SEQUOIA Study Update: Zanubrutinib Prolongs PFS in Chronic Lymphocytic Leukemia

Treatment with zanubrutinib (Brukinsa) in patients with previously chronic lymphocytic leukemia (CLL) led to a significant improvement in progression-free survival (PFS), meeting the primary end point of the phase 3 SEQUOIA clinical trial, announced BeiGene, LTD, in a press release.

SEQUOIA is an international, phase 3, open-label, randomized study (NCT03336333) in which treatment with zanubrutinib is compared with the combination of bendamustine and rituximab (Rituxan; BR) in patients with previously untreated CLL or small lymphocytic lymphoma (SLL). Aside from evaluated PFS as determined by independent central review, the secondary end point of the study included overall response rate, overall survival, duration of response, PFS per investigator assessment, the number of patients with adverse events (AEs), and the number of patients with serious AEs.

According to the topline results from the interim analysis of SEQUOIA, the highly statistically significant improvement with zanubrutinib versus BR occurred after a median follow-up of 35.8 months. PFS per investigator assessment of zanubrutinib was also longer than BR, achieving 1 of the secondary end points of the study. The monotherapy was also well-tolerated in patients, showing consistency with the known safety profile of zanubrutinib.

“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 2,300 patients treated with Brukinsa to date,” said Jane Huang, MD, chief medical officer, Hematology at BeiGene, in a statement.

SEQUOIA is currently recruiting patients who have a confirmed diagnosis of CD20-positive CLL or SLL, requiring treatment who are not candidates for chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab. To be eligible for study enrollment, patients are required to have measurable disease by imaging, an ECOG performance status of 0 to 2, a life expectancy of at least 6 months, as well as adequate bone marrow, renal, and hepatic function.

Multiple factors regarding a patient’s medical history, including things like prior receipt of systemic therapy for CLL or SLL, a prior malignancy within 3 years of the study, central nervous system involvement, and other factors are grounds for exclusion from the study. Pregnant or nursing females and those with known sensitivity to zanubrutinib, bendamustine, rituximab, or venetoclax are also ineligible to be treated in the SEQUOIA trial.

The study will potentially be completed in October 2022.

Zanubrutinib is also being investigated in comparison with ibrutinib (Imbruvica) for the treatment of patients with CLL and SLL in the ALPINE trial (NCT03734016), and several other studies are ongoing to demonstrate its potential in this patient population.

“The combined clinical evidence from SEQUOIA, ALPINE, the 205 trial2, and the AU-003 trial3 validates our confidence in Brukinsa as a regimen which can offer improvements in treatment outcomes for hundreds of thousands of patients living with CLL,” said Jane Huang, MD, chief medical officer, Hematology at BeiGene, in a statement.

_References:

_{BeiGene announces positive topline results from phase 3 SEQUOIA Trial comparing BRUKINSA® (Zanubrutinib) to bendamustine plus rituximab in patients with treatment-naïve chronic lymphocytic leukemia. New release. BeiGene, Ltd. July 29, 2021. Accessed July 29, 2021. https://bit.ly/3zTOBqM}