BeiGene announced at the 63rd ASH Annual Meeting the research results of Baiyueze as the first-line treatment of chronic lymphocytic leukemia in the SEQUOIA trial

BeiGene announced the results of the interim analysis of the SEQUOIA trial, which is a phase 3 trial conducted in newly treated (TN) chronic lymphocytic leukemia (CLL) patients.
Randomized cohort 1 of damustine combined with rituximab (B+R treatment regimen), and evaluation of Baiyueze® combined with Venecla therapy with 17p chromosome deletion (del[17p]) and/or pathogenic TP53 Cohort 3 of patients with variant genes (group D)
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These data were presented twice orally at the 63rd Annual Meeting of the American Society of Hematology (ASH)
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SEQUOIA cohort 1: Baiyueze® vs.
B+R treatment plan for TN CLL patients without del(17p) oral report; Abstract #396; for a brief summary, please see SEQUOIA trial cohort 1.
A total of 479 tumors that did not show del( 17p) TN CLL patients, of which 241 patients were randomized to receive Baiyueze® treatment (group A), and 238 patients were randomized to receive B+R treatment plan (group B)
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The characteristics of the two groups are balanced.
More than 50% of the patients have no mutation in the IGHV gene, and 18% of the patients have del(11q)
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Del (17p) patients usually received poor efficacy after chemoimmunotherapy, and were assigned to be treated with Baiyueze® in cohort 2
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The results of cohort 2 have been announced at the 2020 ASH Annual Meeting
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The primary endpoint of the SEQUOIA trial is the progression-free survival (PFS) based on the independent review committee (IRC) assessment in randomized cohort 1
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Interim analysis showed that in the median follow-up time of 26.
15 months, based on the results of IRC assessment, Baiyueze® exceeded the B+R treatment plan in terms of PFS
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The results include: The safety analysis included 240 patients in group A and 227 patients in group B who received at least one corresponding treatment
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Baiyueze® is generally well tolerated, and its safety characteristics are consistent with its extensive clinical programs, including a low incidence of atrial fibrillation
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The results include: In addition, the effectiveness of cohort 2 (group C) Baiyueze® monotherapy with del (17p) patients was reported in the ASH annual meeting under the condition of extended follow-up period
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During the median follow-up time of 30.
5 months, the 24-month PFS rate was 88.
9% (95% CI: 81.
3, 93.
6)
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Interim analysis summary of SEQUOIA trial cohort 1 SEQUOIA trial cohort 3 (group D): Oral report in the treatment of TN CLL patients with del(17p) and/or TP53 mutations in combination with Veneclax; Abstract #67 of SEQUOIA trial Cohort 3 was designed to test the hypothesis that the additional use of venacola on the basis of Baiyueze® can promote a deeper remission of the tumor
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Based on the safety and effectiveness of Baiyueze® proved in cohort 2, cohort 3 plans to enroll about 80 patients with TN CLL whose tumors show del(17p) or TP53 mutations.
The key endpoints are safety and overall response rate.
(ORR), PFS, and duration of remission (DoR)
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These patients will be treated with Baiyueze® 160 mg twice a day for 3 months, and then receive the same dose of Baiyueze® combined with Venecla.
The dose is escalated to 400 mg once a day for 12 to 24 cycles, until disease progression, unacceptable toxicity or confirmation of undetectable minimal residual disease (uMRD)
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As of the data cutoff date September 7, 2021, cohort 3 enrolled 49 patients, including 46 (93.
9%) patients with positive del (17p) status and 3 (6.
1%) only pathogenic Patients with TP53 variants
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The patients enrolled in cohort 3 also showed other high-risk markers, including 87.
8% of patients without IGHV mutation, 91.
9% of patients with TP53 mutation, and 83.
3% of patients with complex karyotype (at least 3 abnormalities)
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At the short median follow-up time of 12.
0 months, as of the data cutoff date, a higher ORR was observed in 36 patients who had achieved remission evaluation after at least one baseline
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The preliminary effectiveness results evaluated by the investigator include: During the median follow-up time of 7.
9 months, the safety results of all 49 enrolled patients included: When the median follow-up time was 13.
5 months, 34 patients received combination therapy Patient safety results include: