Giuseppe Giaccone, MD, PhD

Giuseppe Giaccone, MD, PhD, professor of medicine at Weill Cornell Medical College, discusses alterations in the 

 gene that can be oncogenic drivers in patients with non­–small cell lung cancer (NSCLC).

 exon 14 skipping mutations are alterations in the 

 gene that are rare oncogenic drivers for NSCLC. 

 exon 14 skipping mutations are a therapeutic target for NSCLC that appear in 3% to 4% of patients with NSCLC, while 

 amplification appears in 1% to 6% of these patients. These alterations can be identified by tissue biopsy or liquid biopsy.

Capmatinib (Tabrecta), a selective inhibitor of the MET receptor, was investigated for use in patients with a 

 exon 14 skipping mutation in the phase 2 GEOMETRY mono-1 trial (NCT02414139). Following results of efficacy and a tolerable safety profile, it was approved by the FDA for use in metastatic NSCLC in May 2020.

Tepotinib (Tepmetko) was investigated in the phase 2 VISION trial (NCT02864992) and was approved by the FDA for use in metastatic NSCLC in February 2021 based on its response rate and duration of response.

 expression really is not a good marker for drugs that actually target 

, because the expression is really dependent on many things. Usually, you have a higher expression if you have high levels of amplification, but that's not necessarily the case when you have the 

 exon 14 skipping mutation. Expression is not something that you use for 

For first line, there are 2 drugs that are approved for 

 exon 14 skipping mutations only. One is tepotinib. That has been approved a few months ago, and the other one is capmatinib. That has been approved a few months earlier. Both have been approved based on single-arm phase 2 data in a reasonably large number of patients with [

] exon 14 skipping mutations, which are not that common; they're about 3% or 4% of lung cancers.

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Giuseppe Giaccone, MD, PhD, discusses alterations in the MET gene that can be oncogenic drivers in patients with non–small cell lung cancer. 

Overview of MET Amplification and MET Exon 14 Skipping Mutations in NSCLC

Giuseppe Giaccone, MD, PhD, professor of medicine at Weill Cornell Medical College, discusses the results of the VISION (NCT02864992) trial of tepotinib (Tepmetko) in patients with non­–small cell lung cancer (NSCLC).

The investigators of the open-label phase 2 VISION trial administered tepotinib to 152 patients with stage IIIb/IV NSCLC who had the 

 exon 14 skipping mutation is found in 3% to 4% of patients with NSCLC. The patients were divided into 2 groups based on whether the mutation was detected by a tissue biopsy or liquid biopsy. Patients received 500 mg of tepotinib daily.

The primary end point was objective response rate (ORR) by an independent review committee. The independent review found a ORR of 46% and a median duration of response of 11.1 months. The ORR was 48% (95% CI, 36%-61%) among the 66 patients in the liquid-biopsy group and 50% (95% CI, 37%-63%) among 60 patients in the tissue-biopsy group. The response rate was similar in patients regardless of previous therapy they had received for advanced or metastatic disease, including platinum-based chemotherapy and immune-oncology.

Grade 3 adverse events related to tepotinib were observed in 28% of patients, including peripheral edema in 7%, and adverse events led to permanent discontinuation of tepotinib in 11% of the patients.

Following the results of the VISION trial, the FDA approved tepotinib for treatment of metastatic NSCLC in patients with the 

What is interesting is that the response rate was similar in patients that had a [tissue] biopsy-proven 

 skipping mutation as well as liquid biopsy. So, again, many of these patients with lung cancer don't have enough tissue, especially after the first-line treatment. The tissue may be exhausted or may not be sufficient for next-generation sequencing. So, liquid biopsy is clearly a good way of addressing the lack of tissue.

What is interesting is that there was activity both in patients who were not previously treated with any treatment—chemotherapy, in most of the cases—and in patients who had never been treated before and patients that were treated before. So there was significant activity in both groups of patients. In fact, the drug is approved for both first-line and second-line all further lines of treatment.

Giuseppe Giaccone, MD, PhD, discusses the results of the VISION trial of tepotinib in patients with non–small cell lung cancer. 

Giuseppe Giaccone, MD, PhD | Authors

Articles

Overview of MET Amplification and MET Exon 14 Skipping Mutations in NSCLC

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