(P 445) TEADES PH1/2 STUDY WITH ODM-212: PRELIMINARY RESULTS IN EHE PATIENTS

Objective: The Hippo signalling pathway regulates organ size and cell proliferation via YAP and TAZ, coactivators that drive oncogenic gene expression by binding TEA domain (TEAD) transcription factors. Epithelioid hemangioendothelioma (EHE) is a rare sarcoma characterized by a WWTR1(TAZ)–CAMTA1 fusion in >90% of cases, which drives constitutive TAZ activation and aberrant TEAD-mediated transcription, making the YAP/TAZ–TEAD interaction an attractive therapeutic target. ODM-212 is a novel small molecule pan-TEAD inhibitor that has shown anti-tumour activity in non-clinical models in vitro and in vivo in solid tumours.

Methods: TEADES is a Phase 1/2 multi-site, open-label, first-in-human trial with two parts (dose escalation and dose expansion) with ODM-212. Phase 1 of the study will enrol subjects ≥18 years of age with various types of advanced, metastatic solid tumours known to harbour mutations affecting or interacting with the Hippo pathway, or where Hippo pathway has been indicated to be involved in tumour growth (basket-type approach). Phase 2 expansion including dose optimization is conducted in parallel cohorts in selected tumour types potentially responsive to TEAD inhibition based on data from Phase I or other scientific data. The primary endpoint of TEADES Phase 1/2 trial is to evaluate safety and tolerability of ODM-212 in human subjects. The trial is currently open and enrolling, with maximum 112 subjects in Phase I.

Results: Three patients with EHE have been treated with ODM-212. One patient achieved a confirmed partial response (PR, >30% tumour shrinkage) that is ongoing beyond 12 months, and two patients had tumour regression ( < 30% shrinkage) with prolonged stable disease (all ongoing >6 months on therapy). ODM-212 has been well tolerated, with no dose-limiting toxicities observed to date. Results of RNA sequencing of paired tumour biopsies from the PR patient will be presented.

Conclusion: TEAD inhibition with ODM-212 has induced durable tumour regression in EHE, demonstrating proof-of-concept for this targeted approach in a TAZ-fusion driven sarcoma. ODM-212 showed encouraging anti-tumour activity and manageable safety, highlighting the potential of targeting the Hippo–YAP/TAZ–TEAD pathway in EHE.