"Osimertinib-Resistant EGFR Lung Cancer Patients, Confirming the Effectiveness of Amivantamab and Lazertinib"

Research Team Led by Professor Jo Byung-chul at Yonsei Cancer Hospital

A new treatment method has been developed for epidermal growth factor receptor (EGFR) mutant lung cancer that has acquired resistance to targeted therapies.

On the 25th, Yonsei Cancer Hospital announced that Professor Byung-Chul Cho's research team at the Lung Cancer Center published the results of a study on the combination therapy of amivantamab and lazertinib for EGFR mutant lung cancer resistant to the third-generation targeted therapy osimertinib.

Patients with EGFR gene mutations use targeted therapies that specifically target the genetic mutation. After using first- or second-generation targeted therapies, resistance may develop due to a mutation called 'T790M,' and the representative strategy is to use third-generation EGFR inhibitors such as osimertinib.

Currently, when resistance to osimertinib occurs, there is no proven effective treatment, so cytotoxic chemotherapy is mainly used. The objective response rate, which is the proportion of patients showing tumor size reduction, is only about 15%, and there are concerns about serious side effects, according to the research team.

Lazertinib, a third-generation targeted therapy like osimertinib, has a higher blood-brain barrier permeability compared to existing therapies, showing excellent effects even in patients with brain metastases. Amivantamab is a bispecific antibody targeting both EGFR and MET.

[Image courtesy of Severance Hospital]

The research team evaluated the efficacy and safety of the combination therapy of lazertinib and amivantamab in 45 patients with EGFR mutant lung cancer resistant to osimertinib. The objective response rate was 36%, showing a higher response rate compared to currently used cytotoxic chemotherapy. Complete remission, where the cancer completely disappeared, was observed in one patient. The duration of response in 16 patients who responded was 9.6 months, with 69% maintaining a response for more than six months. The median progression-free survival for all patients was 4.9 months.

Additionally, the research team explained that patients exhibited side effects such as allergic reactions and skin rashes commonly occurring during drug infusion, confirming the safety of the drug use.

To identify biomarkers predicting the effectiveness of the combination therapy, the research team conducted genetic analysis along with immunohistochemical staining to assess protein expression levels in tumors. Patients whose tumors had an H-score of 400 or higher, indicating the proportion of tumor cells expressing EGFR and MET-related proteins involved in cancer growth and proliferation, showed better outcomes. Patients with an H-score of 400 or higher demonstrated an objective response rate of 90%, progression-free survival of 12.5 months, and duration of response of 9.7 months, outperforming the control group (10%, 4 months, 2.7 months).

Professor Cho stated, "This study is the first clinical research to demonstrate the efficacy of the combination therapy of lazertinib and amivantamab in osimertinib-resistant EGFR mutant lung cancer patients with no treatment alternatives," adding, "We also discovered biomarkers that can identify patients who will respond effectively to the combination therapy."

Meanwhile, the study results were published in the international journal Nature Medicine (IF 82.9).

Professor Jo Byung-chul, Yonsei Cancer Center Lung Cancer Center.
[Photo by Severance Hospital]

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