A single-arm, phase 2 study of neoadjuvant mirvetuximab soravtansine and carboplatin for FRα-expressing advanced-stage serous epithelial ovarian, fallopian tube, or primary peritoneal cancer (M25-231; NCT06890338; GOG-3115).

Abstract

TPS5633 Background: Folate receptor alpha (FRα) has limited expression on normal tissues but is highly expressed in most high-grade serous epithelial ovarian cancers (EOC), making it an attractive therapeutic target. Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate targeting FRα, has demonstrated efficacy and manageable safety in recurrent, FRα-expressing EOC when used as monotherapy. Additionally, a phase 1b/2 study (IMGN853-0402) of MIRV + carboplatin showed promising clinical activity in patients with platinum-sensitive ovarian cancer who had tumor recurrence after platinum-based chemotherapy. The safety and efficacy of neoadjuvant MIRV + carboplatin in newly diagnosed, advanced-stage FRα-expressing high-grade serous ovarian cancer (HGSOC) remains unknown. Methods: This single-arm phase 2 trial will evaluate the safety and efficacy of MIRV + carboplatin in newly diagnosed patients with advanced-stage (Stage III/IV), FRα-expressing (≥75% tumor cells with ≥2+ membrane intensity per the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay [Roche Diagnostics]) HGSOC. Approximately 140 patients (aged ≥18 years) will be enrolled; 5 patients were enrolled as of January 23, 2026. Patients will receive ≤6 cycles of MIRV (6 mg/kg adjusted ideal body weight) and carboplatin (AUC 5) intravenously every three weeks before interval debulking surgery (IDS), with a total of ≤9 cycles pre- and post-IDS. IDS suitability will be evaluated radiologically, and all eligible patients, including those with progressive disease (PD), will undergo IDS after Cycle 3 Day 1. IDS-ineligible patients may receive ≤3 additional cycles and undergo repeat imaging to assess IDS suitability. Patients with complete response (CR), partial response (PR), or stable disease will resume MIRV + carboplatin 3–6 weeks post-IDS following radiologic assessment. At the treating physician’s discretion, bevacizumab may be added post-IDS and standard-of-care maintenance therapy may begin ≥21 days after MIRV + carboplatin ± bevacizumab completion. Imaging will occur every 9 weeks after IDS (for those who undergo IDS) or last radiologic tumor assessment (for those who do not) until 1 year from the first dose of study treatment and then every 12 weeks until PD, death, or withdrawal of consent. The primary endpoint is objective response (OR), defined as best overall response of radiographic CR or PR assessed by Independent Central Review (ICR) per Response Evaluation Criteria in Solid Tumors v1.1 prior to initiation of subsequent anticancer therapy (including IDS). Secondary endpoints include OR by investigator (INV), disease control by ICR and INV, IDS, extent of cytoreduction at the time of IDS, cancer antigen 125 response, progression-free survival by INV, and patient-reported outcomes (NFOSI-18). Clinical trial information: NCT06890338 .