Hematologic Neoplasms
Conditions
Keywords
Hodgkin lymphoma, non-Hodgkin lymphoma, diffused large B-cell lymphoma, indolent lymphoma, chronic lymphocytic leukemia, relapsed, refractory
Brief summary
The primary objective of this study is to characterize the safety, tolerability, dose-limiting toxicities (DLTs), and maximum tolerated dose (MTD) of relatlimab administered alone or in combination with nivolumab to subjects with relapsed or refractory B-cell malignancies. Co-primary objective is to investigate the preliminary efficacy of relatlimab in combination with nivolumab in subjects with relapsed or refractory Hodgkin lymphoma (HL), and relapsed or refractory Diffused Large B Cell lymphoma (DLBCL)
Interventions
BIOLOGICALBMS-986016
Specified Dose on Specified Days
BIOLOGICALBMS-936558
Specified Dose on Specified Days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must have histologic or cytologic confirmation of chronic lymphocytic leukemia, Hodgkin lymphoma, Non-Hodgkin lymphoma, or Multiple Myeloma and have relapsed following prior treatment or been refractory to prior treatment * Must have progressed or been refractory to, at least one prior standard therapy, including radiation, immunomodulatory agents (eg, lenalidomide), immunotherapy, cytotoxic chemotherapy, and select antibody (anti-CD20, alemtuzumab, or anti-CD30) therapy. * Must be more than 100 days post autologous transplant
Exclusion criteria
* Known or suspected central nervous system (CNS) metastases or with the CNS as the only site of active disease (controlled CNS metastases are allowed) * Known or suspected autoimmune disease * History of allergy to anti-PD-1 or anti-PD-L1 antibody therapy or to other monoclonal antibodies or related compounds or to any of their components Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | From first dose to 100 days post last dose (Up to 51 months) | Number of participants with any grade adverse events (AEs), any grade serious adverse events (SAEs) and any grade AEs leading to discontinuation of any drug. The severity of AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. |
| Number of Participants Who Died | From first dose to 135 days post last dose (Up to 52 months) | Number of participants who died due to any cause. |
| Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | From first dose to 30 days post last dose (Up to 49 months) | Number of participants with laboratory abnormalities in specific hepatic tests based on SI unit convention. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * ALP \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN |
| Objective Response Rate (ORR) - Part D | From first dose date to the date of disease progression per investigator or the date of subsequent therapy, whichever occurs first (Up to approximately 95 months) | Investigator-assessed ORR per International Working Group (IWG 2007) response criteria for malignant lymphoma is defined as the number of participants with a best overall documented response (BOR) of either a complete response (CR) or partial response (PR). Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. \>= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by \>=50% of previously involved sites from nadir. |
| Duration of Response (DoR) - Part D | From first dose to the date of the first objectively documented progression, or death due to any cause, whichever occurs first (Up to approximately 95 months) | Investigator-assessed DoR per International Working Group (IWG 2007)) response criteria for malignant lymphoma is defined as the time between the date of first documented response (complete response or partial response) to the date of the first objectively documented progression, or death due to any cause, whichever occurs first. Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. \>= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by \>=50% of previously involved sites from nadir. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 effective elimination half-life that explains the degree of AUC accumulation observed (t 1/2eff AUC). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period |
| BMS-986016 Total Body Clearance (CL/T) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 total body clearance (CL/T). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period |
| BMS-986016 Cmax Accumulation Index (AI_Cmax) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 cmax accumulation index (AI\_Cmax). AI is calculated based on ratio of Cmax at steady state to Cmax after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period |
