Phase 2 BMS-986504 MTA-cooperative PRMT5 inhibitor for MTAP-deleted MPNST

This Phase 2, open-label study evaluates BMS-986504 (navlimetostat), an MTA-cooperative PRMT5 inhibitor, as monotherapy in unresectable malignant peripheral nerve sheath tumor (MPNST) with homozygous MTAP deletion. The design is single-arm dosing on Days 1–28 of each cycle, continuing until progression or intolerance, with outcomes focused on safety and preliminary anti-tumor activity. The biologic rationale is synthetic lethality: MTAP loss (often co-deleted with 9p21/CDKN2A in MPNST) leads to MTA accumulation that creates a PRMT5 dependency, making PRMT5 inhibition selectively toxic to MTAP-null tumors; MTAP loss is reported in roughly 25–50% of MPNST, but only a subset will be homozygous deleted. Bristol Myers Squibb owns BMS-986504, and this trial tests a biomarker-driven approach in a rare sarcoma where systemic options are limited. Today’s care for unresectable/metastatic MPNST is typically surgery when feasible, radiation for local control, and anthracycline/ifosfamide-based chemotherapy or other palliative regimens, with clinical trials strongly favored due to modest durability of responses.