Trial Outcomes & Findings for A Study of BMS-986249 Alone and in Combination With Nivolumab in Advanced Solid Tumors (NCT NCT03369223)

A Study of BMS-986249 Alone and in Combination With Nivolumab in Advanced Solid Tumors

Adverse Events (AEs): Adverse events are any unwanted or harmful medical occurrences in a participant who receives a study drug or intervention. These events may or may not be related to the treatment. Serious Adverse Events (SAEs): Serious adverse events are adverse events that result in death, are life-threatening, require hospitalization or prolong existing hospitalization, cause significant disability or incapacity, or result in a birth defect.

Dose-limiting toxicities (DLTs) were defined by the incidence, intensity, and duration of adverse events (AEs) possibly related to study treatment during the 5-week (35-day) DLT evaluation period for both BMS-986249 monotherapy and combination therapy. Participants who received at least 2 doses and completed or discontinued due to a DLT within this period were considered DLT-evaluable. Those who withdrew or received less than 2 doses for reasons other than a DLT were not DLT-evaluable and could be replaced. Any drug-related AE meeting DLT criteria resulted in discontinuation of study treatment. DLTs guided dose escalation and helped define the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D).

Number of Participants who Died

Number of Participants with Shifts from Baseline in Laboratory Tests

Adverse Events (AEs): Adverse events are any unwanted or harmful medical occurrences in a participant who receives a study drug or intervention. These events may or may not be related to the treatment. Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; no intervention needed. Grade 2: Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling. Grade 4: Life-threatening consequences; urgent intervention required. Grade 5: Death related to the adverse event.

Objective response rate (ORR) is defined as the percent of participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must also have reduction in the short axis to \<10mm. Partial Response (PR): At least a30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

TTD in Global Health Status/QoL and Physical Functioning will be defined as the time from randomization until a clinically meaningful decline (i.e., reduction ≥10 points) from baseline in EORTC QLQ-C30 global health/quality of life subscale score and Physical Functioning Scale score.

Adverse Events (AEs): Adverse events are any unwanted or harmful medical occurrences in a participant who receives a study drug or intervention. These events may or may not be related to the treatment. Serious Adverse Events (SAEs): Serious adverse events are adverse events that result in death, are life-threatening, require hospitalization or prolong existing hospitalization, cause significant disability or incapacity, or result in a birth defect.

Best Overall Response (BOR) is defined as the best response recorded from the start of randomization or first dosing date until the date of objectively documented PD based on RECIST v1.1 criteria or PCWG3 (for prostate cancer), or the date of ubsequent therapy (including tumordirected radiotherapy and tumor-directed surgery which are not for palliative purpose), whichever occurs first.

Defined as the time between the date of randomization (Part 2A), or first dosing for Part 1 and supplemental analysis in Part 2A, and the date of first documented tumor progression, based on investigator assessments (per RECIST v1.1 criteria or PCWG3), or death due to any cause, whichever occurs first.

Defined as the time between the date of first documented response (CR or PR) to the date of the first documented tumor progression, as determined by RECIST v1.1 or PCWG3 criteria, or death due to any cause, whichever occurs first. Subjects who start subsequent therapy without a prior reported progression will be censored at the last evaluable tumor assessments prior to initiation of the subsequent anticancer therapy. Subjects who die without a reported prior progression will be considered to have progressed on the date of their death. Subjects who neither progress nor die, DOR will be censored on the date of their last evaluable tumor assessment. DOR will be evaluated for responders (confirmed CR or PR) only.

Defined as the time from first dosing (Part 1)/randomization (Part 2A) to the date of the first confirmed documented response (CR or PR). TTR will be evaluated for responders (confirmed CR or PR) only.

Objective response rate (ORR) is defined as the percent of participants whose best overall response (BOR) is either complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or Prostate Cancer Working Group (PCWG) 3. For both RECIST v1.1 and PCWG3: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must also have reduction in the short axis to \<10mm. Partial Response (PR): At least a30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Cmax: The highest concentration of BMS-986249 in the blood after dosing. Ctau: The concentration of BMS-986249 in the blood at the end of a dosing interval, just before the next dose

AUC(0-T): The total amount of BMS-986249 in the blood from the time it is given until a specific time point. AUC(TAU): The total amount of BMS-986249 in the blood over one dosing interval

AI\_Cmax: How much the highest concentration of BMS-986249 increases after multiple doses compared to a single dose. AI\_AUC: How much the total exposure to BMS-986249 increases after multiple doses compared to a single dose.

Number of Participants with Shifts from Baseline in Laboratory Tests