| BMS-986016 Accumulation Index (AI_AUC) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 accumulation index (AI\_AUC). AI is calculated based on ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period |
| BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 average concentration over a dosing interval (\[AUC(TAU)/tau\] (Css,avg). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period |
| BMS-986016 Trough Observed Serum Concentration (Ctrough) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 15, 29, 43, Cycle 2 Day 1, 15, 29, Cycle 3 Day 1, 15, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and Cycle 11 Day 1 | BMS-986016 trough observed serum concentration (Ctrough). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period |
| Number of Participants With Anti-BMS-986016 Antibodies (ADA) | From first dose to 135 days post last dose (Up to 52 months) | Number of participants with anti-BMS-986016 antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is defined as a participant with positive seroconversion detected in the last sample before initiation of treatment. ADA-positive participant is a participant with at least one ADA-positive sample relative to baseline after initiation of the treatment. ADA negative participant is defined as a participant with no ADA positive sample after the initiation of treatment. |
| Number of Participants With Anti-Nivolumab Antibodies (ADA) | From first dose to 135 days post last dose (Up to 52 months) | Number of participants with anti-Nivolumab antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is defined as a participant with positive seroconversion detected in the last sample before initiation of treatment. ADA-positive participant is a participant with at least one ADA-positive sample relative to baseline after initiation of the treatment. ADA negative participant is defined as a participant with no ADA positive sample after the initiation of treatment. |
| BMS-986016 Ctau Accumulation Index (AI_Ctau) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 Ctau accumulation index (AI\_Ctau). AI is calculated based on ratio of Ctau at steady state to Ctau after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period |
| BMS-986016 Maximum Observed Serum Concentration (Cmax) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 Maximum Observed Serum Concentration (Cmax). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period |
| BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax). Period 0 = treatment period Period 1 = Re-challenge period |
| BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 Area under the concentration-time curve in one dosing interval (AUC(TAU)). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period |
| BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1 | BMS-986016 Concentration at the end of a dosing interval (Ctau). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BMS-986016 20mg Dose escalation (part A): BMS-986016 20mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 3 |
| BMS-986016 800mg Dose escalation (part A): BMS-986016 800mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 9 |
| BMS-986016 80mg Dose escalation (part A): BMS-986016 80mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 6 |
| BMS-986016 240mg Dose escalation (part A) and dose expansion (part B): BMS-986016 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of BMS-986016 administered on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 20 |
| BMS-986016 80mg + Nivolumab Dose escalation (part C): BMS-986016 IV 80mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 7 |
| BMS-986016 240mg + Nivolumab Dose escalation (part C): BMS-986016 IV 240mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 1 |
| BMS-986016 160mg + Nivolumab Dose escalation (part C) and dose expansion (part D): BMS-986016 IV 160mg + Nivolumab IV 240mg up to twelve 8-week treatment cycles, confirmed progressive disease, until meeting criteria for discontinuation, or clinical deterioration, whichever occurs first. Each treatment cycle comprises 4 doses of Nivolumab followed by BMS-986016 on days 1, 15, 29, and 43. Participants could further receive therapy for up to 6 additional eight-week cycles if re-challenge period criteria are met. | 60 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse event unrelated to study Drug | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Disease progression | 2 | 8 | 4 | 5 | 9 | 3 | 1 | 2 | 28 |
