Cardiff Oncology, Inc. has unveiled promising preclinical data at the AACR Annual Meeting 2026, showcasing the efficacy of its oral PLK1 inhibitor, onvansertib, in combination with the HER2-targeted antibody-drug conjugate (ADC), trastuzumab deruxtecan (T-DXd). This combination therapy demonstrated significant antitumor activity and the ability to overcome resistance in HER2-low breast cancer models, marking a potential advancement in treatment strategies for this challenging cancer subtype.

The data indicate that onvansertib synergistically inhibited the viability of various HER2-low breast cancer cell lines, including those resistant to fulvestrant and CDK4/6 inhibitors. In preclinical models, the combination led to tumor regression in nearly all subjects, with complete response rates reaching 62% in some cases. Moreover, the therapy not only improved tumor growth inhibition but also extended event-free survival, suggesting a robust clinical impact that could translate into improved outcomes for patients with resistant tumors.

This development underscores a significant shift in the therapeutic landscape for HER2-low breast cancer, particularly in the context of overcoming treatment resistance. The findings support further exploration of PLK1 inhibition as a viable strategy to enhance the efficacy of existing ADCs, potentially accelerating drug development timelines and informing clinical trial designs. As Cardiff Oncology continues to investigate onvansertib across various cancer types, including RAS-mutated metastatic colorectal cancer, this combination therapy could pave the way for innovative approaches in oncology, addressing unmet needs in patient populations facing limited treatment options.

Source: globenewswire.com