Small Cell Lung Cancer
Conditions
Brief summary
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.
Interventions
BIOLOGICALBMS-986012 (anti-fucosyl-GM1)
BIOLOGICALNivolumab
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: * Histological or cytological confirmed small cell lung cancer (SCLC) * Performance Status 0-1 * Adequate organ function * Measurable disease
Exclusion criteria
* Known or suspected brain metastasis * Small cell cancer not lung in origin * Significant or acute medical illness * Uncontrolled or significant cardiac disease * Infection * ≥ Grade 2 peripheral neuropathy * Concomitant malignancies * HIV related disease or known or suspected HIV+ * Hepatitis B or C infection * ECG abnormalities as defined by the protocol * Allergies or hypersensitivities to monoclonal antibodies, BMS-986012 or related compounds, including fucosyl-GM1 vaccine and Nivolumab Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From first dose to 100 days post last dose (Up to 64 months) | 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. |
| Number of Participants With Serious Adverse Events (SAEs) | From first dose to 100 days post last dose (Up to 64 months) | 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. |
| Number of Participants With Adverse Events (AEs) Leading to Discontinuation | From first dose to 100 days post last dose (Up to 64 months) | 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. |
| Number of Participants Who Died | From first dose to 100 days post last dose (Up to 64 months) | Number of participants who died due to any cause. |
| Number of Participants With Abnormal Hepatic Test | From first dose to 100 days post last dose (Up to 64 months) | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMS-986012 Total Body Clearance (CLT) | 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 Trough Observed Serum Concentration (Ctrough) | 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 trough observed serum concentration (Ctrough). |
| BMS-986012 Average Concentration Over a Dosing Interval (Css-avg) | Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) | BMS-986012 Average concentration over a dosing interval (\[AUC(TAU)/tau\] (Css-avg). |
| BMS-986012 Accumulation Index (AI_AUC) | Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) | BMS-986012 accumulation index. Ratio of an exposure measure at steady state to that after the first dose. |
| BMS-986012 Cmax Accumulation Index (AI_Cmax) | Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) | BMS-986012 Cmax accumulation index (AI\_Cmax). Ratio of an exposure measure at steady state to that after the first dose. |
| BMS-986012 Ctau Accumulation Index (AI_Ctau) | Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) | BMS-986012 Ctau accumulation index (AI\_Ctau). Ratio of an exposure measure at steady state to that after the first dose. |
| BMS-986012 Maximum Observed Serum Concentration (Cmax) | Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, 8, 24, 72, 168, 336 hours post dose) | BMS-986012 maximum observed serum concentration (Cmax). |
| Best Overall Response (BOR) | From first dose to the last tumor assessment prior to subsequent therapy (Up to 97 months) | 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 |
| Objective Response Rate (ORR) | From first dose date to the date of first documented disease progression (Up to 97 months) | 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 |
| Duration of Response (DoR) | 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) | 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. |
| Progression Free Survival (PFS) | 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) | 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 |
| Progression Free Survival Rate (PFSR) | Weeks 12, 24, 36, 48, 60, 72 | 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 |
| Number of Participants With Anti-BMS-986012 Antibodies (ADA) | From first dose to 100 days following the last BMS-986012 dose (Up to 64 months) | 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. |
| BMS-986012 Effective Elimination (T-HALFeff) | Cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) | BMS-986012 effective elimination (T-HALFeff) that explains the degree of accumulation observed for a specific exposure measure. |
| BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | Cycle 1 day 1, cycle 3 day 1 (including pre-dose, 1, 2, 4, and 8 hours post dose) | BMS-986012 time of maximum observed serum concentration (Tmax). |
| BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | 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 from time zero to time of last quantifiable concentration (AUC (0-T)). |
| BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | 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 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | 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). |
Countries
Australia, Belgium, Canada, Netherlands, Puerto Rico, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMS 70mg 70 mg IV BMS-986012 every 21 days until protocol-specified discontinuation criteria are met | 7 |
| BMS 160mg 160 mg IV BMS-986012 every 21 days until protocol-specified discontinuation criteria are met | 6 |
| BMS 400mg 400 mg IV BMS-986012 every 21 days until protocol-specified discontinuation criteria are met | 29 |
| BMS 1000mg 1000 mg IV BMS-986012 every 21 days until protocol-specified discontinuation criteria are met | 35 |
| BMS 400mg + Nivo 360mg 400 mg IV BMS-986012 + 360 mg Nivolumab every 21 days until protocol-specified discontinuation criteria are met | 21 |
| BMS 1000mg + Nivo 360mg 1000 mg IV BMS-986012 + 360 mg Nivolumab every 21 days until protocol-specified discontinuation criteria are met | 8 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Administrative reason by sponsor | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Adverse Event unrelated to study drug | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Disease Progression | 7 | 4 | 26 | 31 | 16 | 6 |
| Overall Study | Other reasons | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Participant request to discontinue study treatment | 0 | 0 | 1 | 2 | 1 | 0 |
| Overall Study | Study drug toxicity | 0 | 1 | 1 | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | BMS 70mg | BMS 160mg | BMS 400mg | BMS 1000mg | BMS 400mg + Nivo 360mg | BMS 1000mg + Nivo 360mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 65.1 Years STANDARD_DEVIATION 10.6 | 58.3 Years STANDARD_DEVIATION 8.1 | 64.4 Years STANDARD_DEVIATION 9.2 | 61.7 Years STANDARD_DEVIATION 9.5 | 62.1 Years STANDARD_DEVIATION 9.8 | 61.1 Years STANDARD_DEVIATION 7.3 | 62.5 Years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 6 Participants | 26 Participants | 33 Participants | 20 Participants | 8 Participants | 99 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 3 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 7 Participants | 6 Participants | 27 Participants | 30 Participants | 21 Participants | 8 Participants | 99 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 11 Participants | 12 Participants | 9 Participants | 5 Participants | 45 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 18 Participants | 23 Participants | 12 Participants | 3 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk | EG017 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 4 / 4 | 1 / 2 | 1 / 4 | 3 / 3 | 3 / 4 | 9 / 12 | 9 / 10 | 3 / 3 | 5 / 6 | 11 / 12 | 12 / 14 | 2 / 2 | 6 / 6 | 3 / 4 | 4 / 9 | 3 / 3 | 5 / 5 |
| other Total, other adverse events | 3 / 3 | 4 / 4 | 2 / 2 | 4 / 4 | 3 / 3 | 4 / 4 | 12 / 12 | 10 / 10 | 3 / 3 | 6 / 6 | 12 / 12 | 14 / 14 | 2 / 2 | 6 / 6 | 4 / 4 | 9 / 9 | 3 / 3 | 5 / 5 |
| serious Total, serious adverse events | 3 / 3 | 4 / 4 | 2 / 2 | 2 / 4 | 3 / 3 | 4 / 4 | 8 / 12 | 6 / 10 | 3 / 3 | 2 / 6 | 8 / 12 | 11 / 14 | 1 / 2 | 4 / 6 | 2 / 4 | 4 / 9 | 3 / 3 | 2 / 5 |
Outcome results
Primary
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)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS 70mg | Number of Participants Who Died | 3 Participants |
| BMS 160mg | Number of Participants Who Died | 2 Participants |
| BMS 400mg | Number of Participants Who Died | 10 Participants |
| BMS 1000mg | Number of Participants Who Died | 16 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants Who Died | 2 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants Who Died | 4 Participants |
Primary
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)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS 70mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 3XULN | 0 Participants |
| BMS 70mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 5XULN | 0 Participants |
| BMS 70mg | Number of Participants With Abnormal Hepatic Test | ANY OF ALT, AST, TOTAL BILIRUBIN OR ALP > 8XULN | 0 Participants |
| BMS 70mg | Number of Participants With Abnormal Hepatic Test | TOTAL BILIRUBIN > 3XULN | 1 Participants |
