Zanubrutinib Shows Positive Results in Interim Analysis Against Ibrutinib in CLL

Zanubrutinib (Brukinsa) showed noninferiority in objective response rates (ORR) and a trend toward improved progression-free survival (PFS) when compared with ibrutinib (Imbruvica) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL), BeiGene said Wednesday.

Zanubrutinib also showed a statistically significant lower risk of atrial fibrillation or flutter compared with ibrutinib, which is in line with prior studies.

Data from the planned interim analysis of the ongoing phase 3 ALPINE study showed that zanubrutinib was noninferior in ORR when assessed by both the investigator and an independent review committee (IRC) (P < .0001). However, there was superiority in ORR by investigator assessment with zanubrutinib vs ibrutinib that was statistically significant (P = .0006), and also a numerically higher ORR with zanubrutinib by IRC that was not statistically significant (P = .0121). The latter P value was compared with the 2-sided stringent statistical boundary of P < .0099 set for the interim analysis.

The data are based on the 415 of 652 patients enrolled on the ALPINE study who have been followed for a minimum of 1 year. PFS, a secondary end point of the ALPINE study, was immature at the data cutoff for the interim analysis, but descriptive summaries tilted in favor of zanubrutinib.

“The interim results from this head-to-head trial demonstrated that, as a selective inhibitor designed to deliver sustained and continuous inhibition of BTK, Brukinsa provides CLL patients with improvements in response and reduced rates of atrial fibrillation or flutter compared to ibrutinib,” said Jane Huang, MD, chief medical officer, hematology of BeiGene, the developer of zanubrutinib, in a statement.

BeiGene also noted that it plans to consult with regulatory authorities regarding next steps with the ALPINE data, which are slated to be presented at an upcoming medical meeting.

Zanubrutinib is currently approved for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least 1 prior therapy. In February, the FDA accepted a supplemental new drug application of zanubrutinib for the treatment of adult patients with Waldenström macroglobulinemia, with an action date of October 18, 2021.

ALPINE is evaluating 160 mg of oral zanubrutinib twice daily compared with 420 mg of oral ibrutinib once daily in 652 previously treated patients with relapsed/refractory CLL or small lymphocytic lymphoma (SLL) until disease progression or unacceptable toxicity. Patients are randomized 1:1 in the open label trial.

Secondary end points included PFS, duration of response, overall survival, and incidence of adverse events. The prespecified end points of ORR and PFS will be evaluated at the planned final analysis of ALPINE, which is expected in 2022.