Zentalis selects 400 mg azenosertib regimen for Cyclin E1-positive ovarian cancer
Zentalis selected a 400 mg once-daily, 5-days-on/2-days-off azenosertib regimen for Cyclin E1-positive platinum-resistant ovarian cancer after a DENALI Phase 2 interim analysis. The regimen is planned for DENALI and ASPENOVA as the company pursues a potential accelerated approval pathway.
Zentalis Pharmaceuticals reported that a 400 mg once-daily, 5-days-on/2-days-off regimen of azenosertib was selected as the optimal monotherapy dose for Cyclin E1-positive platinum-resistant ovarian cancer following a prespecified interim analysis from the DENALI Part 2a Phase 2 trial. The company said the dose decision was supported by a differentiated response rate, comparable safety and plans for inclusion in both the pivotal DENALI Phase 2 and confirmatory ASPENOVA Phase 3 trials.
The dose selection is central to Zentalis’s pursuit of a potential accelerated approval pathway in this biomarker-selected population. Azenosertib has received Fast Track Designation from the U.S. FDA for treating Cyclin E1-positive platinum-resistant ovarian cancer.
Zentalis also announced preclinical data at the 2026 AACR Annual Meeting indicating that its investigational WEE1 inhibitor azenosertib shows potential efficacy in treating triple-negative breast cancer resistant to antibody-drug conjugates and could expand its applications beyond ovarian cancer. Preclinical data showed azenosertib combinations induce complete tumor responses in ADC-resistant TNBC models.
In addition, real-world data showed that Cyclin E1-positive ovarian cancer patients have significantly poorer outcomes compared with those without this protein overexpression, highlighting the need for effective treatments in this population. The findings support ongoing studies evaluating azenosertib as a targeted therapy for Cyclin E1-positive patients and potential use in novel combination therapies.
Zentalis said the new dose will guide both ongoing and planned trials, with DENALI progress toward a year-end 2026 topline readout and an expanded Part 2c cohort supporting the accelerated approval narrative. The company is a clinical-stage biopharmaceutical company focused on discovering and developing small molecule therapeutics for the treatment of various cancers in the United States.