Dr. Spira on the Rationale of the CHRYSALIS Trial in EGFR-Mutant NSCLC

Alexander Spira, MD, PhD, FACP, a medical oncologist and director of the Virginia Cancer Specialists Research Institute and the Phase 1 Trial Program, discusses the rationale of the phase 1 CHRYSALIS trial with amivantamab (JNJ-61186372) plus lazertinib (YH25448) in EGFR-mutant non–small cell lung cancer (NSCLC).

The rationale for combining amivantamab with lazertinib in advanced EGFR-mutated NSCLC involves several factors, says Spira. With regard to the relapsed/refractory population, many patients will have 1 of 2 mutations when they relapse: a C797S or a c-Met mutation or amplification. That is the main area of resistance for most patients previously treated with an EGFR inhibitor such as osimertinib (Tagrisso).

Amivantamab is a bispecific antibody; therefore, it targets c-Met in an attempt to overcome c-Met resistance, as well as EGFR in a different pathway. As a monoclonal antibody, it binds to the outside of the cell as opposed to a small molecule inhibitor that targets the inside of the cell. Lazertinib is very similar to osimertinib. By adding a second drug, mechanisms of resistance can potentially be overcome; there is a very strong scientific rationale for the study, concludes Spira.