{"entity":{"id":"squire","kind":"trial","name":"SQUIRE","aka":[],"tldr":"An EGFR antibody added to chemotherapy for squamous lung cancer: it worked, by about six weeks, and almost nobody uses it.","summary":"Necitumumab is a second-generation recombinant human IgG1 antibody against EGFR. SQUIRE ran at 184 sites in 26 countries and randomised 1,093 patients with untreated stage IV squamous non-small-cell lung cancer 1:1 to gemcitabine 1,250 mg/m2 on days 1 and 8 with cisplatin 75 mg/m2 on day 1, with or without necitumumab 800 mg on days 1 and 8. Chemotherapy ran for up to six 3-week cycles; necitumumab continued until progression. The trial was open-label because the acne-like rash characteristic of EGFR antibodies would have unmasked it anyway.\n\nOverall survival was significantly longer with necitumumab, by about six weeks at the median, at the cost of hypomagnesaemia, rash and venous thromboembolism. The FDA approved the combination in 2015 and the EMA in 2016 for EGFR-expressing squamous disease.\n\nSQUIRE is a study in what a statistically significant result is worth. The magnitude was small, the regimen was displaced within two years by pembrolizumab with carboplatin and paclitaxel (KEYNOTE-407), and necitumumab is now almost never given. It has no NICE appraisal.","status":"mixed","asOf":"2026-09-25","links":[{"label":"ClinicalTrials.gov NCT00981058","url":"https://clinicaltrials.gov/study/NCT00981058"},{"label":"SQUIRE (Lancet Oncology 2015)","url":"https://doi.org/10.1016/S1470-2045(15)00021-2"}],"tags":[],"related":[],"cancers":["lung-squamous-cell-carcinoma","nsclc"],"sections":[],"technologies":["monoclonal-antibody","cytotoxic-chemotherapy","platinum"],"targets":["egfr"],"drugs":["necitumumab","gemcitabine","cisplatin"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":[],"trials":["keynote-407"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT00981058","phase":"3","setting":"Untreated stage IV squamous non-small-cell lung cancer, performance status 0 to 2: up to six cycles of gemcitabine 1,250 mg/m2 on days 1 and 8 with cisplatin 75 mg/m2 on day 1, with or without necitumumab 800 mg on days 1 and 8 continued to progression, with overall survival as the primary endpoint","sponsor":"Eli Lilly","result":"Overall survival significantly longer with necitumumab added to gemcitabine and cisplatin, by roughly six weeks at the median; hypomagnesaemia, rash and thromboembolism were the added toxicities.","yearReported":2015,"enrolled":1093,"enrolledBasis":"registry","outcomes":[],"replication":"Not replicated. The companion trial in non-squamous disease, INSPIRE, was stopped early for excess thromboembolic death, so the indication is squamous only."},"route":"/trials/squire/","neighbours":{"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"lung-squamous-cell-carcinoma","kind":"cancer","name":"Squamous cell carcinoma of the lung","route":"/cancers/lung-squamous-cell-carcinoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"}],"target":[{"id":"egfr","kind":"target","name":"EGFR","route":"/targets/egfr/"}],"drug":[{"id":"cisplatin","kind":"drug","name":"Cisplatin","route":"/drugs/cisplatin/"},{"id":"gemcitabine","kind":"drug","name":"Gemcitabine","route":"/drugs/gemcitabine/"},{"id":"necitumumab","kind":"drug","name":"Necitumumab","route":"/drugs/necitumumab/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"trial":[{"id":"keynote-407","kind":"trial","name":"KEYNOTE-407","route":"/trials/keynote-407/"}]}}