Safety and efficacy of mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients with platinum-resistant ovarian cancer

• Published in: Gynecologic oncology 2023-03, Vol.170, p.241-247
• Main Authors: Gilbert, Lucy, Oaknin, Ana, Matulonis, Ursula A., Mantia-Smaldone, Gina M., Lim, Peter C., Castro, Cesar M., Provencher, Diane, Memarzadeh, Sanaz, Method, Michael, Wang, Jiuzhou, Moore, Kathleen N., O'Malley, David M.
• Format: Article
• Language: English
• Subjects: Antibody-drug conjugate; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Bevacizumab; Bevacizumab - therapeutic use; Biomarker; Carcinoma, Ovarian Epithelial - drug therapy; Drug Resistance, Neoplasm; Female; Folate Receptor 1; Folate receptor alpha; Humans; Immunoconjugates; Middle Aged; Mirvetuximab soravtansine; Neoplasm Recurrence, Local - drug therapy; Ovarian Neoplasms - pathology; Platinum-resistant ovarian cancer
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1016/j.ygyno.2023.01.020

Evaluate the antitumor activity and safety profile of the combination of mirvetuximab soravtansine and bevacizumab in patients with platinum-resistant ovarian cancer. Patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, whose most recent platinum-free interval was ≤6 months, were administered mirvetuximab soravtansine (6 mg/kg adjusted ideal body weight) and bevacizumab (15 mg/kg), intravenously, once every 3 weeks. Eligibility included FRα expression by immunohistochemistry (IHC; ≥25% of cells with ≥2+ intensity). Prior bevacizumab and/or PARP inhibitor (PARPi) treatment were permitted. The primary endpoint was confirmed objective response rate (ORR). Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and safety. Ninety-four patients received combination treatment with mirvetuximab soravtansine and bevacizumab. Median age was 62 years (range, 39–81). Fifty-two percent had ≥3 prior therapies; 59% had prior bevacizumab; and 27% had prior PARPi. ORR was 44% (95% CI 33, 54) with 5 complete responses, median DOR 9.7 months (95% CI 6.9, 14.1), and median PFS 8.2 months (95% CI 6.8, 10.0). Treatment-related adverse events were consistent with the profiles of each agent, with the most common being blurred vision (all grades 57%; grade 3, 1%), diarrhea (54%; grade 3, 1%), and nausea (51%; grade 3, 1%). The mirvetuximab soravtansine plus bevacizumab doublet is an active and well-tolerated regimen in patients with FRα-expressing platinum-resistant ovarian cancer. Promising activity was observed for patients regardless of level of FRα expression or prior bevacizumab. These data underscore the potential for mirvetuximab soravtansine as the combination partner of choice for bevacizumab in this setting. •Mirvetuximab soravtansine (MIRV) is a biomarker-driven antibody-drug conjugate targeting folate receptor alpha (FRα).•In platinum-resistant ovarian cancer (PROC), objective response rate was 44% (N = 94; 5 complete and 36 partial responses).•Treatment was efficacious across all FRα expression levels, but further improved with higher FRα expression.•These data support MIRV as a promising and novel combination partner of choice for bevacizumab in patients with PROC.