Efficacy and Safety of Mirvetuximab Soravtansine in Patients with Platinum-Resistant Ovarian Cancer with High Folate Receptor Alpha Expression: Results from the SORAYA Study (LBA 4)

Objectives: Available single agent chemotherapies for platinum-resistant ovarian cancer have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is an antibody drug conjugate (ADC) comprising a FRα-binding antibody, cleavable linker, and maytansinoid DM4, a potent tubulin-targeting agent. SORAYA is a global single arm phase 3 study evaluating MIRV in adult patients (pts) with FRα high platinum-resistant high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancers (PROC). Methods: SORAYA enrolled PROC pts with high levels of FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 75% of cells with PS2+ staining intensity) who had received 1-3 prior therapies, including required prior bevacizumab. Pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by investigator (INV); the key secondary endpoint was duration of response (DOR); additional secondary endpoints included safety and tolerability. ORR and DOR by blinded independent central review (BICR) were sensitivity analyses. Results: 106 pts were enrolled; 51% had 3 prior lines; 48% had 1 to 2 prior lines of therapy. All pts received prior bevacizumab; 48% received a prior PARP inhibitor (PARPi). Median follow-up time was 8.5 months at the data cutoff on November 16, 2021. Objective responses by INV were seen in 34 of 105 efficacy evaluable pts for an ORR of 32.4% (95% confidence interval [CI]: 23.6%, 42.2%), including five complete responses (CRs); ORR by BICR was 31.6% (95% CI: 22.4%, 41.9%), including five CRs. The median DOR was 5.9 months (95% CI: 5.6, 7.7). With 15 responders remaining on MIRV at the time of the data cutoff, the DOR continues to evolve. In pts with 1-2 priors, the ORR by INV was 35.3% (95% CI: 22.4%, 49.9) and in pts with 3 priors, it was 30.2% (95% CI: 18.3%, 44.3). In pts with prior PARPi, the ORR by INV was 38.0% (95% CI: 24.7, 52.8) and in those without prior PARPi, it was 27.5% (95% CI: 15.9, 41.7). See table. The most common treatment-related adverse events (all grade, grade 3+) included blurred vision (41%, 6%), keratopathy (36%, 9%), and nausea (29%, 0%). Treatment-related adverse events led to dose reductions in 19%, dose delays in 32%, and discontinuations in 7% of pts; only one patient discontinued treatment due to an ocular event. Conclusions: In PROC, where current therapies are suboptimal and biomarker selected treatment has not been successfully developed, FRα expression predicts benefit from MIRV. MIRV demonstrates clinically meaningful and durable anti-tumor activity with favorable tolerability in pts with high FRα PROC regardless of number of prior therapies (1-2 or 3 prior therapies) or prior PARPi. MIRV represents an important advance for this biomarker selected population.