{"entity":{"id":"amivantamab-plus-lazertinib","kind":"pairing","name":"Amivantamab + lazertinib (first-line EGFR NSCLC)","aka":[],"tldr":"Blocking EGFR from inside (a pill) and outside (an antibody that also blocks MET) beat osimertinib and added more than a year of survival.","summary":"This combination pairs amivantamab, a bispecific antibody against EGFR and MET, with lazertinib, an oral EGFR inhibitor, as first-line treatment for EGFR-mutant non-small-cell lung cancer. Lazertinib blocks EGFR signalling from inside the cell while amivantamab blocks EGFR and MET at the cell surface and recruits immune effectors, so the pairing pre-empts the two main escape routes from osimertinib, MET amplification and the C797S mutation. The phase 3 MARIPOSA trial compared it with osimertinib and showed a progression-free and overall survival benefit. The price is more toxicity, including rash, paronychia, venous thromboembolism and infusion reactions, plus intravenous visits; subcutaneous amivantamab, introduced in 2025, eases the latter.","asOf":"2026-09-06","links":[{"label":"ClinicalTrials.gov NCT04487080: MARIPOSA","url":"https://clinicaltrials.gov/study/NCT04487080"}],"tags":[],"related":[],"cancers":["nsclc","egfr-mutant-nsclc"],"sections":[],"technologies":[],"targets":["egfr","met"],"drugs":["amivantamab","lazertinib","osimertinib"],"companies":[],"institutions":[],"pathways":[],"terms":["met-amplification","c797s"],"trials":["mariposa"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"amivantamab","b":"lazertinib","rationale":"Lazertinib blocks intracellular EGFR signalling while amivantamab blocks EGFR and MET extracellularly and recruits immune effectors, pre-empting the MET-amplification and C797S escape routes.","evidence":"Phase 3 with OS benefit.","pairingType":"combination"},"route":"/pairings/amivantamab-plus-lazertinib/","neighbours":{"cancer":[{"id":"egfr-mutant-nsclc","kind":"cancer","name":"EGFR-mutated non-small-cell lung cancer","route":"/cancers/egfr-mutant-nsclc/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"},{"id":"met","kind":"target","name":"MET","route":"/targets/met/"}],"drug":[{"id":"amivantamab","kind":"drug","name":"Amivantamab","route":"/drugs/amivantamab/"},{"id":"lazertinib","kind":"drug","name":"Lazertinib","route":"/drugs/lazertinib/"},{"id":"osimertinib","kind":"drug","name":"Osimertinib","route":"/drugs/osimertinib/"}],"term":[{"id":"c797s","kind":"term","name":"EGFR C797S","route":"/terms/c797s/"},{"id":"met-amplification","kind":"term","name":"MET amplification (bypass resistance)","route":"/terms/met-amplification/"}],"trial":[{"id":"mariposa","kind":"trial","name":"MARIPOSA","route":"/trials/mariposa/"}]}}