Advanced Cancer
Conditions
Brief summary
The purpose of this study is to determine whether BMS-986258 both monotherapy and in combination with Nivolumab is safe and tolerable in the treatment of advanced malignant tumors.
Interventions
Specified dose on specified days
Specified dose on specified days
Specified dose on specified days
Sponsors
Study design
Eligibility
Inclusion criteria
* Histologic confirmation of one of the 5 tumors \[renal cell carcinoma (RCC), colorectal cancer (CRC), non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), triple negative breast cancer (TNBC)\] (metastatic, recurrent, and/or unresectable), with measurable disease per response evaluation criteria in solid tumors v1.1 (RECIST v1.1) * Eastern Cooperative Oncology Group Performance Status of 0 or 1 * Participants must have received, and then progressed, relapsed, or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting according to solid tumor histologies * Women must agree to follow specific methods of contraception, if applicable
Exclusion criteria
* Active, known or suspected autoimmune disease * Cytotoxic agents, unless at least 4 weeks have elapsed from last dose of prior anti-cancer therapy and initiation of study therapy * Other active malignancy requiring concurrent intervention Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks) | An Adverse Event (AE) is any new untoward medical occurrence or worsening of a preexisting medical condition in a study participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose: * Results in death * Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event) * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect. |
| Number of Participants Who Died During the Study | From first dose until death due to any cause (up to approximately 78 months) | The number of participants who died during the study. |
| Number of Participants With Dose Limiting Toxicities (DLTs) | From first dose (Cycle 1 Day 1) until day 28 (Cycle 1 Day 28) | Dose-limiting toxicity (DLT) refers to a side effect or adverse reaction caused by a drug that is severe enough to prevent an increase in dose or level of that drug. It is typically identified during clinical trials to determine the highest dose of a drug that can be given safely without causing unacceptable side effects. A participant was considered DLT evaluable if they received 1 dose of BMS-986258 in Part A or 1 dose of BMS-986258 and nivolumab 480mg in Part B and completed the DLT observation period. Participants who withdraw from the study during the 4-week DLT evaluation period for reasons other than a DLT may be replaced with a new participant at the same dose level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Plasma Concentration (Cmax) of BMS-986258 | Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks) | Cmax (Maximum Concentration) is the highest level of a drug in the blood after it has been taken. It shows the peak level of the drug, which helps in understanding how much of the drug is absorbed and how strong its effects might be. |
| Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks) | AUC (0-T) is the total exposure to the drug over a specific period; from the time you take it until a specified time. It helps in understanding the overall amount of drug that has been in your body over that time period. |
| Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Part A and B: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks) | AUC(TAU) (Area Under the Curve over the Dosing Interval) is the total exposure to the drug over one complete dosing interval (the time between doses). It helps in understanding how much of the drug is in your body over the entire period between doses, which is important for determining the right dosing schedule. |
| Objective Response Rate (ORR) | From first dose until disease progression or death, whichever occurred first (up to approximately 78 months) | Objective response rate (ORR) is defined as the percent of treated participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. |
| Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks) | Tmax (Time to Reach Maximum Concentration) is the time it takes for the drug to reach its highest level in the blood after taking it. It helps in understanding how quickly the drug starts to work and reaches its peak effect. |
| Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks) | Baseline ADA-positive participant is defined as a participant who has an ADA-detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment |
| Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Part A and B: On Cycle 1 Day 29 and Cycle 3 Day 29 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 29 and Cycle 2 Day 1 predose (1 cycle = 8 weeks) | Ctau (Concentration at the End of the Dosing Interval) is the level of the drug in the blood just before the next dose is due. It shows how much of the drug remains in your body before taking the next dose, which helps in ensuring that the drug levels stay effective without dropping too low. |
| Median Duration of Response (mDOR) | From first dose until disease progression or death whichever occurred first (up to approximately 78 months) | Median duration of response (mDOR) for a participant with a best overall response (BOR) of complete response (CR) or partial response (PR) is defined as the time between the date of first response and the date of the first objectively documented disease progression (DP) per RECIST v1.1 or death, whichever occurred first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Disease Progression (DP): At least a 20% increase in the sum of the diameters of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions. Based on Kaplan-Meier estimates. |
| Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | At 6, 9, and 12 months after first dose | Progression free survival (PFS) for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurred first. Disease Progression (DP): At least a 20% increase in the sum of the diameters of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions. |
Countries
