HUTCHMED has commenced a Phase I/IIa clinical trial of its second antibody-targeted therapy conjugate (ATTC), HMPL-A580, targeting patients with unresectable, advanced or metastatic solid tumours in the US and China.

The first-in-human, multi-centre, open-label trial is designed to assess the tolerability, safety, immunogenicity, preliminary efficacy and pharmacokinetics of HMPL-A580 and consists of two segments.

The Phase I dose escalation portion will administer HMPL-A580 intravenously at preset doses to establish safety, maximum tolerated dose, and the recommended dose for expansion.

In Phase IIa, the study will further characterise the safety profile and preliminary efficacy in specific tumour types, aiming to optimise dosing for subsequent research phases.

HMPL-A580 is a first-in-class ATTC and consists of a potent and selective phosphoinositide 3-kinase / phosphatidylinositol 3-kinase-related kinase (PI3K/PIKK) small-molecule inhibitor payload.

HUTCHMED’s ATTC platform integrates monoclonal antibodies with small-molecule inhibitor payloads to provide dual mechanisms of action.

This approach differs from conventional cytotoxin-based antibody drug conjugates by combining targeted therapies for synergistic anti-tumour activity in preclinical models.

Backed by more than two decades of expertise in targeted therapies, this platform seeks to develop new drug candidates for various cancers by using antibody-guided delivery and tumour-specific payload release.

HMPL-A580’s design aims to deliver precise pathway inhibition directly into epidermal growth factor receptor (EGFR)-expressing tumour cells and improve tolerability while achieving more durable target inhibition.

Earlier this year, HUTCHMED initiated the Phase III stage of its Phase II/III clinical trial assessing the combination of surufatinib, camrelizumab, nab-paclitaxel, and gemcitabine as a first-line treatment for metastatic pancreatic ductal adenocarcinoma (mPDAC), an aggressive form of cancer, in China.