Zentalis Pharmaceuticals Announces First Overall Survival Data for Azenosertib from DENALI Part 1b Published in ESMO Congress 2026 Abstract
No new safety signals were observed in the interim analysis; further development continues in biomarker-selected patients.
Sentiment and the balance of points
Rhea-AI Sentiment reads the wording of the document, how positive or negative its language is on a 1 to 5 scale. The balance of points shown with the takes weighs what the document actually discloses, so the two can disagree, for example when a trial that missed its main goal is described in upbeat language.
Rhea-AI Summary
Zentalis Pharmaceuticals (ZNTL) announced published interim survival data for azenosertib in platinum-resistant ovarian cancer from the DENALI Part 1b study.
At the September 2, 2025 cutoff, median overall survival was 15.8 months in Cyclin E1-positive patients (48 patients; 95% confidence interval, 8.7–17.8 months) and 7.5 months in Cyclin E1-negative patients (46 patients; 5.8–12.3 months). No new safety signals were observed. Overall survival was a secondary endpoint; Cyclin E1 status was determined retrospectively, with 94 of 102 enrolled patients evaluable.
DENALI Part 2b enrollment is complete, while Part 2c is enrolling. Part 2 is designed to support accelerated approval, pending positive outcomes and further FDA discussions. The Phase 3 ASPENOVA confirmatory trial is expected to enroll approximately 420 patients. The survival findings will be presented at ESMO Congress on October 23, 2026.
How this balance works
Rhea-AI gives every point it takes from this document a weight. Minor counts 1, Moderate 3 and Major 9, so one Major point outweighs several Minor ones. The bar adds up the weights on each side, and when neither side holds more than 65% of the total the balance reads Mixed.
It reads the document as published, with the same rules for every company, and it does not look at what the market expected or at how the stock traded, so a point can be objectively good on a day the stock falls.
Rhea-AI Sentiment measures something else, the tone of the wording.
Hollow bars mark forward-looking points. How the balance works
Positive
- Moderate pointMedian overall survival reached 15.8 months in Cyclin E1-positive patients versus 7.5 months in Cyclin E1-negative patients.
- Moderate pointDENALI Part 2b completed enrollment in its expansion cohort of up to approximately 100 patients, including Part 2a patients.
- Moderate point. Forward-looking: it has not happened yet and may not happen.ASPENOVA is expected to enroll approximately 420 patients, comparing azenosertib with standard-of-care single-agent chemotherapy.
- Minor pointInterim safety analysis found no new safety signals.
- Minor pointDENALI Part 2a selected 400 mg once daily, five days on and two days off as the optimal monotherapy dose.
- Minor point. Forward-looking: it has not happened yet and may not happen.DENALI Part 2c is enrolling and is expected to include approximately 40 patients previously treated with taxane-containing therapy for PROC.
Negative
- Moderate point. Forward-looking: it has not happened yet and may not happen.DENALI Part 2's accelerated-approval objective remains dependent on positive study outcomes and further FDA discussions.
- Minor pointSurvival findings are interim secondary-endpoint results, with Cyclin E1 status determined retrospectively in 94 evaluable patients.
Key Figures
- Median overall survival
- 15.8 months
- Cyclin E1-positive subgroup (n=48); 95% CI, 8.7–17.8 months
- Median overall survival
- 7.5 months
- Cyclin E1-negative subgroup (n=46); 95% CI, 5.8–12.3 months
- Biomarker-evaluable patients
- 94 patients
- Cyclin E1 status was retrospectively evaluated
Key Terms
overall survival medical
platinum-resistant ovarian cancer medical
objective response rate medical
progression-free survival medical
immunohistochemistry medical
recist v1.1 medical
AI-generated analysis. How Rhea-AI works. Not financial advice.
- Median overall survival of 15.8 months in Cyclin E1-positive platinum-resistant ovarian cancer patients treated with azenosertib monotherapy
- Data to be presented as a rapid oral presentation at ESMO Congress 2026 on October 23, 2026
SAN DIEGO, Oct. 18, 2026 (GLOBE NEWSWIRE) -- 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, today announced 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) Congress 2026.