Australia, Canada, Japan, United States
Participant flow
Pre-assignment details
Participants were treated in Part A, Part A1, and Part B. No participants were enrolled or treated in Part C. 4 participants in Part A1 transitioned to Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: BMS-986258 8 mg Participants received 8 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 3 |
| Part A: BMS-986258 24 mg Participants received 24 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 3 |
| Part A: BMS-986258 72 mg Participants received 72 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 4 |
| Part A: BMS-986258 200 mg Participants received 200 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 4 |
| Part A: BMS-986258 480 mg Participants received 480 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 4 |
| Part A: BMS-986258 800 mg Participants received 800 mg BMS-986258 IV every 4 weeks (Q4W) for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 9 |
| Part A: BMS-986258 1200 mg Participants received 1200 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 3 |
| Part A: BMS-986258 1600 mg Participants received 1600 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 5 |
| Part A: BMS-986258 2400 mg Participants received 2400 mg BMS-986258 IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 8 |
| Part B: BMS-986258 480 mg + NIVO 480 mg Participants received 480 mg BMS-986258 and 480 mg nivolumab IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 4 |
| Part B: BMS-986258 800 mg + NIVO 480 mg Participants received 800 mg BMS-986258 and 480 mg nivolumab IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 11 |
| Part B: BMS-986258 1200 mg + NIVO 480 mg Participants received 1200 mg BMS-986258 and 480 mg nivolumab IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 4 |
| Part B: BMS-986258 1600 mg + NIVO 480 mg Participants received 1600 mg BMS-986258 and 480 mg nivolumab IV every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 15 |
| Part A1: BMS-986258 1200 mg + ENHANZE Participants received 1200 mg BMS-986258 with rHuPH20 (ENHANZE) SC for the first dose in Cycle 1. All subsequent doses of BMS-986258 were received as monotherapy IV, every 4 weeks (Q4W) twice per cycle for up to 96 weeks (12 treatment cycles (each cycle = 8 weeks)). | 15 |
| Total | 92 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Disease progression | 3 | 3 | 3 | 4 | 4 | 6 | 3 | 4 | 2 | 4 | 9 | 3 | 7 | 7 |
| Overall Study | Not reported | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Participant requested to discontinue study treatment | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Participant withdrew consent | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Study drug toxicity | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A: BMS-986258 8 mg | Part A: BMS-986258 24 mg | Part A: BMS-986258 72 mg | Part A: BMS-986258 200 mg | Part A: BMS-986258 480 mg | Part A: BMS-986258 800 mg | Part A: BMS-986258 1200 mg | Part A: BMS-986258 1600 mg | Part A: BMS-986258 2400 mg | Part B: BMS-986258 480 mg + NIVO 480 mg | Part B: BMS-986258 800 mg + NIVO 480 mg | Part B: BMS-986258 1200 mg + NIVO 480 mg | Part B: BMS-986258 1600 mg + NIVO 480 mg | Part A1: BMS-986258 1200 mg + ENHANZE | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.7 Years STANDARD_DEVIATION 16.17 | 45.7 Years STANDARD_DEVIATION 6.03 | 61.5 Years STANDARD_DEVIATION 3.11 | 67.0 Years STANDARD_DEVIATION 4.24 | 60 Years STANDARD_DEVIATION 12.44 | 61.1 Years STANDARD_DEVIATION 7.1 | 65.3 Years STANDARD_DEVIATION 8.33 | 54.8 Years STANDARD_DEVIATION 8.07 | 58.4 Years STANDARD_DEVIATION 5.85 | 64.5 Years STANDARD_DEVIATION 5.07 | 62.5 Years STANDARD_DEVIATION 7.75 | 57.3 Years STANDARD_DEVIATION 16.2 | 58.5 Years STANDARD_DEVIATION 15 | 57.8 Years STANDARD_DEVIATION 12.27 | 59.6 Years STANDARD_DEVIATION 10.62 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 4 Participants | 4 Participants | 3 Participants | 8 Participants | 3 Participants | 5 Participants | 8 Participants | 3 Participants | 10 Participants | 4 Participants | 11 Participants | 14 Participants | 82 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 4 Participants | 3 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 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 | 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 | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) White | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 2 Participants | 2 Participants | 5 Participants | 3 Participants | 8 Participants | 2 Participants | 8 Participants | 10 Participants | 55 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 4 Participants | 3 Participants | 1 Participants | 4 Participants | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 5 Participants | 4 Participants | 35 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 0 Participants | 1 Participants | 3 Participants | 5 Participants | 0 Participants | 4 Participants | 6 Participants | 2 Participants | 8 Participants | 2 Participants | 10 Participants | 11 Participants | 57 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 3 | 3 / 3 | 3 / 4 | 3 / 4 | 3 / 4 | 7 / 9 | 3 / 3 | 4 / 5 | 5 / 8 | 3 / 4 | 9 / 11 | 0 / 4 | 10 / 15 | 7 / 11 | 1 / 2 | 0 / 2 |
| other Total, other adverse events | 2 / 3 | 2 / 3 | 4 / 4 | 4 / 4 | 4 / 4 | 8 / 9 | 2 / 3 | 5 / 5 | 8 / 8 | 4 / 4 | 9 / 11 | 4 / 4 | 15 / 15 | 9 / 11 | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 1 / 3 | 2 / 3 | 3 / 4 | 1 / 4 | 0 / 4 | 4 / 9 | 1 / 3 | 3 / 5 | 2 / 8 | 2 / 4 | 6 / 11 | 1 / 4 | 6 / 15 | 3 / 11 | 0 / 2 | 0 / 2 |
Outcome results
Number of Participants Who Died During the Study
The number of participants who died during the study.
Time frame: From first dose until death due to any cause (up to approximately 78 months)
