HUTCHMED has initiated a global phase 1/2a clinical trial of HMPL‑A580, its second antibody‑targeted therapy conjugate, in patients with unresectable, advanced or metastatic solid tumours in China and the US. The first patient received a dose on 4 March 2026.
HMPL‑A580 is described as a first‑in‑class ATTC that links a highly selective PI3K/PIKK inhibitor payload to an anti‑EGFR antibody via a cleavable linker. EGFR is widely expressed across multiple solid tumour types and is recognised as a key driver of tumour growth and progression. Preclinical findings have shown that inhibiting the PAM pathway can work synergistically with anti‑EGFR therapy to enhance anti‑tumour activity, with further data due to be presented at an upcoming scientific meeting.
The first‑in‑human study is multicentre and open label, assessing safety, tolerability, pharmacokinetics, immunogenicity and early signs of efficacy. The phase 1 dose‑escalation stage will determine the maximum tolerated dose and recommended dose for expansion.
The phase 2a expansion and optimisation stage will further characterise safety and preliminary anti‑tumour activity in selected solid tumours and identify the recommended dose for the next phase. The trial is listed under identifier NCT07396584.
HUTCHMED’s ATTC platform combines monoclonal antibodies with proprietary small‑molecule inhibitor payloads to deliver dual mechanisms of action. According to the company, this approach differs from traditional antibody drug conjugates by pairing targeted therapies to achieve synergistic anti‑tumour effects and more durable responses in preclinical models. The platform is designed to improve tumour accessibility, reduce off‑tumour toxicity and support combinations with chemotherapy and immunotherapy.
Built on more than 20 years of targeted therapy development, the platform aims to generate candidates for a wide range of cancer types by using antibody‑guided delivery and tumour‑specific payload release to overcome limitations of conventional small‑molecule inhibitors.
