Correlating expression of NaPi2b and FRa in high grade serous ovarian cancer (HGSOC).

Abstract

5545 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. Uptifitamab rilsodotin (UpRi) is a late-stage, first in class NaPi2b-targeting ADC with a novel scaffold-linker-payload that enables high drug to antibody ratio and a controlled bystander effect. Approximately 29% of HGSOC patients have FRa positive tumors (Roche VENTANA FOLR1 (FOLR-2.1) RxDx Assay. USPI 2022); ~59% have NaPi2b positive tumors (Okeke et al, USCAP 2022). With the high unmet medical need in PROC and the evolving landscape of available treatments, understanding biomarker expression and correlation between FRa and NaPi2b is critical. Here we evaluate NaPi2b and FRa RNA expression correlation in HGSOC. Methods: Tumor samples (N=84) from the Ph1b UpRi expansion (EXP) cohort were analyzed via Nanostring (770 immune-focus genes from IO 360 panel + 30 customized ADC-related genes) to evaluate the association between NaPi2b and FRa expression. The cutoff for NaPi2b RNA positive or negative was based on approximately 60% of HGSOC patients having NaPi2b positive tumors (top 60% of samples based on expression deemed NaPi2b positive; bottom 40% NaPi2b negative) and FRa RNA cutoff assumed that ~30% of samples were FRa positive. To correlate the NaPi2b expression level between RNA and IHC, the N=84 samples with known expression levels via IHC were analyzed via Nanostring. Results: When evaluating NaPi2b and FRa RNA expression correlation, 21% (N=18) of samples had both NaPi2b positive and FRa positive expression. 38% (N=32) samples were NaPi2b positive and FRa negative. No statistically significant association was observed (Chi-squared test, p=0.129). NaPi2b RNA and IHC expression was evaluated; a statistically significant association was observed (Kappa statistic, p=0.001). Results are in the Table below. Conclusions: 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. [Table: see text]