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trastuzumab deruxtecan + fluoropyrimidine
- Development stage
- Unknown
- Lead developer
- Daiichi Sankyo
- Modality
- Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous, Oral
01
Overview
trastuzumab deruxtecan + fluoropyrimidine is a combination therapy comprising the HER2-targeted antibody-drug conjugate (ADC) trastuzumab deruxtecan and a fluoropyrimidine antimetabolite, either capecitabine or 5-fluorouracil. Trastuzumab deruxtecan (Enhertu) is composed of a humanized anti-HER2 antibody covalently linked to a topoisomerase I inhibitor payload (deruxtecan) via a cleavable tetrapeptide linker. It functions by binding to HER2 on the surface of tumor cells, undergoing internalization, and releasing the cytotoxic payload to induce DNA damage and apoptosis. The addition of a fluoropyrimidine (capecitabine or 5-fluorouracil) provides complementary antineoplastic activity by inhibiting thymidylate synthase, thereby disrupting DNA synthesis and repair. This specific regimen is being evaluated by the Gruppo Oncologico del Nord-Ovest (GONO) in the Phase II TRINITY trial as an adjuvant treatment for HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma in patients with persistent minimal residual disease (ctDNA positivity) after surgery and FLOT chemotherapy.
- Brand names
- EnhertuXelodaAdrucil
- Other names
- trastuzumab deruxtecan + capecitabinetrastuzumab deruxtecan + 5-fluorouracilT-DXd + capecitabineT-DXd + 5-fluorouracilT-DXd + fluoropyrimidineEnhertu + capecitabineEnhertu + 5-fluorouracil
02
Targets
ERBB2 (Erb-b2 receptor tyrosine kinase 2)TOP1 (DNA Topoisomerase I)
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