What are the applications and fields of capmatinib?

Capmatinib (Capmatinib) is the first targeted drug used to alter the MET gene (especially exon 14 mutations). Results from the GEOMETRYmono-1 trial reported in May 2020 accelerated U.S. Food and Drug Administration (FDA) approval for the treatment of metastatic non-small cell lung cancer with exon 14 skipping mutations. Capmatinib received formal approval from the FDA in August 2022 and is sold under the trade name Tabrecta.

In terms of clinical pharmacology, capmatinib is an oral drug and a highly selective small molecule inhibitor of cMET. It has been shown to have anti-tumor properties against MET-driven solid tumor models in vitro and in vivo. 28 The drug is 30 times more potent than crizotinib, with IC50 values u200bu200bof 0.13 nmol/L and 4 nmol/L respectively, which is slightly stronger than tipotinib's approximately 1.7 nmol/L. After oral administration of capmatinib , Cmax is reached (Tmax) within 1-2 hours. The absorption rate of oral medications exceeds 70%. There was no significant effect of postprandial or fasting status on Cmax or capmatinib exposure (AUC 0-12 hours). The drug is primarily protein bound (96%) in the circulation and its half-life is estimated to be 6.5 hours.

In terms of efficacy, capmatinib, another small molecule inhibitor with intracranial activity, showed impressive activity in patients with non-small cell lung cancer harboring MET exon 14 skipping mutations, with an ORR of 41% in patients who had received one or two prior therapies and an ORR of 68% in previously untreated patients, leading to FDA approval of this indication. Capmatinib was also active, although not as potent, in patients with MET amplification and gene copy numbers of 10 or higher.

Oral targeted therapies are generally well tolerated. Although some side effects are specific to individual drugs, the most common side effects include gastrointestinal toxicity, rash, and AST/ALT elevations.