The purpose of this study is to determine the safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity and pharmacodynamics of BMS-986148 administered alone and in combination with nivolumab in patients with mesothelioma, non-small cell lung cancer, ovarian cancer, pancreatic cancer and gastric cancer.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
126
Moores Cancer Center
La Jolla, California, United States
Duke University Medical Center
Durham, North Carolina, United States
Number of Participants With Adverse Events at Worst CTC Grade
Number of participants with adverse events at worst CTC grade including any grade adverse events (AEs), serious adverse events (SAEs), adverse events leading to discontinuations, and deaths grouped by dose + dose regimen.
Time frame: From first dose to up to 100 days post last dose (Up to 6 months)
Number of Participants With Laboratory Test Toxicity Grade Shifting From Baseline
Number of participants with laboratory test toxicity grade (Grade 0, 1, 2, 3, and 4) in hematology and chemistry shifting from baseline. An increase in baseline indicates a shift of participant to a greater toxicity grade. A decrease in baseline indicates a shift of participant to a lesser toxicity grade. Participants are grouped by dose + dose regimen assessed by NCT CTCAE V 4.03.
Time frame: From first dose to up to 100 days post last dose (Up to 6 months)
Maximum Observed Serum Concentration (Cmax)
Maximum observed serum concentration (Cmax) of BMS-986148 grouped by dose + dose regimen. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
Time frame: PK blood assessed on cycle 1, day 1
Time of Maximum Observed Serum Concentration (Tmax)
Time of maximum observed serum concentration (Tmax) of BMS-986148 grouped by dose + dose regimen.
Time frame: PK blood assessed on cycle 1, day 1
Concentration at the End of a Dosing Interval (Ctau)
Concentration at the end of a dosing interval (Ctau) of BMS-986148 grouped by dose + dose regimen. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
Time frame: PK blood assessed on cycle 1, day 1
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Local Institution - 0013
Liverpool, New South Wales, Australia
Local Institution - 0014
Adelaide, South Australia, Australia
Local Institution - 0004
Clayton, Victoria, Australia
Local Institution - 0015
Nedlands, Western Australia, Australia
Local Institution - 0008
Ghent, Oost-Vlaanderen, Belgium
Local Institution - 0009
Brussels, Belgium
Local Institution - 0002
Edmonton, Alberta, Canada
Local Institution - 0003
Toronto, Ontario, Canada
...and 7 more locations
Trough Observed Serum Concentration (Ctrough)
Trough observed serum concentration (Ctrough) of BMS-986148 grouped by dose + dose regimen. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
Time frame: PK blood assessment include cycle 2-day 1 and cycle 1-day 8
Area Under the Concentration-Time Curve From Time Zero to Time T (AUC(0-t))
Area under the concentration-time curve from time Zero to time T (AUC(0-t)) of BMS-986148 grouped by dose + dose regimen. Note: The geometric CV was not calculated. Arithmetic % CV is reported instead.
Time frame: PK blood assessment include cycle 1-day 1
Area Under the Concentration-Time Curve in One Dosing Interval (AUC[TAU])
Area under the concentration-time curve in one dosing interval (AUC\[TAU\]) of BMS-986148 grouped by dose + dose regimen Note: The geometric CV was not calculated. Arithmetic % CV is reported instead
Time frame: PK blood assessment include cycle 1-day 1
Best Overall Response (BOR)
Best overall response is 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. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Time frame: Up to 58 months
Objective Response Rate (ORR)
Objective response rate is defined as the total percentage of participants whose best overall response (BOR) is either a complete response or partial response divided by the total percentage of participants who are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric). Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \< 10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 58 months
Duration of Response (DoR)
Duration of response is defined as the time between the date of first response and the subsequent date of objectively documented disease progression or death, whichever occurs first. Participants are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).
Time frame: Up to 58 months
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from the first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause. Progression is defined with at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study and the sum must also demonstrate an absolute increase of at least 5 mm. Participants who did not progress nor died will be censored on the date of their last tumor assessment. Participants are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).
Time frame: Up to 58 months
Progression Free Survival Rate (PFSR) at Week t
Progression free survival rate is defined as the proportion of participants who remain progression free and surviving at 't' weeks (t=4-12 months). The proportion will be calculated by the product-limit method (Kaplan-Meier estimate) which takes into account censored data. Participants are grouped by cohorts (Mesothelioma, Pancreatic, Ovarian, Non-smell Cell Lung (NSCL), and Gastric).
Time frame: Total PFS assessed between 4 and 12 months, PFSR at months 4 and 6 to be reported
Changes in QT Corrected by the Fridericia Formula (QTcF) From Baseline, at Selected Times
Changes of participants in QT corrected by the fridericia formula (QTcF) Interval from baseline at \<= 30 msec, \>30 - \<= 60 msec, and \> 60 msec grouped by dose + dose regimen
Time frame: Up to 58 months
Number of Participants With Anti-Drug Antibody (ADA)
Number of participants with anti-drug antibody (ADA) status grouped by dose + dose regimen. Data was not collected for this outcome measure.
Time frame: Up to 58 months