Population: All treated participants. Participants who crossed over from part A1 are accounted for under their original arm assignment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: BMS-986258 8 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part A: BMS-986258 24 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part A: BMS-986258 72 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part A: BMS-986258 200 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part A: BMS-986258 480 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part A: BMS-986258 800 mg | Number of Participants Who Died During the Study | 7 Participants |
| Part A: BMS-986258 1200 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part A: BMS-986258 1600 mg | Number of Participants Who Died During the Study | 4 Participants |
| Part A: BMS-986258 2400 mg | Number of Participants Who Died During the Study | 5 Participants |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Number of Participants Who Died During the Study | 3 Participants |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Number of Participants Who Died During the Study | 9 Participants |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Number of Participants Who Died During the Study | 0 Participants |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Number of Participants Who Died During the Study | 10 Participants |
| Part A1: BMS-986258 1200 mg + ENHANZE | Number of Participants Who Died During the Study | 8 Participants |
Number of Participants With Adverse Events (AEs)
An Adverse Event (AE) is any new untoward medical occurrence or worsening of a preexisting medical condition in a study participant administered study treatment and that does not necessarily have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study treatment, whether or not considered related to the study treatment. A Serious Adverse Event (SAE) is any untoward medical occurrence that, at any dose: * Results in death * Is life-threatening (defined as an event in which the participant was at risk of death at the time of the event) * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect.
Time frame: From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks)
Population: All treated participants. Participants who started in the Part A1 group but transitioned to Part B are accounted for in both treatment groups.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: BMS-986258 8 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A: BMS-986258 8 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 3 Participants |
| Part A: BMS-986258 8 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 1 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 3 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 2 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 3 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 1 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 4 Participants |
| Part A: BMS-986258 200 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 1 Participants |
| Part A: BMS-986258 200 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 4 Participants |
| Part A: BMS-986258 200 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 1 Participants |
| Part A: BMS-986258 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A: BMS-986258 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 4 Participants |
| Part A: BMS-986258 480 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 0 Participants |
| Part A: BMS-986258 800 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 2 Participants |
| Part A: BMS-986258 800 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 8 Participants |
| Part A: BMS-986258 800 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 4 Participants |
| Part A: BMS-986258 1200 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A: BMS-986258 1200 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 2 Participants |
| Part A: BMS-986258 1200 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 1 Participants |
| Part A: BMS-986258 1600 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A: BMS-986258 1600 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 5 Participants |
| Part A: BMS-986258 1600 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 3 Participants |
| Part A: BMS-986258 2400 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A: BMS-986258 2400 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 2 Participants |
| Part A: BMS-986258 2400 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 8 Participants |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 2 Participants |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 4 Participants |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 6 Participants |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 11 Participants |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 1 Participants |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 6 Participants |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 6 Participants |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 3 Participants |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 17 Participants |
| Part A1: BMS-986258 1200 mg + ENHANZE | Number of Participants With Adverse Events (AEs) | Serious Adverse Events (SAEs) | 3 Participants |
| Part A1: BMS-986258 1200 mg + ENHANZE | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) leading to discontinuation of study treatment | 0 Participants |
| Part A1: BMS-986258 1200 mg + ENHANZE | Number of Participants With Adverse Events (AEs) | Adverse Events (AEs) | 13 Participants |
Number of Participants With Dose Limiting Toxicities (DLTs)
Dose-limiting toxicity (DLT) refers to a side effect or adverse reaction caused by a drug that is severe enough to prevent an increase in dose or level of that drug. It is typically identified during clinical trials to determine the highest dose of a drug that can be given safely without causing unacceptable side effects. A participant was considered DLT evaluable if they received 1 dose of BMS-986258 in Part A or 1 dose of BMS-986258 and nivolumab 480mg in Part B and completed the DLT observation period. Participants who withdraw from the study during the 4-week DLT evaluation period for reasons other than a DLT may be replaced with a new participant at the same dose level.
