Core Viewpoint - Hutchison China MediTech Limited (HCM) has initiated global Phase I clinical development for HMPL-A251, a first-in-class PI3K/PIKK-HER2 antibody-drug conjugate (ATTC) designed to target HER2-expressing tumors [1][2]. Group 1: Clinical Development - The Phase I/IIa trial is an open-label, multicenter study aimed at evaluating the safety and efficacy of HMPL-A251 in adult patients with unresectable, HER2-expressing advanced or metastatic solid tumors [2]. - The study consists of two phases: the Phase I dose escalation phase and the Phase IIa dose expansion and optimization phase, focusing on determining the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) [2]. - Primary endpoints include safety, tolerability, and preliminary efficacy, while secondary endpoints encompass initial anti-tumor activity, pharmacokinetics, and immunogenicity of HMPL-A251 [2]. Group 2: Drug Characteristics - HMPL-A251 is the first candidate from HCM's new generation ATTC platform, utilizing a potent and selective PI3K/PIKK inhibitor as the payload [2]. - The drug is designed to precisely target HER2-expressing tumor cells, potentially overcoming systemic toxicity and narrow therapeutic windows associated with traditional PI3K/PIKK inhibitors [2]. - The strategy aims to enhance overall tolerability while achieving more effective and sustained pathway inhibition [2]. Group 3: Preclinical Data - Preclinical data for HMPL-A251 was presented at the 2025 AACR-NCI-EORTC International Conference on Molecular Targeted Therapy and Cancer [3]. - These data support the translational potential of the ATTC platform and the ongoing global clinical evaluation of HMPL-A251 [3]. - The combination of PI3K/PIKK inhibitors with linker-payload technology shows promise for developing a series of future ATTC candidates [3].
和黄医药(00013)启动ATTC候选药物HMPL-A251用于治疗实体瘤的全球临床开发