| BMS 70mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 2XULN | 0 Participants |
| BMS 160mg | Number of Participants With Abnormal Hepatic Test | TOTAL BILIRUBIN > 3XULN | 0 Participants |
| BMS 160mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 2XULN | 0 Participants |
| BMS 160mg | Number of Participants With Abnormal Hepatic Test | ANY OF ALT, AST, TOTAL BILIRUBIN OR ALP > 8XULN | 0 Participants |
| BMS 160mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 5XULN | 0 Participants |
| BMS 160mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 3XULN | 0 Participants |
| BMS 400mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 5XULN | 0 Participants |
| BMS 400mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 2XULN | 0 Participants |
| BMS 400mg | Number of Participants With Abnormal Hepatic Test | ANY OF ALT, AST, TOTAL BILIRUBIN OR ALP > 8XULN | 0 Participants |
| BMS 400mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 3XULN | 0 Participants |
| BMS 400mg | Number of Participants With Abnormal Hepatic Test | TOTAL BILIRUBIN > 3XULN | 0 Participants |
| BMS 1000mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 2XULN | 0 Participants |
| BMS 1000mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 5XULN | 1 Participants |
| BMS 1000mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 3XULN | 0 Participants |
| BMS 1000mg | Number of Participants With Abnormal Hepatic Test | ANY OF ALT, AST, TOTAL BILIRUBIN OR ALP > 8XULN | 1 Participants |
| BMS 1000mg | Number of Participants With Abnormal Hepatic Test | TOTAL BILIRUBIN > 3XULN | 0 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ANY OF ALT, AST, TOTAL BILIRUBIN OR ALP > 8XULN | 0 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 2XULN | 0 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | TOTAL BILIRUBIN > 3XULN | 0 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 5XULN | 1 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 3XULN | 0 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 2XULN | 0 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ANY OF ALT, AST, TOTAL BILIRUBIN OR ALP > 8XULN | 1 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 5XULN | 2 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | TOTAL BILIRUBIN > 3XULN | 1 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Abnormal Hepatic Test | ALT OR AST > 3XULN | 0 Participants |
Primary
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)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS 70mg | Number of Participants With Adverse Events (AEs) | 7 Participants |
| BMS 160mg | Number of Participants With Adverse Events (AEs) | 6 Participants |
| BMS 400mg | Number of Participants With Adverse Events (AEs) | 29 Participants |
| BMS 1000mg | Number of Participants With Adverse Events (AEs) | 35 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Adverse Events (AEs) | 21 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Adverse Events (AEs) | 8 Participants |
Primary
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)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS 70mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation | 0 Participants |
| BMS 160mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation | 1 Participants |
| BMS 400mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation | 2 Participants |
| BMS 1000mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation | 5 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation | 3 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Adverse Events (AEs) Leading to Discontinuation | 2 Participants |
Primary
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)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS 70mg | Number of Participants With Serious Adverse Events (SAEs) | 7 Participants |
| BMS 160mg | Number of Participants With Serious Adverse Events (SAEs) | 4 Participants |
| BMS 400mg | Number of Participants With Serious Adverse Events (SAEs) | 21 Participants |
| BMS 1000mg | Number of Participants With Serious Adverse Events (SAEs) | 24 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Serious Adverse Events (SAEs) | 11 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Serious Adverse Events (SAEs) | 5 Participants |
Secondary
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)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS 70mg | Best Overall Response (BOR) | Progressive Disease | 4 Participants |
| BMS 70mg | Best Overall Response (BOR) | Not evaluable | 2 Participants |
