Dr Simpkins on the Clinical Applicability of Cyclin E1 Protein Expression as a Biomarker for Response to Azenosertib in Ovarian Cancer

“The objective response rate of 34% and median duration of response of 6.3 months is encouraging and warrants further evaluation for this therapy.”

Fiona Simpkins, MD, the Hilarie L. and Mitchell L. Morgan President’s Distinguished Professor in Women’s Health at the University of Pennsylvania Perelman School of Medicine in Philadelphia; an attending physician of gynecologic oncology in the Department of Ob/Gyn in the Hospital of the University of Pennsylvania; director of Clinical & Translational Gynecologic Oncology Research at the Penn Medicine Health System; and active staff of Gynecologic Oncology in the Department of Ob/Gyn at Chester County Hospital, discussed the potential role of cyclin E1 protein expression as a biomarker of response to azenosertib (ZN-c3) in patients with ovarian cancer.

Findings from part 1b of the phase 2 DENALI trial (NCT05128825) demonstrated that cyclin E1 protein expression detected by immunohistochemistry (IHC) is present in approximately 50% of platinum-resistant ovarian cancers, broadening the population that could potentially benefit from WEE1 inhibition beyond those identified by CCNE1 gene amplification. In this heavily pretreated trial population, azenosertib generated an objective response rate of 34.9% (95% CI, 21.0%-50.9%), with a median duration of response of 6.3 months (95% CI, 2.7-not evaluable). Simpkins noted that these findings are encouraging given the historically limited treatment options and low response rates in platinum-resistant ovarian cancer. The activity of azenosertib in this biomarker-defined subset supports continued investigation of WEE1 inhibitors as part of an evolving precision oncology approach for ovarian cancer.

According to Simpkins, ongoing analyses aim to further validate cyclin E1 as a predictive biomarker and explore its integration into clinical practice. These investigations align with the growing emphasis on tailoring therapy based on tumor biology and leveraging biomarkers to refine patient selection. Simpkins concluded that these findings warrant continued development of azenosertib and further prospective biomarker-driven studies to improve outcomes for patients with platinum-resistant ovarian cancer.