China-based Hansoh Pharma has commenced the first Phase III study of HS-10504, a proprietary fourth-generation EGFR tyrosine kinase inhibitor (TKI) designed to overcome both the C797S resistance mutation to third-generation EGFR-TKIs and the T790M spatial steric barrier from first- and second-generation agents. The randomised, open-label, multicentre trial (n=206) compares HS-10504 400 mg once daily against platinum-based doublet chemotherapy (pemetrexed plus cisplatin or carboplatin) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring EGFR C797S resistance after prior EGFR-TKI therapy, with progression-free survival (PFS) as the primary endpoint.

HS-10504 holds China NMPA Breakthrough Therapy designation (May 2026) and is the first fourth-generation EGFR-TKI globally to reach Phase III, ahead of fourteen other clinical-stage candidates.

Early clinical signal supports the advance: among 34 response-evaluable patients with EGFR C797S (with or without T790M), objective response rate (ORR) was 52.9% and median PFS 9.6 months, with most treatment-related adverse events grade 1 to 2 and manageable grade 3 haematologic events.