| BMS 70mg | Best Overall Response (BOR) | Stable Disease | 0 Participants |
| BMS 70mg | Best Overall Response (BOR) | Complete Response | 1 Participants |
| BMS 70mg | Best Overall Response (BOR) | Partial Response | 0 Participants |
| BMS 160mg | Best Overall Response (BOR) | Complete Response | 0 Participants |
| BMS 160mg | Best Overall Response (BOR) | Partial Response | 0 Participants |
| BMS 160mg | Best Overall Response (BOR) | Progressive Disease | 2 Participants |
| BMS 160mg | Best Overall Response (BOR) | Not evaluable | 2 Participants |
| BMS 160mg | Best Overall Response (BOR) | Stable Disease | 2 Participants |
| BMS 400mg | Best Overall Response (BOR) | Complete Response | 0 Participants |
| BMS 400mg | Best Overall Response (BOR) | Stable Disease | 8 Participants |
| BMS 400mg | Best Overall Response (BOR) | Not evaluable | 2 Participants |
| BMS 400mg | Best Overall Response (BOR) | Partial Response | 1 Participants |
| BMS 400mg | Best Overall Response (BOR) | Progressive Disease | 18 Participants |
| BMS 1000mg | Best Overall Response (BOR) | Complete Response | 0 Participants |
| BMS 1000mg | Best Overall Response (BOR) | Partial Response | 1 Participants |
| BMS 1000mg | Best Overall Response (BOR) | Stable Disease | 8 Participants |
| BMS 1000mg | Best Overall Response (BOR) | Progressive Disease | 21 Participants |
| BMS 1000mg | Best Overall Response (BOR) | Not evaluable | 5 Participants |
| BMS 400mg + Nivo 360mg | Best Overall Response (BOR) | Stable Disease | 2 Participants |
| BMS 400mg + Nivo 360mg | Best Overall Response (BOR) | Not evaluable | 1 Participants |
| BMS 400mg + Nivo 360mg | Best Overall Response (BOR) | Progressive Disease | 9 Participants |
| BMS 400mg + Nivo 360mg | Best Overall Response (BOR) | Partial Response | 8 Participants |
| BMS 400mg + Nivo 360mg | Best Overall Response (BOR) | Complete Response | 1 Participants |
| BMS 1000mg + Nivo 360mg | Best Overall Response (BOR) | Stable Disease | 1 Participants |
| BMS 1000mg + Nivo 360mg | Best Overall Response (BOR) | Partial Response | 2 Participants |
| BMS 1000mg + Nivo 360mg | Best Overall Response (BOR) | Complete Response | 0 Participants |
| BMS 1000mg + Nivo 360mg | Best Overall Response (BOR) | Not evaluable | 2 Participants |
| BMS 1000mg + Nivo 360mg | Best Overall Response (BOR) | Progressive Disease | 3 Participants |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BMS 70mg | BMS-986012 Accumulation Index (AI_AUC) | 1.56 Ratio | — |
| BMS 160mg | BMS-986012 Accumulation Index (AI_AUC) | 1.55 Ratio | — |
| BMS 400mg | BMS-986012 Accumulation Index (AI_AUC) | 1.62 Ratio | Geometric Coefficient of Variation 22 |
| BMS 1000mg | BMS-986012 Accumulation Index (AI_AUC) | 1.39 Ratio | Geometric Coefficient of Variation 51 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 70mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 3 day 1 | 7062 h*ug/mL | — |
| BMS 70mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 1 day 1 | 3997 h*ug/mL | Geometric Coefficient of Variation 31 |
| BMS 160mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 3 day 1 | 10560 h*ug/mL | — |
| BMS 160mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 1 day 1 | 5584 h*ug/mL | Geometric Coefficient of Variation 55 |
| BMS 400mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 1 day 1 | 18456 h*ug/mL | Geometric Coefficient of Variation 32 |
| BMS 400mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 3 day 1 | 42583 h*ug/mL | Geometric Coefficient of Variation 8 |
| BMS 1000mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 3 day 1 | 58649 h*ug/mL | Geometric Coefficient of Variation 28 |
| BMS 1000mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 1 day 1 | 36223 h*ug/mL | Geometric Coefficient of Variation 40 |
| BMS 400mg + Nivo 360mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 1 day 1 | 16527 h*ug/mL | Geometric Coefficient of Variation 31 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUC (0-T)) | cycle 1 day 1 | 45126 h*ug/mL | Geometric Coefficient of Variation 24 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 70mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 3 day 1 | 7062 h*ug/mL | — |
| BMS 70mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 1 day 1 | 4300 h*ug/mL | Geometric Coefficient of Variation 29 |
| BMS 160mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 3 day 1 | 10560 h*ug/mL | — |
