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Capmatinib: high antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation


Among patients with non–small-cell lung cancer ( NSCLC ), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%.
Capmatinib ( Tabrecta ), a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation.

Researchers have conducted a multiple-cohort, phase 2 study evaluating Capmatinib in patients with MET-dysregulated advanced NSCLC.
Patients were assigned to cohorts on the basis of previous lines of therapy and MET status ( MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue ).
Patients received Capmatinib ( 400-mg tablet ) twice daily.

The primary end point was overall response ( complete or partial response ), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments.

A total of 364 patients were assigned to the cohorts.

Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% ( 95% confidence interval [ CI ], 29 to 53 ) of 69 patients who had received one or two lines of therapy previously and in 68% ( 95% CI, 48 to 84 ) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months ( 95% CI, 5.6 to 13.0 ) and 12.6 months ( 95% CI, 5.6 to could not be estimated ), respectively.

Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 ( overall response in 7 to 12% of patients ).
Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% ( 95% CI, 19 to 41 ) of previously treated patients and in 40% ( 95% CI, 16 to 68 ) of those who had not received treatment previously.

The most frequently reported adverse events were peripheral edema ( in 51% ) and nausea ( in 45% ); these events were mostly of grade 1 or 2.

In conclusion, Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously.
The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number.
Low-grade peripheral edema and nausea were the main toxic effects. ( Xagena )

Wolf J et al, N Engl J Med 2020; 383: 944-957

XagenaMedicine_2020



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