First-in-human study of DM002, an anti-MUC1/HER3 bispecific antibody-drug conjugate, in patients with advanced solid tumors.

3037 Background: DM002 is a bispecific ADC (BsADC) conjugated to BLD1102, a linker/payload system composed of a linker and a DNA topoisomerase I inhibitor (BCPT02), targeting MUC1 and HER3 with an average DAR value of 8. MUC1 and HER3 are highly co-expressed in several types of solid tumors, for which DM002 has demonstrated robust anti-tumor activity in PDX/CDX models. Methods: This is a First-in-human dose-escalation study (NCT06751329). Patients (pts) with advanced solid tumors received DM002 by IV administration from 1 to 6.0 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 v 1.1. 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 28 Dec 2025, a total of 29 pts from China, United states of America and Australia were enrolled and received ≥1 dose of DM002 across 5 dose cohorts. Median age was 61 years (range 45-80). Baseline ECOG scores were 0 (n=8), 1 (n=21) with all pts progressed after an average of 2.5 (range 1-5) prior lines of available standard therapy. There were three dose-limiting toxicities observed in 2 patients at 6.0 mg/kg. The MTD is 4.5mg/kg. Nineteen pts (65.5%) experienced treatment-related adverse events (TRAEs), mainly manifested as hematological toxicity and gastrointestinal reactions. the most common TRAEs (≥15%) including: nausea (37.9%), neutropenia (37.9%), thrombocytopenia (34.5%), anemia (31%), vomiting (27.6%), leukopenia (20.7%), hyponatremia (20.7%), diarrhea (17.2%), alanine aminotransferase increased (17.2%), hypoalbuminemia (17.2%). Most TRAEs were Grade 1-2 and Grade ≥3 TRAEs reported in 12 pts (9 neutropenia, 5 leukopenia, 4 thrombocytopenia, 3 anemia, 2 lymphocytopenia, hyponatremia and febrile neutropenia, 1 aspartate aminotransferase increased, blood bilirubin increased, monocyte count decreased, myelosuppression, hypocalcemia, malaise and infection). No ILD was observed. Among 15 pts having imaging tumor assessment by RECIST v1.1, there were 3 PRs, including 1 pt with prostate cancer and 1pt with ovarian cancer at 3.0 mg/kg, and 1 pt with pancreatic cancer at 4.5 mg/kg, and 8 pts with stable disease (SD). In the 3.0/4.5/6.0 mg/kg dose groups, a total of 8 pancreatic pts underwent imaging tumor assessment, with 1 pt achieving PR, and 5 pts achieving stable disease (SD). Conclusions: DM002 is safe and tolerable up to 4.5 mg/kg dose level. In pancreatic cancer, prostate cancer and ovarian cancer, DM002 has demonstrated an encouraging efficacy with a manageable safety profile. The putative RDEs are 3.0 and 3.5 mg/kg which will be further evaluated in phase II trials. Clinical trial information: NCT06751329 .