Phase 2 Open‑Label Study of BMS‑986504 Monotherapy and Combination Therapy in Advanced/Metastatic Solid Tumors with Homozygous MTAP Deletion

The primary objective is to assess the objective response rate of BMS‑986504 monotherapy or in combination in patients with advanced or metastatic solid tumors harboring a homozygous MTAP deletion, thereby determining the proportion of participants whose tumors demonstrate measurable shrinkage. Secondary objectives include:

• Evaluation of time to objective response, defined as the interval from treatment initiation to the first documented tumor reduction.
• Assessment of duration of response, measuring how long tumor shrinkage or disappearance persists after response criteria are met.
• Determination of disease control rate, capturing the proportion of participants achieving stable disease, tumor reduction, or complete disappearance for a predefined period.
• Estimation of clinical benefit, reflecting any therapeutic advantage observed in the study population.
• Characterization of safety and tolerability of BMS‑986504, including the incidence and severity of adverse events.

The trial enrolled 137 participants diagnosed with advanced or metastatic solid tumors harboring a homozygous MTAP deletion. Both male and female adults were included, with all subjects being at least 18 years of age at consent. Eligibility required histologically confirmed disease, encompassing unresectable stage III or metastatic stage IV melanoma, advanced gastric adenocarcinoma or squamous esophageal cancer, locally advanced or metastatic urothelial carcinoma, supratentorial glioblastoma (including gliosarcoma), metastatic non‑small cell lung cancer, and metastatic pancreatic ductal adenocarcinoma. Selection was based on documented histopathology and confirmation of the MTAP gene deletion. General health status was limited to patients with the specified advanced malignancies; no additional lifestyle criteria such as diet or physical activity were stipulated in the available information.

The study is a phase II, open‑label, multi‑center trial evaluating BMS‑986504 as monotherapy and in combination with selected anticancer agents in adults with advanced or metastatic solid tumors harboring a homozygous MTAP deletion. Participants are enrolled after a screening visit that confirms eligibility, histology, and MTAP status; the screening window allows baseline assessments and laboratory tests. Eligible subjects receive the investigational product orally or intravenously according to the assigned regimen and are followed with serial safety and efficacy evaluations at defined intervals throughout the treatment period. Follow‑up visits include physical examination, tumor imaging, laboratory monitoring, and adverse‑event reporting to determine the primary endpoint of confirmed objective response and to assess secondary endpoints such as time to response, duration of response, and safety outcomes. The overall trial recruitment period spans from May 2026 to May 2032, with each participant remaining in the study from the first dose until disease progression, unacceptable toxicity, withdrawal of consent, or the end‑of‑study visit, whichever occurs first. Early termination criteria include documented grade ≥ 3 treatment‑related adverse events that are not manageable, rapid disease progression, or failure to meet required dosing compliance. The design does not incorporate blinding or randomization, and all assessments are performed in an open‑label manner.

Temozolomide is administered orally as a tablet (pharmaceutical form not specified) at a dose of 9999 mg per administration. The route of delivery is oral and dosing follows the study‑defined schedule, typically repeated in each treatment cycle. Oral intake is verified by patient diary and pill count to assess compliance.

Gemcitabine is supplied for intravenous infusion (form not specified) at a concentration of 9999 mg/mL. It is given by intravenous injection according to the protocol‑specified cycle, with infusion records maintained to ensure accurate administration and adherence.

Paclitaxel is provided for intravenous infusion (form not specified) at a concentration of 9999 mg/mL. The drug is administered intravenously on the days outlined in the trial schedule, and infusion documentation is used to monitor dosing compliance.

Paclitaxel albumin‑bound is delivered intravenously as a solution (form not specified) at a dose of 9999 mg per infusion. Administration follows the protocol‑defined timing, and infusion logs are reviewed to confirm correct delivery.

Pumitamig (commercially identified as BNT327) is supplied as a concentrate for solution for infusion at two strengths, 20 mg/mL and 50 mg/mL. Each preparation is administered intravenously at a dose of 9999 mg/mL according to the assigned treatment arm, with infusion records used for compliance monitoring.

Pemetrexed is prepared for intravenous infusion (form not specified) at a concentration of 9999 mg/mL. It is given intravenously per the study schedule, and dosing accuracy is verified through infusion documentation.

Navlimetostat is formulated as a film‑coated tablet and taken orally at a dose of 9999 mg per administration. Oral dosing follows the protocol‑defined frequency, with compliance assessed by pill count and patient diaries.

Carboplatin is administered intravenously as a solution (form not specified) at a concentration of 9999 mg/mL. Dosing occurs according to the protocol‑specified cycle, and infusion records are maintained for compliance verification.

Cisplatin is provided for intravenous infusion (form not specified) at a dose of 9999 mg/m². The drug is given intravenously on the schedule defined in the protocol, and dosing compliance is monitored through infusion logs and dose calculations.

Efficacy will be evaluated primarily by the proportion of participants achieving a confirmed objective response, defined as either a complete response or a partial response according to tumor assessment criteria. Secondary efficacy assessments include the time to objective response, measured from the first administered dose to the first documentation of an objective response; the duration of response, calculated from the date of first documented response to disease progression or death; and the best overall response, which encompasses confirmed complete response, partial response, or stable disease. In addition, a clinical benefit endpoint will be recorded when the best overall response is maintained for at least four months after treatment initiation.

All efficacy parameters will be collected from the start of therapy through the observation period until disease progression, death, or study completion. The incidence of each response category and the time‑based endpoints will be summarized using appropriate descriptive statistics, and median values with confidence intervals will be reported for time‑to‑event measures.