Introduction/Background Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate targeting folate receptor alpha (FRα), demonstrated an improvement in progression-free survival (PFS) and overall survival (OS) in patients (pts) with platinum-resistant ovarian cancer (PROC) compared to investigator choice chemotherapy (IC) (Moore K et al. ASCO 2023; LBA5507). Here we present efficacy data by prior PARPi (with nominal p-values).

Methodology 453 PROC pts with high FRα expression with 1–3 priors were randomized 1:1 to MIRV or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. Primary efficacy endpoint was PFS; key secondary endpoints: overall response rate (ORR), overall OS, and patient-reported outcomes (hierarchical order).

Results 227 pts were randomized to the MIRV arm; 226 to the IC arm. Baseline characteristics were well balanced; 14% of pts had one, 39% two, and 47% three prior lines of therapy; 55% received prior PARPi. In pts with prior PARPi (n=251) PFS HR was 0.58 (95% confidence interval 0.43, 0.78, p-value=0.0002) and ORR 45% vs 17%, p-value <0.0001, favoring MIRV. In the PARPi-naïve subset (n=191), PFS HR was 0.74 (0.54, 1.03, p-value=0.0685) and ORR 40% vs 14%, p<0.0001. In pts with prior PARPi, MIRV had lower rates of grade 3+ treatment-emergent adverse events (TEAEs) (45% vs. 58%), serious TEAEs (21% vs. 35%), and discontinuations due to TEAEs (9% vs. 22%) compared with IC. Additional patient characteristics, safety, and OS data will be presented.

Conclusion MIRV is the first treatment to demonstrate both an OS and a PFS benefit compared to IC in a phase III trial in PROC. In this subset analysis, the benefit extends to patients regardless of prior PARPi, with the greatest benefit in pts with prior PARPi exposure. These efficacy data, along with the well-characterized safety profile, position MIRV as a new standard of care for pts with FRα-positive PROC.