Also known as: DS-8201a
Trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki) is marketed as ENHERTU, a HER2-directed antibody and topoisomerase inhibitor conjugate used across multiple advanced HER2-expressing cancers. Labeling includes metastatic HER2-positive breast cancer settings, HER2-low/HER2-ultralow breast cancer, HER2-mutant NSCLC, HER2-positive gastric/GEJ adenocarcinoma, and HER2-positive solid tumors under accelerated approval. U.S. initial approval was in 2019.
Single-cell RNA sequencing of nearly 92,000 cells from the DESTINY-Gastric06 trial reveals distinct primary and acquired resistance mechanisms to trastuzumab deruxtecan in HER2-positive gastric cancer, including MUC3A and CST3 as key drivers.
Over 20 pharmaceutical companies are developing therapies for HER2-positive gastric cancer, with multiple Phase III trials launched in March 2026 testing novel combination treatments for advanced disease.
Trastuzumab deruxtecan is moving into earlier treatment lines for HER2-positive metastatic breast cancer, demonstrating superior efficacy over standard regimens and prompting reconsideration of long-standing treatment sequences.
Recent developments in breast cancer treatment include new clinical trials for advanced disease, findings on CDK4/6 inhibitor sequencing, and discovery of genetic markers explaining drug resistance in HER2-positive breast cancer.
The US FDA granted priority review and the European Medicines Agency validated applications for Enhertu as post-neoadjuvant treatment for HER2-positive early breast cancer, based on Phase III trial data showing 53% reduction in recurrence risk.
Enhertu combined with pertuzumab received FDA approval for first-line treatment of HER2-positive metastatic breast cancer, marking the first new treatment in a decade. Real-world data show trastuzumab deruxtecan efficacy is consistent across patient subgroups.
Former Novartis executive John Tsai has been appointed global head of R&D at Daiichi Sankyo, replacing Ken Takeshita effective April 1. Tsai brings over 25 years of leadership experience in drug development.
New clinical trial data show trastuzumab deruxtecan plus pertuzumab extends progression-free survival as first-line therapy, while MRI-guided treatment shortening reduces toxicity in neoadjuvant settings for HER2-positive breast cancer.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07582887 |
Impact of Genetic Variants on the Toxicity of Antibody-Drug Conjugates in Locally Advanced or Metastatic Breast Cancer: The Role of the UGT1A1 Gene as a Predictive Biomarker of Therapeutic Response |
RECRUITING | |
| NCT07578116 |
Adding Surgery and Radiation to the Usual Treatment for HER2-Positive Breast Cancer That Had Already Spread at Diagnosis |
NOT_YET_RECRUITING | PHASE3 |
| NCT07454668 |
Trastuzumab Deruxtecan + Stereotactic Radiosurgery (SRS) in HER2+ Breast Cancer Brain Metastases |
NOT_YET_RECRUITING | PHASE1 |
| NCT07428044 |
A Study of Trastuzumab Deruxtecan in People With Non-Small Cell Lung Cancer |
RECRUITING | PHASE2 |
| NCT07416253 |
Trastuzumab Rezetecan vs Trastuzumab Deruxtecan in the Neoadjuvant Treatment of HER2 Positive Breast Cancer |
NOT_YET_RECRUITING | PHASE2 |
| NCT07393425 |
Neoadjuvant Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab in HER2+ Breast Cancer |
RECRUITING | PHASE2 |
| NCT07368543 |
Sequencing SG vs. T-DXd in HER2-Low/TROP2-High Metastatic Breast Cancer |
NOT_YET_RECRUITING | PHASE2 |
| NCT07318389 |
ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer |
NOT_YET_RECRUITING | EARLY_PHASE1 |
| NCT07198724 |
ERADICATE: A Phase Ib/II Study of Elacestrant Plus Trastuzumab Deruxtecan in Patients With CDK4/6 Inhibitor and Endocrine-resistant HR+/HER2-low or HER2-ultralow Metastatic Breast Cancer |
RECRUITING | PHASE1/PHASE2 |
| NCT07180264 |
Trastuzumab Deruxtecan in Advanced Breast Cancer |
RECRUITING |
