HUTCHMED Initiates the RAPHAEL Registrational Phase III Trial of HMPL-306 for Patients with IDH1- and/or IDH2-Mutated Relapsed/Refractory Acute Myeloid Leukemia in China

HONG KONG and SHANGHAI, China and FLORHAM PARK, N.J., May 14, 2024 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that it has initiated a registrational Phase III clinical trial of HMPL-306 in patients with mutated isocitrate dehydrogenase (“IDH”) 1 or 2 relapsed / refractory acute myeloid leukemia (“AML”) in China. The first patient received their first dose on May 11, 2024.

HMPL-306 is a novel dual-inhibitor of IDH1 and IDH2 enzymes. Mutations of IDH1 and IDH2 have been implicated as drivers of certain hematological malignancies, gliomas and solid tumors, particularly among AML patients. Although some IDH inhibitors have been approved in certain markets for AML, isoform switching between the cytoplasmic mutant IDH1 and mitochondrial mutant IDH2 often leads to acquired resistance to single inhibitors of IDH1 or IDH2. Targeting both IDH1 and IDH2 mutations may provide therapeutic benefits in cancer patients by overcoming this acquired resistance.

RAPHAEL is a multicenter, randomized, open-label, registrational Phase III clinical trial designed to evaluate the safety and efficacy of HMPL-306 as a monotherapy in patients with relapsed or refractory AML harboring IDH1 and/or IDH2 mutations. The primary endpoint of overall survival (OS) and the secondary endpoints, including event-free survival (EFS) and complete remission (“CR”) rate, will be tested in comparison with current salvage chemotherapy regimens. The Company is looking to enroll approximately 320 patients for this registrational study, which is being led by principal investigator Prof Xiaojun Huang of Peking University People’s Hospital. Additional details may be found at clinicaltrials.gov, using identifier NCT06387069.

The study follows positive data from a two-stage, open-label Phase I study evaluating the safety, pharmacokinetics, pharmacodynamics and efficacy of HMPL-306 in this indication (NCT04272957). The first-in-human dose-escalation stage data was presented at the European Hematology Association Congress (“EHA”) in June 2023.¹ Results of the dose expansion stage of the study in over 50 patients demonstrated promising CR rates at the recommended Phase II dose are expected to be presented at the EHA Congress in June 2024.