{"entity":{"id":"leap-012","kind":"trial","name":"LEAP-012","aka":[],"tldr":"Adding lenvatinib and pembrolizumab to TACE delayed progression by four and a half months but did not help patients live longer.","summary":"LEAP-012, trial NCT04246177 sponsored by Merck and Eisai and reported in 2024, found that adding lenvatinib and pembrolizumab to transarterial chemoembolisation for unresectable non-metastatic hepatocellular carcinoma delayed progression by about four and a half months but did not help patients live longer. It randomised 480 patients and met its primary progression-free survival endpoint, but grade 3 or worse adverse events were far more common and the final overall survival analysis in 2026 showed no difference. OnCo links it to TACE, lenvatinib, pembrolizumab and the pairing of TACE with immunotherapy and anti-VEGF drugs. The record calls it the clearest demonstration that progression-free survival is a poor surrogate in TACE combination trials, and whether regulators should accept that endpoint in this setting is the open question.","status":"mixed","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04246177","url":"https://clinicaltrials.gov/study/NCT04246177"},{"label":"Lancet","url":"https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)02575-3/abstract"}],"tags":["lesson:surrogate-endpoint"],"related":[],"cancers":["hcc","hcc-intermediate"],"sections":[],"technologies":["tace"],"targets":[],"drugs":["lenvatinib","pembrolizumab"],"companies":["eisai"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT04246177","phase":"3","setting":"Unresectable non-metastatic HCC: TACE + lenvatinib + pembrolizumab vs TACE + placebo","sponsor":"Merck / Eisai","result":"PFS HR 0.66; final OS HR 0.98.","started":"2020-05-22","startedType":"actual","yearReported":2024,"enrolled":480,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival","primary":true,"unit":"months","arms":[{"name":"TACE + lenvatinib + pembrolizumab","value":14.6},{"name":"TACE + placebo","value":10}],"hr":0.66,"p":"0.0002"},{"endpoint":"Overall survival (final)","primary":true,"arms":[{"name":"TACE + lenvatinib + pembrolizumab"},{"name":"TACE + placebo"}],"hr":0.98}]},"route":"/trials/leap-012/","neighbours":{"cancer":[{"id":"hcc","kind":"cancer","name":"Hepatocellular carcinoma","route":"/cancers/hcc/"},{"id":"hcc-intermediate","kind":"cancer","name":"Intermediate hepatocellular carcinoma (BCLC B)","route":"/cancers/hcc-intermediate/"}],"technology":[{"id":"tace","kind":"technology","name":"Transarterial chemoembolisation (TACE)","route":"/technologies/tace/"}],"drug":[{"id":"lenvatinib","kind":"drug","name":"Lenvatinib","route":"/drugs/lenvatinib/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"eisai","kind":"company","name":"Eisai","route":"/companies/eisai/"}],"pairing":[{"id":"tace-plus-systemic","kind":"pairing","name":"TACE + immunotherapy/anti-VEGF","route":"/pairings/tace-plus-systemic/"}],"paper":[{"id":"paper-leap-012-lancet-2025","kind":"paper","name":"LEAP-012: transarterial chemoembolisation with lenvatinib plus pembrolizumab versus placebo for unresectable non-metastatic hepatocellular carcinoma","route":"/key-papers/paper-leap-012-lancet-2025/"}]}}