Lumakras is a new opportunity for lung cancer patients

[Interview] Kim Hye-ryeon, Professor of Oncology at Yonsei Cancer Hospital

The first and only KRAS targeted anticancer drug

Good synergy with immuno-cancer drugs, combined therapy clinical expectations

"Lumakras is the first-in-class and best-in-class for patients with KRAS G12C mutated non-small cell lung cancer who failed existing treatment.

 

The reliability of drugs has also increased over the past two years with long-term data, and it is expected that they may be used in combination with other drugs such as immuno-cancer drugs in the future." Kim Hye-ryeon, a professor of oncology at Yonsei Cancer Hospital, expressed the meaning of the launch of the new cancer drug Lumakras.

 

Lumakras is the first and only KRAS targeted anticancer drug that was approved by the MFDS in February.

 

It targets non-small cell lung cancer KRAS G12C mutations.

 

KRAS gene mutation is common in non-small cell lung cancer.

 

In Asia, EGFR mutations are the second most common.

 

Although the KRAS tumor gene was already discovered 40 years ago, it remained a homework that could not be solved for a long time due to molecular biological characteristics and drug toxicity.

 

Amgen succeeded in commercializing it with FDA approval three and a half years after first discovering the Lumaras candidate material in November 2017.

 

Lumakras binds to a P2 pocket near KRAS G12C Switch II to immobilize the mutant protein in an inactive state.

 

By selectively blocking tumor-causing signals, only cancer cell growth can be prevented without affecting the KRAS normal gene.

 

Professor Kim said in a meeting with Dailypharm, "The prognosis of patients for KRAS mutated non-small cell lung cancer has not been good because there is no targeted treatment.

 

KRAS mutated non-small cell lung cancer is closely related to smoking, and nine out of 10 people have previously smoked or are currently smoking, so the high tumor heterogeneity is also considered a cause of poor prognosis, he said.

 

"The launch of Lumakras is significant in that it has met the medical demand for lung cancer treatment." Since KRAS mutations generally do not overlap with other gene mutations with targeted treatments such as EGFR and ALK, chemotherapy was the only drug that patients could use.

 

Fortunately, immuno-cancer drugs that can be used by patients without EGFR and ALK mutations have recently emerged, but the regret remains that there are no targeted treatments.

 

This is because drugs that have a definite response and guarantee effectiveness are rare as targeted treatments that target specific gene mutations.

 

Professor Kim said, "It is a retrospective study, but there are reports that the survival rate of patients has increased after targeted treatment in lung cancer treatment.

 

Given the experience of prescribing other gene mutations, I think it is basic to use the treatment first." Amgen recently released long-term Lumakras data for two years, increasing reliability.

 

This is the result of follow-up observation of 174 patients who participated in the Phase 1/2 CodeBreaK100 study, which was the basis for permission, for two years.

 

It is the longest-running follow-up observation among targeted treatments for non-small cell lung cancer of KRAS G12C mutation.

 

In this study, Lumakras confirmed long-term efficacy and safety.

 

The ORR including CR and PR in the Lumakras administration group was 40.7%, and the reaction duration mDOR was 12.3 months.

 

In addition, DCR 83.7%, mPFS 6.3 months, and OS 12.5 months were found.

 

At the time of two years of treatment, 32.5% of all patients were alive.

 

For two years of treatment, there were no reports of new adverse reactions that had not existed before.

 

Regarding the two-year long-term data, Professor Kim said, "From the perspective of medical staff, 'long-term data' means really reliable," adding, "There are treatments that usually show good results in the first half of the phase, but Lumakras showed better response rates in the two-year long-term follow-up." In particular, considering that they are patients who have failed existing treatments, I think they are clinically valuable." The release of Lumakras has also changed the diagnosis of lung cancer.

 

Professor Kim said, "When diagnosed with non-small cell lung cancer adenocarcinoma, this hospital based on five tests, including PD-L1, an indicator of immuno-cancer drugs, along with representative lung cancer genetic mutations such as EGFR, ALK, BRAF, and ROS1.

 

With the emergence of treatments targeting minority mutations, including KRAS targeted treatments, we will now conduct additional NGS (next-generation gene sequencing) tests that can check other gene mutations together if all four previous gene mutations are confirmed negative, she explained.

 

Professor Kim highly predicted the possibility of expanding Lumakras in the future.

 

This is because immuno-cancer drugs and good synergy are expected.

 

She said, "There have been no cases in which targeted treatments and immuno-cancer drugs have been approved for other gene mutations such as EGFR and ALK.

 

This is because the treatment effect was not significant and the drug toxicity was strong.

 

However, the KRAS mutation showed good results in the target + immunotherapy in the in vivo test.

 

It is speculated that the high association with smoking may be affected, he said.

 

"The response rate is also high when treating immuno-cancer drugs, so clinical trials related to targeted + immuno-combination therapy are actively being conducted."