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 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 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
About Zentalis Pharmaceuticals
Zentalis is a clinical oncology innovator developing a treatment approach for ovarian cancer and multiple tumor types. Leveraging therapeutics development and biomarker expertise, Zentalis is advancing monotherapy and combination studies of its investigational first-in-class WEE1 inhibitor, azenosertib. Focused on translating WEE1 science into clinical practice, we aim to equip physicians with a targeted, non-chemo, orally available medicine that enhances treatment experience, choice, and outcomes. Our mission: to unburden cancer patients with more convenience and care.
For more information, please visit www.zentalis.com. Follow Zentalis on LinkedIn at www.linkedin.com/company/zentalis-pharmaceuticals
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this press release that do not relate to matters of historical fact should be considered forward-looking statements, including, but not limited to, statements regarding the continued development of azenosertib; the clinical and therapeutic potential of azenosertib; the potential for azenosertib to be first-in-class; the broad franchise potential of azenosertib; the Company’s biomarker-driven strategy for azenosertib, including the ability of Cyclin E1 to be a highly selective and predictive biomarker for response to azenosertib; and our participation in conference presentations. The terms “anticipate,” “advance,” “believe,” “design,” “develop,” “expect,” “intent,” “look forward,” “on track,” “plan,” “position,” “potential,” “runway,” “strategy,” “support,” “target,” “upcoming,” and “will” and similar references are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are neither promises nor guarantees, but involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, but not limited to, the following: our limited operating history, which may make it difficult to evaluate our current business and predict our future success and viability; we have and expect to continue to incur significant losses; our need for additional funding, which may not be available; our substantial dependence on the success of azenosertib; our plans, including the costs thereof, of development of companion diagnostics; the outcome of preclinical testing and early trials may not be predictive of the success of later clinical trials; potential unforeseen events during clinical trials could cause delays or other adverse consequences; risks relating to the regulatory approval process or ongoing regulatory obligations; our product candidates may cause serious adverse side effects; inability to maintain our collaborations, or the failure of these collaborations; our reliance on third parties; effects of significant competition; the possibility of system failures or security breaches; risks relating to intellectual property; our ability to attract, retain and motivate qualified personnel, and risks relating to management transitions; significant costs as a result of operating as a public company; and the other important factors discussed under the caption “Risk Factors” in our most recently filed periodic report on Form 10-K or 10-Q and subsequent filings with the U.S. Securities and Exchange Commission (SEC) and our other filings with the SEC. Any such forward-looking statements represent management’s estimates as of the date of this press release. While we may elect to update such forward-looking statements at some point in the future, we disclaim any obligation to do so, even if subsequent events cause our views to change.
ZENTALIS® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release.
Contact:
Aron Feingold
VP, Investor Relations & Corporate Communications
ir@zentalis.com
FAQ
AI-generated questions and answers. How Rhea-AI works. Not financial advice.
What survival results did Zentalis report for azenosertib in DENALI Part 1b?
Median overall survival was 15.8 months in the Cyclin E1-positive subgroup and 7.5 months in the Cyclin E1-negative subgroup at the September 2, 2025 cutoff. These interim results involved 48 and 46 patients, respectively. No new safety signals were observed.
How were patients treated in Zentalis' DENALI Part 1b study?
All 102 patients received azenosertib at 400 mg once daily for five days, followed by two days without treatment. Patients had received between one and five prior lines of therapy, and prior bevacizumab was required. The primary endpoint was objective response rate, which measures the proportion of patients whose tumors shrink to a specified extent.
What will Zentalis' ASPENOVA trial measure?
ASPENOVA's primary endpoint is progression-free survival, the time patients live without their cancer worsening. The randomized Phase 3 trial compares azenosertib with investigator-selected paclitaxel, pegylated liposomal doxorubicin, gemcitabine or topotecan in Cyclin E1-positive platinum-resistant ovarian cancer. Secondary endpoints include overall survival and overall response rate; the trial is designed to support full approval.