A Study of Zanubrutinib (BGB-3111) Versus Ibrutinib in Participants With Relapsed/Refractory Chronic Lymphocytic Leukemia

Summary

This study is designed to compare the overall response rate of zanubrutinib versus ibrutinib in participants with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Timeline

Start

2018-11-01

Primary completion

2022-08-08

Completion

2024-02-28

Outcome

Met primary endpoint

registry analysis (superiority test); Zanubrutinib vs Ibrutinib; p = 0.0035; Cochran-Mantel-Haenszel NCT03734016 ↗

registry analysis (superiority test); Zanubrutinib vs Ibrutinib; p = 0.0007; Cochran-Mantel-Haenszel NCT03734016 ↗

release “As previously announced, the ALPINE trial met its primary endpoint, with BRUKINSA demonstrating non-inferiority in objective response rate (ORR)” beonemedicines.com ↗

release “ALPINE trial comparing BRUKINSA to ibrutinib in adult patients with relapsed or refractory (R/R) CLL or SLL demonstrated superiority in the primary endpoint” beonemedicines.com ↗

release “today announced results from the Phase 3 ALPINE trial showing BTK inhibitor BRUKINSA® (zanubrutinib) demonstrated superiority versus ibrutinib in overall response rate” beonemedicines.com ↗

release “in this final response analysis, BRUKINSA met the primary endpoint of superiority over ibrutinib in ORR as determined by IRC” beonemedicines.com ↗

release “The ALPINE trial results demonstrate superiority for both PFS and ORR versus ibrutinib in relapsed or refractory CLL/SLL” beonemedicines.com ↗

release “BRUKINSA continues to show sustained PFS benefit versus ibrutinib in the global Phase 3 ALPINE trial of patients with R/R CLL/SLL” beonemedicines.com ↗

release “In an extended follow-up of the ALPINE study at a median follow-up of 39 months, BRUKINSA showed sustained PFS improvement versus ibrutinib” beonemedicines.com ↗

release “As ORR superiority was demonstrated, progression-free survival was tested for noninferiority and superiority under hierarchical testing.” beonemedicines.com ↗

Publications

• Background Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kazmierczak M, Lamanna N, O'Brien SM, Tam CS, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Wang MD, Fu L, Li J, Wu K, Cohen A, Shadman M. Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. N Engl J Med. 2023 Jan 26;388(4):319-332. doi: 10.1056/NEJMoa2211582. Epub 2022 Dec 13.
• Background Hillmen P, Eichhorst B, Brown JR, Lamanna N, O'Brien SM, Tam CS, Qiu L, Kazmierczak M, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Shadman M, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Ji M, Yecies J, Idoine A, Wu K, Huang J, Jurczak W. Zanubrutinib Versus Ibrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: Interim Analysis of a Randomized Phase III Trial. J Clin Oncol. 2023 Feb 10;41(5):1035-1045. doi: 10.1200/JCO.22.00510. Epub 2022 Nov 17.
• Results Hillmen P, Brown JR, Eichhorst BF, Lamanna N, O'Brien SM, Qiu L, Salmi T, Hilger J, Wu K, Cohen A, Huang J, Tam CS. ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Future Oncol. 2020 Apr;16(10):517-523. doi: 10.2217/fon-2019-0844. Epub 2020 Mar 24.
• Tam CS, Shadman M, Ong SY, Wu K, Salmi T, Korde R, Barnes G, Brown JR, Zhou K, Qiu L. Zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: health-related quality of life in a subgroup of Chinese patients in the ALPINE trial. Curr Med Res Opin. 2026 Jan;42(1):139-146. doi: 10.1080/03007995.2026.2623629. Epub 2026 Feb 13.
• Rhee JW, Lamanna N, Aldairy W, Chen L, Zhang J, Ramirez D, White WB. Hypertension in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma in ALPINE: a secondary analysis. Blood Neoplasia. 2025 Aug 4;2(4):100150. doi: 10.1016/j.bneo.2025.100150. eCollection 2025 Nov.
• Brown JR, Li J, Eichhorst BF, Lamanna N, O'Brien SM, Tam CS, Qiu L, Huang R, Shi Y, Idoine A, Salmi T, Cohen AC, Shadman M. Acquired mutations in patients with relapsed/refractory CLL who progressed in the ALPINE study. Blood Adv. 2025 Apr 22;9(8):1918-1926. doi: 10.1182/bloodadvances.2024014206.
• Brown JR, Eichhorst B, Lamanna N, O'Brien SM, Tam CS, Qiu L, Jurczak W, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Wang M, Salmi T, Wang L, Li J, Wu K, Cohen A, Shadman M. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024 Dec 26;144(26):2706-2717. doi: 10.1182/blood.2024024667.
• Zhou K, Wang T, Pan L, Xu W, Jin J, Zhang W, Hu Y, Hu J, Feng R, Li P, Liu Z, Liu P, Jing H, Gao S, Zhang H, Yu K, Wang Z, Zhu X, Sun Z, Li F, Yan D, Weng J, Fu L, Wang L, Salmi T, Wu K, Qiu L. Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE. Ann Hematol. 2024 Oct;103(10):4183-4191. doi: 10.1007/s00277-024-05823-8. Epub 2024 Jun 18.
• Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
• Brown JR, Eichhorst B, Hillmen P, Jurczak W, Kazmierczak M, Lamanna N, O'Brien SM, Tam CS, Qiu L, Zhou K, Simkovic M, Mayer J, Gillespie-Twardy A, Ferrajoli A, Ganly PS, Weinkove R, Grosicki S, Mital A, Robak T, Osterborg A, Yimer HA, Salmi T, Wang MD, Fu L, Li J, Wu K, Cohen A, Shadman M. Plain language summary of zanubrutinib or ibrutinib in chronic lymphocytic leukemia that is resistant to treatment or has come back after treatment. Future Oncol. 2024 Apr;20(12):717-726. doi: 10.2217/fon-2023-0849. Epub 2023 Dec 13.
• Tam CS, Lamanna N, O'Brien SM, Qiu L, Yang K, Barnes G, Wu K, Salmi T, Brown JR. Health-related quality of life outcomes associated with zanubrutinib versus ibrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: results from the ALPINE Trial. Curr Med Res Opin. 2023 Nov;39(11):1497-1503. doi: 10.1080/03007995.2023.2262378. Epub 2023 Oct 27.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Ibrutinib	Small molecule	420 mg	Oral
Subject	Zanubrutinib	Small molecule	160 mg	Oral

Indications