Rinatabart Sesutecan FRα-ADC Yields ~50% ORR After PD-1/Platinum Failure in Advanced Endometrial Cancer

Rinatabart sesutecan is a folate-receptor-α–targeted antibody-drug conjugate linked to the exatecan topoisomerase-I payload. In the GTC1184-01 phase 1/2 expansion (NCT05579366), 64 heavily pre-treated metastatic endometrial cancer patients (median 3 prior lines, with PD-(L)1 treatment and prior platinum) received 100 mg/m² or 120 mg/m² rinatabart sesutecan every 3 weeks. Among efficacy-evaluable cohorts, unconfirmed ORR reached 50% (2 CRs) at 100 mg and 45.5% at 120 mg, with disease-control rates of 100% and 82%, and >80% of responses ongoing at ~19 weeks’ follow-up. Grade 3-4 cytopenias were common (neutropenia 48%, anemia 36%, thrombocytopenia 22%), but dose reductions (16%) and discontinuations (3%) were infrequent; no ILD, neuropathy, or ocular events emerged. Historically, mirvetuximab soravtansine (Elahere) treatment in endometrial cancer patients with high-FOLR1 expression showed an objective response rate (ORR) of 45% (95% CI: 21.1–68.9%). Confirmed partial responses were observed in 15% (95% CI: 0–32.1%) of these patients. FRα is highly over-expressed in roughly 20–50% of endometrial tumors, underscoring the biologic and clinical rationale for this ADC.