TPS5618 Background: Despite radical primary surgery and carboplatin/paclitaxel-based chemotherapy in combination with anti-angiogenic bevacizumab and/or PARP inhibitors (PARPi), most patients (pts) with advanced ovarian cancer (OC) will relapse. Following the implementation of these targeted therapies to first-line treatment, repeated use of bevacizumab and/or PARPi is often not approved nor has conclusively been proven efficacious for all pts with recurrent OC. New combination partners for platinum-based chemotherapy remain important to improve outcome. The antibody-drug conjugate Mirvetuximab soravtansine (MIRV) is comprised of a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. Results from the phase III trial FORWARD I revealed in an exploratory analysis that pts with high FRα expression following PS2+ Scoring (cut off: ≥75% of tumor cells with FRα membrane staining and ≥ 2+ intensity) had significant progression-free survival (PFS) improvements with a hazard ratio of 0.55 compared to mono-chemotherapy (median PFS 5.6 vs 3.2 months, P=0.015) and high activity was most recently confirmed in the SORAYA trial with an overall response rate (ORR) of 32.4%. Preliminary data for the combination of MIRV with carboplatin exist from the Phase 1b FORWARD II trial, which resulted in an ORR of 71%, observed in 17 pts with a median PFS of 15 months, and an ORR of 80% in the FRα medium/high (>50% PS2+) subset of 10 pts. MIRV is well-tolerated with a manageable safety profile. Methods: Eligible pts for this multicenter, randomized, two-arm, open-label, comparative phase II trial must have recurrent, FRα high epithelial cancer of the ovary, fallopian tube or peritoneum and have measurable disease. Pts are eligible for platinum-based chemotherapy with a platinum-free interval of more than 3 months and had at least one prior chemotherapy, but are not candidates to receive bevacizumab for the current relapse. Pts can be included irrespective of wildtype BRCA1/2 mutation status, pts with a deleterious mutation are required to have received prior PARPi therapy. Following pre-screening for high FRα expression in FFPE tumor tissue according to PS2+ scoring, 136 pts are randomized (1:1) to: a) Control arm: Platinum-based combination chemotherapy (for 6 cycles) followed by PARPi if indicated or standard of care or b) Experimental arm: Carboplatin + MIRV 6 mg/kg adjusted ideal body weight (AIBW) IV d1 (6 cycles q21d) followed by MIRV monotherapy 6 mg/kg AIBW IV q21d until disease progression. The primary endpoint of PFS will be assessed by modified RECIST 1.1. Key secondary endpoints include overall survival, ORR, and quality of life. Enrollment started in September 2021. Clinical trial information: NCT04274426.