Zanubrutinib Demonstrates Positive Results at Interim Analysis in Treating Chronic Lymphocytic Leukemia

An interim analysis from the phase 3 ALPINE trial comparing zanubrutinib (Brukinsa, BeiGene) against ibrutinib demonstrated positive results in the treatment of relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma.

The ongoing phase 3 trial was fully enrolled, with the interim analysis of the data based on 415 of the total 652 patients who were followed over a period of at least 12 months. The investigators found that in this patient population, zanubrutinib met the primary endpoint of non-inferiority in objective response rate (ORR) by both investigator and independent review committee (IRC) assessments (p < 0.0001).

By investigator assessment, the data demonstrated superior ORR due to the statistically significant improvement in ORR for zanubrutinib when compared against ibrutinib (p = 0.0006). Additionally, by IRC, there was a numerically higher ORR but not statistically significant improvement (p = 0.0121 compared to the 2-sided stringent statistical boundary of p < 0.0099 set for the interim analysis).

The second endpoint of the trial was progression-free survival (PFS), which was assessed in all of the 652 patients. For this endpoint, the data were immature at the planned cutoff point for the interim analysis. However, the PFS summaries did show an early trend that was favorable for zanubrutinib.

There was also a pre-specified secondary endpoint related to the safety of zanubrutinib compared to ibrutinib, which the trial data were found to meet. In the analysis, zanubrutinib demonstrated a statistically significant decreased risk of atrial fibrillation or flutter, which is characterized by an irregular heartbeat that can cause blood clots, stroke, heart failure, and other heart-related conditions.

Overall, the investigators found that zanubrutinib had a safety profile that was consistent with what was observed in the previously conducted clinical development program.

“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, in a press release. “Data from this interim analysis, in addition to Brukinsa’s comprehensive clinical program, provide important new information to support its benefit-risk profile.”

As next steps, BeiGene has planned to consult with global regulatory authorities and present the trial’s findings at upcoming medical conferences. Additionally, ORR will be further assessed by IRC at the set final analysis point, with patients followed to assess the key secondary endpoints including PFS during the analysis.

REFERENCE

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. Cambridge, MA: BeiGene; April 28, 2021. https://ir.beigene.com/news-releases/news-release-details/brukinsar-zanubrutinib-demonstrates-superior-objective-response. Accessed May 4, 2021.