Zentalis(US:ZNTL) Globenewswire·2025-01-29 12:00Core Insights - Zentalis Pharmaceuticals has reported promising clinical data for azenosertib in patients with Cyclin E1+ platinum-resistant ovarian cancer (PROC), showing an Objective Response Rate (ORR) of approximately 35% in heavily pretreated patients [1][3][13] - The company has aligned with the FDA on the seamless design for DENALI Part 2, which is expected to begin in the first half of 2025, with topline data anticipated by the end of 2026 [1][4][20] - Azenosertib has demonstrated a median duration of response of about 5.5 months, with a well-characterized safety profile and no new safety signals reported [3][6][14] Clinical Development - The DENALI Part 2 study will confirm the primary dose of interest (400mg QD 5:2) and will enroll approximately 30 patients at two dose levels [4] - The MAMMOTH study evaluated azenosertib monotherapy and combination therapy, with the monotherapy arm showing an ORR of 31.3% in Cyclin E1+ patients [9][10] - The ZN-c3-001 study has fully enrolled 274 patients, with encouraging results for azenosertib monotherapy in solid tumors [5][6] Safety and Tolerability - Azenosertib has shown a tolerable safety profile at total daily doses ≥ 300mg, with low rates of Grade 3+ treatment-related adverse events [7][10][14] - In the DENALI Part 1b study, the safety profile was consistent with previous studies, with a low incidence of serious adverse events [14] Market Opportunity - Approximately 50% of PROC patients are Cyclin E1+, indicating a substantial therapeutic and commercial opportunity for azenosertib in this treatment-refractory population [3][20] - The successful outcome of DENALI Part 2 could support accelerated product approval, enhancing Zentalis's position in the market [3][4]