Zentalis Announces Updated Clinical Data From Part 1b Of DENALI Trial Of Azenosertib In PROC

(RTTNews) - Zentalis Pharmaceuticals Inc. (ZNTL) announced updated clinical data from Part 1b of the ongoing DENALI clinical trial of azenosertib in patients with platinum-resistant ovarian cancer or PROC in an oral presentation at the Society of Gynecologic Oncology (SGO) 2025 Annual Meeting on Women's Cancer.

DENALI Part 1b is a Phase 2 single-arm study that evaluated azenosertib monotherapy at the 400mg QD 5:2 dose (once daily, five days on, two days off) in patients with PROC.

As of the January 13, 2025 data cutoff, patients with Cyclin E1+ PROC tumors who were response-evaluable (patients who had at least one scan after receiving azenosertib) demonstrated an ORR of 34.9%. In the intent-to-treat patients with Cyclin E1+ PROC (patients who received at least one dose of azenosertib), the ORR was 31.3%, and an mDOR of 6.3 months. The median duration of response (mDOR) is subject to change since there were patients with ongoing responses as of the cutoff date.

According to the company, the presentation also demonstrates Cyclin E1 protein overexpression, regardless of CCNE1 gene amplification, as a sensitive and specific predictive biomarker that can be used to identify patients who could potentially derive benefit from azenosertib. Zentalis estimates that about half of PROC patients overexpress Cyclin E1 based on its proprietary immunohistochemistry cutoff.

As of the January 13, 2025 data cutoff, the safety and tolerability profile was consistent with the safety and tolerability profile from the company's January 29, 2025 investor event, which included data based off a cutoff date of December 2, 2024, with no new safety findings. Gastrointestinal toxicities and fatigue were found to be the most common treatment-related adverse events.

The company said it is on track to initiate enrollment of DENALI Part 2 in the first half of 2025 and expects to disclose topline data from DENALI Part 2 by year end 2026. DENALI Part 2, if successful, has the potential to support an accelerated approval, subject to FDA review. Zentalis plans to treat the same patient population in a Phase 3 randomized confirmatory study, subject to FDA review, which the company plans to enroll concurrently with DENALI Part 2b.

On Sunday, the company will also present preclinical data of azenosertib during a poster presentation at the SGO Annual Meeting. The poster data highlights synergistic effects and significantly improved tumor growth inhibition in in vitro and in vivo preclinical models using a combination of azenosertib and microtubule inhibitor-based ADCs. The results indicate that azenosertib could be used as a generalizable combination partner with ADCs for improving responses in patients with advanced solid tumors.

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