Zentalis reports 15.8-month median overall survival with azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer in the DENALI Part 1b study.
Written By: Kirti Kumbhar, M. Pharm (QA)
Reviewed By: Pharmacally Editorial Team
Zentalis Pharmaceuticals has reported a median overall survival (OS) of 15.8 months with investigational WEE1 inhibitor azenosertib in patients with Cyclin E1-positive platinum-resistant ovarian cancer (PROC), according to an interim analysis of the Phase 2 DENALI Part 1b study. The findings provide an early survival signal for a biomarker-selected population with limited treatment options, although the non-randomized analysis does not establish azenosertib’s survival benefit over standard chemotherapy.
Survival Outcomes Differ by Cyclin E1 Status
The analysis included 94 patients whose Cyclin E1 status could be evaluated retrospectively using immunohistochemistry and a proprietary cutoff. Among 48 patients classified as Cyclin E1-positive, median OS was 15.8 months (95% CI, 8.7–17.8). In the 46 Cyclin E1-negative patients, median OS was 7.5 months (95% CI, 5.8–12.3).
Overall survival was a secondary endpoint, and the data cutoff was September 2, 2025. The company reported no new safety signals in the interim analysis.
The difference in median OS between the biomarker-defined groups supports further investigation of Cyclin E1 expression as a potential tool for identifying patients more likely to benefit from azenosertib. However, these results alone do not establish that Cyclin E1 is predictive of treatment benefit, because the reported analysis does not provide a randomized comparison or demonstrate a treatment-by-biomarker interaction.
WEE1 Inhibition Targets Cancer Cell-Cycle Control
Azenosertib is an investigational, orally available, selective inhibitor of WEE1, a kinase that regulates cell-cycle checkpoints through negative regulation of CDK1 and CDK2. These checkpoints prevent cells with damaged DNA from progressing through replication and division.
By inhibiting WEE1, azenosertib can allow cancer cells with DNA damage to continue through the cell cycle, potentially triggering mitotic catastrophe and cell death.
Platinum-resistant ovarian cancer remains a challenging disease to treat because tumors progress despite platinum-based chemotherapy. According to Zentalis, Cyclin E1 protein overexpression occurs in approximately 50% of patients with PROC. The company reports that no treatment is specifically approved for this biomarker-defined population.
DENALI Study Evaluates Azenosertib Monotherapy
DENALI Part 1b (NCT05128825; GOG-3066) enrolled 102 patients with PROC who had received one to five prior lines of therapy, with previous bevacizumab treatment required. Patients received azenosertib at 400 mg once daily for five consecutive days, followed by two days off treatment, in a repeating schedule.
The primary endpoint was objective response rate according to RECIST version 1.1. Secondary endpoints included duration of response, progression-free survival, overall survival and safety.
Zentalis reported that the median OS in Cyclin E1-positive patients compared favorably with historical benchmarks for single-agent chemotherapy. However, historical comparisons cannot establish superiority because differences in patient characteristics, treatment history and study design may affect outcomes.
The survival analysis will be presented at the European Society for Medical Oncology (ESMO) Congress 2026 in Madrid on October 23, during a rapid oral session on gynecological cancers.
Phase 3 Trial Will Test Clinical Benefit
Zentalis is advancing azenosertib through the ongoing DENALI Part 2 program and the Phase 3 ASPENOVA trial. DENALI Part 2 prospectively enrolls patients with Cyclin E1 overexpression. The company selected the 400 mg once-daily, five-days-on/two-days-off regimen after evaluating two doses in Part 2a. Enrollment in the Part 2b expansion cohort is complete, while Part 2c is enrolling patients previously treated with a taxane-containing regimen.
ASPENOVA is expected to enroll approximately 420 patients with Cyclin E1-positive PROC. The randomized trial compares azenosertib monotherapy with investigator-selected chemotherapy, including paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan. Progression-free survival is the primary endpoint, with overall survival and objective response rate among the key secondary endpoints.
The Phase 3 results will be important in determining whether the survival signal observed in DENALI Part 1b translates into a clinically meaningful benefit over standard treatment and supports regulatory approval.
Reference
Zentalis Pharmaceuticals Announces First Overall Survival Data for Azenosertib from DENALI Part 1b Published in ESMO Congress 2026 Abstract, Zentalis Pharmaceuticals, 18 October 2026
A Study of Azenosertib (ZN-c3) in Subjects with Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer (DENALI), ClinicalTrials.gov ID NCT05128825
About the Writer
Kirti Kumbhar (LinkedIn) is an M.Pharm graduate with experience in Quality Assurance at Lupin Limited and a strong interest in clinical research, regulatory affairs, and Trial Master File (TMF) management. She has developed knowledge of regulatory documentation, quality systems, compliance, and healthcare research through her professional experience. Passionate about clinical development and continuous learning, Kirti is committed to supporting high-quality healthcare documentation, regulatory excellence, and research-driven healthcare advancements.