| Overall Study | Maximum clinical benefit | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 6 |
| Overall Study | Other reasons | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 6 |
| Overall Study | Participant no longer meets study criteria | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Participant request to discontinue study treatment | 0 | 0 | 2 | 2 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Study Drug toxicity | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 2 | 6 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | BMS-986016 20mg | BMS-986016 800mg | BMS-986016 80mg | BMS-986016 240mg | BMS-986016 80mg + Nivolumab | BMS-986016 240mg + Nivolumab | BMS-986016 160mg + Nivolumab | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 6 Participants | 1 Participants | 8 Participants | 4 Participants | 0 Participants | 14 Participants | 34 Participants |
| Age, Categorical Between 18 and 65 years | 2 Participants | 3 Participants | 5 Participants | 12 Participants | 3 Participants | 1 Participants | 46 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 9 Participants | 5 Participants | 19 Participants | 7 Participants | 1 Participants | 58 Participants | 102 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 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 | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) White | 1 Participants | 8 Participants | 5 Participants | 16 Participants | 7 Participants | 1 Participants | 45 Participants | 83 Participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 1 Participants | 6 Participants | 4 Participants | 0 Participants | 22 Participants | 38 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 5 Participants | 14 Participants | 3 Participants | 1 Participants | 38 Participants | 68 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 3 / 9 | 0 / 9 | 1 / 6 | 1 / 2 | 2 / 2 | 0 / 4 | 0 / 3 | 5 / 7 | 2 / 4 | 0 / 1 | 1 / 21 | 13 / 15 | 3 / 20 |
| other Total, other adverse events | 3 / 3 | 9 / 9 | 8 / 9 | 5 / 6 | 2 / 2 | 2 / 2 | 4 / 4 | 3 / 3 | 7 / 7 | 4 / 4 | 1 / 1 | 20 / 21 | 11 / 15 | 20 / 20 |
| serious Total, serious adverse events | 1 / 3 | 5 / 9 | 1 / 9 | 2 / 6 | 1 / 2 | 2 / 2 | 2 / 4 | 1 / 3 | 4 / 7 | 2 / 4 | 0 / 1 | 6 / 21 | 11 / 15 | 9 / 20 |
Outcome results
Primary
Duration of Response (DoR) - Part D
Investigator-assessed DoR per International Working Group (IWG 2007)) response criteria for malignant lymphoma is defined as the time between the date of first documented response (complete response or partial response) to the date of the first objectively documented progression, or death due to any cause, whichever occurs first. Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. \>= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by \>=50% of previously involved sites from nadir.
Time frame: From first dose to the date of the first objectively documented progression, or death due to any cause, whichever occurs first (Up to approximately 95 months)
Population: Pre-specified only to be collected in all responders (CR or PR) by tumor type for Part D
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| BMS-986016 20mg | Duration of Response (DoR) - Part D | 14.16 Months |
| BMS-986016 80mg | Duration of Response (DoR) - Part D | NA Months |
| BMS-986016 800mg | Duration of Response (DoR) - Part D | 6.37 Months |
Primary
Number of Participants Who Died
Number of participants who died due to any cause.
Time frame: From first dose to 135 days post last dose (Up to 52 months)
Population: All treated participants
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BMS-986016 20mg | Number of Participants Who Died | 0 Participants |
| BMS-986016 80mg | Number of Participants Who Died | 2 Participants |
| BMS-986016 800mg | Number of Participants Who Died | 1 Participants |
| BMS-986016 240mg | Number of Participants Who Died | 2 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants Who Died | 2 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants Who Died | 0 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants Who Died | 10 Participants |
Primary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation
Number of participants with any grade adverse events (AEs), any grade serious adverse events (SAEs) and any grade AEs leading to discontinuation of any drug. The severity of AEs will be graded using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. An AE is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment.