| BMS 160mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 1 day 1 | 8356 h*ug/mL | Geometric Coefficient of Variation 28 |
| BMS 400mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 1 day 1 | 19865 h*ug/mL | Geometric Coefficient of Variation 28 |
| BMS 400mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 3 day 1 | 42583 h*ug/mL | Geometric Coefficient of Variation 8 |
| BMS 1000mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 3 day 1 | 62634 h*ug/mL | Geometric Coefficient of Variation 33 |
| BMS 1000mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 1 day 1 | 40979 h*ug/mL | Geometric Coefficient of Variation 34 |
| BMS 400mg + Nivo 360mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 1 day 1 | 18161 h*ug/mL | Geometric Coefficient of Variation 30 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Area Under the Serum Concentration-time Curve in One Dosing Interval AUC (TAU) | cycle 1 day 1 | 49031 h*ug/mL | Geometric Coefficient of Variation 26 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BMS 70mg | BMS-986012 Average Concentration Over a Dosing Interval (Css-avg) | 13.9 ug/mL | — |
| BMS 160mg | BMS-986012 Average Concentration Over a Dosing Interval (Css-avg) | 22.0 ug/mL | — |
| BMS 400mg | BMS-986012 Average Concentration Over a Dosing Interval (Css-avg) | 82.1 ug/mL | Geometric Coefficient of Variation 11 |
| BMS 1000mg | BMS-986012 Average Concentration Over a Dosing Interval (Css-avg) | 119 ug/mL | Geometric Coefficient of Variation 33 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BMS 70mg | BMS-986012 Cmax Accumulation Index (AI_Cmax) | 0.994 Ratio | — |
| BMS 160mg | BMS-986012 Cmax Accumulation Index (AI_Cmax) | 1.47 Ratio | — |
| BMS 400mg | BMS-986012 Cmax Accumulation Index (AI_Cmax) | 1.22 Ratio | Geometric Coefficient of Variation 11 |
| BMS 1000mg | BMS-986012 Cmax Accumulation Index (AI_Cmax) | 0.940 Ratio | Geometric Coefficient of Variation 70 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| BMS 70mg | BMS-986012 Ctau Accumulation Index (AI_Ctau) | 1.81 Ratio | — |
| BMS 160mg | BMS-986012 Ctau Accumulation Index (AI_Ctau) | 2.31 Ratio | — |
| BMS 400mg | BMS-986012 Ctau Accumulation Index (AI_Ctau) | 1.76 Ratio | Geometric Coefficient of Variation 0 |
| BMS 1000mg | BMS-986012 Ctau Accumulation Index (AI_Ctau) | 1.08 Ratio | Geometric Coefficient of Variation 82 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BMS 70mg | BMS-986012 Effective Elimination (T-HALFeff) | 342 Hours | — |
| BMS 160mg | BMS-986012 Effective Elimination (T-HALFeff) | 319 Hours | — |
| BMS 400mg | BMS-986012 Effective Elimination (T-HALFeff) | 384 Hours | Standard Deviation 154.2 |
| BMS 1000mg | BMS-986012 Effective Elimination (T-HALFeff) | 583 Hours | — |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 70mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 3 day 1 | 33.8 ug/mL | — |
| BMS 70mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 1 day 1 | 27.5 ug/mL | Geometric Coefficient of Variation 31 |
| BMS 160mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 1 day 1 | 53.8 ug/mL | Geometric Coefficient of Variation 28 |
| BMS 160mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 3 day 1 | 46.9 ug/mL | — |
| BMS 400mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 1 day 1 | 121 ug/mL | Geometric Coefficient of Variation 26 |
| BMS 400mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 3 day 1 | 221 ug/mL | Geometric Coefficient of Variation 1 |
| BMS 1000mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 1 day 1 | 276 ug/mL | Geometric Coefficient of Variation 37 |
| BMS 1000mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 3 day 1 | 279 ug/mL | Geometric Coefficient of Variation 37 |
| BMS 400mg + Nivo 360mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 1 day 1 | 111 ug/mL | Geometric Coefficient of Variation 33 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Maximum Observed Serum Concentration (Cmax) | cycle 1 day 1 | 339 ug/mL | Geometric Coefficient of Variation 25 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 70mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 3 day 1 | 7.39 ug/mL | — |
| BMS 70mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 1 day 1 | 3.44 ug/mL | Geometric Coefficient of Variation 38 |
| BMS 160mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 3 day 1 | 13.6 ug/mL | — |
| BMS 160mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 1 day 1 | 6.24 ug/mL | Geometric Coefficient of Variation 31 |
