DM005 (EGFR/c-MET bispecific topo-I ADC) shows 46% unconfirmed ORR in heavily pretreated EGFRm NSCLC (FIH)

DM005 is a first-in-human anti-EGFR/c-MET bispecific antibody–drug conjugate (DAR≈4) delivering a DNA topoisomerase I inhibitor payload (BCPT02) via the BLD1102 linker/payload system, designed to exploit EGFR/c-MET co-expression and resistance biology. In the Phase 1 dose-escalation 3+3 study (NCT06515990), 45 patients with advanced solid tumors (median 3 prior lines; ECOG 0–1) received 0.5–6.5mg/kg IV Q3W; no DLTs were seen through 6.5mg/kg and MTD was not reached, with Grade ≥3 TRAEs in 10/45 (22%) and no ILD or infusion reactions. Among 32 evaluable patients, there were 8 PRs and 14 SD (unconfirmed ORR 25% overall), and in the EGFR-mutant NSCLC subset across 3.3/4.2/5.2mg/kg (n=13) there were 6 PR + 5 SD (unconfirmed ORR 46.2%, DCR 84.6%)—numerically in the ballpark of targeted post-osimertinib options like amivantamab + lazertinib (~35% ORR after osimertinib + platinum) and generally above historical single-agent chemo activity in this setting.