Abstract 5910: Characterizing spatial expression patterns and prevalence of folate receptor alpha in relation to other existing and emerging ovarian cancer biomarkers

Abstract The ovarian cancer treatment landscape has seen an emergence of biomarker-targeted therapies following accelerated approval of the folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) mirvetuximab soravtansine-gynx (MIRV, Elahere) in November 2022 (with full US approval granted in March 2024). Many therapies in development are biomarker-directed ADCs with distinct cytotoxic payloads, which is the major effector component of the ADC. Data suggest mechanisms of resistance may be largely payload specific, meaning patients may only be able to receive a limited number of these therapies; thus making it paramount to identify the therapy from which each individual patient will derive maximal clinical benefit. Eligibility for MIRV is currently evaluated by FRα expression as assessed by the immunohistochemical VENTANA FOLR1 (FOLR1-2.1) RxDx Assay (FOLR1 CDx). FRα is expressed in roughly 95% of high-grade serous ovarian cancer, with around 36% prevalence observed at the cutoff for MIRV eligibility (PS2 ≥ 75%, or ≥75% of viable tumor cells with ≥2+ staining). The goal of this study was to characterize the spatial overlap of FRα expression and prevalence with biomarkers that are currently being or could be leveraged for targeted therapeutics in the ovarian space. FRα expression was evaluated in commercially procured, formalin-fixed, paraffin-embedded (FFPE) primary ovarian tumor specimens using the FOLR1 CDx. HER2, Muc16, Mesothelin, TROP2, CLDN6, B7-H4, CDH6, Tissue factor and Napi2B were also evaluated by immunohistochemistry from serial sections taken from the same FFPE blocks. Intensity staining for each biomarker was correlated to FRα intensity staining to identify overlapping eligible patient populations. In addition to intensity overlap, spatial expression patterns of each biomarker relative to FRα were also evaluated to understand sequencing and combinability options. These data shed light on biomarker co-expression in ovarian cancer to best match patients to the ideal targeted therapy and to best tailor optimal combination therapies in ovarian cancer patients. Citation Format: Marian Themeles, Kevin Kolahi, Amita Mistry, Erik Huntzicker, Peter Ansell, Emily Deutschman. Characterizing spatial expression patterns and prevalence of folate receptor alpha in relation to other existing and emerging ovarian cancer biomarkers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5910.