Carboplatin Plus Mirvetuximab Soravtansine In Platinum-Sensitive Ovarian Cancer: A Phase 2 Nonrandomized Clinical Trial

Purpose: Evaluate efficacy and safety of carboplatin plus mirvetuximab soravtansine (MIRV) in folate receptor alpha (FRa)-expressing recurrent PSOC. Patients and Methods: This phase 2, single arm trial enrolled patients with recurrent FRa-expressing (≥25% of tumor cells with ≥2+ membrane intensity) PSOC and 1 prior platinum-based therapy. Patients received up to 6-8 cycles of carboplatin (AUC 5) plus MIRV (6mg/kg AIBW) Q3W, followed by single-agent MIRV. Primary and key secondary endpoints were investigator-assessed objective response rate (ORR) per RECIST v1.1 in the FRa ≥50% group and FRa ≥25% group (ie, overall population), respectively. Results: Among 125 enrolled patients (102 FRα ≥50%; 61 prior PARPi), ORR by end of 6 combination cycles was 62.7% (95% CI, 52.6–72.1) in the FRα ≥50% group and 62.4% (95% CI, 53.3–70.9) in the overall population. Most patients (n=101; 81%) transitioned to single-agent MIRV continuation with durable responses. Patients with FRa ≥25% had median duration of response of 11.2 months (95% CI, 8.5–13.6) and median progression-free survival of 11.0 months (95% CI, 9.8–13.1). Most common adverse events (AEs) were blurred vision (81%) and corneal events (74%); 96.7% of corneal cases resolved or had final grade 1. Treatment-emergent AEs led to MIRV and carboplatin discontinuation in 15% and 9%, respectively. Adjudicated treatment-related pneumonitis occurred in 19 (15.2%) patients: 14 grade 1–2; 3 grade 3–4, and 2 fatal cases. Conclusions: Carboplatin plus MIRV was manageable with dose modifications for AEs and showed meaningful activity, including in PARPi-exposed patients, supporting further evaluation in PSOC.