Phase 1 GS-2426 MAT2A small‑molecule inhibitor in MTAP‑deleted advanced solid tumors

This Phase 1, multicenter, open-label Gilead Sciences study evaluates GS-2426, a small-molecule inhibitor of methionine adenosyltransferase 2A (MAT2A), in adults with advanced/metastatic solid tumors harboring MTAP deletion. It uses a Phase 1a dose-escalation design to define maximum tolerated/maximum administered dose and select a recommended Phase 2 dose, followed by Phase 1b indication-specific expansion cohorts at the chosen dose. MTAP loss is a relatively common tumor-suppressor–adjacent deletion across cancers (often co-deleted with CDKN2A) and creates a metabolic vulnerability that MAT2A inhibition is designed to exploit via synthetic lethality-like biology. Participants must have limited effective standard options, since today’s care for advanced solid tumors remains tumor-specific systemic therapy (targeted therapy when driver-positive, immunotherapy when indicated, and otherwise sequential chemotherapy/ADCs), with no approved therapies specifically for MTAP deletion. Commercially, this positions Gilead in the competitive MTAP-deletion landscape where MAT2A and PRMT5 programs are both being advanced, and the trial’s exclusion of prior PRMT5/MAT2A exposure helps interpret early safety/PK/PD signals.