Time frame: From first dose to 100 days post last dose (Up to 51 months)
Population: All treated participants
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986016 20mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 3 Participants |
| BMS-986016 20mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 1 Participants |
| BMS-986016 20mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 1 Participants |
| BMS-986016 80mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 2 Participants |
| BMS-986016 80mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 9 Participants |
| BMS-986016 80mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 4 Participants |
| BMS-986016 800mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 2 Participants |
| BMS-986016 800mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 0 Participants |
| BMS-986016 800mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 5 Participants |
| BMS-986016 240mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 1 Participants |
| BMS-986016 240mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 19 Participants |
| BMS-986016 240mg | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 6 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 4 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 1 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 7 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 1 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 0 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs | 59 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | AEs leading to discontinuation | 9 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and AEs Leading to Discontinuation | SAEs | 26 Participants |
Primary
Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests
Number of participants with laboratory abnormalities in specific hepatic tests based on SI unit convention. The number of participants with the following laboratory abnormalities from on-treatment evaluations will be summarized: * ALT or AST \> 3 x ULN, \> 5 x ULN, \> 10 x ULN and \> 20 x ULN * Total bilirubin \> 2 x ULN * ALP \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 1.5 x ULN * Concurrent (within 1 day) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN * Concurrent (within 30 days) ALT or AST \> 3 x ULN and total bilirubin \> 2 x ULN
Time frame: From first dose to 30 days post last dose (Up to 49 months)
Population: All treated participants with at least one on-treatment measurement of the corresponding laboratory parameter
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 1 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 20mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 0 Participants |
| BMS-986016 80mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 1 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 800mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 1 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 1 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 0 Participants |
| BMS-986016 240mg | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 1 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 0 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN 30 DAYS | 1 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN ONE DAY | 2 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 1.5XULN WITHIN 30 DAYS | 2 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 10XULN | 1 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | CONCURRENT ALT OR AST ELEVATION > 3XULN WITH TOTAL BILIRUBIN > 2XULN WITHIN ONE DAY | 1 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 20XULN | 1 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALP > 1.5XULN | 8 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 3XULN | 5 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | ALT OR AST > 5XULN | 1 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With On-Treatment Laboratory Abnormalities in Specific Hepatics Tests | TOTAL BILIRUBIN > 2XULN | 1 Participants |
Primary
Objective Response Rate (ORR) - Part D
Investigator-assessed ORR per International Working Group (IWG 2007) response criteria for malignant lymphoma is defined as the number of participants with a best overall documented response (BOR) of either a complete response (CR) or partial response (PR). Complete response: Disappearance of all evidence of disease. Partial response: Regression of measurable disease and no new sites. \>= 50% decrease in sum of the produce of the diameters of up to 6 largest dominant masses (index lesions); no increase in size of other nodes (non-index lesions). Progressive disease: Any new lesion or increase by \>=50% of previously involved sites from nadir.
Time frame: From first dose date to the date of disease progression per investigator or the date of subsequent therapy, whichever occurs first (Up to approximately 95 months)
Population: Pre-specified only to be collected in all treated participants by tumor type for Part D
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| BMS-986016 20mg | Objective Response Rate (ORR) - Part D | 61.9 Percentage of participants |
| BMS-986016 80mg | Objective Response Rate (ORR) - Part D | 6.7 Percentage of participants |
| BMS-986016 800mg | Objective Response Rate (ORR) - Part D | 15.0 Percentage of participants |
Secondary
BMS-986016 Accumulation Index (AI_AUC)
BMS-986016 accumulation index (AI\_AUC). AI is calculated based on ratio of AUC(TAU) at steady state to AUC(TAU) after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 1.577 Ratio |
| BMS-986016 80mg | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 1.850 Ratio |
| BMS-986016 800mg | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 2.894 Ratio |
| BMS-986016 240mg | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 2.186 Ratio |
| BMS-986016 80mg + Nivolumab | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 2.017 Ratio |
