The First MET-14 Targeted Drug Might Be Launched within Months

On February, FDA granted priority approval for the oral MET targeted drug camatinib (INC280). If all goes well, the first targeted drug for the treatment of non-small cell lung cancer with MET exon 14 skip mutation will be available in months.

The Geometry mono-1 study showed that carmartinib monotherapy for advanced non-small cell lung cancer with skip mutations in MET exon 14 has an objective response rate of 67.9% in newly treated patients, and an objective response rate of 40.6% in patients who have previously received chemotherapy. The most common adverse reactions were peripheral edema, nausea and vomiting, most of which were mild.

Camatinib is effective in treating MET mutations

Jumping mutations in exon 14 of MET account for 3-4% of newly diagnosed advanced non-small cell lung cancer, and no corresponding targeted drugs have been approved for marketing. The Geometry mono-1 study showed that camatinib as a single agent (dose 400mg orally twice a day) was used to treat MET exon 14 skipping mutations, and EGFR\ALK are wild-type advanced non-small cell lung cancer, the objective remission rate of 67.9% in newly treated patients, and the median progression-free survival was 9.13 months. The objective response rate of patients who had previously received chemotherapy was also as high as 40.6%, and the median progression-free survival was 5.42 months.

The most common (incidence rate>25%) treatment-related adverse reactions of camatinib monotherapy include peripheral edema, nausea, and vomiting, most of which are mild. 33.1% of patients had grade 3/4 serious adverse reactions, 10.3% of patients discontinued the drug due to suspected adverse reactions related to carmartinib treatment, and grade 3/4 serious adverse reactions related to carmartinib treatment included peripheral edema. Nausea, vomiting, fatigue and decreased appetite.

Camatinib can also combat EGFR-targeted drug resistance

MET gene amplification is an important cause of EGFR-targeted drug resistance. A previous clinical study was that patients with EGFR-targeted drug resistance and MET gene amplification or MET protein overexpression received camatinib in combination with gefitinib, the overall objective response rate was 29%. In the study, the dose of carmartinib was 400 mg orally twice a day, and the dose of gefitinib was 250 mg orally once a day.

Studies have shown that the MET gene is highly amplified, that is, patients with gene amplification groups ≥ 6 (GCN ≥ 6) have the best curative effect. The objective remission rate of camatinib combined with gefitinib is 47%, and the median progression-free survival period is 5.49 months. Patients with high MET protein expression, that is, patients with 3+ MET immunohistochemistry (IHC) results also have a higher objective remission rate, reaching 32%.

Camatinib combined with gefitinib is well tolerated. The most common adverse reactions (≥20%) are: nausea (28%), peripheral edema (22%), decreased appetite (21%), and skin rash (20%). 29% of patients had grade 3/4 adverse reactions, mainly including increased levels of amylase and lipase.