Interim analysis of the phase 3 ALPINE study in patients with R/R CLL/SLL reveals zanubrutinib superiority over ibrutinib with regards to efficacy and safety
First generation BTK inhibitor ibrutinib is the standard of care for treatment of CLL/SLL. However, ibrutnib is associated with adverse events such as atrial fibrillation, which might be due to off-target kinase inhibitions. Zanubrutinib BRUKINSA®, a second generation BTK inhibitor, was designed to reduce off-target effects and increase efficacy. 1
ALPINE (BGB-3111-305) is a randomized, global phase 3 study comparing zanubrutinib with ibrutinib in patients with R/R CLL/SLL. The primary efficacy endpoint is overall response rate determined by investigator assessment. Participants will be randomized in a 1:1 manner to either zanubrutinib or ibrutinib.2
The results of a pre-planned interim analysis scheduled approximately 12 months after the first 415 out of 652 patients were enrolled will be featured at the presidential symposium of EHA 2021.3,4
Zanubrutinib treatment resulted in a significantly higher ORR after a median follow-up of 15 months (78.3% zanubrutinib vs. 62.5% ibrutinib). Overall PFS after 12 months was higher in zanubrutinib compared to ibrutinib (94.9% vs. 84.0%). Additionally, atrial fibrillation was significantly lower with zanubrutinib vs. ibrutinib (2.5% vs. 10.1%). Also, other AEs were lower in the zanubrutinib arm.4
Thus, the interim analysis of the ALPINE study confirms that more selective BTK inhibition with zanubrutinib results in improved efficacy and safety outcomes as compared with ibrutinib in R/R CLL/SLL patients.4
- Tam, C. S. et al. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood 134, 851–859 (2019).
- BeiGene. A Phase 3, Randomized Study of Zanubrutinib (BGB-3111) Compared With Ibrutinib in Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. Available at: https://clinicaltrials.gov/ct2/show/NCT03734016. Accessed June 2, 2021.
- BeiGene Announces First Presentation of the Phase 3 ALPINE Trial Comparing BRUKINSA® (Zanubrutinib) to Ibrutinib in Chronic Lymphocytic Leukemia to Be Featured in Presidential Symposium at EHA2021 | BeiGene LTD. Available at: https://ir.beigene.com/news-releases/news-release-details/beigene-announces-first-presentation-phase-3-alpine-trial/. Accessed June 2, 2021.
- Hillmen, P. et al. First interim analysis of alpine study: results of a phase 3 randomized study of zanubrutinib vs ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma. Available at: https://library.ehaweb.org. Accessed June 2, 2021.