| BMS-986016 240mg + Nivolumab | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 3.647 Ratio |
| BMS-986016 240mg + Nivolumab | BMS-986016 Accumulation Index (AI_AUC) | P1C3D1 | 3.417 Ratio |
| BMS-986016 160mg + Nivolumab | BMS-986016 Accumulation Index (AI_AUC) | P1C3D1 | 2.967 Ratio |
| BMS-986016 160mg + Nivolumab | BMS-986016 Accumulation Index (AI_AUC) | P0C3D1 | 3.268 Ratio |
| Unknown | BMS-986016 Accumulation Index (AI_AUC) | P1C1D1 | — Ratio |
| Unknown | BMS-986016 Accumulation Index (AI_AUC) | Period 0, Cycle 1, Day 1 (P0C1D1) | — Ratio |
Secondary
BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU))
BMS-986016 Area under the concentration-time curve in one dosing interval (AUC(TAU)). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 712.408 h*ug/mL |
| BMS-986016 20mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 401.438 h*ug/mL |
| BMS-986016 80mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 4898.034 h*ug/mL |
| BMS-986016 80mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 2852.533 h*ug/mL |
| BMS-986016 800mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 176405.369 h*ug/mL |
| BMS-986016 800mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 44296.525 h*ug/mL |
| BMS-986016 240mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 18783.970 h*ug/mL |
| BMS-986016 240mg | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 9086.827 h*ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 6166.165 h*ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 2908.011 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 9480.758 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P1C3D1 | 38472.003 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 34573.957 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P1C1D1 | 11259.871 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P1C3D1 | 33919.259 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P0C3D1 | 20464.075 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | P1C1D1 | 11433.253 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Area Under the Concentration-time Curve in One Dosing Interval (AUC(TAU)) | Period 0, Cycle 1, Day 1 (P0C1D1) | 5327.954 h*ug/mL |
Secondary
BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg)
BMS-986016 average concentration over a dosing interval (\[AUC(TAU)/tau\] (Css,avg). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 2.117 ug/mL |
| BMS-986016 80mg | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 14.738 ug/mL |
| BMS-986016 800mg | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 526.269 ug/mL |
| BMS-986016 240mg | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 57.790 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 18.345 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 103.805 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P1C3D1 | 120.595 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P1C3D1 | 109.013 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P0C3D1 | 61.385 ug/mL |
| Unknown | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | P1C1D1 | — ug/mL |
| Unknown | BMS-986016 Average Concentration Over a Dosing Interval ([AUC(TAU)/Tau] (Css,Avg) | Period 0, Cycle 1, Day 1 (P0C1D1) | — ug/mL |
Secondary
BMS-986016 Cmax Accumulation Index (AI_Cmax)
BMS-986016 cmax accumulation index (AI\_Cmax). AI is calculated based on ratio of Cmax at steady state to Cmax after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 1.981 ug/mL |
| BMS-986016 80mg | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 1.701 ug/mL |
| BMS-986016 800mg | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 2.009 ug/mL |
| BMS-986016 240mg | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 1.734 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 2.369 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 2.573 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P1C3D1 | 2.768 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P1C3D1 | 2.383 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P0C3D1 | 2.139 ug/mL |
| Unknown | BMS-986016 Cmax Accumulation Index (AI_Cmax) | P1C1D1 | — ug/mL |
| Unknown | BMS-986016 Cmax Accumulation Index (AI_Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | — ug/mL |
Secondary
BMS-986016 Concentration at the End of a Dosing Interval (Ctau)
BMS-986016 Concentration at the end of a dosing interval (Ctau). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 0.256 h*ug/mL |
| BMS-986016 20mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 0.158 h*ug/mL |
| BMS-986016 80mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 2.266 h*ug/mL |
| BMS-986016 80mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 1.037 h*ug/mL |
| BMS-986016 800mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 293.000 h*ug/mL |
| BMS-986016 800mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 75.589 h*ug/mL |
| BMS-986016 240mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 30.970 h*ug/mL |
| BMS-986016 240mg | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 12.221 h*ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 9.556 h*ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 3.848 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 19.500 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P1C3D1 | 86.600 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 103.000 h*ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P1C1D1 | 25.900 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P1C3D1 | 86.100 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P0C3D1 | 47.016 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | P1C1D1 | 24.200 h*ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Concentration at the End of a Dosing Interval (Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | 8.417 h*ug/mL |
Secondary
BMS-986016 Ctau Accumulation Index (AI_Ctau)
