Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FR alpha)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer

Resumen:
Purpose. To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FR alpha) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FR alpha-positive, platinum-resistant ovarian cancer. Methods. Patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer were administered mirvetuximab soravtansine (6 mg/kg. adjusted ideal body weight) and bevacizumab (15 mg/kg) once every 3 weeks. Eligibility included FR alpha positivity by immunochemistry and prior bevacizumab exposure was permitted. Adverse events, tumor response, and progression-free survival (PFS) were determined. Results. Sixty-six patients, with a median of 3 prior lines of therapy (range, 1-8), received the combination of mirvetuximab soravtansine and bevacizumab at full dosing during the escalation and expansion stages of the study. Adverse events were generally mild-to-moderate (<= grade 2) with diarrhea, blurred vision, nausea, and fatigue being the most common treatment-related toxici ties. Six cases of pneumonitis (9%: all grade 1 or 2), an adverse event of special interest, were observed. The confirmed objective response rate (ORR) was 39%, including 5 complete responses and 21 partial responses, and the median PFS was 6.9 months. The combination was particularly active in the subset of patients (n = 16) who were bevacizumab-naive, less heavily pretreated (1-2 prior lines), and whose tumors exhibited medium/high FR alpha expression (ORR, 56% with a median duration of response of 12 months; PFS, 9.9 months). Conclusion. The combination of mirvetuximab soravtansine with bevacizumab is well tolerated in patients with platinum-resistant. recurrent ovarian cancer. The encouraging efficacy measures compare favorably to reported outcomes for bevacizumab combined with standard chemotherapy in similar patient populations. (C) 2020 Elsevier Inc. All rights reserved.