Phase 1b study of mirvetuximab soravtansine, a folate receptor alpha (FRα)–targeting antibody-drug conjugate, in combination with carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer

Evaluate the antitumor activity and safety profile of the triplet combination of mirvetuximab soravtansine (MIRV), carboplatin, and bevacizumab in recurrent, platinum-sensitive ovarian cancer. Participants with recurrent, platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer (1–2 prior lines of therapy) received MIRV (6 mg/kg adjusted ideal body weight), carboplatin (AUC5), and bevacizumab (15 mg/kg) once every 3 weeks. Carboplatin could be discontinued after 6 cycles per investigator discretion; continuation of MIRV+bevacizumab as maintenance therapy was permitted. Eligibility included folate receptor alpha (FRα) expression by immunohistochemistry (≥50% of cells with ≥2+ intensity; PS2+ scoring); prior bevacizumab was allowed. Tumor response, duration of response (DOR), progression-free survival (PFS), and adverse events (AEs) were assessed. Forty-one participants received triplet therapy, with a median of 6, 12, and 13 cycles of carboplatin, MIRV, and bevacizumab, respectively. The confirmed objective response rate was 83% (9 complete and 25 partial responses). The median DOR was 10.9 months; median PFS was 13.5 months. AEs (any grade) occurred as expected, based on each agent's safety profile; most common were diarrhea (83%), nausea (76%), fatigue (73%), thrombocytopenia (71%), and blurred vision (68%). Most cases were mild to moderate (grade ≤2), except for thrombocytopenia, for which most drug-related discontinuations occurred, and neutropenia. This triplet regimen (MIRV+carboplatin+bevacizumab) was highly active, with a tolerable AE profile in participants with recurrent, platinum-sensitive, FRα-expressing ovarian cancer. Thrombocytopenia was the primary cause of dose modifications. These outcomes compare favorably to historical data reported for platinum-based chemotherapy plus bevacizumab regimens in similar patient populations. •Mirvetuximab soravtansine (MIRV) is an FDA-approved antibody-drug conjugate that targets folate receptor alpha (FRα).•The confirmed objective response rate was 83% (n = 34/41; 95% CI, 68–93), including 9 complete and 25 partial responses.•Tumor regression occurred in 40/41 participants with FRα expression ≥50%; median progression-free survival was 13.5 months.•Grade ≥3 treatment-related thrombocytopenia and neutropenia occurred in 51% and 44% of participants, respectively.•Treatment-emergent adverse events led to 24 discontinuations (any drug); thrombocytopenia led to most dose modifications.