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O'Malley DM , Matulonis UA , Birrer MJ , Castro CM , Gilbert L , Vergote I , Martin LP , Mantia-Smaldone GM , Martin AG , Bratos R , Penson RT , Malek K , Moore KN
Phase Ib study of mirvetuximab soravtansine, a folate receptor alpha (FRalpha)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer
Gynecol Oncol. 2020 May;157(2) :379-385
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PURPOSE: To evaluate the safety and clinical activity of mirvetuximab soravtansine, an antibody-drug conjugate comprising a humanized anti-folate receptor alpha (FRalpha) monoclonal antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent, in combination with bevacizumab in patients with FRalpha-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 FRalpha 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 toxicities. 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 FRalpha 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.
1095-6859 O'Malley, David M Matulonis, Ursula A Birrer, Michael J Castro, Cesar M Gilbert, Lucy Vergote, Ignace Martin, Lainie P Mantia-Smaldone, Gina M Martin, Antonio Gonzalez Bratos, Raquel Penson, Richard T Malek, Karim Moore, Kathleen N Journal Article United States Gynecol Oncol. 2020 May;157(2):379-385. doi: 10.1016/j.ygyno.2020.01.037. Epub 2020 Feb 18.