Time frame: From first dose (Cycle 1 Day 1) until day 28 (Cycle 1 Day 28)
Population: All treated participants who were evaluable for DLTs.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: BMS-986258 8 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 200 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 480 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 800 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 1200 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 1600 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A: BMS-986258 2400 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| Part A1: BMS-986258 1200 mg + ENHANZE | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258
AUC (0-T) is the total exposure to the drug over a specific period; from the time you take it until a specified time. It helps in understanding the overall amount of drug that has been in your body over that time period.
Time frame: Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)
Population: All treated participants with available PK results. PK evaluable participants who crossed over from Part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: BMS-986258 8 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 53.7 h*ug/mL | Geometric Coefficient of Variation 50.8 |
| Part A: BMS-986258 24 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 457 h*ug/mL | Geometric Coefficient of Variation 56 |
| Part A: BMS-986258 24 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 1400 h*ug/mL | — |
| Part A: BMS-986258 72 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 4690 h*ug/mL | Geometric Coefficient of Variation 43.3 |
| Part A: BMS-986258 200 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 8180 h*ug/mL | Geometric Coefficient of Variation 101 |
| Part A: BMS-986258 200 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 13400 h*ug/mL | — |
| Part A: BMS-986258 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 26100 h*ug/mL | Geometric Coefficient of Variation 46.7 |
| Part A: BMS-986258 800 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 102000 h*ug/mL | — |
| Part A: BMS-986258 800 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 46000 h*ug/mL | Geometric Coefficient of Variation 83.9 |
| Part A: BMS-986258 1200 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 97000 h*ug/mL | Geometric Coefficient of Variation 23.3 |
| Part A: BMS-986258 1600 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 75300 h*ug/mL | Geometric Coefficient of Variation 44.5 |
| Part A: BMS-986258 2400 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 179000 h*ug/mL | Geometric Coefficient of Variation 24.3 |
| Part A: BMS-986258 2400 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 135000 h*ug/mL | — |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 29000 h*ug/mL | Geometric Coefficient of Variation 51.4 |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 29800 h*ug/mL | — |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 38200 h*ug/mL | — |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 44300 h*ug/mL | Geometric Coefficient of Variation 34.9 |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 84100 h*ug/mL | Geometric Coefficient of Variation 83.2 |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 89000 h*ug/mL | — |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 118000 h*ug/mL | Geometric Coefficient of Variation 25.4 |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 3 Day 1 | 171000 h*ug/mL | Geometric Coefficient of Variation 27 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 1 | 48500 h*ug/mL | Geometric Coefficient of Variation 51.1 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Area Under the Curve From Time 0 to T (AUC(0-T)) of BMS-986258 | Cycle 1 Day 29 | 138000 h*ug/mL | Geometric Coefficient of Variation 21 |
Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258
AUC(TAU) (Area Under the Curve over the Dosing Interval) is the total exposure to the drug over one complete dosing interval (the time between doses). It helps in understanding how much of the drug is in your body over the entire period between doses, which is important for determining the right dosing schedule.
