AML, a challenging hematological malignancy, often involves mutations of IDH1 and IDH2 enzymes, necessitating innovative treatment strategies. HMPL-306, as a novel dual-inhibitor, addresses this need by targeting both IDH1 and IDH2 mutations concurrently, potentially offering therapeutic advantages by overcoming acquired resistance seen with single inhibitors.

The registrational Phase III clinical trial, named RAPHAEL, is a multicenter, randomized, open-label study designed to assess the safety and efficacy of HMPL-306 monotherapy in patients with relapsed or refractory AML harboring IDH1 and/or IDH2 mutations. Led by principal investigator Prof Xiaojun Huang of Peking University People’s Hospital, the trial aims to enroll approximately 320 patients. The primary endpoint of overall survival (OS) and secondary endpoints including event-free survival (EFS) and complete remission (“CR”) rate will be evaluated, comparing HMPL-306 with current salvage chemotherapy regimens. Further details about the trial can be found at clinicaltrials.gov (Identifier: NCT06387069).

The initiation of the Phase III trial follows encouraging results from a Phase I study (NCT04272957), with data from the first-in-human dose-escalation stage presented at the European Hematology Association Congress (“EHA”) in June 2023. Promising CR rates from the dose expansion stage, involving over 50 patients, are anticipated to be showcased at the upcoming EHA Congress in June 2024.

HUTCHMED remains committed to advancing innovative therapies to address unmet medical needs in hematological malignancies and solid tumors, aiming to improve patient outcomes and quality of life.