| BMS 400mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 1 day 1 | 17.4 ug/mL | Geometric Coefficient of Variation 32 |
| BMS 400mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 3 day 1 | 42.4 ug/mL | Geometric Coefficient of Variation 13 |
| BMS 1000mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 3 day 1 | 59.2 ug/mL | Geometric Coefficient of Variation 19 |
| BMS 1000mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 1 day 1 | 30.2 ug/mL | Geometric Coefficient of Variation 59 |
| BMS 400mg + Nivo 360mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 1 day 1 | 14.6 ug/mL | Geometric Coefficient of Variation 44 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Observed Serum Concentration at the End of a Dosing Interval (Ctau) | cycle 1 day 1 | 39.5 ug/mL | Geometric Coefficient of Variation 40 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BMS 70mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 3 day 1 | 1.93 hours |
| BMS 70mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 1 day 1 | 2.08 hours |
| BMS 160mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 3 day 1 | 4.00 hours |
| BMS 160mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 1 day 1 | 2.02 hours |
| BMS 400mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 1 day 1 | 2.00 hours |
| BMS 400mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 3 day 1 | 2.04 hours |
| BMS 1000mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 3 day 1 | 2.30 hours |
| BMS 1000mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 1 day 1 | 1.58 hours |
| BMS 400mg + Nivo 360mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 1 day 1 | 4.00 hours |
| BMS 1000mg + Nivo 360mg | BMS-986012 Time of Maximum Observed Serum Concentration (Tmax) | cycle 1 day 1 | 1.53 hours |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 70mg | BMS-986012 Total Body Clearance (CLT) | cycle 3 day 1 | 9.91 mL/h | — |
| BMS 70mg | BMS-986012 Total Body Clearance (CLT) | cycle 1 day 1 | 16.3 mL/h | Geometric Coefficient of Variation 38 |
| BMS 160mg | BMS-986012 Total Body Clearance (CLT) | cycle 1 day 1 | 19.1 mL/h | Geometric Coefficient of Variation 27 |
| BMS 160mg | BMS-986012 Total Body Clearance (CLT) | cycle 3 day 1 | 15.2 mL/h | — |
| BMS 400mg | BMS-986012 Total Body Clearance (CLT) | cycle 3 day 1 | 9.39 mL/h | Geometric Coefficient of Variation 8 |
| BMS 400mg | BMS-986012 Total Body Clearance (CLT) | cycle 1 day 1 | 20.1 mL/h | Geometric Coefficient of Variation 24 |
| BMS 1000mg | BMS-986012 Total Body Clearance (CLT) | cycle 1 day 1 | 24.4 mL/h | Geometric Coefficient of Variation 86 |
| BMS 1000mg | BMS-986012 Total Body Clearance (CLT) | cycle 3 day 1 | 16.0 mL/h | Geometric Coefficient of Variation 40 |
| BMS 400mg + Nivo 360mg | BMS-986012 Total Body Clearance (CLT) | cycle 1 day 1 | 22.0 mL/h | Geometric Coefficient of Variation 30 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Total Body Clearance (CLT) | cycle 1 day 1 | 20.4 mL/h | Geometric Coefficient of Variation 28 |
Secondary
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)
Population: All participants who receive at least 1 dose of BMS-986012 (and Nivolumab in the combination therapy) and have available serum concentration data for the corresponding analyte
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| BMS 70mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 4 day 1 | 7390 ng/mL | — |
| BMS 70mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 11 day 1 | 9930 ng/mL | — |
| BMS 70mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 2 day 1 | 4186 ng/mL | Geometric Coefficient of Variation 27 |
| BMS 70mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 3 day 1 | 6570 ng/mL | — |
| BMS 70mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 7 day 1 | 9040 ng/mL | — |
| BMS 70mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 15 day 1 | 8029 ng/mL | — |
| BMS 160mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 7 day 1 | 13700 ng/mL | — |
| BMS 160mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 2 day 1 | 7211 ng/mL | Geometric Coefficient of Variation 17 |
| BMS 160mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 3 day 1 | 9100 ng/mL | — |
| BMS 160mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 4 day 1 | 13600 ng/mL | — |
| BMS 400mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 2 day 1 | 18810 ng/mL | Geometric Coefficient of Variation 29 |
| BMS 400mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 3 day 1 | 29232 ng/mL | Geometric Coefficient of Variation 36 |