Time frame: Part A and B: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: 0 to 28 days post-dose on Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)
Population: All treated participants with available PK results. PK evaluable participants who crossed over from Part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: BMS-986258 24 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 587 h*ug/mL | Geometric Coefficient of Variation 41.9 |
| Part A: BMS-986258 24 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 1440 h*ug/mL | — |
| Part A: BMS-986258 72 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 4870 h*ug/mL | Geometric Coefficient of Variation 43.7 |
| Part A: BMS-986258 200 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 13400 h*ug/mL | — |
| Part A: BMS-986258 200 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 8400 h*ug/mL | Geometric Coefficient of Variation 105 |
| Part A: BMS-986258 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 26900 h*ug/mL | Geometric Coefficient of Variation 47.4 |
| Part A: BMS-986258 800 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 56400 h*ug/mL | Geometric Coefficient of Variation 45 |
| Part A: BMS-986258 800 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 102000 h*ug/mL | — |
| Part A: BMS-986258 1200 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 100000 h*ug/mL | Geometric Coefficient of Variation 18 |
| Part A: BMS-986258 1600 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 85800 h*ug/mL | Geometric Coefficient of Variation 21.9 |
| Part A: BMS-986258 2400 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 187000 h*ug/mL | Geometric Coefficient of Variation 29.5 |
| Part A: BMS-986258 2400 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 135000 h*ug/mL | — |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 29000 h*ug/mL | Geometric Coefficient of Variation 51.4 |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 18600 h*ug/mL | — |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 47300 h*ug/mL | Geometric Coefficient of Variation 29.4 |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 38200 h*ug/mL | — |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 89600 h*ug/mL | Geometric Coefficient of Variation 67.9 |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 89000 h*ug/mL | — |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 3 Day 1 | 172000 h*ug/mL | Geometric Coefficient of Variation 26.1 |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 120000 h*ug/mL | Geometric Coefficient of Variation 22.5 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 29 | 134000 h*ug/mL | Geometric Coefficient of Variation 17.3 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Area Under the Curve Over the Dosing Interval AUC(TAU) of BMS-986258 | Cycle 1 Day 1 | 46200 h*ug/mL | Geometric Coefficient of Variation 53.9 |
Concentration at the End of the Dosing Interval (Ctau) of BMS-986258
Ctau (Concentration at the End of the Dosing Interval) is the level of the drug in the blood just before the next dose is due. It shows how much of the drug remains in your body before taking the next dose, which helps in ensuring that the drug levels stay effective without dropping too low.
Time frame: Part A and B: On Cycle 1 Day 29 and Cycle 3 Day 29 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 29 and Cycle 2 Day 1 predose (1 cycle = 8 weeks)
Population: All treated participants with available PK results. PK evaluable participants who crossed over from Part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: BMS-986258 24 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 0.0711 ug/mL | — |
| Part A: BMS-986258 24 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 0.0245 ug/mL | Geometric Coefficient of Variation 52.3 |
| Part A: BMS-986258 72 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 1.58 ug/mL | Geometric Coefficient of Variation 116 |
| Part A: BMS-986258 200 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 2.59 ug/mL | Geometric Coefficient of Variation 369 |
| Part A: BMS-986258 200 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 8.32 ug/mL | — |
| Part A: BMS-986258 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 15.5 ug/mL | Geometric Coefficient of Variation 68.6 |
| Part A: BMS-986258 800 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 37.2 ug/mL | Geometric Coefficient of Variation 62.9 |
| Part A: BMS-986258 800 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 80.3 ug/mL | — |
| Part A: BMS-986258 1200 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 55.7 ug/mL | Geometric Coefficient of Variation 55.2 |
| Part A: BMS-986258 1600 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 36.9 ug/mL | Geometric Coefficient of Variation 68.5 |
| Part A: BMS-986258 2400 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 109 ug/mL | Geometric Coefficient of Variation 44.6 |
| Part A: BMS-986258 2400 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 71.3 ug/mL | — |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 15.6 ug/mL | Geometric Coefficient of Variation 82.3 |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 7.77 ug/mL | — |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 25 ug/mL | — |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 23.5 ug/mL | Geometric Coefficient of Variation 70.3 |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 39.8 ug/mL | Geometric Coefficient of Variation 229 |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 37.1 ug/mL | — |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 68.4 ug/mL | Geometric Coefficient of Variation 47.1 |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 3 Day 29 predose | 121 ug/mL | Geometric Coefficient of Variation 36.6 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 1 Day 29 predose | 37.7 ug/mL | Geometric Coefficient of Variation 80.2 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Concentration at the End of the Dosing Interval (Ctau) of BMS-986258 | Cycle 2 Day 1 predose | 114 ug/mL | Geometric Coefficient of Variation 13 |
Maximum Plasma Concentration (Cmax) of BMS-986258
Cmax (Maximum Concentration) is the highest level of a drug in the blood after it has been taken. It shows the peak level of the drug, which helps in understanding how much of the drug is absorbed and how strong its effects might be.
