BRUKINSA® (Zanubrutinib) Demonstrates Superior Objective Response Rate by Investigator Assessment and Reduced Rates of Atrial Fibrillation or Flutter at Interim Analysis in Head-to-Head Trial Against Ibrutinib in Chronic Lymphocytic Leukemia
BRUKINSA met the primary endpoint of the trial, demonstrating non-inferiority in objective response rate (ORR) by both investigator and independent review committee (IRC) assessments (p < 0.0001). The trial also demonstrated superior ORR with a statistically significant improvement in ORR for BRUKINSA vs. ibrutinib (p = 0.0006) by investigator assessment, as well as a numerically higher ORR but not statistically significant improvement by IRC (p = 0.0121 compared to the two-sided stringent statistical boundary of p < 0.0099 set for the interim analysis). The interim analysis from this fully-enrolled, ongoing trial is based on 415 of 652 patients followed for a minimum of 12 months.
Data pertaining to progression-free survival (PFS) in the 652 patients, a secondary endpoint of the trial, were immature at the data cutoff for the interim analysis. However, the descriptive summaries of PFS showed an early trend favoring BRUKINSA.
The trial also met a pre-specified secondary endpoint related to safety. Compared to ibrutinib, BRUKINSA demonstrated a statistically significant lower risk of atrial fibrillation or flutter, which is characterized by an irregular heartbeat that can lead to blood clots, stroke, heart failure and other heart-related complications. Overall, the safety profile of BRUKINSA was consistent with the previously seen profile in its clinical development program.
ALPINE is BeiGene’s second Phase 3 head-to-head trial comparing BRUKINSA to ibrutinib.
About Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, with a global incidence of approximately 114,000 new cases in 2017.1,2 CLL affects white blood cells or lymphocytes in the bone marrow.1 Proliferation of cancer cells (leukemia) in the marrow result in reduced ability to fight infection and spread into the blood, which affects other parts of the body including the lymph nodes, liver and spleen.1,3 The BTK pathway is a known route that signals malignant B cells and contributes to the onset of CLL.4 Small lymphocytic lymphoma (SLL) is a non-Hodgkin’s lymphoma affecting the B-lymphocytes of the immune system, which shares many similarities to CLL but with cancer cells found mostly in lymph nodes.5
ALPINE is a randomized, global Phase 3 trial (NCT03734016) comparing BRUKINSA against ibrutinib in previously treated patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
In the trial, a total of 652 patients were randomized into two arms with the first receiving BRUKINSA (160 mg orally twice daily) and the second receiving ibrutinib (420 mg orally once daily) until disease progression or unacceptable toxicity. The primary analysis of objective response rate (ORR), defined by pre-specified non-inferiority of BRUKINSA versus ibrutinib, was assessed by investigator and independent review committee (IRC) using the modified 2008 iwCLL guidelines with modification for treatment-related lymphocytosis for patients with CLL and per Lugano Classification for non-Hodgkin’s lymphoma for patients with SLL. There was hierarchical testing of non-inferiority followed by superiority in ORR as assessed by investigator and IRC. Key secondary endpoints include progression-free survival (PFS), duration of response, overall survival, and incidence of adverse events. The study is ongoing, with pre-specified endpoints of ORR and PFS to be evaluated at the planned final analysis expected in 2022.
BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by
BRUKINSA is approved in the following indications and regions:
- For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (
United States, November 2019)*;
- For the treatment of MCL in adult patients who have received at least one prior therapy (
China, June 2020)**;
- For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (
China, June 2020)**;
- For the treatment of relapsed or refractory MCL (
United Arab Emirates, February 2021); and
- For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (
Canada, March 2021).
To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of
* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.
Please see the full
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 results from the interim analysis of the Phase 3 ALPINE trial and the potential implications of these data for patients, BeiGene’s plan to consult global regulatory authorities on next steps and present the data at an upcoming medical conference, the expected timing for the final analysis of the ALPINE trial,
American Cancer Society. Cancer Facts & Figures 2021. Atlanta; American Cancer Society; 2021. Available here: Cancer Facts and Figures 2021
- Global Burden of Disease Cancer Collaboration. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017. JAMA Oncol. 2019;5(12):1749-1768.
National Cancer Institute. Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version. Available here: Chronic Lymphocytic Leukemia Treatment (PDQ®)–Patient Version
- Haselager MV et al. Proliferative Signals in Chronic Lymphocytic Leukemia; What Are We Missing? Front Oncol. 2020; 10: 592205.
Cancer Support Community. Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. Available here: https://www.cancersupportcommunity.org/chronic-lymphocytic-leukemiasmall-lymphocytic-lymphoma.