{"entity":{"id":"clear","kind":"trial","name":"CLEAR (KEYNOTE-581)","aka":[],"tldr":"The combination with the longest progression-free survival ever reported in first-line kidney cancer, at nearly two years.","summary":"CLEAR, also KEYNOTE-581, trial NCT02811861 sponsored by Eisai and Merck and reported in 2021, produced the combination with the longest progression-free survival ever reported in first-line kidney cancer, at nearly two years. It randomised 1,069 patients with untreated advanced clear-cell renal cell carcinoma to lenvatinib plus pembrolizumab, lenvatinib plus everolimus or sunitinib, met its primary progression-free survival endpoint with a very large effect and a high response rate including many complete responses, and showed a survival benefit whose curves separated late, leading to FDA approval in August 2021, although the 20 mg lenvatinib dose drives high toxicity with dose reductions in about seventy percent. Whether a lower lenvatinib starting dose would keep the efficacy is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02811861","url":"https://clinicaltrials.gov/study/NCT02811861"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["antiangiogenic","kinase-inhibitors"],"targets":[],"drugs":["lenvatinib","pembrolizumab","sunitinib","everolimus"],"companies":["eisai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":["robert-motzer"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02811861","phase":"3","setting":"Untreated advanced clear-cell RCC: lenvatinib + pembrolizumab vs sunitinib (and lenvatinib + everolimus arm)","sponsor":"Eisai / Merck","result":"PFS 23.9 vs 9.2 months (HR 0.39); OS HR 0.79.","started":"2016-10-13","startedType":"actual","yearReported":2021,"enrolled":1069,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"Lenvatinib + pembrolizumab","n":355,"value":23.9},{"name":"Sunitinib","n":357,"value":9.2}],"hr":0.39,"ci":[0.32,0.49],"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2035716"},{"endpoint":"Overall survival (final)","unit":"months","arms":[{"name":"Lenvatinib + pembrolizumab","value":53.7},{"name":"Sunitinib","value":54.3}],"hr":0.79,"ci":[0.63,0.99],"source":"https://ascopubs.org/doi/10.1200/JCO.23.01569"}],"replication":"Consistent with other IO-TKI doublets; lenvatinib-everolimus arm improved PFS but not OS versus sunitinib."},"route":"/trials/clear/","neighbours":{"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"antiangiogenic","kind":"technology","name":"Anti-angiogenic therapy","route":"/technologies/antiangiogenic/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"drug":[{"id":"everolimus","kind":"drug","name":"Everolimus","route":"/drugs/everolimus/"},{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"},{"id":"sunitinib","kind":"drug","name":"Sunitinib","route":"/drugs/sunitinib/"}],"company":[{"id":"eisai","kind":"company","name":"Eisai","route":"/companies/eisai/"}],"person":[{"id":"robert-motzer","kind":"person","name":"Robert J. Motzer","route":"/people/robert-motzer/"}],"term":[{"id":"imdc-risk","kind":"term","name":"IMDC risk groups (favourable / intermediate / poor)","route":"/terms/imdc-risk/"}]}}