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trastuzumab deruxtecan + onvansertib
- Development stage
- Preclinical
- Lead developer
- Cardiff Oncology
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Small Molecules
- Administration
- Intravenous, Oral
01
Overview
Trastuzumab deruxtecan + onvansertib is an investigational, preclinical combination therapy that pairs the HER2-directed antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) with onvansertib, an oral, highly selective polo-like kinase 1 (PLK1) inhibitor. Trastuzumab deruxtecan consists of a HER2-targeting monoclonal antibody linked to a topoisomerase I inhibitor payload (deruxtecan). Onvansertib enhances the antitumor activity of T-DXd and overcomes resistance by synergistically inducing DNA damage and apoptosis. Preclinical studies have demonstrated robust efficacy, tumor regression, and favorable tolerability of this combination in HER2-low and hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer models, including those resistant to endocrine therapy, CDK4/6 inhibitors, and T-DXd.
- Other names
- onvansertib + T-DXdonvansertib + trastuzumab deruxtecanT-DXd + onvansertib
02
Targets
FcγR (Low affinity immunoglobulin gamma Fc region receptor II-c)ERBB2 (Erb-b2 receptor tyrosine kinase 2)PLK1 (Polo like kinase 1)
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