnormalities (LIVER AND KIDNEY FUNCTION) 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 timeThe Number of Participants With Clinical Laboratory Test Abnormalities (OTHER CHEMISTRY TESTING ) 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 Outcome Measures
Name Time Method Objective Response Rate (ORR) From baseline up to approximately 2.5 years The total number of participants whose best overall response (BOR) is either a complete response (CR) or partial response (PR) based on assessment of tumor response using RECIST v1.1.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions:
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Overall Response (OR) = CR + PR Baseline is defined as the last non-missing measurement prior to the first dosing date and time.Duration of Response (DOR) From baseline up to approximately 2.5 years The time between the date of first response and the subsequent date of disease progression or death (death after re-treatment will not be considered), whichever occurs first in participants with a best overall response (BOR) of complete response (CR) or partial response (PR).
Best overall response (BOR) is assessed per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions:
Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions.
Baseline is defined as the last non-missing measurement prior to the first dosing date and time.
Due to high percentage of censored response, median estimate may be misleadingAUC(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) The area under the serum concentration-time curve in 1 dosing interval was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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) The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.Progression Free Survival (PFS) Rate at 24 Weeks 24 weeks after first dose The percentage of treated participants remaining progression free and surviving at 24 weeks since the first dosing date.
Cmax: Maximum Observed Serum Concentration Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) The maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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) The time of maximum observed serum concentration was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab
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) The area under the serum concentration-time curve from time 0 to time t was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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) The observed serum concentration at the end of a dosing interval when intensive samples are collected was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.CLT: Total Body Clearance Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose) The total body clearance was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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) The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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) The effective elimination half-life that explains the degree of accumulation observed for a specific exposure measure was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab
Ctrough: Trough Observed Plasma Concentration Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose) Trough observed plasma concentration (this includes predose concentrations and Ctau concentrations) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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 with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of BMS-986178 administered alone or in combination with nivolumab and/or ipilimumab. ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (\>=) than baseline positive titer) at any time after initiation of treatment.
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) The Number of Participants Showing a Change in Soluble OX40 and Peripheral OX40 Receptor Occupancy Pharmacodynamic Biomarkers in Part 8. A threshold of 80% receptor occupancy following treatment was applied.
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) Tumor pharmacodynamics of BMS-986178 in combination with nivolumab or nivolumab monotherapy
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) The average concentration over a dosing interval (AUC(TAU)/tau) was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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) The ratio of an exposure measure at steady state to that after the first dose was measured after dosing to assess the pharmacokinetics of BMS-986178 administered alone or in combination with Nivolumab and/or Ipilimumab.
Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.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 positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Nivolumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (\>=) than baseline positive titer) at any time after initiation of treatment.
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) The number of participants with Sustained T Cell Expansion with DPV-001 in Combination with Nivolumab or Nivolumab Monotherapy was assessed to show a change in pharmacodynamics biomarkers
Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab. Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose) The number of participants with positive anti-drug antibodies (ADA) is assessed to characterize the immunogenicity of Ipilimumab administered with BMS-986178 ADA Positive: A participant with at least one ADA-positive sample relative to baseline (ADA negative at baseline or ADA titer to be at least 4-fold or greater (\>=) than baseline positive titer) at any time after initiation of treatment.
Trial Locations
- Locations (17)
John Theurer Cancer Center at Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
IRCCS Istituto Nazionale Tumori Milano
🇮🇹Milano, Italy
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
University Of Colorado
🇺🇸Aurora, Colorado, United States
Columbia University Medical Center (Cumc)
🇺🇸New York, New York, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Local Institution
🇳🇱Utrecht, Netherlands
H. Univ. Vall dHebron
🇪🇸Barcelona, Spain
Istituto Clinico Humanitas
🇮🇹Rozzano, Italy
Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hosp. Univ. Puerta De Hierro
🇪🇸Majadahonda - Madrid, Spain
Clinica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Universitario Virgen De La Victoria
🇪🇸Malaga, Spain
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Oregon Health & Science University
🇺🇸Portland, Oregon, United States