Phase III, randomized trial of mirvetuximab soravtansine versus chemotherapy in patients with platinum-resistant ovarian cancer: primary analysis of FORWARD I.

Background: Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. The randomized, open-label, phase III study FORWARD I compared MIRV and investigator's choice chemotherapy in patients with platinum-resistant epithelial ovarian cancer (EOC).
Patients and Methods: Eligible patients with 1-3 prior lines of therapy and whose tumors were positive for FRα expression were randomly assigned, in a 2 : 1 ratio, to receive MIRV (6 mg/kg, adjusted ideal body weight) or chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan). The primary endpoint was progression-free survival [PFS, Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, blinded independent central review] in the intention-to-treat (ITT) population and in the prespecified FRα high population.
Results: A total of 366 patients were randomized; 243 received MIRV and 109 received chemotherapy. The primary endpoint, PFS, did not reach statistical significance in either the ITT [hazard ratio (HR), 0.98, P = 0.897] or the FRα high population (HR, 0.69, P = 0.049). Superior outcomes for MIRV over chemotherapy were observed in all secondary endpoints in the FRα high population including improved objective response rate (24% versus 10%), CA-125 responses (53% versus 25%), and patient-reported outcomes (27% versus 13%). Fewer treatment-related grade 3 or higher adverse events (25.1% versus 44.0%), and fewer events leading to dose reduction (19.8% versus 30.3%) and treatment discontinuation (4.5% versus 8.3%) were seen with MIRV compared with chemotherapy.
Conclusions: In patients with platinum-resistant EOC, MIRV did not result in a significant improvement in PFS compared with chemotherapy. Secondary endpoints consistently favored MIRV, particularly in patients with high FRα expression. MIRV showed a differentiated and more manageable safety profile than chemotherapy.
Competing Interests: Disclosure KNM reports advisory roles for AstraZeneca, AbbVie, Aravive, Eisai, ImmunoGen, GSK/Tesaro, Genentech/Roche, Merck, Mersana, Myriad, Vavotar, and VBL Therapeutics, and research funding from PTC Therapeutics, Lilly, Merck, GSK/Tesaro. DL reports personal fees from Amgen, GSK, PharmaMar, Roche, and Clovis; consulting roles with AstraZeneca, GSK, Merck Sharp & Dohme, Clovis, Amgen, Genmab; and research funding from GSK and Merck. GEK reports personal fees from AstraZeneca, Clovis, and GSK/Tesaro; research funding from Lilly and Merck. HH reports advisory roles and personal fees from AstraZeneca and Merck; research funding from AstraZeneca, GSK, Merck, Roche, and ImmunoGen. BJM reports consulting roles for AbbVie, Amgen, Aravive, AstraZeneca, Clovis, GOG Foundation, Gradalis, ImmunoGen, Laekna Healthcare, Merck, Mersana, Myriad, NuCana, OncoMed, OncoQuest, Pfizer, Roche/Genentech, and Tesaro/GSK. JW and AB report employment with ImmunoGen. All other authors have declared no conflicts of interest.
(Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)