SAN MATEO -
The presentation will feature data from arm D of SEQUOIA evaluating BRUKINSA in combination with venetoclax in treatment-naive (TN) patients with high-risk chronic lymphocytic leukemia (CLL) and/or small lymphocytic lymphoma (SLL) with del(17p) and/or TP53 mutation. The preliminary data demonstrate that in the 65 response-evaluable patients treated with the combination, the overall response rate (ORR) was 100%, and the rate of complete response (CR) plus CR with incomplete hematopoietic recovery (CRi) was 48%. The safety profile of the combination is consistent with that of the treatment components, and no new safety signals were seen.
'Patients with untreated CLL with del(17p) or TP53 mutations often face a poor prognosis, even in the front-line setting, so there is a critical need to better understand how this patient population responds to combination approaches,' said
Overall, 66 patients with centrally assessed del(17p) and/or TP53 mutation were enrolled in this arm of the SEQUOIA study. Patients received BRUKINSA at 160 mg twice daily for three months, followed by combination treatment of BRUKINSA at the same dose and venetoclax with a ramp-up dosing to 400 mg once daily for 12 to 24 cycles until progressive disease, unacceptable toxicity or confirmed undetectable minimal residual disease (MRD). In the 65 response-evaluable patients, ORR was 100%; the rate of CR+CRi was 48% (CR=46%; CRi=2%). Undetectable MRD was achieved in 59% of patients in 1 peripheral blood sample and with a median study follow up of 31.6 months. Median progression-free survival (PFS) was not reached; 12- and 24-month PFS estimates were 95% and 94%, respectively.
'SEQUOIA has shown that BRUKINSA is a highly effective monotherapy treatment for TN CLL patients, including those with high-risk markers like del(17p) and/or TP53 mutation. With one of the largest pools of high-risk patients of any published study to date, SEQUOIA arm D demonstrates how BCL2 inhibitor therapies can complement BRUKINSA as a backbone therapy to achieve deep clinical response even in this patient population,' said
The safety profile of BRUKINSA plus venetoclax was consistent with results of prior studies of both medicines, and no new safety signals were identified. In total, 97% of patients experienced 1 treatment emergent adverse effect (TEAE). The most common all-grade non-hematologic TEAEs were infections (71%), COVID-19 (55%), diarrhea (39%), nausea (30%) and contusion (29%). Grade 3 non-hematologic TEAEs occurred in 44% of patients; the most common were infections (15%), diarrhea (9%), hypertension (8%) and second primary malignancies (8%). The most common all grade and grade 3 hematologic toxicity was neutropenia (22% and 17%, respectively). The proportion of patients at high risk for tumor lysis syndrome (TLS) decreased 91% from 35% at screening to 3% after three cycles of lead-in BRUKINSA, and no TLS was reported.
About SEQUOIA
SEQUOIA (NCT03336333) is a randomized, multicenter, global Phase 3 trial designed to evaluate the efficacy and safety of BRUKINSA in patients with TN CLL or SLL. The trial consists of three cohorts: Cohort 1 (n=479): randomized 1:1 to receive BRUKINSA (n=241) or bendamustine plus rituximab (n=238) until disease progression or unacceptable toxicity, in patients not harboring del(17p); data from this group comprise the primary endpoint; Cohort 2 (n=110): patients with del(17p) receiving BRUKINSA as a monotherapy and Cohort 3/arm D (n=114): 66 patients with del(17p) and/or pathogenic TP53 mutation received BRUKINSA in combination with venetoclax. While patients without del(17p) (n=48) were later included in this cohort, the data presented at EHA2024 do not include these patients.
The results of Cohort 1 of the SEQUOIA study led to the regulatory approval of zanubrutinib monotherapy in the treatment of TN CLL in many countries across the world, including approvals by the
About BRUKINSA (zanubrutinib)
BRUKINSA is a small molecule inhibitor of Bruton's tyrosine kinase (BTK) designed to deliver complete and sustained inhibition of the BTK protein by optimizing bioavailability, half-life, and selectivity. With differentiated pharmacokinetics compared with other approved BTK inhibitors, BRUKINSA has been demonstrated to inhibit the proliferation of malignant B cells within a number of disease-relevant tissues.
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Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding the efficacy and tolerability of zanubrutinib in combination with a BCL2 inhibitor for high-risk CLL patients; BRUKINSA's ability to complement BCL2 therapies to achieve clinical response in high-risk CLL patients; the future progression of the SEQUOIA trial and
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