Zentalis Pharmaceuticals announced on April 9 that a prespecified interim analysis from Part IIa of the DENALI trial has identified 400mg once daily on a five-days-on, two-days-off schedule as the dose to carry forward for azenosertib in Cyclin E1-positive platinum-resistant ovarian cancer. The company described the response rate it characterized as "meaningful and clearly differentiated" over the 300mg arm and comparable safety profiles across both dose groups.
Azenosertib inhibits WEE1 kinase, a regulator of the G2-M cell cycle checkpoint, forcing cells with unrepaired DNA damage into mitosis. The DENALI trial (NCT05128825) is a multi-part, registration-intended Phase II study assessing azenosertib in patients with Cyclin E1-positive platinum-resistant ovarian cancer.
Part IIa is enrolling approximately 30 patients per dose group. The seamless adaptive design means Part IIa data will be incorporated into the full Part II dataset rather than reported as a standalone readout, a structure Zentalis said is intended to preserve the integrity of the pivotal dataset in support of a potential accelerated approval pathway. Enrollment in Part IIb, targeting up to approximately 100 patients at the 400mg QD 5:2 dose, is ongoing. A third cohort, Part IIc, broadening eligibility to patients previously treated with a taxane-containing regimen for platinum-resistant ovarian cancer, is planned to initiate in Q2 2026. Zentalis said it expects to complete enrollment across all Part II cohorts and report topline data by year-end 2026. The data remain interim and are based on a subset of enrolled patients; no efficacy data with full numerical detail were reported at this stage.
The ASPENOVA Phase III confirmatory trial, designed to enroll approximately 420 patients and compare azenosertib monotherapy against investigator's choice of single-agent chemotherapy — paclitaxel, pegylated liposomal doxorubicin, gemcitabine, or topotecan — is expected to initiate in Q2 2026. No approved therapy is currently indicated specifically for the Cyclin E1-positive biomarker-selected subpopulation, which Zentalis estimates comprises approximately 50% of platinum-resistant ovarian cancer patients.
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