Zentalis® Pharmaceuticals, Inc. announced the monotherapy recommended Phase 2 dose (RP2D) for azenosertib, the Company's potentially first-in-class WEE1 inhibitor. Based on encouraging Phase 1 dose optimization clinical data, the RP2D for azenosertib as a monotherapy is 400 mg daily (QD) on a 5 days on, 2 days off (5:2) weekly administration schedule. This intermittent dosing schedule more than doubled steady state drug exposure in comparison to continuous dosing, and achieved promising efficacy signals, while maintaining safety and improving tolerability.

As of April 24, 2023, a total of 127 heavily pretreated patients with advanced solid tumors were treated with monotherapy azenosertib at doses = 300 mg at either continuous daily dosing or intermittent weekly administration schedules. Across all tumor types, 74 patients were treated with continuous dosing schedules and 53 patients were treated with intermittent dosing schedules. The confirmed objective response rate (ORR) was 36.8% (7/19) in the combined ovarian cancer and uterine serous carcinoma (USC) subgroups who received an intermittent dosing schedule, versus 19.2% (5/26) in those who received a continuous dosing schedule.

Steady state exposure, as measured by AUC0-24, more than doubled at the new intermittent RP2D, compared to AUC observed at 300 mg QD with continuous administration. Intermittent dosing maintained azenosertib safety and improved tolerability as compared to continuous dosing. Gastrointestinal, fatigue, and hematologic Grade 3 and 4 treatment-related adverse events (TRAEs) were comparable or favorable versus continuous dosing.

No discontinuations due to TRAEs were observed in the intermittent cohorts. The Company is currently enrolling patients at the new RP2D in three ongoing Phase 2 trials evaluating monotherapy azenosertib in the following patient populations: Cyclin E1+, platinum-resistant high-grade serous ovarian cancer, USC and PARP inhibitor-resistant and platinum-resistant ovarian cancer (new cohort of ongoing study).