Tabrecta and Tepmetko are approved simultaneously for NSCLC

Two MET inhibitors for NSCLC, Tabrecta and Tepmetko, are approved in Korea

Both simultaneously approved for the treatment of non-small cell lung cancer in patients with MET exon 14 skipping mutation

Novartis vs. Merck… studies on combination with EGFR inhibitor also active

Two new anticancer drugs that target the MET gene to treat non-small cell lung cancer have entered the Korean market.

 

The two drugs are Novartis’ ‘Tabrecta (capmatinib)’ and Merck’s ‘Tepmetko (tepotinib)’ The Ministry of Food and Drug Safety approved Tabrecta and Tepmetko together on the 23rd.

 

Both are targeted therapies that target MET mutations and have the same indications.

 

Tabrecta and Tepmetko may both be used to treat locally advanced or metastatic NSCLC harboring MET exon 14 skipping mutations.

 

Various mutations that induce cancer cell growth occur in NSCLC.

 

Dysregulation in the proto-oncogene MET that is located in the long arm of chromosome 7 is also one of such many mutations.

 

MET dysregulation can largely be divided into MET amplification or MET mutation.

 

The MET exon 14 skipping mutation that is targeted by Tabrecta is one of the most commonly reported oncogenic MET mutations.

 

MET exon 14 skipping mutation overstimulates the MET pathway that plays a key role in the signaling, proliferation, and survival of cells, resulting in the proliferation of cancer cells.

 

MET exon 14 skipping (METex14) alterations are rare, occurring in only around 3% of all patients with metastatic NSCLC.

 

However, its prognosis is poor due to its aggressive nature.

 

In particular, retrospective analysis on patients with MET exon 14 skipping mutations showed that 37% of the patients had brain metastasis and 49% had bone metastasis at diagnosis.

 

Tabrecta and Tepmetko are drugs that selectively inhibit the MET receptor tyrosine kinase.

 

It blocks the MET phosphorylation response by binding to the intracellular kinase domain.

 

In the US, Novartis’ Tabrecta was first approved and listed as the first MET targeted anticancer therapy.

 

Tabrecta was approved in May last year, and Tepmetko in February of this year by the US FDA.

 

In Korea, both were authorized simultaneously and are on an equal footing.

 

At the pivotal GEOMETRY mono-1 trial, Tabrecta demonstrated a 68% objective response rate (ORR) and 41% ORR in treatment-naïve and previously treated patients, respectively.

 

The duration of response (DoR) was 12.6 months and 9.7 months, respectively.

 

Tepmetko demonstrated a 43% ORR in patients regardless of treatment experience, and DoR was 10.8 months ORR in treatment-naïve patients and 11.1 months in previously treated patients Both companies are also actively studying the combined use of their respective drugs with EGFR-targeted therapies with the hope that it could address the issue of resistance that patients acquire after treatment with EGFR inhibitors.

 

MET mutation or amplification are key mutations that cause EGFR-TKI resistance.

 

In this context, the companies are studying the combination of Tabrecta with Iressa, Tagrisso, etc, and Tepmetko with Tagrisso.