Targeting MET Exon 14 Skipping Mutations in NSCLC

Characteristics of the MET Exon 14 Skipping Mutation NSCLC Population

Mark A. Socinski, MD, discusses the patient population of the trials targeting MET exon 14 skipping mutations in non–small cell lung cancer.

Mark A. Socinski, MD, executive medical director at the AdventHealth Cancer Institute and member of the Thoracic Oncology Program in Orlando, Florida, discusses the patient population of the trials targeting MET exon 14 skipping mutations in non–small cell lung cancer (NSCLC).

The MET exon 14 skipping mutation is a biomarker that is an oncogenic driver as well as a therapeutic target for NSCLC. It occurs in 3% to 4% of patients with NSCLC, which is more frequent than other known biomarker mutations, according to Socinski.

The phase 2, single-arm VISION trial (NCT02864992) of tepotinib (Tepmetko) investigated 153 patients who had a detected MET exon 14 skipping mutation, 66 of whom had the mutation positively identified by liquid biopsy, 60 by a tissue biopsy, and 27 by both methods. According to Socinski, the patient population of the VISION trial was similar to the overall patient population, though the study recruited less symptomatic patients with an ECOG performance score of 0 or 1. The same was true of the phase 2 GEOMETRY Mono-1 trial (NCT02414139) of capmatinib (Tabrecta), which studied both MET exon 14 skipping and MET amplification. The VISION trial’s patient population had a relatively high median age of 74, and 46% had a history of smoking.

Both tepotinib and capmatinib showed efficacy and safety in patients with the MET exon 14 skipping mutation and both drugs have been approved by the FDA for use in these patients.


0:08 | The MET exon 14 skipping population tends to be a little bit older than the average driver mutation population. It also is likely to occur in smokers as well as non-smokers, so smoking status shouldn't necessarily be a criterion for testing or not. They almost always have adenocarcinoma of the lung; however, it has also been described in squamous [histology]. It's important to be aware of that when you're deciding on who to test for and who not to test for. Again, this occurs in roughly 3% to 4% of all of lung cancer, so it tends to be more common than we might see [in], say ROS1 alterations, or RET fusions, or NTRK fusions, and these sorts of things. So this should definitely be on the radar screen of any practicing oncologist to make sure that adequate testing is done here.

Specifically looking at the clinical trials for both tepotinib as well as capmatinib—these trials, since you're selecting patients based on a biomarker that's a molecular alteration—I think the patients in the trials of all of these agents were relatively representative of what you would see in practice. There was nothing unusual about it. Of course, these are patients that had to have good performance status. These were ambulatory, relatively asymptomatic, or minimally symptomatic patients. So, I think both in the VISION trial as well as the [GEOMETRY mono-1] capmatinib trial, the patients that you see and the outcomes that were described in these trials should be the expected outcomes that you would see in practice, again, because these patients are chosen for the clinical trial based on a molecular alteration.