The interim analysis showed positive response and safety data in adult patients with relapsed or refractory CLL or SLL treated with zanubrutinib compared with those receiving ibrutinib.
Research investigating the efficacy of zanubrutinib (Brukinsa) compared with ibrutinib (Imbruvica) to treat adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) reported positive results at the interim analysis, according to a BeiGene press release.
The phase 3 randomized, global, head-to-head ALPINE trial (NCT03734016) met its primary end point by demonstrating noninferiority in overall response rate (ORR) with zanubrutinib compared with ibrutinib.
“The interim results from this head-to-head trial demonstrated that, as a selective inhibitor designed to deliver sustained and continuous inhibition of [Bruton tyrosine kinase], Brukinsa provides [patients with CLL] with improvements in response and reduced rates of atrial fibrillation or flutter compared to ibrutinib,” Jane Huang, MD, chief medical officer of Hematology of BeiGene, explained in a press release.
The data from the analysis focused on 415 of 652 total patients included in the ongoing trial, with a minimum follow-up of 12 months.
Noninferiority of ORR was measured by both investigator assessment and independent review committee (IRC) (P <.0001), with zanubrutinib demonstrating a statistically significant improvement in ORR by investigator assessment (P = .0006). While there was a numerical improvement in ORR by IRC with zanubrutinib, that improvement was not statistically significant.
Early data for progression-free survival (PFS) is trending positively for zanubrutinib, but the results were immature at the interim cutoff.
Along with PFS, the secondary end point of safety with zanubrutinib demonstrated a statistically significantly lower risk of atrial fibrillation or flutter when compared with ibrutinib. Atrial fibrillation is characterized by “irregular heartbeat that can lead to blood clots, stroke, heart failure, and other heart-related complications.” This safety profile was consistent with existing data on zanubrutinib in its clinical development program.
“Data from this interim analysis, in addition to Brukinsa’s comprehensive clinical program, provide important new information to support its benefit-risk profile,” said Huang.
The ALPINE trial randomized 652 patients to 2 therapy arms. The experiemental arm received zanubrutinib 160 mg orally twice daily and the control arm received ibrutinib 420 mg orally once daily until either disease progression or unacceptable toxicity.
Duration of response and overall survival are other key secondary end points alongside PFS and the adverse events profile. The pre-specified endpoints of ORR and PFS are expected to be fully evaluated at the final analysis in 2022.
BRUKINSA® (Zanubrutinib) Demonstrates Superior Objective Response Rate by Investigator Assessment and Reduced Rates of Atrial Fibrillation or Flutter at Interim Analysis in Head-to-Head Trial Against Ibrutinib in Chronic Lymphocytic Leukemia. News release. BeiGene. April 28, 2021. Accessed April 28, 2021. https://ir.beigene.com/news-releases/news-release-details/brukinsar-zanubrutinib-demonstrates-superior-objective-response?loc=us