Zentalis Picks 400mg Dose Of Azenosertib After Strong DENALI Trial Results, Advancing Drug Toward Phase 3 And Potential Approval

Zentalis Pharmaceuticals, Inc., a clinical-stage oncology company developing innovative cancer therapies, announced that it has selected 400mg once daily on a 5-days-on, 2-days-off schedule as the optimal monotherapy dose of azenosertib. Azenosertib is the company’s investigational first-in-class WEE1 inhibitor being studied as a biomarker-driven treatment for patients with Cyclin E1-positive platinum-resistant ovarian cancer. The decision was based on the prespecified interim analysis from Part 2a of the DENALI clinical trial. This dose will now be advanced in both the ongoing DENALI Phase 2 study and the confirmatory ASPENOVA Phase 3 trial.

According to the company’s Chief Executive Officer, selecting the pivotal monotherapy dose marks an important step forward in positioning azenosertib for potential registration. With this decision in place, the company is beginning preparations for a possible future commercial launch. These efforts include expanding commercial capabilities, scaling up manufacturing capacity, and continuing work on a companion diagnostic to support patient selection. 

The therapeutic profile observed at the selected dose in the DENALI Part 2a interim review also gives the company confidence to explore broader clinical opportunities for azenosertib, including use in first-line maintenance or platinum-sensitive ovarian cancer, as well as evaluating the drug in new tumor types through combination strategies.

The company’s Chief Medical Officer noted that the interim analysis from DENALI Part 2a showed a clearly differentiated and meaningful improvement in response rate at the 400mg dose compared to the 300mg dose. Both groups demonstrated similar safety profiles, and several encouraging safety trends were also seen at the selected dose. 

These included a discontinuation rate due to adverse events that was approximately half of what had been reported earlier in Part 1b of the trial, along with the absence of any treatment-related deaths. The results support the ongoing evaluation of azenosertib as an oral monotherapy that may provide patients with Cyclin E1-positive platinum-resistant ovarian cancer an effective and more convenient alternative to currently available intravenous chemotherapies, if approved.

In the DENALI Part 2a interim analysis, the choice of the 400mg dose was supported by several key observations. The response rate was stronger and more clearly favorable at 400mg than at 300mg. Safety findings were consistent across both dose groups, and improvements were seen in specific measures that further strengthened the benefit-risk assessment. The trial’s seamless design means that all data from Part 2a will flow directly into the full Part 2 dataset upon study completion. This approach helps maintain the overall integrity of the pivotal dataset and is intended to support a potential accelerated approval pathway.

Zentalis also announced updates to the DENALI Part 2 trial design in response to the evolving treatment landscape for platinum-resistant ovarian cancer. To ensure that the study population continues to reflect current clinical practice and approved treatment options, a new cohort, known as Part 2c, has been added. This cohort will include patients who have previously received a taxane-based regimen for platinum-resistant ovarian cancer. Enrollment for Part 2c is expected to begin in the second quarter of 2026.

With all three cohorts— Parts 2a, 2b, and 2c— DENALI Part 2 has been structured to support a potential accelerated approval for azenosertib in patients selected through the Cyclin E1 biomarker, pending regulatory evaluation. Zentalis expects to complete enrollment across all cohorts and release topline results by the end of 2026.