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sotorasib + trastuzumab deruxtecan
- Development stage
- Unknown
- Lead developer
- National Cancer Institute
- Modality
- Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics
- Administration
- Oral, Intravenous
01
Overview
Sotorasib + trastuzumab deruxtecan is a combination therapy being investigated for the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation. This regimen combines sotorasib, a first-in-class small molecule that covalently inhibits the KRAS G12C mutant protein by locking it in an inactive GDP-bound state, with trastuzumab deruxtecan (T-DXd), a HER2-directed antibody-drug conjugate. T-DXd consists of a humanized anti-HER2 IgG1 monoclonal antibody linked to a topoisomerase I inhibitor payload (deruxtecan) via a cleavable tetrapeptide linker. The National Cancer Institute (NCI) is sponsoring Phase I/II clinical trials to evaluate the safety and efficacy of this combination, potentially targeting cross-talk between the HER2 and KRAS signaling pathways to overcome resistance or enhance antitumor activity in KRAS-mutated lung cancers.
- Brand names
- LumakrasEnhertu
- Other names
- fam-trastuzumab deruxtecan-nxki
02
Targets
TOP1 (DNA Topoisomerase I)KRASG12C (Kirsten rat sarcoma viral oncogene homolog G12C)ERBB2 (Erb-b2 receptor tyrosine kinase 2)
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