# SEQUOIA

Source: https://onco.cc/trials/sequoia/  
OnCo record `sequoia` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Also known as: SEQUOIA pegilodecakin; AM0010 phase 3
- Registry id: 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)
- Enrolled: 590
- Result: PFS HR 0.42 vs BR; 5-year PFS 72.2% in del(17p).
- Outcomes: Progression-free survival (cohort 1): Zanubrutinib vs Bendamustine + rituximab, HR 0.42; Progression-free survival at 5 years, del(17p) (arm C): Zanubrutinib 72.2%; Overall survival: Pegilodecakin + FOLFOX 5.8 months vs FOLFOX 6.3 months, HR 1.045
- Replication: ALPINE confirmed zanubrutinib's efficacy against ibrutinib in relapse; ELEVATE-TN shows the same class effect frontline.

## Notes

- UK sites (registry, 5): Addenbrooke's Hospital Cambridge; Hammersmith Hospital; Velindre Hospital Cardiff; University College London Hospitals; Guy's and St Thomas'.

## Sources

- ClinicalTrials.gov NCT03336333: https://clinicaltrials.gov/study/NCT03336333
- ClinicalTrials.gov NCT02923921: https://clinicaltrials.gov/study/NCT02923921
- Hecht et al., SEQUOIA (JCO 2021): https://doi.org/10.1200/JCO.20.02232

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Chronic lymphocytic leukaemia, first treatment](https://onco.cc/cancers/cll-treatment-naive/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/)
- drugs: [FOLFOX (5-FU, leucovorin, oxaliplatin)](https://onco.cc/drugs/folfox/), [Pegilodecakin](https://onco.cc/drugs/pegilodecakin/), [Rituximab](https://onco.cc/drugs/rituximab/), [Venetoclax](https://onco.cc/drugs/venetoclax/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- companies: [Eli Lilly (incl. Loxo)](https://onco.cc/companies/eli-lilly/)
- terms: [del(17p) / TP53 aberration in CLL](https://onco.cc/terms/del17p-tp53/), [Hot vs cold tumours](https://onco.cc/terms/cold-vs-hot/), [Pancreatic cancer: the failed and stopped programmes and why](https://onco.cc/terms/pancreatic-failed-programmes/)
- people: [Constantine S. Tam](https://onco.cc/people/constantine-tam/), [John Oyler](https://onco.cc/people/oyler-john/)
- pairings: [BTK inhibitor + venetoclax, fixed duration](https://onco.cc/pairings/btki-plus-venetoclax-fixed-duration/), [Caution: chemoimmunotherapy in del(17p)/TP53 CLL](https://onco.cc/pairings/cit-in-del17p-caution/)
- key papers: [ELEVATE-TN: acalabrutinib, alone or with obinutuzumab, against chemo-immunotherapy in untreated CLL](https://onco.cc/key-papers/paper-elevate-tn-acalabrutinib-lancet-2020/), [Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial](https://onco.cc/key-papers/paper-zanubrutinib-cll-lancet-oncol-2022/)

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