Integrated safety summary of single-agent mirvetuximab soravtansine in patients with folate receptor α (FRα)-positive recurrent ovarian cancer: Phase 1 and 3 clinical trials.

Kathleen N. Moore Division of Obstetrics and Gynecology, Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Stephenson Cancer Center, Oklahoma City, OK info_outline Kathleen N. Moore, Domenica Lorusso, Ana Oaknin, Amit M. Oza, Nicoletta Colombo, Toon Van Gorp, David M. O'Malley, Susana N. Banerjee, Conleth G. Murphy, Philipp Harter, Gottfried E. Konecny, Patricia Pautier, Michael W. Method, Jiuzhou Wang, Michael J. Birrer, Robert L. Coleman, Ursula A. Matulonis

Authors Kathleen N. Moore Division of Obstetrics and Gynecology, Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Stephenson Cancer Center, Oklahoma City, OK info_outline Kathleen N. Moore, Domenica Lorusso, Ana Oaknin, Amit M. Oza, Nicoletta Colombo, Toon Van Gorp, David M. O'Malley, Susana N. Banerjee, Conleth G. Murphy, Philipp Harter, Gottfried E. Konecny, Patricia Pautier, Michael W. Method, Jiuzhou Wang, Michael J. Birrer, Robert L. Coleman, Ursula A. Matulonis Organizations Division of Obstetrics and Gynecology, Department of Gynecologic Oncology, University of Oklahoma Health Science Center, Stephenson Cancer Center, Oklahoma City, OK, Fondazione Policlinico Gemelli IRCCS, Rome, Italy, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, and Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada, Gynecologic Oncology, European Institute of Oncology IRCCS and Università degli Studi di Milano Bicocca, Milan, Italy, Belgium and Luxembourg Gynaecological Oncology Group (BCOG), Leuven Cancer Institute, University Hospitals Leuven, Leuven, Belgium, The Ohio State University Wexner Medical Center and James Cancer Hospital, Columbus, OH, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, National Cancer Research Institute (NCRI), London, United Kingdom, Bon Secours Cork Cancer Centre, Cork, Ireland, Evangelische Kliniken Essen-Mitte, Essen, Essen, Germany, University of California Los Angeles Medical Center, Santa Monica, CA, GINECO, French Sarcoma Group and Gustave Roussy Cancer Center, Villejuif, France, Michiana Hematology Oncology, PC, Mishawaka, IN, ImmunoGen, Inc., Waltham, MA, The University of Alabama at Birmingham, Birmingham, AL, U.S. Oncology Research, The Woodlands, TX, Dana-Farber Cancer Institute, Boston, MA Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: Available chemotherapies for platinum-resistant ovarian cancer (PROC) have limited clinical activity and considerable toxicity. Mirvetuximab soravtansine (MIRV) is a first-in-class antibody drug conjugate (ADC) comprising a folate receptor alpha (FRα)-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin-targeting agent that has demonstrated significant anti-tumor activity in this difficult to treat population. The objective is to characterize the tolerability profile of MIRV in a pooled analysis of experience when administered as monotherapy in patients (pts) with FRα positive recurrent ovarian cancer. Methods: Retrospective pooled analysis included pts enrolled across three studies: phase 1 first-in-human, phase 3 FORWARD I, and phase 3 SORAYA. Analysis included pts with FRα positive recurrent ovarian cancer and those pts with low, medium, and high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 25% of cells with PS2+ staining intensity). All pts received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, on Day 1 of a 21-day cycle until disease progression or unacceptable toxicity. Results: 464 pts were included from 15 countries, with key characteristics: median age 63 yrs, 87% 1-3 prior therapies, 91% platinum free interval ≤6 months, 65% prior bevacizumab, and 25% prior PARPi. The most common treatment-related adverse events (TRAE) (all grade, grade 3+) included blurred vision (42%, 3%), nausea (40%, 2%), diarrhea (33%, 2%), fatigue (31%, 2%), keratopathy (26%, 3%), and dry eye (22%, 1%). TRAEs leading to a dose delay or reduction occurred in 33% and 21% of pts, respectively. Seven % discontinued due to a TRAE. Four pts ( < 1%) discontinued MIRV due to an ocular event. Ninety % of pts with a grade 2+ blurred vision resolved to grade 0 or 1, 93% of pts with grade 2+ keratopathy resolved to grade 0 or 1. No corneal ulcers or perforation have been reported and no patient with a serious ocular event has been reported to have permanent sequelae. Conclusions: In a pooled analysis of 464 patients, MIRV monotherapy has a differentiated and predictable safety profile consisting primarily of low grade and reversible gastrointestinal and ocular events. These events were managed with supportive care and dose modifications if needed, with a low rate of treatment-related discontinuation. The safety profile of MIRV in recurrent ovarian cancer along with the anti-tumor activity in PROC (32.4% ORR Matulonis SGO 2022) support a favorable benefit/risk in this population. Clinical trial information: NCT01609556, NCT04296890, NCT02631876.