한빛사 논문
Jiyeon Yun1, Soo-Hwan Lee2, Seok-Young Kim1, Seo-Yoon Jeong1, Jae-Hwan Kim1, Kyoung-Ho Pyo1, Chae-Won Park1, Seong Gu Heo1, Mi Ran Yun2, Sangbin Lim1, Sun Min Lim3, Min Hee Hong3, Hye Ryun Kim3, Meena Thayu4, Joshua C. Curtin4, Roland E. Knoblauch4, Matthew V. Lorenzi4, Amy Roshak4 and Byoung Chul Cho3,*
1Severance Biomedical Science Institute, Brain Korea 21 PLUS Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Republic of Korea.
2JE-UK Institute for Cancer Research, JEUK Co. Ltd., Gumi-City, Kyungbuk, Republic of Korea.
3Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea.
4Janssen Research and Development, Spring House, Pennsylvania, United States.
*Corresponding Author
Abstract
EGFR exon 20 insertion driver mutations (Exon20ins) in NSCLC are insensitive to EGFRTKIs. Amivantamab (JNJ-61186372), a bispecific antibody targeting EGFR/cMet, has shown preclinical activity in TKI-sensitive EGFR-mutated NSCLC models and in an ongoing first-in-human study in advanced NSCLC patients. However, the activity of amivantamab in Exon20ins-driven tumors has not yet been described. Ba/F3 cells and patient-derived cells/organoids/xenograft models harboring diverse Exon20ins were used to characterize the antitumor mechanism of amivantamab. Amivantamab inhibited proliferation by effectively downmodulating EGFR/cMet levels and inducing immune-directed antitumor activity with increased IFN-γ secretion in various models. Importantly, in vivo efficacy of amivantamab was superior to cetuximab or poziotinib, an experimental Exon20ins targeted-TKI. Amivantamab produced robust tumor responses in two Exon20ins patients, highlighting the important translational nature of this preclinical work. These findings provide mechanistic insight into the activity of amivantamab and support its continued clinical development in Exon20ins patients, an area of high unmet medical need.
논문정보
TOP52020년 후보
관련 링크
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기