{"entity":{"id":"paper-chrysalis-nat-med-2023","kind":"paper","name":"Amivantamab plus lazertinib in osimertinib-relapsed EGFR-mutant advanced non-small cell lung cancer: a phase 1 trial","aka":[],"tldr":"Published report from the CHRYSALIS trial registered as NCT02609776, in Nature Medicine (2023), chosen as the most cited paper whose own text cites the registry id.","summary":"Patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) often develop resistance to current standard third-generation EGFR tyrosine kinase inhibitors (TKIs); no targeted treatments are approved in the osimertinib-relapsed setting. In this open-label, dose-escalation and dose-expansion phase 1 trial, the potential for improved anti-tumor activity by combining amivantamab, an EGFR-MET bispecific antibody, with lazertinib, a third-generation EGFR TKI, was evaluated in patients with EGFR-mutant NSCLC whose disease progressed on third-generation TKI monotherapy but were chemotherapy naive (CHRYSALIS cohort E). In the dose-escalation phase, the recommended phase 2 combination dose was established; in the dose-expansion phase, the primary endpoints were safety and overall response rate, and key secondary endpoints included progression-free survival and overall survival. The safety profile of amivantamab and lazertinib was generally consistent with previous experience of each agent alone, with 4% experiencing grade ≥3 events; no new safety signals were identified. In an exploratory cohort of 45 patients who were enrolled without biomarker selection, the primary endpoint of investigator-assessed overall response rate was 36% (95% confidence interval, 22-51). The median duration of response was 9.6 months, and the median progression-free survival was 4.9 months. Next-generation sequencing and immunohistochemistry analyses identified high EGFR and/or MET expression as potential predictive biomarkers of response, which will need to be validated with prospective assessment. ClinicalTrials.gov identifier: NCT02609776.\n\nIndexed on Europe PMC as PubMed record 37710001 (DOI 10.1038/s41591-023-02554-7). Its abstract cites the registry id NCT02609776, which is how it was matched to this trial; no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Nat Med 2023","url":"https://doi.org/10.1038/s41591-023-02554-7"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/37710001/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/37710001"},{"label":"ClinicalTrials.gov NCT02609776","url":"https://clinicaltrials.gov/study/NCT02609776"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["chrysalis"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2023,"doi":"10.1038/s41591-023-02554-7","pmid":"37710001","authors":"Cho BC, Kim DW, Spira AI, et al.","paperType":"observational","findings":[],"whatItMeans":"This is the paper Europe PMC returns for registry id NCT02609776 with the most citations, so it is the natural first reading for anyone following the CHRYSALIS trial. Read the abstract above alongside the trial page and the registry entry; the record was linked automatically and its figures have not been checked by hand.","caveats":["Matched to the trial by the registry id cited in the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper."]},"route":"/key-papers/paper-chrysalis-nat-med-2023/","neighbours":{"trial":[{"id":"chrysalis","kind":"trial","name":"CHRYSALIS","route":"/trials/chrysalis/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}]}}