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] - Cyclin E1 overexpression is identified as a predictive biomarker for patient selection, with an estimated 50% of PROC patients overexpressing Cyclin E1 [2] 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 PROC patients [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] - The safety profile remains consistent with previous reports, with gastrointestinal toxicities and fatigue being the most common treatment-related adverse events [3] Future Development Plans - Enrollment for DENALI Part 2 is expected to begin in the first half of 2025, with the potential for accelerated approval if successful [4] - The company plans to conduct a Phase 3 randomized confirmatory study concurrently with DENALI Part 2b, subject to FDA review [4] Preclinical Data - Preclinical data presented at the SGO Annual Meeting indicates that azenosertib shows synergistic effects when combined with microtubule inhibitor-based antibody drug conjugates (ADCs), enhancing tumor growth inhibition [5][6] - Azenosertib is being evaluated as a generalizable combination partner with ADCs for advanced solid tumors [6] Company Overview - Zentalis Pharmaceuticals is a clinical-stage biopharmaceutical company focused on developing azenosertib for patients with Cyclin E1+ PROC and other tumor types [8] - Azenosertib is a selective, orally bioavailable WEE1 inhibitor that targets cell cycle regulation to induce cancer cell death [7]