Phase 1/2 ODM-212 pan-TEAD (Hippo/YAP–TEAD) inhibitor combinations in solid tumors

Orion Corporation (Orion Pharma) is running this open-label, multi-cohort Phase 1/2 study to define safety, tolerability, pharmacokinetics/pharmacodynamics, and early efficacy of ODM-212, an oral small-molecule pan-TEAD inhibitor that blocks YAP/TAZ-driven transcription in Hippo-pathway–activated cancers. Part 1 dose-escalates ODM-212 in combinations across advanced/unresectable solid tumors, including Arm A mesothelioma, Arm B pancreatic ductal adenocarcinoma (PDAC), and Arm C KRAS G12C-mutant non-small cell lung cancer (NSCLC). Part 2 expands into indication-specific cohorts: ODM-212 with Bristol Myers Squibb’s ipilimumab (CTLA-4 antibody) plus nivolumab (PD-1 antibody) in checkpoint-naïve mesothelioma; with gemcitabine (antimetabolite) + nab-paclitaxel/Abraxane (microtubule inhibitor; Bristol Myers Squibb) in PDAC without prior gem/nab-paclitaxel; and with Amgen’s sotorasib (KRAS G12C inhibitor) in KRAS G12C NSCLC in both 1st-line and post–KRAS G12C inhibitor settings. The commercial/scientific angle is testing whether TEAD pathway suppression can deepen or re-sensitize responses to established chemo, IO, and KRAS G12C targeted therapy; today’s care is ipilimumab/nivolumab for unresectable mesothelioma, gemcitabine+nab-paclitaxel or FOLFIRINOX for metastatic PDAC, and KRAS G12C-directed therapy after prior systemic treatment for KRAS G12C NSCLC (with 1st-line typically chemo-immunotherapy when eligible).