{"entity":{"id":"sequoia","kind":"trial","name":"SEQUOIA","aka":["SEQUOIA pegilodecakin","AM0010 phase 3"],"tldr":"Zanubrutinib beat chemoimmunotherapy in untreated CLL and delivered a 72% five-year progression-free rate in the hardest genetic subgroup.","summary":"SEQUOIA, trial NCT03336333 sponsored by BeOne, formerly BeiGene, published in Lancet Oncology in 2022 with five-year data in JCO in 2025, showed that zanubrutinib beats bendamustine and rituximab in previously untreated chronic lymphocytic leukaemia unsuitable for FCR, and delivered a high five-year progression-free rate in del(17p) disease. Cohort 1 randomised 479 patients and met its primary progression-free survival endpoint with a large effect maintained at five years, arm C treated 111 patients with del(17p) with most progression-free at five years, and arm D combined zanubrutinib with venetoclax with very high undetectable MRD rates, the basis of the January 2023 CLL approval. Whether the arm D doublet becomes a fixed-duration standard is the open question.","status":"positive","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT03336333","url":"https://clinicaltrials.gov/study/NCT03336333"},{"label":"ClinicalTrials.gov NCT02923921","url":"https://clinicaltrials.gov/study/NCT02923921"},{"label":"Hecht et al., SEQUOIA (JCO 2021)","url":"https://doi.org/10.1200/JCO.20.02232"}],"tags":[],"related":[],"cancers":["cll","cll-treatment-naive","pancreatic","metastatic-pdac"],"sections":[],"technologies":["kinase-inhibitors","cytotoxic-chemotherapy"],"targets":["btk"],"drugs":["zanubrutinib","venetoclax","rituximab","pegilodecakin","folfox"],"companies":["eli-lilly"],"institutions":[],"pathways":[],"terms":["del17p-tp53","cold-vs-hot","pancreatic-failed-programmes"],"trials":[],"people":["oyler-john","constantine-tam"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["UK sites (registry, 5): Addenbrooke's Hospital Cambridge; Hammersmith Hospital; Velindre Hospital Cardiff; University College London Hospitals; Guy's and St Thomas'."],"nct":"NCT03336333","phase":"3","setting":"Previously untreated CLL/SLL unsuitable for FCR: zanubrutinib vs bendamustine-rituximab (cohort 1); zanubrutinib in del(17p) (arm C); zanubrutinib + venetoclax (arm D)","sponsor":"BeOne (BeiGene)","result":"PFS HR 0.42 vs BR; 5-year PFS 72.2% in del(17p).","started":"2017-10-31","startedType":"actual","yearReported":2022,"enrolled":590,"enrolledBasis":"registry","outcomes":[{"endpoint":"Progression-free survival (cohort 1)","primary":true,"arms":[{"name":"Zanubrutinib","n":241},{"name":"Bendamustine + rituximab","n":238}],"hr":0.42,"ci":[0.28,0.63],"p":"<0.0001","source":"https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(22)00293-5/fulltext"},{"endpoint":"Progression-free survival at 5 years, del(17p) (arm C)","unit":"%","arms":[{"name":"Zanubrutinib","n":111,"value":72.2}],"source":"https://ashpublications.org/ashclinicalnews/news/8659/Five-Year-Results-of-SEQUOIA-Trial-Show"},{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Pegilodecakin + FOLFOX","n":283,"value":5.8},{"name":"FOLFOX","n":284,"value":6.3}],"hr":1.045,"ci":[0.863,1.265],"source":"https://doi.org/10.1200/JCO.20.02232"}],"replication":"ALPINE confirmed zanubrutinib's efficacy against ibrutinib in relapse; ELEVATE-TN shows the same class effect frontline."},"route":"/trials/sequoia/","neighbours":{"cancer":[{"id":"cll","kind":"cancer","name":"Chronic lymphocytic leukaemia","route":"/cancers/cll/"},{"id":"cll-treatment-naive","kind":"cancer","name":"Chronic lymphocytic leukaemia, first treatment","route":"/cancers/cll-treatment-naive/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"kinase-inhibitors","kind":"technology","name":"Small-molecule kinase inhibitors","route":"/technologies/kinase-inhibitors/"}],"target":[{"id":"btk","kind":"target","name":"BTK (Bruton tyrosine kinase)","route":"/targets/btk/"}],"drug":[{"id":"folfox","kind":"drug","name":"FOLFOX (5-FU, leucovorin, oxaliplatin)","route":"/drugs/folfox/"},{"id":"pegilodecakin","kind":"drug","name":"Pegilodecakin","route":"/drugs/pegilodecakin/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"venetoclax","kind":"drug","name":"Venetoclax","route":"/drugs/venetoclax/"},{"id":"zanubrutinib","kind":"drug","name":"Zanubrutinib","route":"/drugs/zanubrutinib/"}],"company":[{"id":"eli-lilly","kind":"company","name":"Eli Lilly (incl. Loxo)","route":"/companies/eli-lilly/"}],"term":[{"id":"del17p-tp53","kind":"term","name":"del(17p) / TP53 aberration in CLL","route":"/terms/del17p-tp53/"},{"id":"cold-vs-hot","kind":"term","name":"Hot vs cold tumours","route":"/terms/cold-vs-hot/"},{"id":"pancreatic-failed-programmes","kind":"term","name":"Pancreatic cancer: the failed and stopped programmes and why","route":"/terms/pancreatic-failed-programmes/"}],"person":[{"id":"constantine-tam","kind":"person","name":"Constantine S. Tam","route":"/people/constantine-tam/"},{"id":"oyler-john","kind":"person","name":"John Oyler","route":"/people/oyler-john/"}],"pairing":[{"id":"btki-plus-venetoclax-fixed-duration","kind":"pairing","name":"BTK inhibitor + venetoclax, fixed duration","route":"/pairings/btki-plus-venetoclax-fixed-duration/"},{"id":"cit-in-del17p-caution","kind":"pairing","name":"Caution: chemoimmunotherapy in del(17p)/TP53 CLL","route":"/pairings/cit-in-del17p-caution/"}],"paper":[{"id":"paper-elevate-tn-acalabrutinib-lancet-2020","kind":"paper","name":"ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL","route":"/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/"},{"id":"paper-zanubrutinib-cll-lancet-oncol-2022","kind":"paper","name":"Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial","route":"/key-papers/paper-zanubrutinib-cll-lancet-oncol-2022/"}]}}