The control rate of lung cancer brain metastasis reached 92.3%! MET targeted drug carbamatinib has a strong effect on the brain
Approximately 70% of all non-small cell lung cancer (NSCLC) patients carry genomic mutations, among which MET is a receptor tyrosine kinase encoded by the MET gene, which typically plays a crucial role in cell signaling, proliferation, and survival. Capmatinib, a potent and selective MET inhibitor, is a novel first-line treatment option for patients with METex14-mutant metastatic NSCLC.
International research data on Capmatinib Capmatinib
The pivotal, multi-cohort phase 2 clinical trial GEOMETRY mono-1 evaluated the role of capmatinib in patients with advanced NSCLC exhibiting dysregulation of MET regulation, enrolling a total of 364 patients. Patients were grouped according to their prior treatment regimen and MET status (METex14 mutation or MET amplification based on gene copy number in tumor tissue). Patients received capmatinib (400 mg tablets) twice daily. The primary endpoint was overall response (OR, including complete or partial response); the key secondary endpoint was disease-free response (DOR).
The latest data published in these studies include the efficacy of capmatinib in METex14-mutant NSCLC patients (n=97) confirmed by the Blinded Independent Committee for Radiology (BIRC): (1) in treatment-naïve patients (n=28), the ORR was 68% (95% CI, 48–84) and the DCR was 96.4%; (2) in patients who had received first- or second-line therapy (n=69), the ORR was 41% (95% CI, 29–53); (3) in treatment-naïve patients (19 responders), the median DOR was 12.6 months (95% CI, 5.6–unpredictable); (4) in treatment-naïve patients (28 responders), the median DOR was 9.7 months (95% CI, 5.6–13.0).
For patients who have previously received treatment, have MET amplification, and have a gene copy number of less than 10, capmatinib has limited efficacy, with an odds ratio (OR) of 7%–12%. For patients with MET amplification and a gene copy number of 10 or higher: the OR was 29% (95% CI, 19–41) in previously treated patients and 40% (95% CI, 16–68) in previously untreated patients.
At baseline, approximately half of the patients with brain metastases experienced an intracranial response after treatment with capmatinib (7 out of 13; 54%). Among these patients, 4 achieved complete resolution of brain lesions (31%), with an intracranial disease control rate (DCR) of 92.3% (13/12).
In addition, the most common treatment-related adverse events associated with capmatinib (incidence ≥20%) were peripheral edema (43%), nausea (34%), elevated serum creatinine (18%), and vomiting (19%). Most adverse events were grade 1 or 2.
Capmatinib Drug Introduction
Drug name: Capmatinib
Product name: Tabrecta
Chinese name: Camatinib
Manufacturer: Novartis
Capmatinib Capmatinib is a kinase inhibitor that targets MET, including mutants produced by exon 14 jumps. Skipping MET exon 14 will cause the protein to lack the regulatory domain, thereby reducing its negative regulation, resulting in an increase in downstream MET signaling. Capmatinib inhibits MET phosphorylation triggered by hepatocyte growth factor binding or MET amplification, as well as MET-mediated downstream signaling protein phosphorylation and MET-dependent cancer cell proliferation and survival.
Reminder: Capmatinib Capmatinib is the first therapy approved by the FDA specifically for metastatic NSCLC with METex14 mutations. Its listing has made a breakthrough in targeted therapy for patients with METex14 mutations.
