T-DXd is fam-trastuzumab deruxtecan-nxki, marketed as ENHERTU, a HER2-directed antibody and topoisomerase inhibitor conjugate used across multiple HER2-expressing advanced cancers. Labeling includes metastatic HER2-positive breast cancer settings (including first-line combination with pertuzumab), 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.
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.
The ASCENT-04 trial showed sacituzumab govitecan plus pembrolizumab improved progression-free survival in PD-L1-positive TNBC without increased toxicity. Meanwhile, experts debate whether ADCs function as targeted therapy or advanced chemotherapy, with sequencing questions remaining unresolved.
Exploratory analysis from a phase 1/2 trial shows CD47 expression levels predict response to evorpacept plus zanidatamab in heavily pretreated HER2-positive metastatic breast cancer patients, supporting biomarker-driven patient selection.
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.
| NCT ID | Title | Status | Phase |
|---|---|---|---|
| NCT07529613 |
Trastuzumab Deruxtecan Plus Nivolumab Plus Capecitabine Plus Oxaliplatin for HER2 Low Gastric and Gastroesophageal Junction Adenocarcinoma |
COMPLETED | PHASE1/PHASE2 |
| NCT07417241 |
SHR-A1811 vs Pyrotinib/Capecitabine in Trastuzumab-Resistant HER2+ Advanced Breast Cancer: A Randomized Study |
NOT_YET_RECRUITING | PHASE2 |
| NCT07371585 |
Trastuzumab Deruxtecan in First-Line HER2-Positive Metastatic Breast Cancer With Proactive Toxicity Management |
RECRUITING | PHASE2 |
| NCT07134153 |
Phase I/II Study of Intrathecal/Ommaya T-DXd in HER2-Expressing Breast Cancer With Leptomeningeal/Brain Metastases |
RECRUITING | PHASE1/PHASE2 |
| NCT06548178 |
T-DXd Versus THP for Medium-risk HER2-positive Early Breast Cancer |
NOT_YET_RECRUITING | PHASE2 |
| NCT06244485 |
A Study of Valemetostat Tosylate in Combination With DXd ADCs in Subjects With Solid Tumors |
RECRUITING | PHASE1 |
| NCT06174987 |
A Study to Provide Continued Access to and Assess Long-Term Safety of the Study Drug(s) |
RECRUITING | PHASE3 |
| NCT06135194 |
Efficacy of T-Dxd in the Treatment of HER2-positive BCBM After Prior Pyrotinib |
RECRUITING | |
| NCT05765851 |
A Study of DS-1103a Combination Therapy in Participants With Advanced Solid Tumors |
ACTIVE_NOT_RECRUITING | PHASE1 |
| NCT04686305 |
Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC |
RECRUITING | PHASE1 |
