The development of next lung cancer txs is in full swing

Targeted anticancer drugs, from common mutations to minority mutations, are all caught

From the left, Lumakras, Rybrevant & Tabrecta

Starting with EGFR, treatments have been released.

 

The first dual inhibitor was also released.

 

Non-small cell lung cancer treatment is facing a new turning point with the emergence of various targeted anticancer drugs.

 

Precise treatment began by pioneering areas where there were no treatments, such as KRAS, MET, and EGFR Exon 20.

 

◆ New KRAS drug in 40 years, 8 global companies will develop For the first time in 40 years this year, a new drug targeting KRAS mutations has emerged.

 

It is Amgen's Lumakras, approved by the MFDS on the 14th.

 

Lumakras can be used as a secondary treatment for KRAS G12C mutation local progression or metastatic non-small cell lung cancer.

 

Non-small cell lung cancer patients show various genetic mutations, and KRAS mutations account for the largest proportion of them.

 

About 25% of the world represents KRAS mutations.

 

In Korea, it is about 5 to 8%.

 

Lumakras succeeded in entering the KRAS field for the first time.

 

The KRAS tumor gene was discovered early in 1982, but it did not lead to the development of a treatment.

 

This is because clinical trials have repeatedly failed due to the complex molecular biological activity mechanism of KRAS.

 

The binding site was also very small, so the development of target materials was a challenge.

 

Starting with Lumakras, KRAS target treatments are expected to appear one after another.

 

This is because many global pharmaceutical companies have entered the development of KRAS-targeted anticancer drugs.

 

Eight companies, including ▲Mirati Theraputics ▲ Novartis ▲ Roche ▲ Boehringer Ingelheim ▲ MSD ▲ Eli Lilly ▲ Sanofi ▲ InventisBio, are conducting KRAS clinical trials in Korea.

 

Among them, Mirati is closely chasing Amgen as the most advanced step.

 

Mirati's Adagrasib is undergoing phase 3 in Korea and is undergoing FDA approval review in the United States.

 

The development of other pharmaceutical companies is in phase 1/2.

 

◆Dual inhibiton of EGFR and MET have also emerged Treatment of non-small cell lung cancer is facing a new turning point.

 

For non-small cell lung cancer, targeted treatment began with the emergence of Iressa, the first EGFR target anticancer drug, and in 2017, immuno-cancer drugs entered and presented a new paradigm for the treatment of non-small cell lung cancer, which cannot be used.

 

Recently, the area of anticancer drugs targeting non-small cell lung cancer has increased further.

 

In addition to relatively common KRAS mutations, minority mutations found in less than 3% of all patients can be detected.

 

Janssen's Rybrevant, which was approved by the MFDS on the 15th, shows a clear difference from the existing EGFR targeted anticancer drugs.

 

It aimed at a blind spot called Exon 20 insertion mutation, not Exon 19 defect and L858R substitution mutation, which are common in EGFR.

 

EGFR Exon20 insertion mutation non-small cell lung cancer is rarely found as the third most common mutation among EGFR mutations.

 

Rybrevant is clearly different in that it targets not only EGFR but also MET variations.

 

With the approval of Rybrevant, the EGFR target anticancer drug market is also expected to change.

 

Already, in the EGFR area, third-generation drugs represented by Tagrisso and Leclaza through the first and second generations are becoming standard treatments.

 

Although it remains in the second treatment due to clinical problems in Korea, global guidelines have already recommended the third generation Tagrisso as the top priority treatment.

 

A new anticancer drug that directly targets MET gene mutations also appeared for the first time last year.

 

It is Novartis' Tabrecta and Merck's Tepmeko.

 

Both drugs, which were approved by the MFDS side by side in November last year, can be used in patients with local progressive or metastatic non-small cell lung cancer whose MET exon 14 deficiency was confirmed.

 

MET mutation is also one of the genetic mutations caused by non-small cell lung cancer.

 

The adverse reactions in the MET gene are largely divided into MET amplification and MET mutation, and the MET exon14 defect targeted by Tabrecta and Tepmeko is a representative MET mutation.

 

Targeted anticancer drugs targeting RET genes are also expected to be released soon.

 

Roche and Lilly are undergoing domestic approval procedures for their own Gavreto and Retevmo.

 

These drugs can inhibit primary mutations in the RET gene as well as secondary mutations that cause anticancer treatment resistance.

 

The incidence of RET mutations in non-small cell lung cancer is reported to be around 2%.