Phase III MIRASOL (GOG 3045/ENGOT-ov55) study: Initial report of mirvetuximab soravtansine vs. investigator's choice of chemotherapy in platinum-resistant, advanced high-grade epithelial ovarian, primary peritoneal, or fallopian tube cancers with high folate receptor-alpha expression.

Background: Mirvetuximab soravtansine (MIRV), an antibody drug conjugate targeting FR alpha, demonstrated clinically meaningful antitumor activity in a single arm trial reported previously (Matulonis, JCO 2023). MIRASOL is a randomized phase 3 trial to confirm the efficacy of MIRV vs standard-of-care chemotherapy in patients (pts) with PROC. Methods: 453 PROC pts with high FR alpha expression (Roche FOLR1 Assay) with 1-3 priors were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or IC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was progression-free survival (PFS) by investigator (INV) with key secondary endpoints ORR, overall survival (OS), and patient-reported outcomes in hierarchical order; other endpoints included safety and tolerability. Blinded independent central review (BICR) for PFS and ORR were sensitivity analyses. Results: With a data cutoff of March 6, 2023, 227 pts were randomized to the MIRV arm; 226 to the IC arm. Median follow-up was 13.1 months. Baseline characteristics were well balanced across arms; 14% of pts had one, 39% two, and 47% three prior lines of therapy; 62% received prior bev; and 55% received prior PARPi therapy. The study met its primary and key secondary endpoints with statistically significant results in PFS (INV), ORR (INV), and OS (Table). In the bev-pretreated subset (n=281), PFS HR was 0.64 (0.492, 0.842) and OS HR was 0.74 (0.535, 1.036); in the bev-naive subset (n=172), PFS HR was 0.66 (0.459, 0.942) and OS HR was 0.51 (0.306, 0.860). The adverse event (AE) profile of MIRV was consistent with prior reports: predominantly low-grade ocular (MIRV vs IC all grade 56% vs 9%; grade 3+ 14% vs 0%) and gastrointestinal events (MIRV vs IC all grade 70% vs 66%; grade 3+ 13% vs 15%). Compared with IC, MIRV was associated with lower rates of grade 3+ treatment-emergent AEs (42% vs 54%), serious AEs (24% vs 33%), and discontinuations due to TEAEs (9% vs 16%). Fourteen percent of pts on the MIRV arm remained on study drug vs 3% on the IC arm. Conclusion: MIRV is the first treatment to demonstrate a PFS and OS benefit in PROC compared to IC. The efficacy data, along with the well-characterized safety profile, position MIRV as a new, standard of care for pts with FR alpha positive PROC. Clinical trial information: NCT04209855.Efficacy EndpointsMIRV (n=227)IC (n=226)Hazard RatioP-valuemPFS (INV) (months, 95% CI)5.62 (4.34, 5.95)3.98 (2.86, 4.47)0.65 (0.52, 0.81)<0.0001mPFS (BICR) (months, 95% CI)5.91 (4.93, 6.97)4.34 (3.52, 4.99)0.72 (0.56, 0.92)0.0082 ORR (INV)(95% CI)42.3 (35.8, 49.0)15.9 (11.4, 21.4) NA<0.0001Complete response % (n)5.3 (12)0NANAPartial response % (n)37.0 (84)15.9 (36)NANAORR (BICR) (95% CI)36.1 (29.9, 42.7)14.6 (10.3, 19.9)NA<0.0001mOS(months, 95% CI)16.46 (14.46, 24.57)12.75 (10.91, 14.36)0.67 (0.50, 0.88)0.0046