Dr Simpkins on the Predictive Utility of Cyclin E1 for Azenosertib Response in Ovarian Cancer

"[These were] very exciting results suggesting that Cyclin E1 protein expression is predictive of response to azenosertib [in platinum-resistant disease.]"

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, discusses the utility of cyclin E1 positivity as a predictive biomarker of response to azenosertib for patients with platinum-resistant ovarian cancer.

Part 1b of the phase 2 DENALI trial (NCT05128825) enrolled 102 patients with platinum-resistant ovarian cancer who had received 1 to 5 prior lines of therapy, including prior bevacizumab (Avastin). The trial included all patients irrespective of cyclin E1 status.Eligible patients received azenosertib at a dose of 400 mg daily on a 5-days-on, 2-days-off weekly dosing schedule. The primary end points were the frequency and severity of treatment-emergent adverse effects (AEs), incidence of dose modifications, and ORR per revised RECIST 1.1 criteria and by independent review committee.

Data from part 1b, which were presented during the 2025 SGO Annual Meeting on Women’s Cancer, suggested that cyclin E1 positivity was a predictive biomarker of response to azenosertib, Simpkins reported. At the January 13, 2025, data cutoff, the ORR among all response-evaluable patients (n = 93) was 20.4% (95% CI, 12.8%-30.1%), whereas the ORR in the intention-to-treat (ITT) population (n = 102) was 18.6% (95% CI, 11.6%-27.6%). In patients with cyclin E1–positive tumors, the ORRs were higher: 34.9% (95% CI, 21.0%-50.9%) among response-evaluable patients (n = 43) and 31.3% (95% CI, 18.7%-46.3%) in the ITT population (n = 48).

Among cyclin E1–positive patients in the ITT population, the median duration of response was 6.3 months (95% CI, 2.7–not evaluable), and the median progression-free survival was 4.1 months (95% CI, 2.8–6.8), she continued. Notably, 4 patients were continuing to respond at the time of the analysis. These findings support further evaluation of cyclin E1 as a predictive biomarker for azenosertib activity and demonstrate the potential of this agent in a subset of patients with platinum-resistant ovarian cancer, a population with limited effective therapeutic options, Simpkins concluded.

Disclosures: Simpkins reported performing consulting/advisory roles with AstraZeneca, GlaxoSmithKline, Repare Therapeutics, and FoRx Therapeutics; and receiving research funding from AstraZeneca, AstraZeneca/MedImmune, Instill Bio, Repare Therapeutics, and Sierra Oncology.