Primary Outcome Measures
- Safety is measured by incidence of adverse events (AEs) at its worst grade, serious adverse events (SAEs) at its worst grade, adverse events leading to discontinuations, deaths, frequency of laboratory test toxicity grade shifting from baseline [ Time Frame: Approximately 5 years ]
Secondary Outcome Measures
- Maximum observed serum or plasma concentration (Cmax) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Time of maximum observed serum or plasma concentration (Tmax) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Concentration at the end of a dosing interval (Ctau) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Trough observed serum or plasma concentration (this includes pre-dose concentrations and Ctau concentrations) (Ctrough) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Area under the concentration-time curve from time 0 to time t (AUC(0-t)) of BMS-986148 (t= t last) [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Area under the concentration-time curve in one dosing interval (AUC(TAU)) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Terminal serum or plasma half-life (T-Half) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Total body clearance calculated as Dose divided by AUC(TAU) (CLT) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Volume of distribution at steady-state (Vss) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Volume of distribution of terminal phase (Vz) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Accumulation index; ratio of Cmax at steady-state to Cmax after the first dose (AI_Cmax) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Accumulation index; ratio of Ctau at steady-state to Ctau after the first dose (AI_Ctau) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Average concentration over a dosing interval calculated by dividing AUC(TAU) by tau (Cavg) of BMS-986148 [ Time Frame: Day 1 through day 21 and day 66 through day 87 ]
- Best overall response (BOR) of BMS-986148 [ Time Frame: Approximately 5 years ]. Best overall response (BOR): defined as the best response designation over the study as a whole, recorded between the dates of first dose until the last tumor assessment prior to subsequent therapy
- Objective Response rate (ORR) [ Time Frame: Approximately 5 years ]. Objective Response Rate (ORR): defined as the total number of patients whose best overall response (BOR) is either a Complete Response (CR) or Partical Response (PR) divided by the total number of patients in the population of interest
- Duration of response [ Time Frame: Approximately 5 years ]. Duration of Response: defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first
- Progression free survival [ Time Frame: Approximately 5 years ].Duration of Response: defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first
- Progression free survival rate [ Time Frame: Approximately 5 years ]. Progression Free Survival Rate (PFSR) at week ‘t’: defined as the proportion of patients who remain progression free and surviving at ‘t’ weeks (t=12, 24, 36, etc)
- Overall survival [ Time Frame: Approximately 5 years ]. Overall Survival (OS): defined as the time between the date of first dose of study medication and the date of death
- Overall survival rate [ Time Frame: Approximately 5 years ]. Overall Survival Rate (OSR) at month ‘t’: defined as the probability of patients surviving at ‘t’ months (eg, t=6, 12, 24 months, etc)
- Changes in QTcF of BMS-986148 [ Time Frame: Day 1 through day 7 and day 66 through day 73 ]
- Immunogenicity of BMS-986148 [ Time Frame: Day 1 through day 100 ].Immunogenicity as measured by positive Anti-drug antibody (ADA)
Eligibility
- Inclusion Criteria
- Must have pancreatic, ovarian, gastric, non-small cell cancer or mesothelioma. For dose expansion, must have tumor that is positive for mesothelin
- Expected to have life expectancy of at least 3 months
- Men and women 18 years old or older (or local age of majority)
- Must have measurable tumor per Response Evaluation Criteria In Solid Tumors (RECIST) or modified RECIST for malignant pleural mesothelioma
- ECOG of 0 to 1
- Exclusion Criteria
- Cancer metastases in the brain
- Moderate eye disorders
- Active infection or past hepatitis B or C infection
- Major surgery less than 1 month before the start of the study
- Uncontrolled heart disease
- Impaired liver or bone marrow function
- History of allergy to mesothelin-directed antibodies, tubulysin, monoclonal antibodies, nivolumab or related compounds
