{"entity":{"id":"dreamseq","kind":"trial","name":"DREAMseq (ECOG-ACRIN EA6134)","aka":[],"tldr":"Settled the order question: for BRAF-mutant melanoma, start with immunotherapy and save the targeted pills for later.","summary":"DREAMseq, ECOG-ACRIN trial EA6134, NCT02224781, sponsored by ECOG-ACRIN and the NCI and reported in 2021, settled the order question in BRAF-mutant metastatic melanoma: start with immunotherapy and save the targeted tablets for later. It randomised 265 patients to nivolumab plus ipilimumab followed by dabrafenib plus trametinib at progression, or the reverse sequence, and was stopped early for benefit when two-year overall survival clearly favoured immunotherapy first, since targeted therapy remained effective after immunotherapy while immunotherapy after BRAF and MEK failure performed poorly. OnCo links it to BRAF, PD-1 and CTLA-4 as targets, the drugs, ECOG-ACRIN and the pairing that places immunotherapy first, and the Italian phase 2 SECOMBIT reached the same conclusion. Whether a short targeted induction before immunotherapy could improve on either sequence is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT02224781","url":"https://clinicaltrials.gov/study/NCT02224781"},{"label":"JCO 2023","url":"https://ascopubs.org/doi/10.1200/JCO.22.01763"}],"tags":[],"related":[],"cancers":["melanoma","braf-v600-melanoma","advanced-melanoma"],"sections":[],"technologies":["checkpoint-inhibitor"],"targets":["braf","pd1","ctla4"],"drugs":["nivolumab","ipilimumab","dabrafenib-trametinib"],"companies":["ecog-acrin"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NCT02224781","phase":"3","setting":"Untreated BRAF V600 metastatic melanoma: nivolumab + ipilimumab then dabrafenib + trametinib at progression, vs the reverse sequence","sponsor":"ECOG-ACRIN / NCI","result":"2-year OS 71.8% vs 51.5%.","started":"2015-09-08","startedType":"actual","yearReported":2021,"enrolled":267,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival at 2 years","primary":true,"unit":"%","arms":[{"name":"Immunotherapy first","value":71.8},{"name":"Targeted therapy first","value":51.5}],"p":"0.010","source":"https://ascopubs.org/doi/10.1200/JCO.22.01763"}],"replication":"SECOMBIT (phase 2, Italy) independently favoured immunotherapy first."},"route":"/trials/dreamseq/","neighbours":{"cancer":[{"id":"advanced-melanoma","kind":"cancer","name":"Advanced melanoma (unresectable stage III and stage IV)","route":"/cancers/advanced-melanoma/"},{"id":"braf-v600-melanoma","kind":"cancer","name":"BRAF V600-mutant melanoma","route":"/cancers/braf-v600-melanoma/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"}],"technology":[{"id":"checkpoint-inhibitor","kind":"technology","name":"Immune checkpoint inhibitors","route":"/technologies/checkpoint-inhibitor/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"ctla4","kind":"target","name":"CTLA-4","route":"/targets/ctla4/"},{"id":"pd1","kind":"target","name":"PD-1","route":"/targets/pd1/"}],"drug":[{"id":"dabrafenib-trametinib","kind":"drug","name":"Dabrafenib + trametinib","route":"/drugs/dabrafenib-trametinib/"},{"id":"ipilimumab","kind":"drug","name":"Ipilimumab","route":"/drugs/ipilimumab/"},{"id":"nivolumab","kind":"drug","name":"Nivolumab","route":"/drugs/nivolumab/"}],"company":[{"id":"ecog-acrin","kind":"company","name":"ECOG-ACRIN Cancer Research Group","route":"/companies/ecog-acrin/"}],"pairing":[{"id":"io-first-then-braf-mek","kind":"pairing","name":"Immunotherapy first, then BRAF/MEK (BRAF-mutant melanoma)","route":"/pairings/io-first-then-braf-mek/"}],"paper":[{"id":"paper-dreamseq-jco-2023","kind":"paper","name":"DREAMseq (ECOG-ACRIN EA6134): sequencing dabrafenib-trametinib and nivolumab-ipilimumab in BRAF-mutant metastatic melanoma","route":"/key-papers/paper-dreamseq-jco-2023/"}],"roadmap":[{"id":"targeted-therapy-roadmap","kind":"roadmap","name":"Targeted therapy roadmap: imatinib → designed for resistance → the undruggable drivers fall","route":"/roadmaps/targeted-therapy-roadmap/"}]}}