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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
166
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
University Of Colorado
Aurora, Colorado, United States
The Number of Participants Experiencing Dose-Limiting Toxicities (DLTs)
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.
Time frame: From first dose to 28 days after first dose
The Number of Participants Experiencing Adverse Events (AEs)
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.
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)
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.
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
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Specified dose on specified days
DPV-001 (UbiLT3 and UbiLT6): Specified dose on specified days
Specified dose on specified days
Georgetown University Medical Center
Washington D.C., District of Columbia, United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack, New Jersey, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Columbia University Medical Center (Cumc)
New York, New York, United States
Providence Portland Medical Center
Portland, Oregon, United States
Oregon Health & Science University
Portland, Oregon, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
Cross Cancer Institute
Edmonton, Alberta, Canada
Local Institution
Ottawa, Ontario, Canada
...and 12 more locations
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.
Time frame: From first dose to 100 days after last dose (up to approximately 2.5 years)
The Number of Participant Deaths
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.
Time frame: From first dose to study completion (up to approximately 4 years 5 months)
The Number of Participants With Clinical Laboratory Test Abnormalities (Hematology)
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
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 (LIVER AND KIDNEY FUNCTION)
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
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 (OTHER CHEMISTRY TESTING )
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
Time frame: From baseline to 100 days after last dose (up to approximately 2.5 years)
Objective Response Rate (ORR)
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.
Time frame: From baseline up to approximately 2.5 years
Duration of Response (DOR)
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 misleading
Time frame: From baseline up to approximately 2.5 years
Progression Free Survival (PFS) Rate at 24 Weeks
The percentage of treated participants remaining progression free and surviving at 24 weeks since the first dosing date.
Time frame: 24 weeks after first dose
Cmax: Maximum Observed Serum Concentration
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.
Time frame: 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
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
Time frame: 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
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.
Time frame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
AUC(TAU): Area Under the Serum Concentration-time Curve in 1 Dosing Interval
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.
Time frame: 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
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.
Time frame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
CLT: Total Body Clearance
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.
Time frame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
Css-avg: Average Concentration Over a Dosing Interval (AUC(TAU)/Tau)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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.
Time frame: 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)
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
Time frame: Cycle 1-9 timepoints can include (Pre-dose, 0.30, 4, 24, 72, 168, 336, 696 hours post dose)
Ctrough: Trough Observed Plasma Concentration
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.
Time frame: Cycle 1-17 timepoints can include (Pre-dose, 336, 504, 672 hours post dose)
Frequency of Positive Anti-Drug Antibodies (ADA) to BMS-986178
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.
Time frame: Cycle 1-6 timepoints can include (Pre-dose, 696 hours post dose)
Frequency of Positive Anti-Drug Antibodies (ADA) to Nivolumab
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.
Time frame: Cycle 1-6 timepoints can include (Pre-dose, 336, 696 hours post dose)
Frequency of Positive Anti-Drug Antibodies (ADA) to Ipilimumab.
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.
Time frame: 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
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.
Time frame: 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
Tumor pharmacodynamics of BMS-986178 in combination with nivolumab or nivolumab monotherapy
Time frame: Screening, cycle 1-2 timepoints can include (Pre-dose, 336, 1848 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
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
Time frame: Cycle 1-6 timepoints can include (Pre-dose, 24, 168, 336, 672, 1848 hours post dose)