SW-682 + combination therapy

SW-682 is an investigational, orally bioavailable small molecule inhibitor of the TEA Domain (TEAD) family of transcription factors, originally developed by SpringWorks Therapeutics. It is designed to target the Hippo signaling pathway, which is frequently dysregulated in various cancers, including mesothelioma and tumors with NF2 mutations. SW-682 works by binding to the highly conserved palmitoylation pocket of all four TEAD isoforms (TEAD1, TEAD2, TEAD3, and TEAD4), which disrupts the critical interaction between TEAD and its transcriptional co-activators, YAP (Yes-associated protein) and TAZ (transcriptional co-activator with PDZ-binding motif). By preventing the formation of the YAP/TAZ-TEAD complex, SW-682 inhibits the expression of genes that drive oncogenic cell proliferation, survival, and epithelial-to-mesenchymal transition. In clinical development, SW-682 has been evaluated in Phase 1a/1b studies both as a monotherapy and in combination with other anti-cancer agents for patients with advanced solid tumors. However, as of March 2026, development of the compound was discontinued following strategic decisions by Merck KGaA, which had acquired SpringWorks Therapeutics.