Ozuriftamab Vedotin Shrinks Tumors in 4 out of 5 Refractory Melanoma Patients via ROR2-Targeted α-MMAE Delivery

Ozuriftamab vedotin is a conditionally active antibody-drug conjugate that binds the non-canonical WNT receptor ROR2 and releases MMAE preferentially in the acidic tumor milieu. In the first-in-human phase 1 study (NCT03504488), five heavily pre-treated patients (2 uveal, 3 cutaneous; median prior lines = 3) received IV ozuriftamab at 1.8 or 3 mg/kg Q2W. Confirmed objective responses were seen in four patients (80%): one complete remission (CR, –89% target lesions) now ongoing >5 years and three partial responses (1 uveal [case 2]; 31.9–43.7% shrinkage) lasting up to 16 months. Median time to progression has not been reached for two responders (475 days and >2,079 days). Grade ≥3 treatment-related events were neutropenia (n = 2) and grade 2 neuropathy (n = 3); all resolved or improved with dose adjustment, and no treatment discontinuations occurred. In comparison, salvage ipilimumab ± nivolumab or dacarbazine typically achieves ≤15% ORR and median PFS ~3 months in this setting. Notably, the durable CR occurred in the only tumor with high ROR2 expression by IHC.