Mirvetuximab soravtansine (MIRV) in patients with platinum-resistant ovarian cancer with high folate receptor alpha (FRα) expression: Characterization of antitumor activity in the SORAYA study.

person Ursula A. Matulonis Dana-Farber Cancer Institute, Boston, MA info_outline Ursula A. Matulonis, Ana Oaknin, Sandro Pignata, Hannelore denys, Nicoletta Colombo, Toon Van Gorp, Jason A. Konner, Marga Romeo, Philipp Harter, Conleth G. Murphy, Jiuzhou Wang, Michael W. Method, Brooke Esteves, Robert L. Coleman, Domenica Lorusso

Authors person Ursula A. Matulonis Dana-Farber Cancer Institute, Boston, MA info_outline Ursula A. Matulonis, Ana Oaknin, Sandro Pignata, Hannelore denys, Nicoletta Colombo, Toon Van Gorp, Jason A. Konner, Marga Romeo, Philipp Harter, Conleth G. Murphy, Jiuzhou Wang, Michael W. Method, Brooke Esteves, Robert L. Coleman, Domenica Lorusso Organizations Dana-Farber Cancer Institute, Boston, MA, Vall d'Hebron Institute of Oncology, Hospital Universitari Vall d’Hebron, and Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain, Department of Urology and Gynecology, Istituto Nazionale Tumori di Napoli IRCCS Fondazione G Pascale, Naples, Italy, BGOG and University Hospital, Ghent, Belgium, 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, Memorial Sloan Kettering Monmouth, Middletown, NJ, Institut Català d'Oncologia Badalona, Hospital Germans Trias i Pujol, Badalona, Spain, AGO Study Group & Evang. Kliniken Essen-Mitte, Essen, Germany, Bon Secours Cork Cancer Centre, Cork, Ireland, ImmunoGen, Inc., Waltham, MA, Michiana Hematology Oncology, PC, Mishawaka, IN, Kadmon Rsrch Inst, Wilmington, MA, U.S. Oncology Research, The Woodlands, TX, Catholic University of Sacred Heart and Fondazione Policlinico Gemelli IRCCS, Rome, Italy Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Background: SORAYA is a global single arm phase 3 study evaluating MIRV in patients (pts) with FRα high platinum-resistant ovarian cancer (PROC). MIRV is an antibody drug conjugate comprising a FRα-binding antibody, cleavable linker, and maytansinoid DM4, a potent tubulin-targeting agent. In this study, MIRV demonstrated activity in a broad population of PROC, regardless of number of prior lines of therapy or prior PARPi (Matulonis, SGO 2022). Here we describe details of response to treatment important for clinical decision making. Methods: SORAYA enrolled PROC pts with high FRα expression by immunohistochemistry (Roche FOLR1 Assay ≥ 75% of cells with PS2+ staining intensity) who had received 1-3 prior therapies, including required prior bevacizumab. 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. The primary endpoint was confirmed objective response rate (ORR) per RECIST v1.1 by investigator (INV) and the key secondary endpoint was duration of response (DOR); additional endpoints included time to response, CA-125 response, safety and tolerability. Results: 106 pts were enrolled; 51% had 3 prior lines; 48% had 1-2 prior lines of therapy; 48% received prior PARPi. ORR by INV was 32.4% (95% confidence interval [CI]: 23.6%, 42.2%), including five complete responses. Median time to response was 1.5 mos (range 1.0 to 5.6) and 71% of pts demonstrated tumor reduction. At the time of the protocol specified primary analysis (16 Nov 2021), the median DOR was 5.9 mos (95% CI: 5.6, 7.7). With 15 responders remaining on MIRV, the DOR continues to evolve. In the 86 response-evaluable patients for CA-125 (by Gynecologic Cancer Intergroup criteria), responses were observed in 46.5% (95% CI: 35.7, 57.6). Updated data will be presented including depth and duration of responses and impact of dose modifications. The most common treatment-related adverse events (TRAE; all grade, grade 3+) included blurred vision (41%, 6%), keratopathy (36%, 9%), and nausea (29%, 0%). TRAEs led to dose delays in 32%, dose reductions in 19%, and discontinuations in 7% of pts; one patient discontinued treatment due to an ocular event. The tolerability profile of MIRV consists of low-grade, reversible ocular and GI events, managed with dose modifications and supportive care. Conclusions: Treatment options for pts with PROC are limited. MIRV is the first biomarker-directed therapy demonstrating anti-tumor activity in pts with FRα high PROC. These results support the clinically meaningful impact MIRV has for pts with FRα high PROC, irrespective of prior therapies or dose modifications. Clinical trial information: NCT04209855.