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. 2025 Apr:195:173-179.
doi: 10.1016/j.ygyno.2025.03.023. Epub 2025 Mar 22.

Patient outcomes in advanced ovarian cancer treated with an anti-FOLR1 antibody-drug conjugate

Paul Johannet  1 , Matthew Flint  2 , M Herman Chui  3 , Jason Konner  1 , Claire Friedman  1 , Angela K Green  1 , Robin Guo  1 , Martee L Hensley  1 , Chrisann Kyi  1 , Ying Liu  1 , Vicky Makker  1 , Maria Rubinstein  1 , Paul Sabbatini  4 , William P Tew  1 , Michael B Foote  1 , Britta Weigelt  3 , Carol Aghajanian  1 , Rachel N Grisham  1 , Roisin E O'Cearbhaill  5
Affiliations

Patient outcomes in advanced ovarian cancer treated with an anti-FOLR1 antibody-drug conjugate

Paul Johannet et al. Gynecol Oncol. 2025 Apr.

Abstract

Background: Mirvetuximab soravtansine-gynx (MIRV) is a FOLR1-binding antibody-drug conjugate (ADC) with a microtubule inhibitor payload. We investigated MIRV's efficacy, toxicity profile, and determinants of resistance in a cohort of patients with recurrent/persistent high FOLR1-expressing high-grade serous ovarian cancer (HGSOC).

Methods: This retrospective study included 170 patients with recurrent/persistent FOLR1-high (≥75 % of tumor cells with ≥2+ membranous staining intensity) HGSOC who received standard-of-care MIRV monotherapy. We evaluated progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier method and multivariable Cox proportional hazards models. We classified adverse events using CTCAE v5.0.

Results: Overall, median PFS was 3.5 months (95 % CI, 3.0-4.1). However, 22.4 % had PFS ≥6 months and were less likely to have progressed on or within one month of prior taxane-based therapy (P = 0.008). Patients with previous progression on a taxane had worse PFS (HR, 1.69; 95 % CI, 1.19-2.40; adjusted P = 0.003) and OS (HR, 2.34; 95 % CI, 1.45-3.77; adjusted P = 0.0005). FOLR1 expression was lower in post-MIRV samples (n = 12; P = 0.005). New or worsening neuropathy was observed in 37.6 % of patients. Among the 34.1 % who experienced ocular toxicity, median onset was 42.5 days. Treatment was discontinued in 5.3 % of patients due to toxicity.

Discussion: MIRV confers meaningful PFS benefit for a subset of individuals with HGSOC. Resistance may be associated with decreased FOLR1 target expression or payload resistance. FOLR1-targeted ADCs with a different payload should be evaluated for patients who progress on MIRV but retain high tumor FOLR1 expression.

Keywords: Antibody-drug conjugate; FOLR1; High-grade serous ovarian cancer; Mirvetuximab soravtansine-gynx; Resistance.

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Conflict of interest statement

Declaration of competing interest J.K. reported grants or contracts paid to the institution from Immunogen, Inc. C.F. reported grants or contracts paid to the institution from Merck, Mersana, AstraZeneca, BMS, Hotspot Therapeutics, Marengo, Volastra, and Immunocore; consulting fees from BMS, Seagen, Aadi Biosciences, and Eli Lilly; honoraria from OncLive; travel support from Puma Biotechnology; and unpaid board participation for Merck, Genentech, and Marengo. A.K.G. reported grants or contracts paid to the institution from Merck, Lilly, Aadi, Mereo Biopharma, and ASCO; consulting fees from Stemline Menarini and Merck; travel support from ASCO; and board participation for Stemline Menarini. R.G. reported travel support from Prelude Therapeutics; and board participation for Prelude Therapeutics, AstraZeneca, and Merck. M.L.H. reported royalties from Up To Date; board participation for Aadi and Targeted Oncology; and spouse employed with Sanofi until February 2024. C.K. reported grants paid to the institution from Merus, Gritstone, and BMS; consulting fees from Scenic Immunology B.V.; honoraria from OncLive; travel support from Conquer Cancer Foundation and Gritstone; and board participation for Scenic Immunology. Y.L. reported grants or contracts paid to the institution from AstraZeneca, GSK, Repare Therapeutics, and Artios Pharma; and honoraria from Topline Bio and HMP Education. V.M. reported grants or contracts paid to the institution from Merck, Eisai, AstraZeneca, Clovis, Bayer, Takeda, Duality, Zymeworks, Karyopharm, Faeth, BMS, Lilly, and Cullinan; travel support from Eisai, Merck, and AstraZeneca; unpaid board participation for Duality, Novartis, Morphosys, AstraZeneca, ArQule, Eisai, Cullinan, Clovis, Karyopharm, GSK, Merck, Faeth, Jazz, Immunocore, Iteos Therapeutics, Ideaya, Kartos Therapeutics, Lilly, Moreo, Prelude, Takeda, and Zymeworks; and other financial or nonfinancial interests with IBM. M.R. reported grants or contracts paid to the institution from Merck, Faeth, Duality, and Debiopharm; consulting fees from PeerTalk and MDO Activeer; and honoraria from OncLive. M.B.F. reported grants or contracts from NIH (K08CA279922); and board participation for Genzyme, BMS, and Abbott. B.W. reported grants or contracts paid to the institution from Repare Therapeutics; and an immediate family member employed with AstraZeneca. C.A. reported grants or contracts paid to the institution from Abbvie, AstraZeneca, Clovis, and Genentech/Roche; board participation for Merck and AstraZeneca; and unpaid board of directors participation for GOG Foundation and NRG Oncology. R.N.G. reported honoraria from GSK, AstraZeneca, Natera, Springworks, Corcept, MJH, and PER. R.E.O. reported grants or contracts paid to the institution from Bayer/Celgene/Juno, Arsenalbio, Tesaro/GSK, Merck, Ludwig Cancer Institute, Abbvie/StemCentrx, Regeneron, TCR2 Therapeutics, Atara Biotherapeutics, Marker Therapeutics, Syndax Pharmaceuticals, Genmab/Seagen Therapeutics, Genentech, Alkermes/Mural Oncology, Kite Pharma, Acrivon, OnCusp Therapeutics, Gynecologic Oncology Foundation, Lyell Immunopharma; honoraria from GSK, Seattle Genetics/SeaGen/Pfizer Immunogen, Bayer, R-Pharm, Miltenyi, 2seventybio, Bayer, Loxo, OnCusp Therapeutics, Takeda, Curio/OncLive/PER/MJH/Aptitude Health, and SITC, Gynecologic Oncology Canada; travel support from Hitech Health, Gathering Around Cancer Ireland, GOG Foundation, and SGO; unpaid board participation for AstraZeneca (DU0–0), GSK (Moonstone, Prima), Acrivon, Mural Oncology, Carina Biotech, Link Therapeutics; and a leadership role with SGO (vice-chair, CPC) and NRG Oncology (Chair, DT Committee). P.J., M.F., M.H.C., P.S., and W.P.T. reported no conflicts to disclose.

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