Phase 1b/2 navlimetostat (BMS-986504) PRMT5 inhibitor + pemetrexed antifolate in MTAP-deleted tumors.

This Phase 1b/2 basket study at Northwestern University evaluates navlimetostat (BMS-986504; Bristol Myers Squibb)—an MTA-cooperative PRMT5 inhibitor that exploits the MTAP-deletion synthetic-lethality biology—combined with pemetrexed, an antifolate that inhibits thymidylate synthase–dependent nucleotide synthesis. The trial uses oral BMS-986504 daily on days 1–21 plus IV pemetrexed on day 1 of each 21-day cycle, with dose/safety monitoring and preliminary efficacy readouts across cohorts, alongside CT imaging and blood-based pharmacology assessments. Eligible patients have metastatic, progressive solid tumors with MTAP deletion (including a GI-focused cohort such as pancreatic, biliary, esophageal, and colon cancers; plus a broader solid-tumor cohort), generally after at least one prior line, and it also allows MTAP-deleted metastatic NSCLC after progression (2nd line+). Scientifically, the key angle is pairing a targeted epigenetic vulnerability (PRMT5 dependence in MTAP loss) with a widely used antimetabolite backbone to look for synergy and a practical, scalable regimen. Today’s care for these metastatic settings is still histology-driven systemic therapy—platinum- or immunotherapy-based regimens in NSCLC and multi-agent chemotherapy sequences in GI cancers—so this explores a biomarker-defined add-on strategy for a subgroup where MTAP loss is not rare in several solid tumors.