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Enhertu (trastuzumab-deruxtecan)
Enhertu works by binding to the HER2 protein and releasing a cytotoxic payload to kill cancer cells.
At a glance
| Generic name | trastuzumab-deruxtecan |
|---|---|
| Sponsor | Daiichi Sankyo |
| Target | Receptor tyrosine-protein kinase erbB-2 |
| Modality | Monoclonal antibody |
| Therapeutic area | Oncology |
| Phase | FDA-approved |
| First approval | 2019 |
| Annual revenue | 2900 |
Mechanism of action
Fam-trastuzumab deruxtecan-nxki is HER2-directed antibody-drug conjugate. The antibody is humanized anti-HER2 IgG1. The small molecule, DXd, is topoisomerase inhibitor attached to the antibody by cleavable linker. Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death.
Approved indications
- Advanced HER2positive gastric or gastroesophageal junction (GEJ) adenocarcinoma
- Metastatic human epidermal growth factor 2 positive carcinoma of breast
Boxed warnings
- WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and the need to immediately report symptoms [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] . Embryo-Fetal Toxicity: Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ] . WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. ( 2.3 , 5.1 ) Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception. ( 5.4 , 8.1 , 8.3 )
Common side effects
- Nausea
- White blood cell count decreased
- Hemoglobin decreased
- Neutrophil count decreased
- Fatigue
- Vomiting
- Alopecia
- Aspartate aminotransferase increased
- Alanine aminotransferase increased
- Platelet count decreased
- Constipation
- Decreased appetite
Key clinical trials
- DS-8201a in Human Epidermal Growth Factor Receptor 2 (HER2)-Expressing Gastric Cancer [DESTINY-Gastric01] (PHASE2)
- A Study of DS-8201a in Metastatic Breast Cancer Previously Treated With Trastuzumab Emtansine (T-DM1) (PHASE2)
- Testing the Safety of the Combination of Anti-Cancer Drugs CX-5461 (Pidnarulex) and Trastuzumab Deruxtecan (T-DXd) for Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Solid Tumors and Breast Cancer (PHASE1)
- Testing the Safety and Tolerability of the Anti-cancer Drugs Trastuzumab Deruxtecan and Neratinib for Cancers With Changes in the HER2 Gene (PHASE1)
- Personalized Antibody-Drug Conjugate Therapy Based on RNA and Protein Testing for the Treatment of Advanced or Metastatic Solid Tumors (The ADC MATCH Screening and Treatment Trial) (PHASE2)
- Testing the Combination of DS-8201a and Olaparib in HER2-Expressing Cancers With Expansion in Patients With Platinum Resistant Ovarian Cancer (PHASE1)
- Testing the Combination of the Anticancer Drugs Trastuzumab Deruxtecan (DS-8201a) and Azenosertib (ZN-c3) in Patients With Stomach or Other Solid Tumors (PHASE1)
- Trastuzumab Deruxtecan for the Treatment of HER2+ Newly Diagnosed or Recurrent Osteosarcoma (PHASE2)
Patents
| Patent | Expiry | Type |
|---|---|---|
| Biologic Exclusivity |
Primary sources
Every claim on this page is sourced from regulatory or scientific primary sources. See our editorial policy for full methodology.
| Source | Used for |
|---|---|
| FDA label | Mechanism, indications, dosing, boxed warnings, drug interactions |
| ClinicalTrials.gov | Trial enrolment, design, endpoints, results |
| FDA Orange Book | Patents + exclusivity |
| SEC EDGAR | Revenue + earnings |
Competitive intelligence
For the full competitive landscape — auto-detected comparators, recent regulatory actions across the set, upcoming PDUFA, patent timeline, sponsor landscape:
- Enhertu CI brief — competitive landscape report
- Enhertu updates RSS · CI watch RSS
- Daiichi Sankyo portfolio CI