Purpose: Evaluate the antitumor activity and safety profile of the combination of mirvetuximab soravtansine and bevacizumab in patients with platinum-resistant ovarian cancer.
Methods: 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.
Results: 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%).
Conclusion: 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.
Competing Interests: Declaration of Competing Interest LG reports personal fees from Merck and GSK; advisory board participation with AstraZeneca, Alkermes, Merck, Eisai, Eisai-Merck, GSK, and Novocure; institutional funding from OncoQuest Pharmaceuticals, Novocure GmbH, Alkermes Inc., ImmunoGen Inc., AstraZeneca, Esperas Pharma Inc., K-Group Beta Inc., Merck Sharp & Dohme, Roche, Karyopharm, Tesaro, and IMV Inc. AO reports personal fees from AstraZeneca, Doctaforum Servicios S.L, Edizioni Minerva Medica SpA, ESMO, PharmaMar, and Roche; advisory board participation with Agenus, AstraZeneca, Clovis Oncology, Inc., Corcept Therapeutics, Deciphera Pharmaceutical, Eisai Europe Limited, EMD Serono, Inc., F. Hoffmann-La Roche, GlaxoSmithKline, ImmunoGen, KL Logistics, Medison Pharma, Merck Sharp & Dohme de España, Mersana Therapeutics, Novocure GmbH, PharmaMar, prIME Oncology, ROCHE FARMA, Sattucklabs, and Sutro Biopharma, Inc.; funding from AbbVie Deutschland Gmbh & Co Hg, Ability Pharmaceuticals, Advaxis, Agenus, Aprea Therapeutics AB, AstraZeneca AB, Beigene USA, Inc., Belgian Gynaecological Oncology Group (BGOG), Bristol-Myers Squibb International Corporation, Clovis Oncology, Corcept Therapeutics, Eisai, Eli Lilly and Company, F. Hoffmann-La Roche, Grupo Español de Investigación en Cáncer de Ovario (GEICO), ImmunoGen, Iovance Biotherapeutics, Medimmune, Merck Healthcare, Merck Sharp & Dohme, Millennium Pharmaceuticals, Mundipharma Research, Novartis Farmacéutica, Regeneron Pharmaceuticals, Seagen, Seattle Genetics, Sutro Biopharma, Tesaro, University Health Network, and Verastem. UAM reports consulting fees from Merck, GSK, and AstraZeneca; personal fees from Med Learning Group; advisory board participation with 2× Oncology, NextCure, Trillium, Agenus, ImmunoGen, Novartis, Boehringer Ingelheim, Rivkin Foundation, Ovarian Cancer Research Alliance, Clearity Foundation, and Morphosys; data safety monitoring board participation with Alkermes and Symphogen. GMMS reports advisory board participation with ImmunoGen. PCL reports no disclosures. CMC reports personal fees from Qiagen, Inc., Teladoc Health, and InfiniteMD. DP reports no disclosures. SM reports no disclosures. MM reports employment and stock options with ImmunoGen Inc. JW reports employment and stock options with ImmunoGen Inc. KNM reports personal fees from AbbVie, Alkemeres, Aravive, AstraZeneca, Blueprint Pharma, Bristol Myers Squibb, Eisai, Elevar, GSK/Tesaro, Genentech/Roche, iMab, ImmunoGen, Merck, Mereo, Mersana, Myriad, OncXerna, Oncomed, Rubius, Sorrento, Tarveda, Vavotar, and VBL Therapeutics; advisory board participation with Abbvie, Alkemeres, Aravive, AstraZeneca, Blueprint Pharmaceuticals, Eisai, Elevar, Genetech/Roche, GSK/Tesaro, ImmunoGen, Merck, Mereo, Mersana, Myriad, Onco Med, OncXerna, Rubius, Sorrento, Tarveda, Vavotar, VBL Therapeutics; funding from Genentech/Roche, GSK/Tesaro, ImmunoGen, Lilly, Merck, and PTC Therapeutics. DMO reports receiving grants or contracts from AbbVie Inc., Agenus Inc., Ajinomoto Co Inc., Amgen Inc., Array BioPharma Inc., AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Clovis Oncology, Dare Bioscience, Eisai Inc., EMD Serono Inc., Ergomed Plc, Genentech, Genmab, GOG Foundation Inc., ImmunoGen Inc., Iovance Biotherapeutics, Janssen Biotech Inc., Johnson & Johnson Pharmaceuticals, Ludwig Institute for Cancer Research Ltd., Merck, Merck Serono, Mersana Therapeutics, New Mexico Cancer Care Alliance, Novocure Inc., PRA Health Sciences, Regeneron Pharmaceuticals Inc., Seagen Inc., Stemcentrx, Sumitomo, Dainippon Pharma Oncology Inc., Syneos Health, Tesaro, TRACON Pharmaceuticals, VentiRX Pharmaceuticals Inc., and Yale University; data safety monitoring board and/or advisory board participation with AbbVie Inc., Ambry Genetics, Amgen Inc., Arquer Diagnostics, AstraZeneca Pharmacueticals LP, Celsion Corporation, Clovis Oncology, Corcept Therapeutics, Eisai Inc., Elevar Therapeutics, Genentech, GOG Foundation Inc., ImmunoGen Inc., InxMed, Iovance Biotherapeutics, Janssen Biotech Inc., Johnson and Johnson Pharmaceuticals, Merck, Mersana Therapeutics Inc., Novartis, Novocure Inc., Regeneron Pharmaceuticals Inc., Roche Diagnostics MSA, Seagen Inc., Sorrento Therapeutics, Sumitomo Danippon Pharma Oncology Inc., Takeda Pharmaceuticals USA Inc., Tesaro, and Tora; other financial or nonfinancial interests with Agenus Inc., Myriad Genetic Laboratories Inc., Rubis, and Tarveda Therapeutics.
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