BMS-986016 Ctau accumulation index (AI\_Ctau). AI is calculated based on ratio of Ctau at steady state to Ctau after the first dose. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 0.743 Ratio |
| BMS-986016 80mg | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 2.494 Ratio |
| BMS-986016 800mg | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 4.741 Ratio |
| BMS-986016 240mg | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 2.310 Ratio |
| BMS-986016 80mg + Nivolumab | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 1.686 Ratio |
| BMS-986016 240mg + Nivolumab | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 5.282 Ratio |
| BMS-986016 240mg + Nivolumab | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P1C3D1 | 3.344 Ratio |
| BMS-986016 160mg + Nivolumab | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P1C3D1 | 3.558 Ratio |
| BMS-986016 160mg + Nivolumab | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P0C3D1 | 4.162 Ratio |
| Unknown | BMS-986016 Ctau Accumulation Index (AI_Ctau) | P1C1D1 | — Ratio |
| Unknown | BMS-986016 Ctau Accumulation Index (AI_Ctau) | Period 0, Cycle 1, Day 1 (P0C1D1) | — Ratio |
Secondary
BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC)
BMS-986016 effective elimination half-life that explains the degree of AUC accumulation observed (t 1/2eff AUC). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 240.671 Hours | Standard Deviation 143.5338 |
| BMS-986016 80mg | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 742.843 Hours | — |
| BMS-986016 800mg | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 547.986 Hours | — |
| BMS-986016 240mg | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 428.698 Hours | Standard Deviation 346.4046 |
| BMS-986016 80mg + Nivolumab | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 548.741 Hours | Standard Deviation 78.0213 |
| BMS-986016 240mg + Nivolumab | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 720.317 Hours | — |
| BMS-986016 240mg + Nivolumab | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P1C3D1 | 638.597 Hours | — |
| BMS-986016 160mg + Nivolumab | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P1C3D1 | 524.637 Hours | — |
| BMS-986016 160mg + Nivolumab | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P0C3D1 | 674.755 Hours | Standard Deviation 296.9473 |
| Unknown | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | P1C1D1 | — Hours | — |
| Unknown | BMS-986016 Effective Elimination Half-life That Explains the Degree of AUC Accumulation Observed (T 1/2eff AUC) | Period 0, Cycle 1, Day 1 (P0C1D1) | — Hours | — |
Secondary
BMS-986016 Maximum Observed Serum Concentration (Cmax)
BMS-986016 Maximum Observed Serum Concentration (Cmax). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 6.660 ug/mL |
| BMS-986016 20mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 3.697 ug/mL |
| BMS-986016 80mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 31.917 ug/mL |
| BMS-986016 80mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 22.738 ug/mL |
| BMS-986016 800mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 673.000 ug/mL |
| BMS-986016 800mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 224.802 ug/mL |
| BMS-986016 240mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 116.419 ug/mL |
| BMS-986016 240mg | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 68.718 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 19.990 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 44.532 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P1C1D1 | 59.600 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 149.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 57.900 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P1C3D1 | 165.000 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P0C3D1 | 88.196 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 40.402 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P1C1D1 | 68.400 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Maximum Observed Serum Concentration (Cmax) | P1C3D1 | 163.000 ug/mL |
Secondary
BMS-986016 Time of Maximum Observed Serum Concentration (Tmax)
BMS-986016 Time of Maximum Observed Serum Concentration (Tmax). Period 0 = treatment period Period 1 = Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 0.984 Hours |
| BMS-986016 20mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 0.97 Hours |
| BMS-986016 80mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 10.975 Hours |
| BMS-986016 80mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 1.300 Hours |
| BMS-986016 800mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 168.22 Hours |
| BMS-986016 800mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 4.167 Hours |
| BMS-986016 240mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 1.233 Hours |
| BMS-986016 240mg | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 1.825 Hours |
| BMS-986016 80mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 1.017 Hours |
| BMS-986016 80mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 3.950 Hours |
| BMS-986016 240mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 0.97 Hours |
| BMS-986016 240mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P1C3D1 | 24.000 Hours |
| BMS-986016 240mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 1.000 Hours |
| BMS-986016 240mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P1C1D1 | 4.000 Hours |
| BMS-986016 160mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P1C3D1 | 0.900 Hours |
| BMS-986016 160mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P0C3D1 | 3.467 Hours |
| BMS-986016 160mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | P1C1D1 | 1.750 Hours |
| BMS-986016 160mg + Nivolumab | BMS-986016 Time of Maximum Observed Serum Concentration (Tmax) | Period 0, Cycle 1, Day 1 (P0C1D1) | 1.600 Hours |
Secondary
BMS-986016 Total Body Clearance (CL/T)
