Zentalis Begins Part 2 of DENALI Study Doses First Patient In Trial For Cyclin E1+ PROC With Azenosertib

Zentalis Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical-stage biopharmaceutical company, announced that the first patient has been dosed in Part 2 of the Phase 2 DENALI clinical trial (NCT05128825) of azenosertib. This trial targets patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC), a group with significant unmet medical needs.

The DENALI trial is designed in two stages. Part 2a will determine the primary dose-of-interest, enrolling approximately 30 patients at each of two dose levels: 400mg QD 5:2 and 300mg QD 5:2 (five days on, two days off). Following this, Part 2b will enroll around 70 additional patients at the selected dose, depending on FDA feedback. Zentalis expects topline results from DENALI Part 2 by the end of 2026. If positive, the trial could potentially support an accelerated approval, subject to regulatory review.

“Dosing the first patient in Part 2 of the DENALI study is an important milestone for Zentalis as we continue the clinical development of azenosertib,” said Ingmar Bruns, M.D., Chief Medical Officer of Zentalis. “We are proud that azenosertib is one step closer to our goal of addressing a tremendous unmet need. We are grateful to our patients and their families for participating in this trial, which has the potential to result in a treatment option for thousands of women diagnosed with Cyclin E1+ PROC.”

Previously disclosed data from Part 1b of DENALI showed promising results. As of the January 13, 2025 cutoff, among 43 response-evaluable patients, the objective response rate (ORR) was 34.9%, with a median duration of response (mDOR) of 6.3 months. Some patients were still responding at the cutoff date, meaning the mDOR may continue to evolve.

Importantly, the trial identified Cyclin E1 protein overexpression—irrespective of CCNE1 gene amplification—as a strong predictive biomarker for azenosertib efficacy. Zentalis estimates that approximately half of all PROC patients overexpress Cyclin E1, based on their proprietary immunohistochemistry testing method.