{"entity":{"id":"cepheus","kind":"trial","name":"CEPHEUS","aka":[],"tldr":"CEPHEUS extended the quadruplet advantage to patients who do not have a transplant.","summary":"CEPHEUS, trial NCT03652064 sponsored by Janssen and reported in 2024, extended the quadruplet advantage to newly diagnosed myeloma patients who do not have a transplant, adding daratumumab to bortezomib, lenalidomide and dexamethasone. It randomised 395 transplant-ineligible or transplant-deferred patients and met its primary endpoint of MRD negativity, with a clear progression-free survival benefit at 54 months, and it was approved in 2025 alongside IMROZ-era labelling. OnCo links it to multiple myeloma, daratumumab, bortezomib, lenalidomide, the quadruplet pairing and the CEPHEUS paper. It is notable for using MRD negativity as its main endpoint, and whether regulators accept that surrogate more widely is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03652064","url":"https://clinicaltrials.gov/study/NCT03652064"}],"tags":[],"related":[],"cancers":["multiple-myeloma","myeloma-transplant-ineligible"],"sections":[],"technologies":["monoclonal-antibody"],"targets":[],"drugs":["daratumumab","bortezomib","lenalidomide"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT03652064","phase":"3","setting":"Newly diagnosed transplant-ineligible or -deferred myeloma: Dara-VRd vs VRd","sponsor":"Janssen","result":"MRD-neg 60.9% vs 39.4%; PFS HR 0.57.","started":"2018-11-06","startedType":"actual","yearReported":2024,"enrolled":395,"enrolledBasis":"registry","outcomes":[{"endpoint":"MRD negativity (10⁻⁵)","primary":true,"unit":"%","arms":[{"name":"Dara-VRd","n":197,"value":60.9},{"name":"VRd","n":198,"value":39.4}],"p":"<0.0001","source":"https://doi.org/10.1038/s41591-024-03485-7"},{"endpoint":"Progression-free survival at 54 months","unit":"%","arms":[{"name":"Dara-VRd","value":68.1},{"name":"VRd","value":49.5}],"hr":0.57,"ci":[0.41,0.79],"source":"https://doi.org/10.1038/s41591-024-03485-7"}]},"route":"/trials/cepheus/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-transplant-ineligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-ineligible","route":"/cancers/myeloma-transplant-ineligible/"}],"technology":[{"id":"monoclonal-antibody","kind":"technology","name":"Monoclonal antibodies","route":"/technologies/monoclonal-antibody/"}],"drug":[{"id":"bortezomib","kind":"drug","name":"Bortezomib","route":"/drugs/bortezomib/"},{"id":"daratumumab","kind":"drug","name":"Daratumumab","route":"/drugs/daratumumab/"},{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"pairing":[{"id":"cd38-plus-triplet","kind":"pairing","name":"CD38 antibody added to PI-IMiD-dex (quadruplet induction)","route":"/pairings/cd38-plus-triplet/"}],"paper":[{"id":"paper-cepheus-dara-vrd-natmed-2025","kind":"paper","name":"CEPHEUS: daratumumab quadruplet for newly diagnosed myeloma patients not having a transplant, with MRD-negativity as the main endpoint","route":"/key-papers/paper-cepheus-dara-vrd-natmed-2025/"}]}}