ODM-212 (pan-TEAD/YAP–TAZ pathway inhibitor) posts 27.8% ORR in evaluable mesothelioma in first-in-human TEADES

ODM-212 is an oral small-molecule pan-TEAD (TEAD1–4) inhibitor designed to shut down YAP1/TAZ-driven Hippo-pathway transcription and was evaluated in the multi-site, open-label TEADES first-in-human Phase 1/2 (BOIN dose escalation with backfill, then tumor-type expansion; NCT06725758). In dose escalation/early expansion (20–320mg/day once or twice daily), 76 heavily pretreated patients with advanced solid tumors (mesothelioma n=29, EHE n=15, other n=32; ECOG 0–1; prior checkpoint inhibitor n=38 and chemotherapy n=59) had no DLTs and no MTD identified; the most common TRAE was reversible proteinuria (19.7%) leading to treatment adjustment in 7.9%, and Grade≥3 TRAEs occurred in 6.6% (anemia; ↑amylase/lipase/ALT/AST). Among RECIST-evaluable patients, ORR was 15.6% (7/45) overall, with signals in mesothelioma (ORR 27.8% in 18 evaluable; DCR 77.8%) and epithelioid hemangioendothelioma (EHE) (ORR 22.2% in 9 evaluable; DCR 100%)—roughly within the higher end of reported salvage ICI activity in relapsed mesothelioma (ORR often 10–25%) and similar to a prior oral TEAD inhibitor VT3989 reported ORR ~26% in mesothelioma at optimized doses, while EHE systemic therapy benchmarks tend to be disease control–heavy with modest ORR (10% with sirolimus in some series).