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Severance confirms efficacy of amivantamab for mutant lung cancer

Lee Han-soo  Published 2020.05.19  11:38  Updated 2020.05.19 11:38

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A research team at Severance Hospital has confirmed the anticancer efficacy of amivantamab in treating epidermal growth factor receptor (EGFR) Exon20 insertion mutant lung cancer.

Professors Cho Byoung-chul (left) and Yun Ji-yeon

The team, led by Professors Cho Byoung-chul and Yun Ji-yeon, expects the drug will become a new treatment option in treating the disease, which has not had a clear targeted treatment until now, as the researchers have confirmed that the substance inhibits the growth of cancer cells in various EGFR Exon20ins mutant lung cancers.

According to the Health Insurance Review and Assessment Service, the number of patients diagnosed with lung cancer totaled 100,134 last year and had been continuously on the rise since 2015. The total increased from 73,671 in 2015 to 79,729 in 2016, 84,132 in 2017, and 92,747 in 2018.

The number exceeded 100,000 for the first time in 2019. Of the total, some 80 to 85 percent suffer from non-small cell lung cancer (NSCLC).

"About 50 percent of Asian NSCLC patients, including South Koreans, are found to have EGFR gene mutations," the team said in a news release on Tuesday. "Of the patients, the EGFR Exon20ins mutation is an uncommon type, accounting for about 10 percent of all EGFR mutations."

According to the team, mutations in the EGFR amino acid sequence promote cancer cell growth.

Despite such a high unmet medical need, EGFR Exon20ins mutant lung cancer is resistant to existing EGFR targeted therapies – Tagrisso, Iressa, Tarceva and Giotrif -- and no targeted therapeutics have been developed other than cytotoxic anticancer agents so far.

To find a valid treatment, the team confirmed the anticancer effect of amivantamab, which targets EGFR and cMET simultaneously, after administering the treatment in a mouse cell, patient-derived cell line, and animal model with the EGFR Exon20ins mutation.

Amivantamab showed a strong cancer cell killing effect in EGFR Exon20ins mutant mouse cell lines and patient-derived cell lines, which are resistant to existing EGFR targeted therapeutics. The substance also inhibited the activity of EGFR sub-signaling proteins and increased proteins involved in apoptosis.

In the EGFR Exon20ins mutant lung cancer patient-derived tumor mice model, the treatment showed a superior inhibitory effect on cancer cell growth compared to cetuximab, the existing EGFR target antibody.

It also demonstrated more excellent tolerability than poziotinib, a similarly targeted therapeutics, currently in development.

Notably, the researchers demonstrated that amivantamab's effect on the killing of cancer cells is deeply involved in antibody-dependent cell-mediated cytotoxicity using NK cells or macrophage in the patient's immune system.

"This means amivantamab could enhance the immune cells in the human body and kill cancer cells," the team said. "Amivantamab also demonstrated excellent anticancer effects in clinical studies involving ongoing EGFR Exon20ins patients."

When the team administered the substance to two lung cancer patients with EGFR Exon20 insertion mutations, it reduced the tumor by 65 and 38.9 percent, respectively, the team added.

"This study confirmed the superior anticancer effect of amivantamab in EGFR Exon20 insertion lung cancer,” Professor Cho Byoung-chul said. “For patients with EGFR Exon20 insertion mutant lung cancer, who did not have a targeted therapeutic option, amivantamab offers great potential as a new treatment option."

In the future, all lung cancer patients will need to be carefully examined for the presence of EGFR Exon20ins during diagnosis through tissue or blood-based next-generation gene sequencing, Cho added.

Cancer Discovery published the results of the study.

corea022@docdocdoc.co.kr

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