ROR2-targeted ADC ozuriftamab achieves 80% response and 5-year CR in refractory melanoma

Ozuriftamab vedotin is a conditionally active anti-ROR2 antibody–drug conjugate that releases MMAE within the acidic tumor microenvironment. ROR2 is expected to be important to signaling in melanoma and is expressed in an unquantified subset of melanoma patients to date. In the first-in-human Phase 1 trial (NCT03504488), five heavily pre-treated cutaneous (n = 3) or uveal (n = 2) melanoma patients received 1.8–3.0 mg/kg IV every 2 weeks; four of five achieved objective responses (ORR 80%), including one complete remission ongoing >5 years and another partial remission >1 year. Dose-adjusted grade 2 neuropathy and grade 3–4 neutropenia were the main toxicities and caused no discontinuations. For context, salvage ipilimumab ± nivolumab after PD-1 failure delivers ORR ~28% (~10% for ipi monotherapy) with 57% grade ≥3 adverse events, making this small-cohort signal both deeper and seemingly gentler.