BeiGene to Present SEQUOIA Study Data on BRUKINSA® and Venetoclax for High-Risk CLL/SLL at EHA2024

BeiGene, Ltd., a global oncology company, presented new data from the SEQUOIA study analyzing the efficacy of BRUKINSA® (zanubrutinib) in combination with venetoclax for patients with newly diagnosed high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p) and/or TP53 mutation. This data was shared during an oral session at the European Hematology Association 2024 Hybrid Congress (EHA2024) held in Madrid, Spain.

The SEQUOIA study, particularly Arm D, focused on treatment-naïve patients who have a high-risk profile due to genetic mutations. The preliminary findings showed a 100% overall response rate (ORR) in the 65 response-evaluable patients, with 48% achieving complete response (CR) or complete response with incomplete hematopoietic recovery (CRi). The safety profile of the combination was consistent with previous studies of zanubrutinib and venetoclax, with no new safety concerns reported.

Dr. Alessandra Tedeschi, a consultant in hematology and Medical Director at the Niguarda Cancer Center in Milan, highlighted the significance of these findings. She emphasized the poor prognosis typically associated with untreated CLL patients with del(17p) or TP53 mutations and noted the promising efficacy and tolerability of the combination regimen.

The study enrolled 66 patients with del(17p) and/or TP53 mutation. The treatment protocol involved administering BRUKINSA at 160 mg twice daily for the first three months, followed by a combination of BRUKINSA and venetoclax. Venetoclax dosing began at a lower level and ramped up to 400 mg daily over 12 to 24 cycles, continuing until disease progression, unacceptable toxicity, or confirmed undetectable minimal residual disease (MRD). During the median follow-up period of 31.6 months, the undetectable MRD was achieved in 59% of patients in at least one peripheral blood sample. The median progression-free survival (PFS) was not reached, with 12- and 24-month PFS rates of 95% and 94%, respectively.

Dr. Mehrdad Mobasher, Chief Medical Officer of Hematology at BeiGene, praised the SEQUOIA study for its demonstration of BRUKINSA's effectiveness as a monotherapy for treatment-naïve CLL patients, especially those with high-risk genetic markers. He noted that SEQUOIA Arm D is one of the largest studies involving high-risk patients and that the combination therapy with a BCL2 inhibitor like venetoclax shows potential for deep clinical response. He expressed optimism about further exploring time-limited therapy with prolonged follow-up and integrating these findings into the development of BeiGene's next-generation BCL2 inhibitor, sonrotoclax.

The safety data indicated that 97% of patients experienced at least one treatment-emergent adverse effect (TEAE). The most common non-hematologic TEAEs included infections (71%), COVID-19 (55%), diarrhea (39%), nausea (30%), and contusion (29%). Grade 3 or higher non-hematologic TEAEs occurred in 44% of patients, with infections being the most frequent (15%). Hematologic toxicities such as neutropenia were observed in 22% of patients, with 17% experiencing grade 3 or higher severity. Additionally, the proportion of patients at high risk for tumor lysis syndrome (TLS) significantly decreased from 35% at screening to 3% after three cycles of lead-in BRUKINSA, with no TLS cases reported.

The SEQUOIA trial is a global, multicenter Phase 3 study designed to evaluate the efficacy and safety of BRUKINSA in treatment-naïve CLL or SLL patients. The trial includes three cohorts: Cohort 1 compared BRUKINSA with bendamustine plus rituximab in patients without del(17p), Cohort 2 assessed BRUKINSA as a monotherapy in patients with del(17p), and Cohort 3 (Arm D) involved BRUKINSA in combination with venetoclax in patients with del(17p) and/or TP53 mutation.

The results of Cohort 1 have already led to the regulatory approval of zanubrutinib monotherapy for treatment-naïve CLL in several countries, including the United States and the European Union. Cohort 2's outcomes were previously presented, showcasing significant efficacy with an 18-month PFS of 90.6%.

BRUKINSA (zanubrutinib) functions as a Bruton’s tyrosine kinase (BTK) inhibitor, designed to provide sustained inhibition of the BTK protein, which is essential for the proliferation of malignant B cells.