On October 18, 2026 Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical oncology innovator advancing late-stage development of investigational first-in-class WEE1 inhibitor azenosertib as a biomarker-driven treatment approach for ovarian cancer, reported that overall survival (OS) data from an interim analysis of the DENALI Part 1b study (GOG-3066) have been published in the abstract for the upcoming rapid oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2026.

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The published abstract reports results for OS, a secondary endpoint of DENALI Part 1b in patients with platinum-resistant ovarian cancer (PROC), from an interim analysis. As of the September 2, 2025 data cutoff:

In the Cyclin E1-positive subgroup (n=48): median OS of 15.8 months (95% CI, 8.7–17.8);
In the Cyclin E1-negative subgroup (n=46): median OS of 7.5 months (95% CI, 5.8–12.3);
No new safety signals were observed.
DENALI Part 1b enrolled 102 patients with PROC regardless of Cyclin E1 protein expression who had received between one and five prior lines of therapy, with prior bevacizumab required. The primary endpoint was objective response rate; secondary endpoints included duration of response, progression-free survival, OS and safety. Cyclin E1 status was retrospectively determined by immunohistochemistry using a proprietary cutoff, with 94 patients evaluable (Cyclin E1-positive: n=48; Cyclin E1-negative: n=46).

The abstract concludes that Cyclin E1 represents a highly selective and predictive biomarker for response to azenosertib, and that median OS with azenosertib compared favorably to historical single-agent chemotherapy benchmarks in patients with Cyclin E1-positive PROC, supporting further development of azenosertib in this biomarker-selected population in the ongoing DENALI Part 2 and ASPENOVA Phase 3 confirmatory trials.

The abstract is available on the ESMO (Free ESMO Whitepaper) Congress website and a rapid oral presentation is scheduled on October 23, 2026.

Presentation Details:

Title: "Azenosertib in platinum-resistant ovarian cancer (PROC): overall survival analysis from Part 1b of the DENALI study (GOG-3066)"
Session: Rapid Oral Presentation — Gynecological Cancers: Ovarian
Date/Time: Friday, October 23, 2026, 4:15 p.m. – 5:45 p.m. CEST
Presentation Number: 1242RO
Location: ESMO (Free ESMO Whitepaper) Congress 2026, Madrid, Spain
About the DENALI Clinical Trial
DENALI is a multi-part Phase 2 registration-intended clinical trial (NCT05128825, GOG-3066) studying azenosertib in patients with PROC.

Part 1b enrolled 102 patients with PROC regardless of Cyclin E1 protein expression, all treated at 400 mg QD 5:2 (five days of once-daily administration of azenosertib, followed by two days without azenosertib). The primary endpoint was objective response rate per RECIST v1.1; secondary endpoints included duration of response, progression-free survival, overall survival, and safety.

Part 2 is prospectively enrolling PROC patients with Cyclin E1 protein overexpression based on Zentalis’ proprietary immunohistochemistry cutoff. Part 2, in total, is designed to support accelerated approval, pending positive study outcomes and further discussions with the FDA. The study design consists of the following parts:

Part 2a: Dose confirmation evaluated two doses, 300 mg QD 5:2 and 400 mg QD 5:2, with approximately 30 patients enrolled per dose group. 400 mg QD 5:2 was selected as the optimal monotherapy dose. Recruitment at the 300 mg QD 5:2 dose level has been discontinued. All patients enrolled in Part 2a will contribute to the overall safety database submitted to the FDA.
Part 2b: Enrollment expansion at the selected 400 mg QD 5:2 dose up to approximately 100 patients, including patients at this dose in Part 2a. Enrollment in this cohort is complete.
Part 2c: Broadening of the study population, which is expected to include approximately 40 patients previously treated with a taxane-containing regimen for PROC. This cohort is currently enrolling.
For physician and patient information about the DENALI trial, please visit www.denalitrial.com.

About ASPENOVA Clinical Trial
ASPENOVA is a Phase 3 randomized, confirmatory clinical trial designed to support full approval of azenosertib in patients with Cyclin E1-positive PROC. The trial is expected to enroll approximately 420 patients and compare azenosertib monotherapy at 400mg QD 5:2 to investigator’s choice of standard-of-care single-agent chemotherapy (paclitaxel, pegylated liposomal doxorubicin [PLD], gemcitabine, or topotecan) in this biomarker-selected population. The primary endpoint is progression-free survival (PFS); key secondary endpoints include overall survival (OS) and overall response rate (ORR). The trial design was based on feedback from the U.S. FDA regarding requirements for seeking approval under the accelerated approval pathway and requirements to support potential conversion to full approval.

About Azenosertib
Azenosertib is an investigational, potentially first-in-class, selective, and orally bioavailable inhibitor of WEE1 currently being evaluated in clinical studies in ovarian cancer and additional tumor types. WEE1 acts as a master regulator of the G1-S and G2-M cell cycle checkpoints, through negative regulation of both CDK1 and CDK2, to prevent replication of cells with damaged DNA. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage and leading to mitotic catastrophe and cancer cell death.

Azenosertib is in late-stage development as a potential treatment for Cyclin E1-positive platinum-resistant ovarian cancer (PROC). There is currently no approved treatment option specifically for this biomarker-selected population which comprises approximately 50% of PROC patients. Cyclin E1 protein overexpression has been established as a sensitive and specific predictive biomarker for identifying patients who could potentially derive benefit from azenosertib treatment.

(Press release, Zentalis Pharmaceuticals, OCT 18, 2026, View Source [SID1234673547])