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BeiGene Presents Results from SEQUOIA Trial of BRUKINSA (zanubrutinib) in First-Line Chronic Lymphocytic Leukemia at the 63rd ASH Annual Meeting

Published: 2021-12-12 14:30:00 ET
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BRUKINSA demonstrated superiority in progression-free survival over chemoimmunotherapy as a first-line treatment for patients with chronic lymphocytic leukemia

Consistent efficacy was observed across high-risk patient subgroups

Safety results were generally consistent with its previously reported profile

Preliminary safety and efficacy data from Cohort 3 of BRUKINSA in combination with venetoclax for patients with del(17p) or TP53 mutations were reviewed at ASH

CAMBRIDGE, Mass. & BEIJING--(BUSINESS WIRE)-- BeiGene (NASDAQ: BGNE; HKEX: 06160), a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, today announced results from a planned interim analysis of the Phase 3 SEQUOIA trial in patients with treatment-naïve (TN) chronic lymphocytic leukemia (CLL), including the randomized Cohort 1 comparing BRUKINSA to bendamustine plus rituximab (B+R) and Cohort 3 (Arm D) of BRUKINSA in combination with venetoclax in patients with deletion of chromosome 17p (del[17p]) and/or pathogenic TP53 variants. These data were reported in two oral presentations at the 63rd American Society for Hematology (ASH) Annual Meeting.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20211212005018/en/

Summary of results from the interim analysis of Phase 3 SEQUOIA trial of BRUKINSA (zanubrutinib) in patients with treatment-naïve chronic lymphocytic leukemia. (Graphic: Business Wire)

Summary of results from the interim analysis of Phase 3 SEQUOIA trial of BRUKINSA (zanubrutinib) in patients with treatment-naïve chronic lymphocytic leukemia. (Graphic: Business Wire)

“In the positive SEQUOIA trial, BRUKINSA delivered the therapeutic promise of a selective BTK inhibitor as a frontline treatment for CLL patients, with demonstrated superiority over chemoimmunotherapy. These robust data, along with the results from our previously reported Phase 3 ALPINE trial, strengthen our belief that BRUKINSA could become an important new treatment option for patients with CLL,” remarked Jane Huang, M.D., Chief Medical Officer of Hematology at BeiGene. “In addition, BRUKINSA achieved favorable safety advantages in both trials such as lower rates of atrial fibrillation.”

“Compared to chemoimmunotherapy, BRUKINSA demonstrated superior PFS benefit for CLL patients receiving frontline treatment, including those harboring high-risk characteristics, such as unmutated IGHV status and del(11q),” said Constantine Tam, MBBS, M.D., Peter MacCallum Cancer Center, and a principal investigator of the study. “Safety findings in SEQUOIA were similar to what has been reported in other BRUKINSA clinical trials, with consistently low rates of atrial fibrillation. Based on these results, BRUKINSA, as a highly selective BTK inhibitor, can potentially provide a chemo-free treatment option for CLL patients.”

For more information on BeiGene’s clinical program and company updates, please visit BeiGene’s virtual booth at this year’s ASH Annual Meeting at http://www.beigenevirtualexperience.com.

SEQUOIA Cohort 1: BRUKINSA vs. B+R in TN CLL Patients Without del (17p)

Oral Presentation; Abstract #396; Plain language summary available at https://www.beigene.com/pls/ash2021/sequoia

A total of 479 patients with TN CLL whose tumor did not exhibit del(17p) were enrolled in Cohort 1 of the SEQUOIA trial, with 241 patients randomized to receive BRUKINSA (Arm A) and 238 patients randomized to receive B+R (Arm B). Patient characteristics were balanced between the two arms, with more than 50% with unmutated IGHV gene and 18% with del(11q) in each. Patients with del(17p) typically have poor response to chemoimmunotherapy and were assigned to receive BRUKINSA treatment in Cohort 2. Results from Cohort 2 were previously presented at the 2020 ASH Annual Meeting.

The primary endpoint of the SEQUOIA trial is progression-free survival (PFS) per independent review committee (IRC) assessment in the randomized Cohort 1.