Time frame: Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)
Population: All treated participants with available PK results. PK evaluable participants who crossed over from Part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: BMS-986258 8 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 2.27 ug/mL | Geometric Coefficient of Variation 53.8 |
| Part A: BMS-986258 24 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 9.26 ug/mL | — |
| Part A: BMS-986258 24 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 5.34 ug/mL | Geometric Coefficient of Variation 36.2 |
| Part A: BMS-986258 72 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 31.5 ug/mL | Geometric Coefficient of Variation 10.9 |
| Part A: BMS-986258 200 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 50 ug/mL | — |
| Part A: BMS-986258 200 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 47.2 ug/mL | Geometric Coefficient of Variation 120 |
| Part A: BMS-986258 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 121 ug/mL | Geometric Coefficient of Variation 30.7 |
| Part A: BMS-986258 800 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 356 ug/mL | — |
| Part A: BMS-986258 800 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 239 ug/mL | Geometric Coefficient of Variation 35.6 |
| Part A: BMS-986258 1200 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 423 ug/mL | Geometric Coefficient of Variation 12.9 |
| Part A: BMS-986258 1600 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 412 ug/mL | Geometric Coefficient of Variation 26.7 |
| Part A: BMS-986258 2400 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 605 ug/mL | — |
| Part A: BMS-986258 2400 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 890 ug/mL | Geometric Coefficient of Variation 29.2 |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 111 ug/mL | — |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 154 ug/mL | Geometric Coefficient of Variation 43.4 |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 244 ug/mL | Geometric Coefficient of Variation 24.8 |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 161 ug/mL | — |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 422 ug/mL | — |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 449 ug/mL | Geometric Coefficient of Variation 31.5 |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 579 ug/mL | Geometric Coefficient of Variation 19.4 |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 3 Day 1 | 684 ug/mL | Geometric Coefficient of Variation 18.1 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 29 | 479 ug/mL | Geometric Coefficient of Variation 21.2 |
| Part A1: BMS-986258 1200 mg + ENHANZE | Maximum Plasma Concentration (Cmax) of BMS-986258 | Cycle 1 Day 1 | 121 ug/mL | Geometric Coefficient of Variation 44.1 |
Median Duration of Response (mDOR)
Median duration of response (mDOR) for a participant with a best overall response (BOR) of complete response (CR) or partial response (PR) is defined as the time between the date of first response and the date of the first objectively documented disease progression (DP) per RECIST v1.1 or death, whichever occurred first. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Disease Progression (DP): At least a 20% increase in the sum of the diameters of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions. Based on Kaplan-Meier estimates.
Time frame: From first dose until disease progression or death whichever occurred first (up to approximately 78 months)
Population: All treated participants witha complete or partial response. Prespecified to be reported collectively per Part. Response evaluable participants who crossed over from part A1 to Part B are accounted for in both arms.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: BMS-986258 24 mg | Median Duration of Response (mDOR) | NA Months |
Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab
Baseline ADA-positive participant is defined as a participant who has an ADA-detected sample at baseline. ADA-positive participant is a participant with at least 1 ADA-positive sample relative to baseline after initiation of the treatment
Time frame: From first dose until 100 days after last dose of study therapy (up to approximately 78 weeks)
Population: All treated participants with baseline and at least one post-baseline pre-infusion ADA assessment. Prespecified to be reported collectively per Part. PK evaluable participants who crossed over from Part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: BMS-986258 8 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | Baseline ADA positive: BMS-986258 | 0 Participants |
| Part A: BMS-986258 8 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | ADA positive: BMS-986258 | 2 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | ADA positive: BMS-986258 | 0 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | Baseline ADA positive: BMS-986258 | 0 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | Baseline ADA positive: nivolumab | 1 Participants |
| Part A: BMS-986258 24 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | ADA positive: nivolumab | 2 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | ADA positive: nivolumab | 0 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | Baseline ADA positive: nivolumab | 0 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | Baseline ADA positive: BMS-986258 | 0 Participants |
| Part A: BMS-986258 72 mg | Number of Participants With Anti-Drug Antibodies to BMS-986258 or Nivolumab | ADA positive: BMS-986258 | 0 Participants |
Objective Response Rate (ORR)
Objective response rate (ORR) is defined as the percent of treated participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) per RECIST v1.1. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: From first dose until disease progression or death, whichever occurred first (up to approximately 78 months)
Population: All treated participants. Prespecified to be reported collectively per Part. Participants who crossed over from part A1 to Part B are accounted for in both arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: BMS-986258 8 mg | Objective Response Rate (ORR) | 0 Percent of Participants |
| Part A: BMS-986258 24 mg | Objective Response Rate (ORR) | 5.4 Percent of Participants |
| Part A: BMS-986258 72 mg | Objective Response Rate (ORR) | 0 Percent of Participants |
Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months
Progression free survival (PFS) for a participant is defined as the time from the first dosing date to the date of first objectively documented disease progression or death due to any cause, whichever occurred first. Disease Progression (DP): At least a 20% increase in the sum of the diameters of target lesions, with an absolute increase of at least 5 mm, or the appearance of new lesions.
