A Study Comparing BGB-3111 and Ibrutinib in Participants With Waldenström's Macroglobulinemia (WM)

Summary

This study evaluated the safety, efficacy and clinical benefit of BGB-3111 (zanubrutinib) vs ibrutinib in participants with MYD88 Mutation Waldenström's Macroglobulinemia.

Timeline

Start

2017-01-25

Primary completion

2022-06-21

Completion

2022-06-21

Outcome

Missed primary endpoint

registry analysis (superiority test); Arm A: Ibrutinib vs Arm B: Zanubrutinib; p = 0.0921 NCT03053440 ↗

release “While the ASPEN trial did not achieve statistical significance on its primary endpoint” beonemedicines.com ↗

release “Although the primary endpoint of statistical superiority related to deep response, very good partial response (VGPR) or better, was not met in the Phase 3 ASPEN trial” beonemedicines.com ↗

Publications

• Results Tam CS, LeBlond V, Novotny W, Owen RG, Tedeschi A, Atwal S, Cohen A, Huang J, Buske C. A head-to-head Phase III study comparing zanubrutinib versus ibrutinib in patients with Waldenstrom macroglobulinemia. Future Oncol. 2018 Sep;14(22):2229-2237. doi: 10.2217/fon-2018-0163. Epub 2018 Jun 5.
• Garcia-Sanz R, Owen RG, Jurczak W, Dimopoulos MA, McCarthy H, Cull G, Opat SS, Castillo JJ, Kersten MJ, Wahlin BE, Grosicki S, Prathikanti R, Tian T, Allewelt H, Cohen AC, Tam CS. Outcomes after transition from ibrutinib to zanubrutinib in patients with Waldenstrom macroglobulinemia from the ASPEN study. Blood Adv. 2025 Dec 23;9(24):6538-6546. doi: 10.1182/bloodadvances.2024015596.
• Heyman BM, Opat SS, Wahlin BE, Dimopoulos MC, Castillo JJ, Tedeschi A, Tam CS, Buske C, Owen RG, Leblond V, Trotman J, Barnes G, Chan WY, Schneider J, Allewelt H, Cohen A, Matous JV. Peripheral neuropathy in the phase 3 ASPEN study of Bruton tyrosine kinase inhibitors for Waldenstrom macroglobulinemia. Blood Adv. 2025 Feb 25;9(4):722-728. doi: 10.1182/bloodadvances.2024014115.
• Tedeschi A, Tam CS, Owen RG, Buske C, Leblond V, Dimopoulos M, Garcia-Sanz R, Castillo JJ, Trotman J, Treon SP, Yang K, Tang B, Allewelt H, Patel S, Chan WY, Cohen A, Chen S, Barnes G. Health-related quality of life in patients with Waldenstrom macroglobulinemia: results from the ASPEN trial. Future Oncol. 2024;20(25):1789-1798. doi: 10.1080/14796694.2024.2355079. Epub 2024 Jul 29.
• 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.
• Dimopoulos MA, Opat S, D'Sa S, Jurczak W, Lee HP, Cull G, Owen RG, Marlton P, Wahlin BE, Garcia-Sanz R, McCarthy H, Mulligan S, Tedeschi A, Castillo JJ, Czyz J, Fernandez de Larrea C, Belada D, Libby E, Matous J, Motta M, Siddiqi T, Tani M, Trneny M, Minnema MC, Buske C, Leblond V, Treon SP, Trotman J, Chan WY, Schneider J, Allewelt H, Patel S, Cohen A, Tam CS. Zanubrutinib Versus Ibrutinib in Symptomatic Waldenstrom Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study. J Clin Oncol. 2023 Nov 20;41(33):5099-5106. doi: 10.1200/JCO.22.02830. Epub 2023 Jul 21.

Drugs

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

Indications