At the interim analysis, with a median follow-up of 26.15 months, BRUKINSA demonstrated superiority in PFS over B+R, as assessed by IRC. Results included:

  • The 24-month PFS rate was 85.5% (95% CI: 80.1, 89.6) in Arm A, compared to 69.5% (95% CI: 62.4, 75.5) in Arm B, with a hazard ratio (HR) of 0.42 (95% CI: 0.27, 0.63), p <0.0001;
  • PFS benefit was consistently observed across key patient subgroups, including patients with del(11q), unmutated IGHV status, Binet stage C, and bulky disease; and
  • Overall survival (OS) results were early, and at 24 months, OS probability was similar between two arms, with 94.3% (95% CI: 90.4, 96.7) in Arm A and 94.6% (95% CI: 90.6, 96.9) in Arm B.

Safety analysis was based on 240 patients in Arm A and 227 patients in Arm B who received at least one dose of respective treatment. BRUKINSA was generally well tolerated with a safety profile consistent with its broad clinical program, including a low rate of atrial fibrillation. Results included:

  • 224 patients (93.3%) in Arm A experienced at least one adverse event (AE) of any grade, with the most common (≥12%) being contusion (19.2%), upper respiratory tract infection (17.1%), neutropenia (15.4%), diarrhea (13.8%), and arthralgia (13.3%);
  • In comparison, 218 patients (96.0%) in Arm B experienced at least one AE of any grade, with the most common (≥12%) being neutropenia (56.8%), nausea (32.6%), pyrexia (26.4%), rash (19.4%), anemia (18.9%), constipation (18.9%), infusion-related reaction (18.9%), fatigue (15.9%), vomiting (14.5%), thrombocytopenia (13.7%), and diarrhea (13.2%);
  • 126 patients (52.5%) in Arm A experienced at least one Grade ≥3 AE, compared to 181 patients (79.7%) in Arm B, with the most common in both arms being neutropenia (11.3% in Arm A vs. 51.1% in Arm B) and thrombocytopenia (1.7% in Arm A vs. 7.0% in Arm B);
  • 88 patients (36.7%) in Arm A experienced at least one serious AE, compared to 113 patients (49.8%) in Arm B;
  • AEs leading to dose reduction, interruption or delay, and discontinuation occurred in 18 patients (7.5%), 111 patients (46.3%), and 20 patients (8.3%), respectively, in Arm A, compared to 84 patients (37.4%), 154 patients (67.8%), and 31 patients (13.7%), respectively, in Arm B;
  • Fatal AEs were reported in 11 patients (4.6%) in Arm A, compared to 11 patients (4.8%) in Arm B;
  • AEs of interest of any grade included anemia (Arm A vs. Arm B: 4.6% vs. 19.4%), arthralgia (13.3% vs. 8.8%), atrial fibrillation (3.3% vs. 2.6%), bleeding (45.0% vs. 11.0%), diarrhea (13.8% vs. 13.7%), hypertension (14.2% vs. 10.6%), infections (62.1% vs. 55.9%), myalgia (3.8% vs. 1.3%), neutropenia (15.8% vs. 56.8%), other cancers (12.9% vs. 8.8%), and thrombocytopenia (4.6% vs. 17.6%).

In addition, efficacy results with an extended follow-up from Cohort 2 (Arm C) of BRUKINSA as a monotherapy in patients with del(17p) were reported at ASH. With a median follow-up of 30.5 months, the 24-month PFS rate was 88.9% (95% CI: 81.3, 93.6).

Summary of SEQUOIA Cohort 1 Interim Analysis

SEQUOIA Cohort 1

Summary

 

BRUKINSA

(n=241)

 

Bendamustine + Rituximab

(n=238)

Efficacy Results

IRC-Assessed

24-month PFS (Primary Endpoint)

 

85.5%

(95% CI: 80.1, 89.6)

 

69.5%

(95% CI: 62.4, 75.5)

 

Hazard Ratio=0.42 (95%CI: 0.27, 0.63)

2-sided p