SIM0505 (anti-CDH6 topo-I ADC) drives 37% PRs in heavily pretreated gynecologic tumors

SIM0505 is a first-in-class cadherin-6 (CDH6)–targeted antibody–drug conjugate delivering the novel topoisomerase I payload CPT116; it was evaluated in a global Phase I first-in-human dose-escalation study in advanced solid tumors (q3w IV; 1.6–9.6mg/kg; NCT06792552). As of December 26, 2025, 38 patients were treated without CDH6 preselection (ovarian cancer n=29; uterine serous cancer n=4; other n=5), with a median 5 prior regimens and a largely platinum-resistant high-grade serous OC population; among 30 evaluable patients, there were 11 PRs (ORR 36.7%) and 13 SD, including 8 PRs in 14 evaluable OC patients at 4.8–8.0mg/kg (ORR 57.1%), which is above typical single-agent chemo benchmarks historically used in platinum-resistant OC (often ~10–20% ORR; e.g., PLD 19.7% vs topotecan 17.0% in recurrent EOC) and higher than the ~32% ORR seen with mirvetuximab soravtansine in FRα-high platinum-resistant OC (noting SIM0505 did not select for a biomarker in this readout). Safety was dominated by myelosuppression: Grade≥3 TRAEs included thrombocytopenia (23.7%), neutropenia (21.1%), and decreased WBC (18.4%); 1 DLT at 9.6mg/kg (Grade 4 febrile neutropenia + thrombocytopenia) and 1 discontinuation for Grade 2 ILD were reported; MTD was not reached, and PK suggested an ~8-day half-life with apparent ADC stability in circulation.