Azenosertib (WEE1 inhibitor) + weekly paclitaxel delivers 39% ORR in platinum-resistant ovarian cancer

Azenosertib (ZN-c3) is an oral, selective WEE1 kinase inhibitor designed to exploit replication stress and impair DNA-damage checkpoint control; in the MUIR Phase 1b open-label dose-escalation trial (NCT04516447), it was combined with weekly paclitaxel 80mg/m² (days 1/8/15 q28d) in platinum-resistant high-grade serous ovarian/fallopian tube/primary peritoneal cancer after 1–4 prior systemic lines (n=46; all previously exposed to paclitaxel). As of December 1, 2025, confirmed ORR was 39.1% (95% CI 25.1–54.6) with median DOR 5.6 months (95% CI 5.6–9.2), which sits above the ~25–30% ORR typically reported with weekly paclitaxel monotherapy in PROC and ~29–30% in a Phase III weekly paclitaxel control arm, while DOR appears broadly in the range seen with paclitaxel-based approaches. Safety was mainly myelosuppression and fatigue: any-grade fatigue 61%, anemia 59%, nausea 52%, neutropenia 50%; grade ≥3 neutropenia 30% and anemia 20%, with serious TRAEs in 20%—important given PROC patients often need “dose-density” therapy to stay on treatment.