Capmatinib

Capmatinib is a small molecule kinase inhibitor targeted against c-Met (a.k.a. hepatocyte growth factor receptor HGFR), a receptor tyrosine kinase that, in healthy humans, activates signaling cascades involved in organ regeneration and tissue repair.^A199122 Aberrant c-Met activation - via mutations, amplification, and/or overexpression - is known to occur in many types of cancer, and leads to overactivation of multiple downstream signaling pathways such as STAT3, PI3K/ATK, and RAS/MAPK.^A199122 Mutations in MET have been detected in non-small cell lung cancer (NSCLC), and the prevalence of MET amplification in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-naive patients with NSCLC has been reported to be 1.4% - 21%.^A199122 This co-occurrence has made c-Met a desirable target in the treatment of NSCLC.

Manufactured by Novartis and marketed under the brand name Tabrecta, capmatinib was granted accelerated approval by the FDA on May 6, 2020,^L13380 for the treatment of NSCLC in patients whose tumors have a mutation that leads to mesenchymal-epithelial transition (MET) exon 14 skipping.^L13347 The presence of the mutation must be confirmed by an FDA-approved test, such as the FoundationOne CDx assay (manufactured by Foundation Medicine, Inc.), which was approved by the FDA on the same day.^L13380 As this indication was granted under an accelerated approval, its continued approval is contingent upon verification of capmatinib's benefit in confirmatory trials.^L13347 Capmatinib was approved by Health Canada on June 8, 2022.^L42015