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Amivantamab & Lazertinib Combination May Overcome Osimertinib Resistance in Patients With EGFR-Positive NSCLC

*July 2021*

Combination targeting of epidermal growth factor receptor (EGFR) with amivantamab/lazertinib achieved durable responses in more than one-third of chemotherapy-naive patients with EGFR-mutant non–small cell lung cancer (NSCLC) that had progressed on osimertinib, according to a cohort analysis of the CHRYSALIS trial presented at the 2021 ASCO Annual Meeting.1

The study also provided insights into resistance mechanisms in patients previously treated with osimertinib. “Biomarker analysis with next-generation sequencing identified a subgroup of patients more likely to respond to this combination: those with EGFR/MET-based resistance. Immunohistochemistry (IHC) suggests that high EGFR and MET expression may be an alternate way to identify responders to this combination,” said presenting author Byoung Chul Cho, MD, of Yonsei Cancer Center, Seoul, Korea.

Amivantamab is a fully human bispecific antibody targeting EGFR and MET that was recently approved by the U.S. Food and Drug Administration for the frontline treatment of adults with EGFR exon 20 insertion–mutant NSCLC. Lazertinib is a potent third-generation EGFR tyrosine kinase inhibitor with good tolerability.

“[We] targeted two different mechanisms with these two drugs,” Dr. Cho told listeners.

“Despite osimertinib’s efficacy in NSCLC, resistance develops and the mechanisms of resistance to osimertinib are complex. In fact, resistance mechanisms are unknown in 50% of patients, and co-occurrence of multiple mechanisms of resistance have been observed. Following resistance to osimertinib, platinum-based chemotherapy is typically used, but this has limited activity,” Dr. Cho said, explaining part of the rationale for the CHRYSALIS study.

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