Zentalis to present azenosertib preclinical data in TNBC at AACR meeting

Zentalis (ZNTL) announced data from two posters being presented at the 2026 American Association for Cancer Research Annual Meeting, taking place April 17-22, 2026, in San Diego, CA. The data show encouraging preclinical activity of azenosertib in triple-negative breast cancer and highlight the poor prognosis of Cyclin E1-positive ovarian cancer patients with currently available treatments in a real-world data analysis. “The preclinical data in triple-negative breast cancer being presented at AACR showed that azenosertib combinations can induce complete tumor responses in a model resistant to emerging ADC therapies, supporting the potential to broaden the impact of azenosertib beyond ovarian cancer,” said Julie Eastland, CEO of Zentalis. “This includes potential development of azenosertib through differentiated combination strategies with antibody-drug conjugates and chemotherapy. As ADCs advance toward first-line use in TNBC, effective post-ADC treatment strategies represent a growing unmet need that azenosertib combinations may be uniquely positioned to fill. Our data suggest azenosertib may achieve this through multiple mechanisms – possibly resensitizing tumors to chemotherapy, enhancing the responses to ADC, and extending the duration of response – which is an exciting potential future direction for our pipeline.” Preclinical evidence supports azenosertib as a therapeutic strategy in TNBC: TNBC cell lines showed higher Cyclin E1 expression and greater sensitivity to WEE1 inhibition compared to other breast cancer cell lines. Azenosertib monotherapy demonstrated meaningful antitumor activity across a diverse panel of 12 TNBC in vivo xenograft models. In a patient-derived xenograft model of TNBC with clinical resistance to sacituzumab govitecan, an approved topoisomerase 1 inhibitor ADC, azenosertib + enfortumab vedotin: Induced complete responses in 7 of 8 mice; 5 mice did not progress after treatment discontinuation; Prevented tumor progression in 8 of 8 mice for more than 52 days compared to 100% progression observed within 30 days with EV alone. Drove deep tumor regression in mice models refractory to sacituzumab govitecan or trastuzumab deruxtecan with large tumor volumes. Combinations of azenosertib with TOPO1i-payload ADCs enhanced both depth and duration of response compared to ADC monotherapy in ADC-naive models. Azenosertib + paclitaxel restored substantial sensitivity to paclitaxel in a model resistant to both paclitaxel and TOPO1i ADCs.