fam-trastuzumab deruxtecan-nxki
Trade name: Enhertu
Approved
Dec 20, 2019
Trastuzumab deruxtecan, sold under the brand name Enhertu, is an antibody-drug conjugate consisting of the humanized monoclonal antibody trastuzumab (Herceptin) covalently linked to the topoisomerase I inhibitor deruxtecan. It is licensed for the treatment of breast cancer, non-small cell lung cancer (NSCLC), gastric or gastroesophageal adenocarcinoma. Trastuzumab binds to and blocks signaling through epidermal growth factor receptor 2 (HER2/neu) on cancers that rely on it for growth. Additionally, once bound to HER2 receptors, the antibody is internalized by the cell, carrying the bound deruxtecan along with it, where it interferes with the cell's ability to make DNA structural changes and replicate its DNA during cell division, leading to DNA damage when the cell attempts to replicate itself, destroying the cell. — Wikipedia
Clinical trial activity
116 trials · 79 clinical orgs · 1 marketing orgs
Earliest trial started Aug 1, 2015 (NCT02564900)
Timeline
2010s
- Jan 1, 2015
Daiichi Sankyo — Earliest Phase 1 Sponsor(trial)
- Jan 1, 2017
Daiichi Sankyo — Earliest Phase 2 Sponsor(trial)
- Jan 1, 2018
Daiichi Sankyo — Earliest Phase 3 Sponsor(trial)
- Dec 20, 2019
Daiichi Sankyo — Earliest FDA Approval
- Dec 20, 2019
Daiichi Sankyo — Marketing Organization
- Dec 20, 2019
Daiichi Sankyo — NDA Organization
Indications
Approved for
Studied for
- Adenocarcinoma · Phase 2
- Biliary Tract Neoplasms · Phase 3
- Biomarkers · Phase 1
- Brain Neoplasms · Phase 4
- Breast Neoplasms · Phase 4
- Carcinoma · Phase 1
- Carcinoma, Non-Small-Cell Lung · Phase 3
- Carcinoma, Transitional Cell · Phase 1
- Colonic Neoplasms · Phase 1
- Colorectal Neoplasms · Phase 2
- Drug-Related Side Effects and Adverse Reactions · Phase 2
- Endometrial Neoplasms · Phase 3
- Esophageal Neoplasms · Phase 3
- Gastrointestinal Neoplasms · Phase 2
- Genes, erbB-2 · Phase 2
- Glioblastoma · Phase 2
- Homologous Recombination · Phase 1/Phase 2
- Lung Neoplasms · Phase 1/Phase 2
- Neoplasm Metastasis · Phase 2
- Neoplasms · Phase 3
- Osteosarcoma · Phase 2
- Ovarian Neoplasms · Phase 3
- Precursor B-Cell Lymphoblastic Leukemia-Lymphoma · Early Phase 1
- Prostatic Neoplasms · Phase 2
- Prostatic Neoplasms, Castration-Resistant · Phase 2
- Radiotherapy · Phase 2
- Salivary Gland Neoplasms · Phase 1
- Stomach Neoplasms · Phase 3
- Triple Negative Breast Neoplasms · Phase 2
- Uterine Neoplasms · Phase 1
Mechanism of action
- Receptor protein-tyrosine kinase erbB-2ANTAGONIST
ERBB2 antagonist
- Receptor protein-tyrosine kinase erbB-2BINDING AGENT
Receptor protein-tyrosine kinase erbB-2 binding agent
The antibody binds to HER2-expressing tumor cells, is internalised and the small molecule DXd is released. DXd causes DNA damage and apoptotic cell death. Approval based on tumor response rate and duration of response.
- P-selectinINHIBITOR
SELP inhibitor
- DNA topoisomerase IINHIBITOR
DNA topoisomerase I inhibitor
The antibody binds to HER2-expressing tumor cells, is internalised and the small molecule DXd is released. DXd causes DNA damage and apoptotic cell death. Approval based on tumor response rate and duration of response.
