DM005: An anti-EGFR/c-MET bispecific antibody-drug conjugate for advanced solid tumors.

• DOI: 10.1200/jco.2025.43.16_suppl.e15010
• Publication Date: 2025-05-28T15:26:18Z
• Authors: Haochen Wei; Wenjuan Dai; Wenjuan Yu; Shuhua Ma; Lingying Zhu; Xi Cheng; Rong Chen; Yuelei Shen
• Keywords: Antibody-drug conjugate; Conjugate; Solid tumor

e15010 Background: Bispecific ADCs (BsADCs) enhance efficacy, reduce toxicity, and overcome drug resistance by increasing internalization tumor specificity. EGFR c-MET are frequently co-expressed in various solid tumors, including non-small cell lung cancer (NSCLC), small (SCLC), colorectal (CRC), head neck cancer, etc. DM005 is a BsADC conjugated to BLD1102 (linker/DNA topoisomerase I inhibitor BCPT02), targeting with an average drug-to-antibody ratio (DAR) of 4. Preclinical studies shows has robust anti-tumor activity PDX/CDX models favorable safefy/tolerance monkeys. Methods: The first-in-human clinical trial multi-center, open-label, dose-escalation/expansion study assess safety, tolerability, preliminary pharmacokinetics immunogenicity advanced tumors (NCT06515990). Part 1 (dose escalation): Determine maximum tolerated dose (MTD) and/or the recommended for expansion (RDE) via 3+3 dose-escalation algorithm. 2 expansion): Evaluate PK 3 cohorts: a) subjects metastatic or locally mut NSCLC who have been treated ≥1 prior systemic anticancer therapy. b) wt (± other actionable genomic alterations), ≥ line c) squamous carcinoma (HNSCC) experienced disease progression on after treatment lines, chemotherapy immune checkpoint inhibitors. Patient recruitment ongoing Australia, USA, China. Preliminary data from expected late 2025. Results: successfully initiated, patient actively Building extensive preclinical studies, demonstrated strong activity, safety profile, well-tolerated toxicokinetics animal models, establishing foundation development. This multi-center designed evaluate DM005's pharmacokinetics, efficacy patients phase Conclusions: DM005, bispecific ADC c-MET, promising therapy tumors. With data, this marks milestone its aims address significant unmet oncology needs guide future applications. Clinical information: NCT06515990 .