Phase 2 FHD-286 SMARCA4/2 (BRG1/BRM) ATPase inhibitor in POU2F3+ SCLC

This single-arm Phase 2 study tests FHD-286, an oral small-molecule dual SMARCA4/SMARCA2 (BRG1/BRM) ATPase inhibitor that targets the SWI/SNF (BAF) chromatin remodeling complex, in people with POU2F3-expressing small cell lung cancer that has progressed after at least one prior platinum-based regimen. Participants receive once-daily FHD-286 in 21-day cycles, with safety-driven dose modifications allowed, and the primary endpoint is objective response rate. The study is run at Dana-Farber Cancer Institute, with Foghorn Therapeutics providing the investigational drug and supporting the research. The scientific angle is biomarker-enrichment: POU2F3+ SCLC is a molecularly defined subset where SWI/SNF pathway dependence has preclinical rationale, so this trial asks whether epigenetic/chromatin remodeling inhibition can translate into meaningful responses in a population with limited targeted options. After relapse on platinum (often given with an anti–PD-L1 agent in first line), current care is typically sequential single-agent chemotherapy (e.g., topotecan or lurbinectedin) and clinical trials, with modest response rates and short durability.