Safety and activity findings from a phase 1b escalation study of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin in patients with platinum-sensitive ovarian cancer.
Moore KN, O'Malley DM, Vergote I, Martin LP, Gonzalez-Martin A, Malek K, Birrer MJ
Gynecol Oncol 151 46-52 01/01/2018
PURPOSE: To evaluate the safety profile and preliminary antitumor activity of mirvetuximab soravtansine when administered in combination with carboplatin to relapsed ovarian cancer patients.
METHODS: Patients with recurrent, platinum-sensitive epithelial ovarian or fallopian tube cancer were enrolled. Eligibility included a minimum requirement of tumor FRα positivity (≥25% of cells with ≥2+ staining intensity). Patients received escalating doses of mirvetuximab soravtansine and carboplatin on day 1 of a 21-day cycle (once every 3 weeks). Mirvetuximab soravtansine maintenance therapy was permitted, at the investigators discretion, following cessation of carboplatin treatment. Adverse events, tumor response, and progression-free survival (PFS) were determined.
RESULTS: Eighteen patients were enrolled and dosed with combination therapy; thirteen continued with mirvetuximab soravtansine maintenance following carboplatin discontinuation. Mirvetuximab soravtansine dosing was escalated from 5 to 6 mg/kg (adjusted ideal body weight) and carboplatin from AUC4 to AUC5. Adverse events were generally mild (≤ grade 2) with nausea, diarrhea, thrombocytopenia, blurred vision, and fatigue being the most common treatment-emergent toxicities. For all evaluable patients (n = 17), the confirmed objective response rate (ORR) was 71%, including three complete responses and nine partial responses, and the median PFS was 15 months. A median duration of response was not reached.
CONCLUSION: These data demonstrate that mirvetuximab soravtansine combined with carboplatin is a well-tolerated and highly active regimen in recurrent, platinum-sensitive ovarian cancer. Further evaluation of this combination in a randomized fashion is warranted.