| BMS 400mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 11 day 1 | 32251 ng/mL | Geometric Coefficient of Variation 14 |
| BMS 400mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 7 day 1 | 38315 ng/mL | Geometric Coefficient of Variation 27 |
| BMS 400mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 4 day 1 | 35122 ng/mL | Geometric Coefficient of Variation 26 |
| BMS 1000mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 7 day 1 | 107444 ng/mL | Geometric Coefficient of Variation 58 |
| BMS 1000mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 2 day 1 | 36990 ng/mL | Geometric Coefficient of Variation 54 |
| BMS 1000mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 3 day 1 | 68589 ng/mL | Geometric Coefficient of Variation 57 |
| BMS 1000mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 4 day 1 | 90207 ng/mL | Geometric Coefficient of Variation 68 |
| BMS 1000mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 11 day 1 | 102980 ng/mL | Geometric Coefficient of Variation 67 |
| BMS 400mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 4 day 1 | 26102 ng/mL | Geometric Coefficient of Variation 63 |
| BMS 400mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 11 day 1 | 34400 ng/mL | — |
| BMS 400mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 3 day 1 | 26016 ng/mL | Geometric Coefficient of Variation 37 |
| BMS 400mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 7 day 1 | 38405 ng/mL | Geometric Coefficient of Variation 9 |
| BMS 400mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 2 day 1 | 14544 ng/mL | Geometric Coefficient of Variation 84 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 3 day 1 | 158801 ng/mL | Geometric Coefficient of Variation 85 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 2 day 1 | 36391 ng/mL | Geometric Coefficient of Variation 43 |
| BMS 1000mg + Nivo 360mg | BMS-986012 Trough Observed Serum Concentration (Ctrough) | cycle 4 day 1 | 157000 ng/mL | — |
Secondary
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)
Population: Median DoR is pre-specified to only be evaluated provided there are enough responders (CR or PR) to warrant inclusion (Only Cohorts with at least 5 events are analyzed)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BMS 400mg + Nivo 360mg | Duration of Response (DoR) | 120.57 Weeks |
Secondary
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)
Population: All treated participants who had at least 1 post-treatment immunogenicity assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS 70mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA positive | 0 Participants |
| BMS 70mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | Baseline ADA positive | 0 Participants |
| BMS 70mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA negative | 5 Participants |
| BMS 160mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | Baseline ADA positive | 0 Participants |
| BMS 160mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA positive | 0 Participants |
| BMS 160mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA negative | 5 Participants |
| BMS 400mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA negative | 27 Participants |
| BMS 400mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA positive | 0 Participants |
| BMS 400mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | Baseline ADA positive | 0 Participants |
| BMS 1000mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA negative | 25 Participants |
| BMS 1000mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA positive | 0 Participants |
| BMS 1000mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | Baseline ADA positive | 1 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | Baseline ADA positive | 0 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA negative | 14 Participants |
| BMS 400mg + Nivo 360mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA positive | 0 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA positive | 0 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | ADA negative | 7 Participants |
| BMS 1000mg + Nivo 360mg | Number of Participants With Anti-BMS-986012 Antibodies (ADA) | Baseline ADA positive | 0 Participants |
Secondary
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)
Population: All treated participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS 70mg | Objective Response Rate (ORR) | 14.3 Percent of participants |
