Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR-cMet Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion-Driven NSCLC

EGFR exon 20 insertion driver mutations (Exon20ins) in NSCLC are insensitive to EGFR-TKIs. 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 patient...

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Published in:Cancer discovery 2020-05
Main Authors: Yun, Jiyeon, Lee, Soo-Hwan, Kim, Seok-Young, Jeong, Seo-Yoon, Kim, Jae-Hwan, Pyo, Kyoung-Ho, Park, Chae-Won, Heo, Seong Gu, Yun, Mi Ran, Lim, Sangbin, Lim, Sun Min, Hong, Min Hee, Kim, Hye Ryun, Thayu, Meena, Curtin, Joshua C, Knoblauch, Roland E, Lorenzi, Matthew V, Roshak, Amy, Cho, Byoung Chul
Format: Article
Language:English
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Summary:EGFR exon 20 insertion driver mutations (Exon20ins) in NSCLC are insensitive to EGFR-TKIs. 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.
ISSN:2159-8290