On April 9, 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 the selection of 400mg once daily on a 5-days-on, 2-days-off schedule (400mg QD 5:2) as the optimal monotherapy dose of azenosertib in patients with Cyclin E1-positive platinum-resistant ovarian cancer (PROC) based on the prespecified interim data analysis from DENALI Part 2a. This dose will be carried forward in the ongoing potentially pivotal DENALI Phase 2 clinical trial as well as the confirmatory ASPENOVA Phase 3 clinical trial.

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"Selecting the pivotal monotherapy dose for azenosertib is a key inflection point that supports our registration-intended path. Beyond executing on DENALI and ASPENOVA, we are initiating launch preparedness by adding commercial capabilities to our organization, scaling manufacturing capacity, and advancing companion diagnostic development," said Julie Eastland, Chief Executive Officer of Zentalis. "Importantly, the therapeutic profile of the selected dose from the DENALI Part 2a interim analysis provides us confidence to further pursue expansion of the clinical pipeline for azenosertib into first-line maintenance, or platinum sensitive, ovarian cancer and explore combinations in new tumor types."

"The emerging DENALI Part 2a data from the planned interim analysis provide a favorable benefit-risk profile at the 400mg QD 5:2 dose over 300mg QD 5:2. A meaningful, differentiated response rate with the selected dose and comparable safety profiles across both dose groups were observed in this interim analysis," said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. "While DENALI is an ongoing trial, we are encouraged by the interim Part 2a data and continued momentum of the clinical study. As an oral monotherapy, azenosertib may offer Cyclin E1-positive PROC patients an efficacious, convenient alternative to current standard-of-care intravenous chemotherapy, if approved."

DENALI Part 2a Interim Analysis

A comprehensive review of the interim data from DENALI Part 2a informed the selection of the 400mg QD 5:2 dose over 300mg QD 5:2. A prespecified interim analysis showed:

A meaningful and clearly differentiated response rate at 400mg QD 5:2 over 300mg QD 5:2 dose
Comparable safety profiles across the two dose groups and observed improvements in several key measures, such as a discontinuation rate due to adverse events at approximately half of the rate reported in DENALI Part 1b and no treatment-related deaths.

Consistent with the seamless design of the registration-intended DENALI Part 2 trial, data from Part 2a will be included in the ongoing, full Part 2 dataset after the trial is completed, rather than reported separately. This approach is intended to preserve the integrity of the overall pivotal dataset and support the potential accelerated approval pathway.

DENALI Part 2 Trial Design Updated to Address Evolving PROC Landscape

The treatment landscape in PROC is evolving. The DENALI Part 2 study has been expanded to maintain alignment between the study population and available approved treatment options.

A new DENALI cohort that broadens inclusion to patients previously treated with a taxane-containing regimen for PROC, called Part 2c, intends to further align the study with the evolving treatment landscape. Enrollment in Part 2c is planned to initiate in Q2 2026.

Together, all three DENALI Part 2 cohorts are designed to support a potential accelerated approval pathway in the Cyclin E1 biomarker selected patient population, subject to regulatory review. Zentalis expects to complete enrollment in all cohorts of DENALI Part 2 and provide a topline readout by year-end 2026.

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, based on retrospective analysis of azenosertib studies in PROC. Validation of the Cyclin E1 companion diagnostic assay is ongoing in the DENALI and ASPENOVA trials.

Azenosertib has been granted Fast Track Designation by the U.S. FDA for the treatment of patients with Cyclin E1-positive platinum-resistant ovarian cancer. Fast Track Designation is intended to facilitate the development and expedite the review of therapies that have the potential to treat serious conditions and address unmet medical needs.

About DENALI Clinical Trial
DENALI is a multi-part Phase 2 registration-intended clinical trial (NCT05128825) studying azenosertib in PROC patients.

Part 1b enrolled patients with PROC regardless of Cyclin E1 protein expression, all treated at 400mg QD 5:2. 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 study outcome and discussions with the FDA. The study design consists of the following parts:

Part 2a: Dose confirmation evaluated two doses, 300mg QD 5:2 and 400mg QD 5:2, with approximately 30 patients enrolled per dose group. 400mg QD 5:2 was selected as the optimal monotherapy dose. Recruitment at the 300mg 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 dose up to approximately 100 patients, including patients at the 400mg QD 5:2 dose in Part 2a. This cohort is currently enrolling.
Part 2c: Broadening study population to include approximately 40 patients previously treated with a taxane-containing regimen for PROC. Enrollment is expected to initiate in this cohort in Q2 2026.

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 platinum-resistant ovarian cancer (PROC). The trial will 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 trial design was aligned with the U.S. FDA to meet requirements for the accelerated approval pathway and potential conversion to full approval. ASPENOVA is expected to initiate in Q2 2026.

(Press release, Zentalis Pharmaceuticals, APR 9, 2026, View Source [SID1234664293])