| BMS 160mg | Objective Response Rate (ORR) | 0 Percent of participants |
| BMS 400mg | Objective Response Rate (ORR) | 3.4 Percent of participants |
| BMS 1000mg | Objective Response Rate (ORR) | 2.9 Percent of participants |
| BMS 400mg + Nivo 360mg | Objective Response Rate (ORR) | 42.9 Percent of participants |
| BMS 1000mg + Nivo 360mg | Objective Response Rate (ORR) | 25.0 Percent of participants |
Secondary
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)
Population: All treated participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BMS 70mg | Progression Free Survival (PFS) | 5.50 Weeks |
| BMS 160mg | Progression Free Survival (PFS) | 5.86 Weeks |
| BMS 400mg | Progression Free Survival (PFS) | 5.79 Weeks |
| BMS 1000mg | Progression Free Survival (PFS) | 5.36 Weeks |
| BMS 400mg + Nivo 360mg | Progression Free Survival (PFS) | 17.71 Weeks |
| BMS 1000mg + Nivo 360mg | Progression Free Survival (PFS) | 5.71 Weeks |
Secondary
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
Population: All treated participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| BMS 70mg | Progression Free Survival Rate (PFSR) | Week 72 | NA Percent of participants |
| BMS 70mg | Progression Free Survival Rate (PFSR) | Week 24 | NA Percent of participants |
| BMS 70mg | Progression Free Survival Rate (PFSR) | Week 36 | NA Percent of participants |
| BMS 70mg | Progression Free Survival Rate (PFSR) | Week 48 | NA Percent of participants |
| BMS 70mg | Progression Free Survival Rate (PFSR) | Week 60 | NA Percent of participants |
| BMS 70mg | Progression Free Survival Rate (PFSR) | Week 12 | NA Percent of participants |
| BMS 160mg | Progression Free Survival Rate (PFSR) | Week 12 | NA Percent of participants |
| BMS 160mg | Progression Free Survival Rate (PFSR) | Week 60 | NA Percent of participants |
| BMS 160mg | Progression Free Survival Rate (PFSR) | Week 36 | NA Percent of participants |
| BMS 160mg | Progression Free Survival Rate (PFSR) | Week 48 | NA Percent of participants |
| BMS 160mg | Progression Free Survival Rate (PFSR) | Week 72 | NA Percent of participants |
| BMS 160mg | Progression Free Survival Rate (PFSR) | Week 24 | NA Percent of participants |
| BMS 400mg | Progression Free Survival Rate (PFSR) | Week 48 | NA Percent of participants |
| BMS 400mg | Progression Free Survival Rate (PFSR) | Week 60 | NA Percent of participants |
| BMS 400mg | Progression Free Survival Rate (PFSR) | Week 72 | NA Percent of participants |
| BMS 400mg | Progression Free Survival Rate (PFSR) | Week 36 | NA Percent of participants |
| BMS 400mg | Progression Free Survival Rate (PFSR) | Week 24 | NA Percent of participants |
| BMS 400mg | Progression Free Survival Rate (PFSR) | Week 12 | 21.4 Percent of participants |
| BMS 1000mg | Progression Free Survival Rate (PFSR) | Week 24 | NA Percent of participants |
| BMS 1000mg | Progression Free Survival Rate (PFSR) | Week 36 | NA Percent of participants |
| BMS 1000mg | Progression Free Survival Rate (PFSR) | Week 72 | NA Percent of participants |
| BMS 1000mg | Progression Free Survival Rate (PFSR) | Week 48 | NA Percent of participants |
| BMS 1000mg | Progression Free Survival Rate (PFSR) | Week 60 | NA Percent of participants |
| BMS 1000mg | Progression Free Survival Rate (PFSR) | Week 12 | 20.6 Percent of participants |
| BMS 400mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 72 | 35.0 Percent of participants |
| BMS 400mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 36 | 45.0 Percent of participants |
| BMS 400mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 60 | 35.0 Percent of participants |
| BMS 400mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 24 | 45.0 Percent of participants |
| BMS 400mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 12 | 55.0 Percent of participants |
| BMS 400mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 48 | 35.0 Percent of participants |
| BMS 1000mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 72 | NA Percent of participants |
| BMS 1000mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 12 | NA Percent of participants |
| BMS 1000mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 24 | NA Percent of participants |
| BMS 1000mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 36 | NA Percent of participants |
| BMS 1000mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 48 | NA Percent of participants |
| BMS 1000mg + Nivo 360mg | Progression Free Survival Rate (PFSR) | Week 60 | NA Percent of participants |