TEST:

VENTANA FOLR1 RxDx Assay

Mirvetuximab soravtansine-gynx, an FRα-targeting ADC, has been approved by the FDA and EMA for the treatment of FRα-positive, platinum-resistant ovarian cancer... These findings highlight the critical importance of standardized, validated assays for FRα detection to ensure accurate patient selection for targeted therapies. The study emphasizes the need for further optimization of alternative antibodies before clinical implementation.

Mirvetuximab soravtansine (MIRV) is an antibody-drug conjugate approved for the treatment of adult patients with folate receptor 1 (FRα; FOLR1) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens...Our study highlights several factors contributing to heterogeneity in FOLR1 reporting. Future studies are needed to better understand the impact of FOLR1 heterogeneity on patient response to therapy.

Pathologists demonstrated high reproducibility in FRα IHC assessment, particularly in estimating percentage positivity and control adequacy. These findings support the clinical utility of FRα IHC but underscore the need for standardized scoring criteria and potential integration of digital tools to enhance consistency, especially in borderline cases.

An immunohistochemical (IHC) evaluation of FRα expression using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay is now approved as a companion diagnostic for selecting patients eligible for mirvetuximab soravtansine, an FRα-targeted antibody-drug conjugate...We also discuss heterogeneity in FRα expression across histological subtypes and tumor sites, as well as the impact of archival versus fresh tissue. Understanding FRα expression patterns across histologic subtypes and tissue samples is critical for optimizing clinical decision-making and expanding the role of FRα-targeted therapies in gynecologic oncology.

These data highlight the need for caution in antibody selection when developing immunohistochemistry-based assays, as some antibodies failed to cleanly and specifically identify FRα expression. We identified 2 antibodies appropriate for further investigation; however, as developed, these antibodies may overselect patients for treatment with FRα-targeted therapies.

Our results highlight a need for standardized protocols for FRα testing to ensure accurate biomarker evaluation across varied clinical settings. The heterogeneity in FRα expression, influenced by tumor histology and anatomical origin, warrant further investigation to optimize therapeutic outcomes.

"Roche...announced today that it has received CE Mark for its VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. This is the first immunohistochemistry (IHC) companion diagnostic test to be made widely available in Europe to aid in identifying epithelial ovarian cancer (EOC) patients who may be eligible for targeted treatment with ELAHERE (mirvetuximab soravtansine). ELAHERE is a first-in-class antibody-drug conjugate (ADC) therapy developed by AbbVie for the treatment of FRɑ-positive platinum-resistant ovarian cancer."

97.5% had prior taxanes, 81% prior poly (ADP-ribose) polymerase inhibitors (PARPi) [74.7% of whom progressed while on PARPi], 64.6% prior bevacizumab, 98.8% had 2+ prior lines of therapy, and BRCA status was 27.8% positive, 72.2% negative. MIRV demonstrated notable efficacy in this heavily pretreated PSOC population, including among those who may have PARPi resistance. MIRV continues to demonstrate a differentiated safety profile consisting primarily of low-grade neurosensory, GI, and resolvable ocular AEs. These data position MIRV to become a novel treatment option for patients in ≥3L PSOC with FRα positive expression.

Our data highlight the need for caution in antibody selection when developing immunohistochemical-based assays, as some FRα antibodies failed to cleanly and specifically identify FRα expression. We identified two antibodies appropriate for further investigation; however, as developed, both stain more intensely than the FDAapproved test and may, therefore, over-select patients for treatment with FRα-targeted therapies intended for use with the FDA-approved companion diagnostic. From these data, we advise the use of the FDAapproved assay for patient selection.

Cell block samples show significantly less staining for FOLR1 compared to tissue sections from the same patients. Pathologists should be aware of this limitation.

Here, we report updated nonanalytical results based on a median follow-up of 16.7 months. 453 PROC pts with high FRα expression (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay) with 1-3 prior therapies were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or ICC: paclitaxel (PAC), pegylated liposomal doxorubicin (PLD), or topotecan (Topo). With a median follow-up of 16.7 months, MIRV demonstrated improved efficacy vs ICC in pts with PROC. The efficacy data, along with the well-characterized safety profile, supports MIRV as the standard of care for pts with FRα positive PROC. Clinical Trial Information: NCT04209855.

97.5% had prior taxanes, 81% prior poly (ADP-ribose) polymerase inhibitors (PARPi) [74.7% of whom progressed while on PARPi], 64.6% prior bevacizumab, 98.8% had 2+ prior lines of therapy, and BRCA status was 27.8% positive, 72.2% negative. MIRV demonstrated clinically meaningful antitumor activity and favorable tolerability in patients with FRα-high PSOC. The efficacy and safety data support the use of MIRV in PSOC patients with ≥ 2 prior platinum-containing regimens or platinum allergy. Clinical Trial: NCT05041257.