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trastuzumab deruxtecan + FLO
- Development stage
- Phase 2
- Lead developer
- Daiichi Sankyo
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, DNA Intercalators/Alkylators → Nucleic Acid-Directed Small Molecules → Small Molecules, Metabolically Activated Prodrugs → Prodrugs/Conditional Activator Small Molecules → Small Molecules
- Administration
- Intravenous
01
Overview
Trastuzumab deruxtecan + FLO is a combination therapy consisting of the antibody-drug conjugate trastuzumab deruxtecan (T-DXd) and the chemotherapy regimen known as FLO (fluorouracil, leucovorin, and oxaliplatin). Trastuzumab deruxtecan is a HER2-targeted antibody-drug conjugate composed of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase I inhibitor payload (deruxtecan) via a cleavable linker. The ADC binds to HER2-expressing tumor cells, is internalized, and releases its cytotoxic payload after cleavage by lysosomal enzymes in cancer cells. This results in DNA damage and cell death. The bystander effect allows for cytotoxic activity against neighboring tumor cells with lower HER2 expression[1][4]. FLO is a standard chemotherapy regimen combining fluorouracil (an antimetabolite), leucovorin (a folinic acid that enhances fluorouracil's efficacy), and oxaliplatin (a platinum-based DNA crosslinker). This combination is used primarily for gastrointestinal cancers. The combination of trastuzumab deruxtecan with the FLO regimen has been investigated as neoadjuvant therapy for patients with resectable HER2-positive esophagogastric adenocarcinoma[2][3].
- Brand names
- Enhertu + FLO
- Other names
- T-DXd + FLODS-8201a + FLOtrastuzumab deruxtecan plus fluorouracil/leucovorin/oxaliplatin
02
Targets
ERBB2 (Erb-b2 receptor tyrosine kinase 2)TS (Thymidylate synthase)
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