Characterization of long-term survivors from four clinical trials examining patients with folate receptor alpha–positive recurrent ovarian cancer treated with single-agent mirvetuximab soravtansine.

person David M. O'Malley The Ohio State University, Hilliard, OH info_outline David M. O'Malley, Domenica Lorusso, Ana Oaknin, Toon Van Gorp, Susana N. Banerjee, Antonio González-Martín, Conleth G. Murphy, Nikolaus de Gregorio, Gottfried E. Konecny, Michael W. Method, Yuemei Wang, Robert L. Coleman, Ursula A. Matulonis, Kathleen N. Moore, Nicoletta Colombo

Authors person David M. O'Malley The Ohio State University, Hilliard, OH info_outline David M. O'Malley, Domenica Lorusso, Ana Oaknin, Toon Van Gorp, Susana N. Banerjee, Antonio González-Martín, Conleth G. Murphy, Nikolaus de Gregorio, Gottfried E. Konecny, Michael W. Method, Yuemei Wang, Robert L. Coleman, Ursula A. Matulonis, Kathleen N. Moore, Nicoletta Colombo Organizations The Ohio State University, Hilliard, OH, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, Gynaecologic Cancer Programme, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d’Hebron, Barcelona, Spain, University Hospital Leuven, Leuven Cancer Institute and BGOG, Leuven, Belgium, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom, Department of Medical Oncology, Clínica Universidad de Navarra, Madrid, Spain, Bon Secours Hospital Cork and Cancer Trials Ireland, Cork, Ireland, Heilbronn Women's Clinic, Heilbronn, Germany, University of California, Los Angeles Medical Center, Santa Monica, CA, ImmunoGen Inc., Waltham, MA, ImmunoGen, Inc, Waltham, MA, US Oncology Research, Texas Oncology and Gynecologic Oncology Group (GOG) Foundation, Shenandoah, TX, Dana-Farber Cancer Institute, Boston, MA, University of Oklahoma Health Sciences Center, Oklahoma City, OK, European Institute of Oncology, Milan, Italy Abstract Disclosures Research Funding Immunogen, Inc. Background: Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate targeting folate receptor-alpha (FRα), is the first novel treatment to demonstrate a benefit in overall survival (OS) in platinum-resistant ovarian cancer (PROC). Here, we characterize the patients with FRα-positive recurrent ovarian cancer with extended survival following MIRV monotherapy across four clinical trials. Methods: This retrospective, exploratory pooled analysis included patients enrolled across four clinical trials: phase 1 first-in-human, phase 2 SORAYA, and phase 3 FORWARD I and MIRASOL. The analysis used ≥ 15 months as the threshold for a meaningful difference in OS based on the upper bound of the 95% confidence interval of 14.36 months that was observed for the chemotherapy control arm of the MIRASOL trial. The population included patients with low, medium, and high FRα expression (PS2+) by immunohistochemistry (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay). All patients received intravenous MIRV at 6 mg/kg, adjusted ideal body weight, every three weeks until disease progression or unacceptable toxicity. Results: Of the 682 patients included in the analysis, 230 (34%) had an OS ≥15 months. The median age for the long-term survivor cohort was 63 years; 20% of patients had 1 prior, 41% had 2 priors, 38% had 3 priors, 58% were treated with prior bevacizumab and 33% were treated with prior PARPi. The population included a range of FRα expression; 1% had low, 20% had medium, and 79% had high expression. Long-term survival (LTS) patients had a median OS of 28.35 months (95% CI 25.72, NR), with 66% and 40% alive at 24 and 30 months, respectively. The overall response rate was 55.7%, with 21 (9.1%) patients achieving a complete response and 107 (46.5%) patients achieving a partial response by RECIST v1.1 with a duration of response of 8 months (95% CI 5.9, 9.6). The most common treatment-related adverse events (TRAEs) included blurred vision (60.9%), keratopathy (43.9%), nausea (40.0%), dry eye (36.1%), fatigue (33.5%), diarrhea (33.0%), and peripheral neuropathy (21.7%). TRAEs led to dose delay or reduction in 55.2% and 36.5% of patients, respectively, and discontinuation in 10.4% of patients. Conclusions: In a pooled analysis of 682 patients, long-term survival was observed in 34% of patients, with a median overall survival of 28.35 months and with 66% and 40% alive at 24 and 30 months, respectively. The observed MIRV tolerability in this patient cohort was generally consistent with the safety profile as reported in the U.S. prescribing information. These data add support to MIRV as a new standard of care for patients with FRα positive PROC. Clinical trial information: NCT04296890 ; NCT04209855 ; NCT02631876 ; NCT01609556 .

Clinical