This is an open-label, multicenter Phase 2 study evaluating BMS-986504 in participants with advanced and/or metastatic solid tumors that have MTAP deletion. The study includes a monotherapy component and a combination component in which BMS-986504 is given with other anti-cancer agents. The trial will assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of BMS-986504 alone and in combination regimens.
Participant must have histologically confirmed diagnosis of advanced and/or metastatic solid tumor malignancy with homozygous deletion of the MTAP gene detected in tumor tissue.
Depending on the cohort enrolled, participants must have received standard therapies appropriate for their tumor type and stage with disease progression on or after the most recent treatment (there must be no available treatment with curative intent or participant is ineligible or declines treatment) or be treatment-naïve with no prior systemic anticancer therapy for their unresectable or metastatic disease.
Participant must have presence of at least one measurable tumor lesion per RECIST v1.1 or mRECIST at baseline.
Coagulation function: International normalized ratio (INR) and activated partial thromboplastin time (APTT) must be ≤ 1.5 × ULN; subjects with liver metastasis or liver cancer must be ≤ 2 × ULN.
Participants must not have prior treatment with a PRMT5 or Methionine adenosyl transferase 2A (MAT2A) inhibitor.
Participants must not have active brain metastases or carcinomatous meningitis. Participants are eligible if brain metastases are adequately treated, and participants are neurologically stable for at least 2 weeks prior to enrollment without the use of corticosteroids or are on a stable or decreasing dose of ≤ 10 mg daily prednisone (or equivalent).
Participants must not have history of gastrointestinal disease or other gastrointestinal conditions within 6 months prior to enrollment (including uncontrolled nausea, vomiting, malabsorption syndrome or non-gastrointestinal fistula, gastrointestinal perforation, or intra-abdominal abscess) likely to alter absorption of study treatment or result in inability to swallow oral medications.
Participants must not have inadequate organ function, as determined by laboratory testing within the screening period.
Single group
BMS-986504
DrugSpecified dose on specified days
Daraxonrasib
DrugSpecified dose on specified days
Nivolumab + Relatlimab FDC
DrugSpecified dose on specified days
Temozolomide
DrugSpecified dose on specified days
Pumitamig
DrugSpecified dose on specified days
Pemetrexed
DrugSpecified dose on specified days
Carboplatin
DrugSpecified dose on specified days
Nab-paclitaxel
DrugSpecified dose on specified days
Gemcitabine
DrugSpecified dose on specified days
Paclitaxel
DrugSpecified dose on specified days
8
Treatment groupsSee each treatment group below.
Part 1: Number of participants who achieve Objective Response (OR)
OR is defined as confirmed complete response (CR) or partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Response Assessment in Neuro-Oncology (RANO) v2 or Modified RECIST v1.1
Part 2: Number of participants with adverse events meeting protocol defined dose limiting toxicities (DLTs) criteria
Part 2: Number of participants with adverse events (AE)
Part 2: Number of participants with Serious AEs (SAEs)
Part 1 and 2: Time to objective response (TTOR)
Defined as time from first dose to the date of the first documentation of objective tumor response (CR or PR) by RECIST v1.1 or RANO v2 or Modified RECIST v1.1
Part 1 and 2: Duration of response (DOR)
Defined as the time between the date of the first documentation of objective tumor response (CR or PR) and the date of disease progression or to death from any cause (whichever occurs first) by RECIST v1.1. or RANO v2 or Modified RECIST v1.1
Part 1 and 2: Number of participants who achieve disease control (DC)
Best Overall Response (BOR) of confirmed CR, confirmed PR, or stable disease (SD) for at least 4 months after start of treatment) by RECIST v1.1 or RANO v2 or Modified RECIST v1.1
Part 1: Number of participants with adverse events (AE)
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