{"entity":{"id":"litespark-022","kind":"trial","name":"LITESPARK-022","aka":[],"tldr":"Adding the HIF-2α pill to a year of adjuvant pembrolizumab further reduced recurrence, and became the first adjuvant combination approved in kidney cancer.","summary":"LITESPARK-022, trial NCT05239728 sponsored by Merck and reported at ASCO GU 2026, showed that adding the HIF-2-alpha inhibitor belzutifan to a year of adjuvant pembrolizumab after nephrectomy for high-risk clear-cell renal cell carcinoma further reduced recurrence, and it became the first adjuvant combination approved in kidney cancer. It randomised 1,841 patients, met its primary disease-free survival endpoint at the first interim analysis with overall survival immature, and led to FDA approval in the second quarter of 2026, with severe adverse events rising from about thirty to about fifty percent. OnCo links it to renal cell carcinoma, HIF-2-alpha as a target, belzutifan, pembrolizumab and the idea of biomarker-selected adjuvant therapy. Whether the added toxicity is justified in patients who would never have relapsed is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT05239728","url":"https://clinicaltrials.gov/study/NCT05239728"},{"label":"Merck ASCO GU 2026","url":"https://www.merck.com/news/merck-advances-treatment-of-bladder-and-kidney-cancers-with-new-data-at-2026-asco-gu-cancers-symposium/"}],"tags":[],"related":[],"cancers":["rcc"],"sections":[],"technologies":["kinase-inhibitors"],"targets":["hif2a"],"drugs":["belzutifan","pembrolizumab"],"companies":["merck"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT05239728","phase":"3","setting":"Clear-cell RCC at high risk after nephrectomy: adjuvant pembrolizumab + belzutifan vs pembrolizumab + placebo","sponsor":"Merck","result":"DFS significantly improved vs pembrolizumab (interim; HR presented ASCO GU 2026).","started":"2022-03-15","startedType":"actual","yearReported":2026,"enrolled":1841,"enrolledBasis":"registry","outcomes":[{"endpoint":"Disease-free survival at 24 months (investigator-assessed)","primary":true,"unit":"%","arms":[{"name":"Pembrolizumab + belzutifan","n":921,"value":80.7},{"name":"Pembrolizumab + placebo","n":920,"value":73.7}],"hr":0.72,"ci":[0.59,0.87],"p":"<0.001","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2518245"},{"endpoint":"Overall survival at 24 months (interim, 29% of final events)","unit":"%","arms":[{"name":"Pembrolizumab + belzutifan","value":96.2,"note":"Not significant; immature"},{"name":"Pembrolizumab + placebo","value":95.7}],"hr":0.78,"ci":[0.51,1.19],"p":"0.24","source":"https://www.nejm.org/doi/full/10.1056/NEJMoa2518245"}],"replication":"First adjuvant RCC trial to beat pembrolizumab (KEYNOTE-564) rather than placebo; single trial, OS immature, and grade >=3 adverse events rose from 30% to 52%."},"route":"/trials/litespark-022/","neighbours":{"cancer":[{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"technology":[{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"hif2a","kind":"target","name":"HIF-2α","route":"/targets/hif2a/"}],"drug":[{"id":"belzutifan","kind":"drug","name":"Belzutifan","route":"/drugs/belzutifan/"},{"id":"pembrolizumab","kind":"drug","name":"Pembrolizumab","route":"/drugs/pembrolizumab/"}],"company":[{"id":"merck","kind":"company","name":"Merck & Co. (MSD)","route":"/companies/merck/"}],"idea":[{"id":"idea-adjuvant-selection-rcc","kind":"idea","name":"Biomarker-selected adjuvant therapy in RCC (ctDNA, CAIX PET, gene signatures)","route":"/ideas/idea-adjuvant-selection-rcc/"}]}}