Phase 2/3 Randomized Study of BMS-986504 with Nab-Paclitaxel and Gemcitabine vs. Placebo in Metastatic Pancreatic Ductal Adenocarcinoma with Homozygous MTAP Deletion

Metastatic pancreatic ductal adenocarcinoma participants receive BMS‑986504 in combination with nab‑paclitaxel and gemcitabine versus placebo with the same chemotherapy backbone. The primary objective is to determine whether the investigational regimen prolongs (1) the time to disease worsening on radiographic assessment and (2) overall survival. Demonstrating a delay in radiologic progression and an extension of survival would address the poor prognosis associated with this disease stage.

Secondary objectives include assessing the overall efficacy of BMS‑986504 combined with nab‑paclitaxel and gemcitabine, encompassing measures such as response rates and disease control parameters.

The trial enrolled 308 participants diagnosed with metastatic pancreatic ductal adenocarcinoma. Eligible individuals were adults older than 18 years, comprising both male and female patients. Enrollment required histologic or cytologic confirmation of metastatic disease with at least one measurable lesion per RECIST v1.1, and documented homozygous MTAP deletion or loss in tumor tissue. Participants could not have received systemic anticancer therapy in the metastatic setting, although receipt of a single cycle of standard‑of‑care nab‑paclitaxel/gemcitabine prior to randomization was permitted. General health status was required to be sufficient to undergo study treatment; specific lifestyle factors such as diet or physical activity were not stipulated in the protocol.

The study is a randomized, double‑blind, placebo‑controlled phase 2/3 trial evaluating BMS‑986504 in combination with nab‑paclitaxel and gemcitabine versus matching placebo with nab‑paclitaxel and gemcitabine in participants with untreated metastatic pancreatic ductal adenocarcinoma harboring a homozygous MTAP deletion. After an initial screening visit to confirm eligibility (histologic diagnosis, MTAP deletion, measurable disease per RECIST v1.1, and absence of prior systemic therapy in the metastatic setting), participants are randomized 1:1 to receive either the investigational regimen or placebo. Treatment cycles are administered intravenously on a standard schedule, with oral study drug (MRTX1719 or matching placebo) taken concomitantly. Follow‑up visits occur at regular intervals for safety assessments, imaging to determine time to disease worsening, and collection of efficacy endpoints, including tumor response and survival data. The trial concludes with an end‑of‑study visit after treatment discontinuation, defined by disease progression, unacceptable toxicity, withdrawal of consent, or death. Participant involvement spans from the screening visit through the end‑of‑study assessment, with the overall trial projected to run from December 2025 to May 2029.

The experimental arm includes intravenous administration of gemcitabine at a dose of 9999 mg per infusion. The drug is supplied in an injectable solution and is delivered via the intravenous route according to the study dosing schedule. Administration details, including infusion rate and timing, are recorded in the participant’s case report form to ensure protocol adherence.

The combination regimen also contains intravenous paclitaxel albumin‑bound administered at a dose of 9999 mg/m² per infusion. The product is provided as a sterile solution for intravenous infusion and is given according to the protocol‑specified schedule. Infusion parameters and any dose modifications are documented for each treatment cycle.

An oral investigational agent, MRTX1719, is provided as a film‑coated tablet with a dosage of 9999 mg per dose. The tablet is taken by mouth as directed by the study protocol, with dosing frequency defined in the protocol. Compliance is monitored through pill counts and patient diaries, and any missed doses are recorded.

Participants in the control arm receive a matching oral placebo identical in appearance to the MRTX1719 tablet, also at a dose of 9999 mg. The placebo is administered orally on the same schedule as the active oral agent, and compliance monitoring procedures mirror those used for the investigational tablet.

All intravenous agents are administered in a clinical setting by qualified personnel, with vital signs and infusion reactions monitored before, during, and after each infusion. Oral study medication dispensing is tracked, and adherence is assessed at each study visit to ensure accurate evaluation of treatment exposure.

Efficacy will be evaluated using pre‑specified time‑to‑event and tumor‑response parameters in participants with untreated metastatic pancreatic ductal adenocarcinoma. The primary efficacy assessment comprises time to disease worsening on scans and overall survival (time to death) measured from randomization through the Phase 3 portion of the study.

Secondary efficacy evaluations include the rate of tumor shrinkage, duration of tumor shrinkage, time to tumor shrinkage, and the proportion of participants achieving disease control (tumor growth stabilization or shrinkage). These endpoints will be derived from radiographic assessments performed according to protocol‑specified imaging schedules.