TEST:

VENTANA FOLR1 RxDx Assay

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.

Mirvetuximab soravtansine (MIRV), an FRα-targeting antibody-drug conjugate, is active in high-grade serous epithelial ovarian cancer (HGSOC)... FRα was highest in HGSOC and was associated with advanced stage and BRCA status. Sample age, anatomical site, and PFI did not affect FRα expression, suggesting that any sample is suitable for determining FRα status. Variability was observed in cores from the same specimen, which appeared to be driven by tumour heterogeneity versus biological changes.

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, pegylated liposomal doxorubicin, or topotecan...In the MIRV arm, 36% had prior bevacizumab vs. 45% in the ICC arm, and 55% had prior PARPi vs 59% in the ICC... Dose modifications occurred at similar rates in both treatment arms. MIRV demonstrated a longer PFS, OS, and higher ORR vs ICC in patients with dose modifications. The efficacy data and the well-characterized safety profile support MIRV as the standard of care for pts with FRα positive PROC.

Oncol. (2023) 34 (suppl_2): S458-S497.

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. 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.

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, pegylated liposomal doxorubicin, or topotecan...In the MIRV arm, 57% had prior bevacizumab vs. 67% in the ICC arm, and 57% had prior PARPi experience vs. 58% in the ICC arm in pts ≥ 65... MIRV is the first treatment to demonstrate a PFS, ORR, and OS benefit in PROC compared to ICC. MIRV demonstrated a longer PFS, OS, and higher ORR vs ICC in the older population. Importantly, MIRV had fewer dose discontinuations than ICC, suggesting that TEAEs were more manageable The efficacy data and the well-characterized safety profile support MIRV as the standard of care for pts with FRα positive PROC across all ages.

Recently, the FDA approved mirvetuximab soravtansine for platinum-resistant ovarian carcinoma with FOLR1 overexpression, typically high-grade serous carcinoma... To our knowledge, this is the largest study to date of FOLR1 expression in USC. Nearly 1 in 5 USC patients are FOLR1+, independent of HER2 status. Further research testing the efficacy of FOLR1-targeted therapy in USC is needed, as approval could potentially double the proportion of patients with available targeted therapies.

Our results showed overexpression of FOLR1 and TROP2 in a significant proportion of high-grade EC, suggesting that targeted therapy against these markers may be a novel option for patients with EC. FOLR1 and HER2 positivity appeared mutually exclusive, while co-expression of FOLR1-TROP2 and HER2-TROP2 was also infrequent, observed in <5% of all tumors.

Introduction: Mirvetuximab soravtansine (MIRV) is an anti-folate receptor alpha (FOLR1)-drug conjugate... 41 cervical squamous cell carcinoma (SCC), 35 endocervical adenocarcinoma, 21 uterine serous carcinoma, 14 uterine carcinosarcoma, and 48 ovarian clear cell carcinoma (OCCC) cases were represented in the TMAs and stained with FOLR1 (see Figure 1). 0% of cervical SCC, 0% of endocervical adenocarcinoma, 14% of uterine serous carcinoma, 0% of uterine carcinosarcoma, and 0% of OCCC cases met current FOLR1 positivity criteria (PS2 ≥ 75%) (see Table 1). Figure 1: Examples of H&E and FOLR1 staining in endocervical adenocarcinoma (A-B), uterine serous carcinoma (C-D), and ovarian clear cell carcinoma (E- F) Table 1: FOLR1 PS2 scores of different tumor types Conclusion/Implications: Variable FOLR1 expression was seen in different gynecologic tumor types.

Antitumor activity has been observed at well tolerated dose levels. Dose escalation continues.

Background: Biomarker driven therapies are increasingly being used for gynecologic cancers, with mirvetuximab soravtansine, a Folate Receptor alpha (FRa) targeting antibody drug conjugate (ADC) being a recent FDA approved agent for patients with FRa positive PROC... Based on this analysis of a limited sample size, there does not appear to be an association between FRa and NaPi2b expression, with the majority of NaPi2b positive samples not being FRa positive. Additionally, general NaPi2b prevalence and the correlation of expression between RNA and IHC suggest that NaPi2b may be a rational biomarker to integrate in RNA tumor panel testing. This research underscores the importance of early, comprehensive testing of all relevant biomarkers to guide therapy selection, and suggests that additional research is needed to evaluate the potential association between FRa and NaPi2b expression via IHC.

By testing for FRα expression, you can help identify 35% of patients with EOC that may benefit from a promising FRα targeted therapy; ELAHERETM (mirvetuximab soravtansine). This comprehensive webcast aims to support pathologists with clinical training to better understand FRα biology and scoring of this novel IHC marker for EOC samples. Info Title: FRa Biology and FOLR1 IHC Scoring

"NeoGenomics, Inc...today launched a novel biomarker testing program for patients with epithelial ovarian cancer, including primary peritoneal or fallopian tube cancers (EOC).Through the FR-ASSIST™ program, sponsored by ImmunoGen, Inc...EOC patients will have access to the FOLR1 IHC CDx test (VENTANA FOLR1 RxDx Assay) performed by NeoGenomics to measure the expression of a protein called folate receptor alpha (FRα)...The new testing program is sponsored entirely by ImmunoGen and provides eligible EOC patients with FRα-expression testing through NeoGenomics at no cost, regardless of insurance coverage or test results."

"Roche...announced US Food and Drug Administration (FDA) approval of the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay, the first immunohistochemistry (IHC) companion diagnostic test to aid in identifying epithelial ovarian cancer (EOC) patients who are eligible for targeted treatment with ELAHERE™ (mirvetuximab soravtansine-gynx)....Developed as a predictive biomarker, the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay detects the folate receptor 1 protein (FOLR1 or FRɑ), which is over-expressed in most ovarian cancers. The new test identifies ovarian cancer patients eligible for targeted treatment with ELAHERE....The approval is based on the results of the SORAYA clinical study."