Azenosertib monotherapy achieved 42-99% tumor growth inhibition across a panel of 12 TNBC xenograft models. In an ADC-resistant patient-derived xenograft model, combination of azenosertib with enfortumab vedotin induced complete responses in 7 of 8 mice and halted progression for more than 52 days, while combinations with sacituzumab govitecan, datopotamab deruxtecan, trastuzumab deruxtecan and paclitaxel enhanced both the depth and duration of antitumor activity compared to monotherapies.

Analysis of two independent cohorts showed Cyclin E1-positive ovarian cancer patients experienced shorter time to next treatment—13.2 months for those with gene amplification and 14.9 months without—versus 19.5 months in Cyclin E1-negative patients (p=0.002). Cyclin E1 overexpression was associated with a trend toward reduced clinical benefit from standard platinum-resistant regimens, highlighting a significant unmet need.

These data support the late-stage development of azenosertib as a biomarker-driven therapy in Cyclin E1-positive platinum-resistant ovarian cancer, with DENALI and ASPENOVA trials aiming for registration. The robust preclinical TNBC activity also suggests potential future expansion of the pipeline through differentiated combination strategies with antibody–drug conjugates and chemotherapy to address post-ADC treatment challenges.