Discussion
DISEASE PROGRESSION, DISEASE, SECONDARY
Patients with Overall, the safety profile of the amivantamab and lazertinib regimen was tolerable and generally consistent with previous monotherapy experience of amivantamabIn the osimertinib-relapsed cohort, which was enrolled without biomarker selection, the investigator-assessed ORR was 36%, with anti-tumor activity observed in patients whose disease progressed after osimertinib therapy in the first-line or second-line setting. Furthermore, the median PFS was 4.9 months, which is similar to that observed with standard-of-care platinum-based chemotherapyThis study needs to be interpreted within its limitations. As a non-randomized, single-arm trial with no control arm, interpretation of the data requires historical comparison within the literature or with real-world evidence. The limited sample size of the study leads to lower-than-desired precision, which can impact interpretation and extrapolation. Additionally, the data presented here are not generalizable to all patients who progressed on osimertinib because the study enrolled only those who were also chemotherapy naive. Long-term safety of the amivantamab and lazertinib combination therapy may not be fully captured with the follow-up period explored in this study. Data with longer follow-up (median follow-up of 33.5 months) from this same study and combination in the front-line setting were recently presented, and the safety profile was consistent with previous reportsThe activity of the combination after disease progression on or after osimertinib suggests that dual blockade of EGFR and MET by amivantamab can potentiate the initial anti-EGFR activity of lazertinib and may delay development of resistance through EGFR secondary resistance mutations and MET bypass pathways