BMS-986016 total body clearance (CL/T). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 = Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 1, Cycle 3 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 28.074 mL/h |
| BMS-986016 80mg | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 16.333 mL/h |
| BMS-986016 800mg | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 4.535 mL/h |
| BMS-986016 240mg | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 12.777 mL/h |
| BMS-986016 80mg + Nivolumab | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 12.974 mL/h |
| BMS-986016 240mg + Nivolumab | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 6.942 mL/h |
| BMS-986016 240mg + Nivolumab | BMS-986016 Total Body Clearance (CL/T) | P1C3D1 | 6.238 mL/h |
| BMS-986016 160mg + Nivolumab | BMS-986016 Total Body Clearance (CL/T) | P1C3D1 | 4.717 mL/h |
| BMS-986016 160mg + Nivolumab | BMS-986016 Total Body Clearance (CL/T) | P0C3D1 | 7.819 mL/h |
| Unknown | BMS-986016 Total Body Clearance (CL/T) | P1C1D1 | — mL/h |
| Unknown | BMS-986016 Total Body Clearance (CL/T) | Period 0, Cycle 1, Day 1 (P0C1D1) | — mL/h |
Secondary
BMS-986016 Trough Observed Serum Concentration (Ctrough)
BMS-986016 trough observed serum concentration (Ctrough). Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (% CV) is being reported. Period 0 = treatment period Period 1 - Re-challenge period
Time frame: PK assessment include the following timepoints: pre-dose, 1, 4, 24, 48, 96, 144, 192 hours end-of-infusion on cycle 1 Day 15, 29, 43, Cycle 2 Day 1, 15, 29, Cycle 3 Day 1, 15, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1, and Cycle 11 Day 1
Population: All participants who received at least one dose of BMS-986016 and have evaluable serum concentration data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BMS-986016 20mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 0.064 ug/mL |
| BMS-986016 20mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 0.256 ug/mL |
| BMS-986016 20mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 1.020 ug/mL |
| BMS-986016 20mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 0.777 ug/mL |
| BMS-986016 20mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 0.088 ug/mL |
| BMS-986016 20mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C5D1 | 0.729 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C9D1 | 62.000 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 19.018 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 2.266 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C5D1 | 1.917 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 1.457 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C11D1 | 48.100 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 6.609 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 4.324 ug/mL |
| BMS-986016 80mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C7D1 | 59.600 ug/mL |
| BMS-986016 800mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 293.000 ug/mL |
| BMS-986016 800mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 298.666 ug/mL |
| BMS-986016 800mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D29 | 289.000 ug/mL |
| BMS-986016 800mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 75.589 ug/mL |
| BMS-986016 800mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 313.000 ug/mL |
| BMS-986016 800mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 155.896 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 12.221 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C11D1 | 4.710 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C9D1 | 5.860 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C5D1 | 18.198 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 16.648 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 37.013 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C7D1 | 5.760 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 9.450 ug/mL |
| BMS-986016 240mg | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 20.982 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 9.556 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C5D1 | 23.381 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 13.066 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 9.389 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D43 | 9.435 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C9D1 | 22.800 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D15 | 6.209 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D29 | 26.700 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 3.848 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 6.867 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C11D1 | 31.200 ug/mL |
| BMS-986016 80mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C7D1 | 20.264 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 32.400 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D43 | 44.700 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 59.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D15 | 62.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D29 | 70.900 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 93.300 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 103.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C5D1 | 149.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C7D1 | 143.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C9D1 | 117.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C11D1 | 165.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C1D15 | 25.900 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C1D29 | 43.600 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C1D43 | 61.800 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C2D1 | 73.800 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C2D15 | 84.700 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C2D29 | 81.500 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C3D1 | 94.600 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C3D15 | 86.600 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C5D1 | 109.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C7D1 | 107.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C9D1 | 115.000 ug/mL |
