This is an archive of papers published by the staff and faculty of Fox Chase Cancer Center. For questions about content, please contact Talbot Research Library
Last updated on
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
PMID: 32081463 URL: https://www.ncbi.nlm.nih.gov/pubmed/32081463
AbstractPURPOSE: 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.
Notes1095-6859 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.