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trastuzumab deruxtecan + durvalumab + pemetrexed
- Development stage
- Unknown
- Lead developer
- AstraZeneca
- Modality
- Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
- Administration
- Intravenous
01
Overview
This is a combination regimen consisting of **trastuzumab deruxtecan** (an antibody-drug conjugate targeting HER2), **durvalumab** (a PD-L1 immune checkpoint inhibitor), and **pemetrexed** (a folate antimetabolite chemotherapy). Trastuzumab deruxtecan’s mechanism is HER2-targeted delivery of a cytotoxic topoisomerase I inhibitor payload, causing DNA damage specifically in HER2-expressing cancer cells. Durvalumab binds to PD-L1, blocking its interaction with PD-1 and CD80, thereby lifting immune suppression and promoting anti-tumor immunity. Pemetrexed disrupts folate-dependent metabolic processes, inhibiting enzymes crucial for DNA synthesis and tumor cell proliferation. This combination is being investigated mainly for advanced or metastatic HER2-positive malignancies, especially those of the gastroesophageal junction, and potentially HER2-positive non-squamous non-small cell lung cancers.
- Brand names
- Enhertu (for trastuzumab deruxtecan)Imfinzi (for durvalumab)Alimta (for pemetrexed)Pemfexy (for pemetrexed)Pemrydi RTU (for pemetrexed)Axtle (for pemetrexed)
- Other names
- trastuzumab deruxtecan + durvalumab + pemetrexed
02
Targets
GART (GAR transformylase)TS (Thymidylate synthase)DHFR (Dihydrofolate reductase)TOP1 (DNA Topoisomerase I)ERBB2 (Erb-b2 receptor tyrosine kinase 2)CD274 (Programmed cell death protein 1 ligand 1)ATIC (Aminoimidazole carboxamide ribonucleotide transformylase)
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