3P NaPi2b expression in high grade serous ovarian cancer: Results from combined data sets

Abstract

NaPi2b is a sodium-dependent phosphate transporter broadly expressed in high-grade serous ovarian cancer (HGSOC), with limited expression in normal tissues. Uptifitamab rilsodotin (UpRi) is a first-in-class NaPi2b-targeting antibody drug conjugate (ADC) with a novel scaffold-linker-payload that enables high drug-to-antibody ratio and controlled bystander effect. NaPi2b is a new target currently being studied in ovarian cancer; understanding its expression and prevalence across HGSOCs is key in developing a biomarker-driven therapy. Multiple datasets were used to address the question of NaPi2b expression and prevalence. In all datasets, NaPi2b expression was assessed by IHC with NaPi2b positivity defined as a tumor proportion score ≥75. Sample sets included commercially procured HGSOC representing synchronous sampling of primary and metastatic lesions, matched metachronous samples (“archival” and “fresh”) from the Ph1b UpRi trial and HGSOC tissues sampled at multiple time points throughout the course of their disease. Our results suggest high prevalence of NaPi2b positive expression in HGSOC. In the UpRi Ph1b clinical trial, 64% (50/78; 95% CI 52.4 - 74.7) of patients were determined to be NaPi2b positive, as determined by the GLP (good laboratory practices) assay. When NaPi2b expression was examined from synchronous sampling of primary and metastatic lesions (N=18 pairs), as well as matched metachronous samples (N=56 pairs), there was high concordance rate ranging from 72-76% regardless of whether expression was evaluated over time or between anatomic locations. NaPi2b is a stable biomarker that is highly expressed in the majority of HGSOC patients. Expression remains stable over time - regardless of biopsy sites or treatment history. These data are consistent with data previously published from an investigational companion diagnostic assay study from 398 unique HGSOC tissue samples suggesting a prevalence of 59% (Patel et al., USCAP 2022). These findings support early NaPi2b testing and the continued development of NaPi2b-directed agents for HGSOC. Further analyses from ongoing trials and data sets will provide additional information on NaPi2b expression.