trastuzumab deruxtecan + anti-PD-1 antibody

**Trastuzumab deruxtecan + anti-PD-1 antibody** is a combination regimen pairing the HER2-directed antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd, Enhertu; DS-8201a), developed by Daiichi Sankyo and AstraZeneca, with an anti-programmed cell death protein 1 (PD-1) monoclonal antibody such as nivolumab (Opdivo) or pembrolizumab (Keytruda). T-DXd consists of a humanized anti-HER2 IgG1 monoclonal antibody conjugated via a tetrapeptide-based cleavable linker to a potent topoisomerase I inhibitor payload (DXd, an exatecan derivative), enabling targeted delivery and bystander antitumor effects in HER2-expressing tumors. Preclinical studies demonstrate that T-DXd enhances antitumor immunity by increasing tumor-infiltrating dendritic cells (DCs) and CD8+ T cells, upregulating MHC class I and PD-L1 on tumor cells, which synergizes with anti-PD-1 blockade to improve efficacy beyond monotherapy in HER2-expressing models. Clinically evaluated in phase Ib trials (e.g., NCT03523572) for HER2-positive/low metastatic breast cancer (mBC) and metastatic urothelial cancer (mUC), showing promising objective response rates (e.g., 65.6% in HER2-positive mBC), with ongoing exploration in HER2-positive gastric/GEJ cancer (DESTINY-Gastric05).[1][2][5][6]

Other names

trastuzumab deruxtecan + nivolumabT-DXd + nivolumabEnhertu + OpdivoDS-8201a + pembrolizumabEnhertu + Keytruda