Researchers in South Korea have proposed a new treatment method for atypical EGFR mutation lung cancer patients, for whom existing therapies are ineffective due to the development of resistance.
Combination therapy using the anticancer drugs RAY (ingredient name: lazertinib) from Yuhan Corporation and libretinib (ingredient name: amivantamab) has been shown to be more effective than monotherapy. Researchers noted that this could provide a possibility of overcoming the limitations of existing treatments.
A joint research team led by Professor Hong Min-hee at the Yonsei University Cancer Center and Professor Yoon Mi-ran at Yonsei University College of Medicine announced on the 11th that the combination therapy of lazertinib and amivantamab could achieve higher treatment efficacy for atypical EGFR mutation lung cancer than lazertinib alone.
Most lung cancer patients suffer from non-small cell lung cancer, and among them, 30-40% are diagnosed with EGFR mutations. Approximately 10% of these are classified as atypical EGFR mutations, with representative mutations including G719X, S768I, and L861Q, and multiple mutations can occur simultaneously.
Atypical EGFR mutation treatments have been approved by the U.S. Food and Drug Administration (FDA) for the second-generation EGFR-targeted anticancer drug afatinib. However, there are limited effects on certain mutations, and when resistance occurs, alternative treatment options are scarce. The third-generation EGFR-targeted anticancer drug osimertinib has also demonstrated therapeutic efficacy, but the effects vary with each mutation.
The research team developed a new treatment method that simultaneously targets the MET mutation, a process that causes resistance to EGFR mutation treatments. This method involves using lazertinib, a third-generation EGFR-targeted anticancer drug, alongside the dual-target antibody amivantamab to overcome the limitations of existing therapies.
The researchers conducted experiments treating mice and organoids (mini-organs), as well as human cells, simultaneously with lazertinib and amivantamab. The organoid experiments showed that the dosage exhibiting a reduction effect on EGFR phosphorylation, which promotes cancer cell growth, was six times lower than that of existing treatments. In patient cells that developed resistance to lazertinib monotherapy, antibody-dependent cellular cytotoxicity (ADCC) effects were confirmed. ADCC is a process that helps immune cells destroy cancer cells.
In mouse experiments, the persistence of tumor suppression from the combination therapy was confirmed. While tumor growth began immediately after stopping monotherapy, tumors did not grow for approximately 90 days after discontinuing the combination therapy. Researchers assessed that lazertinib enhanced the efficacy of amivantamab. In actual patients, 40% experienced tumor reduction, and the progression-free survival period lasted more than 16 months, longer than that of existing monotherapy.
Professor Hong Min-hee said, "Combination therapy overcomes the resistance of existing treatments by activating antibody-dependent cellular cytotoxicity, helping human immune cells attack cancer cells."
The research results were introduced in the international journal "Cell Reports Medicine" on the 18th of last month.
Reference materials
Cell Reports Medicine (2025), DOI: https://doi.org/10.1016/j.xcrm.2025.101929