| BMS-986016 240mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 19.500 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C11D1 | 115.000 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C1D15 | 24.200 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C3D1 | 85.500 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C1D29 | 41.000 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C7D1 | 105.000 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C1D43 | 56.000 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C3D15 | 86.100 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C2D1 | 58.700 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C9D1 | 110.000 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C5D1 | 57.068 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D15 | 45.685 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C3D1 | 45.535 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C2D15 | 69.400 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C7D1 | 58.408 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D29 | 36.675 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D15 | 30.218 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C2D1 | 28.428 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C5D1 | 70.100 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C9D1 | 56.054 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D43 | 25.234 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D29 | 18.221 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C1D15 | 10.609 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P1C2D29 | 71.900 ug/mL |
| BMS-986016 160mg + Nivolumab | BMS-986016 Trough Observed Serum Concentration (Ctrough) | P0C11D1 | 67.268 ug/mL |
Secondary
Number of Participants With Anti-BMS-986016 Antibodies (ADA)
Number of participants with anti-BMS-986016 antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is defined as a participant with positive seroconversion detected in the last sample before initiation of treatment. ADA-positive participant is a participant with at least one ADA-positive sample relative to baseline after initiation of the treatment. ADA negative participant is defined as a participant with no ADA positive sample after the initiation of treatment.
Time frame: From first dose to 135 days post last dose (Up to 52 months)
Population: All BMS-986016 treated participants with baseline and at least one post-baseline assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986016 20mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 3 Participants |
| BMS-986016 20mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 0 Participants |
| BMS-986016 20mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 0 Participants |
| BMS-986016 80mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 0 Participants |
| BMS-986016 80mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 1 Participants |
| BMS-986016 80mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 7 Participants |
| BMS-986016 800mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 5 Participants |
| BMS-986016 800mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 1 Participants |
| BMS-986016 800mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 0 Participants |
| BMS-986016 240mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 7 Participants |
| BMS-986016 240mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 6 Participants |
| BMS-986016 240mg | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 12 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 3 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 4 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 1 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 0 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Negative | 48 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | ADA Positive | 4 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Anti-BMS-986016 Antibodies (ADA) | Baseline ADA Positive | 5 Participants |
Secondary
Number of Participants With Anti-Nivolumab Antibodies (ADA)
Number of participants with anti-Nivolumab antibodies (ADA) with status as baseline ADA positive, ADA positive and ADA negative. Baseline ADA positive participant is defined as a participant with positive seroconversion detected in the last sample before initiation of treatment. ADA-positive participant is a participant with at least one ADA-positive sample relative to baseline after initiation of the treatment. ADA negative participant is defined as a participant with no ADA positive sample after the initiation of treatment.
Time frame: From first dose to 135 days post last dose (Up to 52 months)
Population: All Nivolumab treated participants with baseline and at least one post-baseline assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BMS-986016 80mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | ADA Positive | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | Baseline ADA Positive | 0 Participants |
| BMS-986016 80mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | ADA Negative | 4 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | ADA Positive | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | Baseline ADA Positive | 0 Participants |
| BMS-986016 240mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | ADA Negative | 1 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | Baseline ADA Positive | 0 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | ADA Negative | 45 Participants |
| BMS-986016 160mg + Nivolumab | Number of Participants With Anti-Nivolumab Antibodies (ADA) | ADA Positive | 1 Participants |