Approval history
- approvedPriority reviewAcceleratedFast trackBreakthroughDec 20, 2019
Chemistry & pharmacology
SMILES
CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1cc(F)c(C)c3c1c2[C@@H](NC(=O)COCNC(=O)CNC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)CNC(=O)CCCCCN1C(=O)CCC1=O)CC3- Mol. weight
- 1036.08 g/mol
- Chirality
- Single Stereoisomer
- Inorganic
- No
- Polymer
- No
- Availability
- Prescription Only
- Multi-specific
- No
- Payload
- deruxtecan
Oral
No
Parenteral
No
Topical
No
Sources
- WikipediaTrastuzumab deruxtecan ↗
- NCATS5384HK7574 ↗
- ChEMBLCHEMBL4594266 ↗
- ChEMBLCHEMBL4297844 ↗
- ChEMBLCHEMBL2109487 ↗
Also known as
- ds-8201a
- rg-1512
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT07012031 | Phase 1/Phase 2 (Phase 2) | Aug 7, 2026 | National Cancer Institute (NCI), University of Toronto |
| NCT07198724 | Phase 1/Phase 2 (Phase 2) | Mar 31, 2026 | Harvard University, Pipeline Therapeutics, Inc. |
| NCT07294508 | Phase 2/Phase 3 (Phase 3) | Jan 25, 2026 | Shanghai Henlius Biotech |
| NCT07086768 | Phase 1 | Jan 1, 2026 | University of Texas, San Antonio |
| NCT07281001 | N/A | Dec 31, 2025 | Blokhin's Russian Cancer Research Center |
| NCT07137416 | Phase 1 | Dec 9, 2025 | Harvard University, National Cancer Institute (NCI) |
| NCT07152782 | Phase 2 | Nov 30, 2025 | Fudan University |
| NCT07126561 | Phase 2 | Nov 1, 2025 | University of Chicago |
| NCT07022483 | Phase 3 | Oct 31, 2025 | AstraZeneca, Daiichi Sankyo |
| NCT07151586 | Phase 2 | Oct 31, 2025 | Institut Paoli-Calmettes, UNICANCER |
| NCT06899126 | Phase 3 | Oct 7, 2025 | Daiichi Sankyo, Merck |
| NCT07150208 | Phase 2 | Sep 30, 2025 | Fudan University |
| NCT07157956 | Phase 1/Phase 2 (Phase 2) | Sep 10, 2025 | Convalife, Sun Yat-Sen University |
| NCT07060807 | Phase 3 | Jul 21, 2025 | Daiichi Sankyo, Merck |
| NCT07015697 | Phase 1 | Jul 17, 2025 | AstraZeneca, Daiichi Sankyo |
| NCT07069712 | Phase 2 | Jul 17, 2025 | AstraZeneca, Parexel |
| NCT06364410 | Phase 1 | Jul 7, 2025 | National Cancer Institute (NCI), University of Texas at Houston |
| NCT06585969 | Phase 3 | May 1, 2025 | Danish Breast Cancer Cooperative Group |
| NCT07134153 | Phase 1/Phase 2 (Phase 2) | Apr 18, 2025 | Fudan University |
| NCT06832202 | Phase 2 | Mar 31, 2025 | Shanghai Henlius Biotech |
Organizations
Research & Development (79)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Daiichi Sankyo | For profit | 52 | 24 | 3 | 2015 |
| AstraZeneca | For profit | 42 | 21 | 4 | 2017 |
| National Cancer Institute (NCI) | Government | 10 | 9 | 3 | 2020 |
| Fudan University | Academic/Hospital | 8 | 8 | 2 | 2023 |
| Harvard University | Academic/Hospital | 8 | 5 | 3 | 2021 |
| University of Texas at Houston | Academic/Hospital | 7 | 1 | 2 | 2017 |
| MedSIR | Academic/Hospital | 4 | 4 | 1 | 2020 |
| Ludwig Maximilians University | Academic/Hospital | 2 | 0 | 2 | 2021 |
| Merck | For profit | 2 | 1 | 1 | 2025 |
| Shanghai Henlius Biotech | For profit | 2 | 2 | 2 | 2025 |
| Spanish Breast Cancer Research Group | Academic/Hospital | 2 | 1 | 2 | 2020 |
| Sungkyunkwan University | Academic/Hospital | 2 | 2 | 1 | 2023 |
| Sun Yat-Sen University | Academic/Hospital | 2 | 1 | 1 | 2024 |
| Translational Breast Cancer Research Consortium | Academic/Hospital | 2 | 0 | 1 | 2024 |
| UNICANCER | Academic/Hospital | 2 | 2 | 1 | 2019 |
| Yale University | Academic/Hospital | 2 | 1 | 2 | 2022 |
| Yonsei University | Academic/Hospital | 2 | 2 | 1 | 2023 |
| Blokhin's Russian Cancer Research Center | Academic/Hospital | 1 | 1 | 1 | 2025 |
| Boehringer Ingelheim | For profit | 1 | 1 | 1 | 2024 |
| Bristol-Myers Squibb | For profit | 1 | 0 | 1 | 2018 |
Marketing (2)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Daiichi Sankyo | For profit | MKTG | Dec 20, 2019 |
| Daiichi Sankyo | For profit | NDA | Dec 20, 2019 |