CUSP06 CDH6-Targeted Exatecan ADC Shows 36% ORR (50% at ≥4 mg/kg) in Biomarker-Unselected Platinum Refractory/-Resistant Ovarian Cancer

CUSP06 is a cadherin-6 (CDH6)–directed antibody-drug conjugate bearing an exatecan payload (DAR 8) given Q3W in the first-in-human Phase 1a study CUSP06-1001 (NCT06234423). An estimated 65-85% of patients with ovarian tumors express CDH6. Among 37 heavily pre-treated patients (median 4 prior lines) with platinum-refractory/resistant high-grade serous ovarian cancer (HGSOC) and other solid tumors, the HGSOC subset (n = 25) achieved a 36% ORR (5 confirmed, 4 pending) and 92% clinical-benefit rate. The ORR increased to 50% in the 4.0–4.4 mg/kg + G-CSF cohorts. Responses were seen in both low and high CDH6 expressing tumors. Hematologic toxicities (neutropenia, anemia) were the main TRAEs but were manageable; no DLTs emerged. The most common Grade ≥3 TEAEs were neutropenia, thrombocytopenia, and anemia. Historic single-agent chemotherapy in platinum-resistant OC yields a 10–15% ORR and <6 mo PFS, while mirvetuximab delivers a 42% ORR, but only in FRα-high tumors. CUSP06 demonstrated comparable activity without CDH6 pre-selection, which is present in roughly 65–85% of HGSOC cases.