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crizotinib + lorlatinib
- Development stage
- Unknown
- Lead developer
- Pfizer
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules, Allosteric Modulators → Classical Binding Small Molecules → Small Molecules, Irreversible Covalent Inhibitors → Covalent Small Molecules → Small Molecules
- Administration
- Oral
01
Overview
Crizotinib + lorlatinib is a combination of two small molecule tyrosine kinase inhibitors used in the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Crizotinib inhibits ALK, ROS1, and MET kinases, while lorlatinib is a third-generation inhibitor targeting ALK and ROS1 with enhanced central nervous system penetration. This combination has been explored in clinical trials for patients with resistance to prior ALK inhibitors. The rationale for combining or alternating these drugs includes suppressing or delaying the emergence of drug-resistant tumor clones by targeting different resistance pathways, such as MET dysregulation that can arise during lorlatinib therapy[1][3][4]. Both drugs are developed and manufactured by Pfizer.
- Brand names
- Xalkori (crizotinib)Lorbrena (lorlatinib)
- Other names
- crizotinib and lorlatinib combination
02
Targets
ALK (Anaplastic lymphoma kinase receptor tyrosine kinase)MET (Mesenchymal-epithelial transition factor receptor)ROS1 (Proto-oncogene tyrosine-protein kinase ROS)
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