Zentalis Pharmaceuticals Presents Updated Clinical Data at the Society of Gynecologic Oncology 2025 Annual Meeting on Women's Cancer

Core Insights - Zentalis Pharmaceuticals announced updated clinical data for azenosertib, a WEE1 inhibitor, showing a median duration of response (mDOR) of 6.3 months and an objective response rate (ORR) of approximately 35% in patients with platinum-resistant ovarian cancer (PROC) [1][4] - The company is on track to initiate Part 2 of the DENALI clinical trial in the first half of 2025, with topline data expected by the end of 2026 [1][4] - Preclinical data presented indicates that azenosertib demonstrates synergistic antitumor effects when combined with microtubule inhibitor-based antibody drug conjugates (ADCs) [1][6] Clinical Trial Data - DENALI Part 1b is a Phase 2 single-arm study evaluating azenosertib monotherapy at a dose of 400mg QD 5:2 in 102 patients with PROC [1] - As of January 13, 2025, the ORR for response-evaluable patients with Cyclin E1+ PROC tumors was 34.9%, while the intent-to-treat ORR was 31.3% [1][3] - The mDOR of 6.3 months is subject to change as some patients continue to show ongoing responses [1] Biomarker Insights - Cyclin E1 protein overexpression is identified as a sensitive and specific predictive biomarker for azenosertib efficacy, with an estimated 50% of PROC patients overexpressing Cyclin E1 [2] Safety Profile - The safety and tolerability profile of azenosertib remains consistent with previous reports, with gastrointestinal toxicities and fatigue being the most common treatment-related adverse events [3] Future Development Plans - Zentalis plans to enroll patients in DENALI Part 2 concurrently with a Phase 3 randomized confirmatory study, pending FDA review [4] - The company aims for DENALI Part 2 results to support an accelerated approval pathway [4] Combination Therapy Potential - Preclinical data suggests that azenosertib could serve as a generalizable combination partner with ADCs to enhance treatment responses in advanced solid tumors [6][7]