Sofetabart mipitecan (FRα-targeted ADC) posts 50.5% ORR and 8.1-mo mPFS in heavily pretreated HGOC—without keratopathy

Sofetabart mipitecan (Sofe-M) is an FRα-targeting antibody–drug conjugate engineered to broaden activity beyond “FRα-high only” tumors and potentially avoid the ocular toxicity seen with mirvetuximab soravtansine (MIRV). In this multicenter, open-label first-in-human Phase 1 study in high-grade ovarian cancer (n=105; mostly platinum-resistant; median 5 prior lines; 18.1% prior MIRV; 51.4% had FRα <75% at ≥2+), Sofe-M given q21d achieved ORR 50.5% (95% CI 40.5–60.4) with mPFS 8.1 months (95% CI 6.4–8.5); responses were similar in FRα <75% (ORR 44.4%) vs ≥75% (ORR 56.5%) and in prior MIRV-exposed patients (ORR 57.9%). The absence of keratopathy or grade 3 or higher neuropathy was encouraging, but clinically significant toxicity remained: grade ≥3 treatment-related adverse events occurred in 35.3% at the recommended 3 mg/kg dose and 56.4% at 4 mg/kg. Treatment-emergent adverse events led to discontinuation in 10.5% of patients overall. Key SOC benchmarks in platinum-resistant ovarian cancer remain modest—MIRV in FRα-high disease delivered ORR 42.3% vs 15.9% with investigator’s-choice chemo (mPFS 5.62 vs 3.98 months) in MIRASOL—so Sofe-M’s Phase 1 ORR/mPFS look numerically above chemo and even above MIRV’s FRα-high randomized outcomes, albeit cross-trial and in a dose-escalation setting.