# ALPINE

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

## TL;DR

The first head-to-head trial in which a newer BTK inhibitor was both safer and more effective than ibrutinib.

## Summary

ALPINE, trial NCT03734016 sponsored by BeOne, formerly BeiGene, and published in the New England Journal of Medicine in 2023, was the first head-to-head trial in which a newer BTK inhibitor was both safer and more effective than ibrutinib in relapsed or refractory chronic lymphocytic leukaemia. It randomised 652 patients to zanubrutinib or ibrutinib, met its primary progression-free survival endpoint including in del(17p) and TP53 disease, produced a higher response rate, less than half the rate of atrial fibrillation and fewer discontinuations, and the three-year update maintained the advantage. OnCo links it to chronic lymphocytic leukaemia, BTK as a target, zanubrutinib, ibrutinib, John Oyler, Jennifer R. Brown and the caution pairing about ibrutinib in patients with cardiac risk. Whether that superiority reflects the drug or the trial is the open question.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: NCT03734016
- Phase: 3
- Setting: Relapsed or refractory CLL/SLL: zanubrutinib vs ibrutinib
- Sponsor: BeOne (BeiGene)
- Enrolled: 652
- Result: PFS HR 0.65; AF 5.2% vs 13.3%.
- Outcomes: Progression-free survival: Zanubrutinib vs Ibrutinib, HR 0.65; Overall response rate: Zanubrutinib 86.2% vs Ibrutinib 75.7%; Atrial fibrillation/flutter: Zanubrutinib 5.2% vs Ibrutinib 13.3%
- Replication: ELEVATE-RR (acalabrutinib vs ibrutinib) showed non-inferior PFS with less atrial fibrillation; ALPINE is the only trial to show PFS superiority.

## Sources

- ClinicalTrials.gov NCT03734016: https://clinicaltrials.gov/study/NCT03734016

## Connected records

- cancers: [Chronic lymphocytic leukaemia](https://onco.cc/cancers/cll/), [Relapsed or refractory chronic lymphocytic leukaemia](https://onco.cc/cancers/cll-relapsed/)
- technologies: [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BTK (Bruton tyrosine kinase)](https://onco.cc/targets/btk/)
- drugs: [Ibrutinib](https://onco.cc/drugs/ibrutinib/), [Zanubrutinib](https://onco.cc/drugs/zanubrutinib/)
- companies: [BeOne Medicines (formerly BeiGene)](https://onco.cc/companies/beone/)
- people: [Jennifer R. Brown](https://onco.cc/people/jennifer-brown/), [John Oyler](https://onco.cc/people/oyler-john/)
- pairings: [Caution: ibrutinib in patients with cardiac risk](https://onco.cc/pairings/btki-ibrutinib-cardiac-caution/)
- key papers: [Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia](https://onco.cc/key-papers/paper-zanubrutinib-cll-n-engl-j-med-2023/)

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