Phase 3 azenosertib WEE1 inhibitor vs chemotherapy in Cyclin E1+ platinum-resistant HGS ovarian cancer.

This global, randomized, open-label Phase 3 study (ASPENOVA; also referenced as GOG-3147/ENGOT-ov109/APGOT-OV27) tests whether azenosertib (ZN-c3)—a first-in-class, oral WEE1 kinase inhibitor from Zentalis Pharmaceuticals (via its subsidiary sponsor listing)—can improve outcomes versus investigator’s choice single-agent chemotherapy in platinum-resistant high-grade serous ovarian, primary peritoneal, or fallopian tube cancer with Cyclin E1 protein expression by immunohistochemistry. WEE1 inhibition is intended to exploit replication stress and checkpoint dependence in Cyclin E1–driven tumors, pushing cancer cells into lethal DNA damage during replication. The investigational arm uses azenosertib 400 mg on an intermittent 5-days-on/2-days-off schedule, while the control arm uses protocol-defined physician choice chemotherapy reflecting real-world options in this setting. The commercial/scientific angle is a biomarker-selected, registrational attempt to “carve out” a Cyclin E1+ segment within platinum-resistant disease—where today’s care is sequential single-agent therapy (often weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan depending on prior exposures) plus bevacizumab in some patients, with modest response rates and short durability.