osimertinib + trastuzumab deruxtecan

Osimertinib + trastuzumab deruxtecan is an investigational combination regimen consisting of the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib and the HER2-directed antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd). Developed by AstraZeneca and Daiichi Sankyo, this combination is primarily being explored to overcome acquired resistance in patients with EGFR-mutated non-small cell lung cancer (NSCLC). Preclinical studies have shown that treatment with osimertinib can lead to an upregulation of HER2 expression on the cell surface of residual cancer cells, creating a bypass pathway that drives resistance. By combining osimertinib with trastuzumab deruxtecan, the regimen aims to simultaneously inhibit EGFR signaling and selectively eliminate HER2-expressing persister cells. The combination has demonstrated synergistic antitumor activity in patient-derived xenograft (PDX) models and has shown clinical benefit in real-world case studies of patients with EGFR-mutant NSCLC who developed acquired HER2 amplification or mutations following progression on osimertinib.

Other names

Enhertu + TagrissoT-DXd + osimertinibTagrisso + Enhertuosimertinib + T-DXdosimertinib and trastuzumab deruxtecanosimertinib/trastuzumab deruxtecantrastuzumab deruxtecan + osimertinib