Positive Results From SEQUOIA Analyses for Zanubrutinib in Treatment-Naive CLL and SLL

Patients with treatment-naive chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) had superior progression-free survival (PFS) when treated with zanubrutinib (Brukinsa) vs bendamustine and rituximab (B+R), according to an interim analysis of a phase 3 trial.

SEQUOIA is a randomized, multicenter, global phase 3 trial comparing the efficacy and safety of zanubrutinib against B+R in patients with treatment-naive CLL and SLL whose tumor did not exhibit del(17p). The primary end point of the trial was PFS as assessed by independent review committee, and there was a median follow-up of 25.8 months.

The trial has 3 cohorts:

• Cohort 1 has 479 patients randomized 1:1 to receive zanubrutinib or B+R until disease progression or unacceptable toxicity. This cohort does not include patients with del(17p).
• Cohort 2 has 110 patients with del(17p) receiving zanubrutinib as a monotherapy.
• Cohort 3 is currently enrolling patients with del(17p) or pathogenic TP53 variant to receive zanubrutinib in combination with venetoclax.

SEQUOIA also showed that zanubrutinib was generally well tolerated. Previous data have highlighted that the therapy has high tolerability, efficacy, and utility. As a second-generation Bruton tyrosine kinase inhibitor, zanubrutinib has fewer off-target effects.

Results from the phase 3 ALPINE study, presented at the European Hematology Association Virtual Congress 2021, showed that zanubrutinib has a superior response rate, improved PFS, and lower rate of atrial fibrillation/flutter compared with ibrutinib in patients with relapsed/refractory CLL/SLL.

“The combined clinical evidence from SEQUOIA, ALPINE, the 205 trial, and the AU-003 trial validates our confidence in Brukinsa as a regimen which can offer improvements in treatment outcomes for hundreds of thousands of patients living with CLL,” Jane Huang, MD, chief medical officer, hematology at BeiGene, said in a statement. “We are pleased to see that at the interim analysis of the SEQUOIA trial, Brukinsa significantly prolonged progression-free survival for treatment-naïve CLL patients, and that the demonstrated safety profile was consistent with what we have observed in its global development program with more than 2300 patients treated with Brukinsa to date.”