The purpose of this study is to determine the safety, tolerability, pharmacokinetics, immunogenicity, antitumor activity and pharmacodynamics of BMS-986012 alone and in combination with nivolumab in patients with relapsed/refractory SCLC.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
106
Local Institution - 0004
New York, New York, United States
Local Institution - 0001
Durham, North Carolina, United States
Local Institution - 0021
Number of Participants With Adverse Events (AEs)
Number of participants with any grade adverse events (AEs). An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: From first dose to 100 days post last dose (Up to 64 months)
Number of Participants With Serious Adverse Events (SAEs)
Number of participants with any grade serious adverse events (SAEs). A Serious Adverse Event (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 * is an important medical event Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: From first dose to 100 days post last dose (Up to 64 months)
Number of Participants With Adverse Events (AEs) Leading to Discontinuation
Number of participants with any grade adverse events (AEs) leading to discontinuation. An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. Toxicities will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
Time frame: From first dose to 100 days post last dose (Up to 64 months)
Number of Participants Who Died
Number of participants who died due to any cause.
Time frame: From first dose to 100 days post last dose (Up to 64 months)
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Winston-Salem, North Carolina, United States
Local Institution - 0020
St Leonards, New South Wales, Australia
Local Institution - 0011
Brisbane, Queensland, Australia
Local Institution - 0002
Clayton, Victoria, Australia
Local Institution - 0015
Ghent, Belgium
Local Institution - 0012
Liège, Belgium
Local Institution - 0003
Edmonton, Alberta, Canada
Local Institution - 0017
Halifax, Nova Scotia, Canada
...and 6 more locations
Number of Participants With Abnormal Hepatic Test
Number of participants with laboratory abnormalities in specific hepatic tests. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 5xULN, \> 3xULN, and \> 2xULN * Any of ALT, AST, Total Bilirubin or ALP \> 8xULN * Total bilirubin \> 3xULN ALT = Alanine Aminotransferase; AST = Aspartate Aminotransferase; ULN = Upper Limit of Normal
Time frame: From first dose to 100 days post last dose (Up to 64 months)
BMS-986012 Maximum Observed Serum Concentration (Cmax)
BMS-986012 maximum observed serum concentration (Cmax).
Time frame: Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
BMS-986012 Time of Maximum Observed Serum Concentration (Tmax)
BMS-986012 time of maximum observed serum concentration (Tmax).
Time frame: Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T))
BMS-986012 area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC (0-T)).
Time frame: Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU)
BMS-986012 area under the serum concentration-time curve in one dosing interval AUC (TAU).
Time frame: Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau)
BMS-986012 observed serum concentration at the end of a dosing interval (Ctau).
Time frame: Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
BMS-986012 Total Body Clearance (CLT)
BMS-986012 total body clearance (CLT).
Time frame: Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
BMS-986012 Trough Observed Serum Concentration (Ctrough)
BMS-986012 trough observed serum concentration (Ctrough).
Time frame: Cycle 2 day 1, cycle 3 day 1, cycle 4 day 1, cycle 7 day 1, cycle 11 day 1. cycle 15 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose)
BMS-986012 Average Concentration Over a Dosing Interval (Css-avg)
BMS-986012 Average concentration over a dosing interval (\[AUC(TAU)/tau\] (Css-avg).
Time frame: Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Accumulation Index (AI_AUC)
BMS-986012 accumulation index. Ratio of an exposure measure at steady state to that after the first dose.
Time frame: Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Cmax Accumulation Index (AI_Cmax)
BMS-986012 Cmax accumulation index (AI\_Cmax). Ratio of an exposure measure at steady state to that after the first dose.
Time frame: Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Ctau Accumulation Index (AI_Ctau)
BMS-986012 Ctau accumulation index (AI\_Ctau). Ratio of an exposure measure at steady state to that after the first dose.
Time frame: Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
BMS-986012 Effective Elimination (T-HALFeff)
BMS-986012 effective elimination (T-HALFeff) that explains the degree of accumulation observed for a specific exposure measure.
Time frame: Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose)
Best Overall Response (BOR)
BOR defined as the best response designation over the study as a whole. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions; Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
Time frame: From first dose to the last tumor assessment prior to subsequent therapy (Up to 97 months)
Objective Response Rate (ORR)
ORR is defined as the percent of participants whose BOR is either CR or PR. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR) = At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
Time frame: From first dose date to the date of first documented disease progression (Up to 97 months)
Duration of Response (DoR)
DoR is defined as the time from first response (CR or PR) to the date of the first documented tumor progression as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Participants who remain alive and have not progressed will be censored on the date of their last tumor assessment. Complete Response (CR) = Disappearance of all target lesions; Partial Response (PR )= At least a 30% decrease in the sum of diameters of target lesions; Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm Median DOR will only be evaluated provided there are enough responding participants to warrant inclusion.
Time frame: From the date of first dose to the date of the first documented tumor progression or death due to any cause, whichever occurs first (Up to 97 months)
Progression Free Survival (PFS)
PFS is defined as the time from the date of first dose of study medication to the date of the first objective documentation of tumor progression or death due to any cause, if death occurred within 100 days after last BMS-986012 dose. Progressive Disease (PD) = At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
Time frame: From first dose to the date of first documented disease progression or death due to any cause, if death occurred within 100 days after last BMS-986012 dose (Up to 97 months)
Progression Free Survival Rate (PFSR)
PFSR is defined as the percent of participants who remain progression free and surviving at "t" weeks (t= 12, 24, 36, 48, 60, 72). Progressive Disease (PD)=At least a 20% increase in the sum of diameters of target lesions and the sum must demonstrate an absolute increase of at least 5 mm
Time frame: Weeks 12, 24, 36, 48, 60, 72
Number of Participants With Anti-BMS-986012 Antibodies (ADA)
Number of participants with anti-BMS-986012 antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is a participant with baseline ADA positive sample (Day 1 predose). ADA-positive participant is a participant with at least one ADA positive sample relative to baseline at any time after initiation of treatment during the defined observation time period. ADA negative participant is a participant with no ADA positive sample after the initiation of treatment.
Time frame: From first dose to 100 days following the last BMS-986012 dose (Up to 64 months)