Time frame: At 6, 9, and 12 months after first dose
Population: All treated participants. Prespecified to be reported collectively per Part. Treated participants who crossed over from part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part A: BMS-986258 8 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 12-month | 17.1 Percent of Participants |
| Part A: BMS-986258 8 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 9-month | 17.1 Percent of Participants |
| Part A: BMS-986258 8 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 6-month | 21.4 Percent of Participants |
| Part A: BMS-986258 24 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 6-month | 21.9 Percent of Participants |
| Part A: BMS-986258 24 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 9-month | 8.2 Percent of Participants |
| Part A: BMS-986258 24 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 12-month | 0.0 Percent of Participants |
| Part A: BMS-986258 72 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 6-month | 8.7 Percent of Participants |
| Part A: BMS-986258 72 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 12-month | 0.0 Percent of Participants |
| Part A: BMS-986258 72 mg | Progression-Free Survival (PFS) Rate at 6, 9, and 12 Months | 9-month | 8.7 Percent of Participants |
Time to Reach Maximum Concentration (Tmax) of BMS-986258
Tmax (Time to Reach Maximum Concentration) is the time it takes for the drug to reach its highest level in the blood after taking it. It helps in understanding how quickly the drug starts to work and reaches its peak effect.
Time frame: Part A and B: On Cycle 1 Day 1 and Cycle 3 Day 1 (1 cycle = 8 weeks); Part A1: On Cycle 1 Day 1 and Cycle 1 Day 29 (1 cycle = 8 weeks)
Population: All treated participants with available PK results. PK evaluable participants who crossed over from Part A1 to Part B are accounted for in both arms.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Part A: BMS-986258 8 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 0.808 Hours |
| Part A: BMS-986258 24 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 1.23 Hours |
| Part A: BMS-986258 24 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 4 Hours |
| Part A: BMS-986258 72 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 1.4 Hours |
| Part A: BMS-986258 200 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 0.7 Hours |
| Part A: BMS-986258 200 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 2.11 Hours |
| Part A: BMS-986258 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 3.92 Hours |
| Part A: BMS-986258 800 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 0.998 Hours |
| Part A: BMS-986258 800 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 4.27 Hours |
| Part A: BMS-986258 1200 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 1.09 Hours |
| Part A: BMS-986258 1600 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 1.47 Hours |
| Part A: BMS-986258 2400 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 3.11 Hours |
| Part A: BMS-986258 2400 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 2 Hours |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 0.499 Hours |
| Part B: BMS-986258 480 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 0.812 Hours |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 0.467 Hours |
| Part B: BMS-986258 800 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 4.18 Hours |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 1.02 Hours |
| Part B: BMS-986258 1200 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 2.02 Hours |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 2.29 Hours |
| Part B: BMS-986258 1600 mg + NIVO 480 mg | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 3 Day 1 | 2.74 Hours |
| Part A1: BMS-986258 1200 mg + ENHANZE | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 29 | 1.26 Hours |
| Part A1: BMS-986258 1200 mg + ENHANZE | Time to Reach Maximum Concentration (Tmax) of BMS-986258 | Cycle 1 Day 1 | 123 Hours |