BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global leader in oncology, has unveiled new findings from the SEQUOIA study of BRUKINSA® (zanubrutinib) today at EHA2024 in Madrid, Spain. The presentation highlighted results from arm D, exploring BRUKINSA in conjunction with venetoclax for treatment-naïve patients with high-risk chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) carrying del(17p) and/or TP53 mutations.
The preliminary data, based on 65 response-evaluable patients, demonstrated a remarkable overall response rate (ORR) of 100%, with a combined complete response (CR) and CR with incomplete hematopoietic recovery (CRi) rate of 48%. The safety profile mirrored that of individual treatments, with no new safety concerns identified. Alessandra Tedeschi, M.D., Ph.D., noted, “Patients with untreated CLL and del(17p) or TP53 mutations often face a poor prognosis, highlighting the need for effective treatment strategies.”
In this SEQUOIA arm, 66 patients with centrally assessed del(17p) and/or TP53 mutation received BRUKINSA followed by combination therapy with venetoclax, achieving undetectable minimal residual disease (MRD) in 59% of patients in at least one peripheral blood sample. Median progression-free survival (PFS) was not reached, with estimated PFS rates of 95% at 12 months and 94% at 24 months.
Mehrdad Mobasher, M.D., M.P.H., emphasized, “SEQUOIA arm D underscores BRUKINSA’s efficacy as monotherapy and in combination for TN CLL patients, particularly those with high-risk markers. These results demonstrate the potential for deep clinical responses with BCL2 inhibitor therapies, informing our ongoing development efforts for sonrotoclax, our next-generation investigational BCL2 inhibitor.”
The safety analysis of BRUKINSA plus venetoclax revealed a consistent profile with previous studies. Treatment-emergent adverse effects (TEAEs) were reported in 97% of patients, with common non-hematologic TEAEs including infections (71%), COVID-19 (55%), diarrhea (39%), nausea (30%), and contusion (29%). Grade ≥3 non-hematologic TEAEs occurred in 44% of patients, with infections (15%), diarrhea (9%), hypertension (8%), and second primary malignancies (8%) being most frequent. Hematologic toxicities primarily included neutropenia (22% all-grade, 17% grade ≥3). The incidence of tumor lysis syndrome (TLS) risk decreased substantially with lead-in BRUKINSA cycles.
These findings underscore the potential of combining BRUKINSA with venetoclax to address critical unmet needs in high-risk CLL/SLL patients, offering insights into optimizing treatment approaches and improving clinical outcomes
