First-in-human study of DM005, an anti-EGFR/c-MET bispecific antibody-drug conjugate, in patients with advanced solid tumors.

Abstract

8530 Background: DM005 is a bispecific ADC (BsADC) conjugated to BLD1102, a linker/payload system composed of a linker and a DNA topoisomerase I inhibitor (BCPT02), targeting EGFR and c-MET with an average DAR value of 4. EGFR and c-MET are highly co-expressed in NSCLC, SCLC, HNSCC, breast cancer, gastric cancer, colorectal cancer, and some other solid tumors, for which DM005 has demonstrated robust anti-tumor activity in PDX/CDX models. Methods: This is a First-in-human dose-escalation study (NCT 06515990). Patients (pts) with advanced solid tumors received DM005 by IV administration from 0.5 to 6.5 mg/kg Q3W. The classical “3+3” design was utilized to evaluate safety, tolerability and preliminary efficacy. Tumor response was evaluated by the Investigators based on RECIST v1.1. A Safety Monitoring Committee (SMC) was established to determine the dose levels, dose regimen, and the maximum tolerated dose (MTD)/ recommended dose for expansion (RDE). Results: As of 2 Jan 2026, a total of 45 pts from China, United states of America and Australia were enrolled and received ≥1 dose of DM005 across 8 dose cohorts. Median age was 59 years (range 40-76). Baseline ECOG scores were 0 (n = 7), 1 (n = 38) with all pts progressed after an average of 3 (range 1-7) prior lines of available standard therapy. There were no dose limiting toxicities (DLT) observed up to 6.5 mg/kg. The MTD was not reached. Thirty-six pts (80%) experienced treatment-related adverse events (TRAEs), the most common TRAEs (≥10%) including: nausea (28.9%), anemia (28.9%), fatigue (26.7%), decreased appetite (26.7%), leukopenia (20%), aspartate aminotransferase increased (15.6%), lymphopenia (13.3%), constipation (11.1%). Most TRAEs were Grade 1-2 and Grade ≥3 TRAEs reported in 10 pts (2 lymphopenia, 1 neutropenia, anemia, leukopenia, nausea, stomatitis, vomiting, fatigue, pain, urinary tract infection, hypoxia, hypotension). No ILD or Infusion reaction were observed. Among 32 patients evaluable, there were 8 PRs, including 1pt with NSCLC EGFR-mutant (NSCLCm) at 3.3 mg/kg, 4 pts with NSCLCm and 1pt with SCLC at 4.2 mg/kg, and 1pt with NSCLCm and 1pt with NSCLC EGFR wildtype (NSCLCw) at 5.2mg/kg, and 14 pts with stable disease (SD). In the 3.3/4.2/5.2 mg/kg dose groups, a total of 13 NSCLCm pts underwent imaging tumor assessment, with 6 subjects achieving PR, and 5 subjects achieving SD. The unconfirmed objective response rate (ORR) is 46.2%, and the disease control rate (DCR) is 84.6%. Conclusions: DM005 is safe and tolerable up to 6.5 mg/kg dose level. In both NSCLCm and NSCLCw pts, and SCLC pts, DM005 has demonstrated an encouraging efficacy with a manageable safety profile. The putative RDE ranges from 4.2 to 6.5 mg/kg which will be further evaluated in phase II trials. Clinical trial information: NCT06515990 .