BRUKINSA Achieves Landmark 74% Six-Year Progression-Free Survival in Treatment-Naïve Chronic Lymphocytic Leukemia Patients
BeOne Medicines Ltd., a global oncology company, reaffirms its position as the leader in chronic lymphocytic leukemia (CLL) innovation by showcasing the depth, quality, and momentum of its hematology portfolio at the 67th ASH Annual Meeting and Exposition in Orlando, Florida. The totality of BeOne’s ASH data reinforce BRUKINSA® (zanubrutinib) as the foundational Bruton’s tyrosine kinase inhibitor (BTKi) of choice.
“At ASH 2025, we will present new data from across our CLL franchise, highlighting both the strength of BRUKINSA and the potential of BGB-16673,” said Amit Agarwal, M.D., Ph.D., Chief Medical Officer, Hematology, BeOne. “Long-term data are the gold standard in CLL, and BRUKINSA continues to deliver the high levels of durable progression-free and overall survival that patients and physicians should demand from a BTK inhibitor. BGB-16673, the most advanced BTK degrader in the clinic with over 800 patients dosed to date, potentially represents the next wave of foundational innovation in oncology.”
BRUKINSA continues to demonstrate unprecedented long-term efficacy with a favorable safety profile over more than six years of follow-up in treatment-naïve CLL/SLL.
In SEQUOIA (NCT03336333), a randomized, multicenter, global Phase 3 trial, BRUKINSA maintained progression-free survival (PFS) superiority versus bendamustine plus rituximab (BR) with an estimated 74% PFS at six years in treatment-naïve CLL or small lymphocytic lymphoma (SLL) compared with 32% PFS for BR. Highlights include:
- Arms A, B and C: BRUKINSA vs BR, as well as BRUKINSA in patients with del(17p) (Poster Presentation: 2129)
- COVID-19 adjusted PFS rates were 77% (95% CI, 70.1-81.8) for BRUKINSA and 33% (95% CI, 25.5-40.4) for BR.
- The overall survival (OS) at 72 months was 84% for BRUKINSA and 80% with BR. After adjusting for COVID-19, the OS rates were 88% and 82%, respectively.
- In patients with del(17p), the six-year PFS was 64% (65% after COVID-19 adjustment) and the 72-month OS was 83%.
- The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.
“SEQUOIA’s longer follow-up strengthens the evidence for continuous zanubrutinib use,” said Constantine Tam, M.B.B.S., M.D., Head of Lymphoma Service at Alfred Health and Professor of Haematology at Monash University. “Patients continued to show durable disease control and consistent safety across study arms, meaningfully raising the bar for CLL patients, including those with harder-to-treat CLL.”
- Arm D: BRUKINSA plus venetoclax in patients with or without del(17p) and/or TP53 mutations (Poster Presentation: 5669)
- In the overall patient population, in which 58% of patients had del(17p) and/or TP53 mutation, the median PFS was not reached; the 36-month PFS rate was 87%.
- The 36-month PFS rate for patients with del(17p) and/or TP53 mutation was 87% and for patients without del(17p) and TP53 mutation was 89%.
- A total of 42 patients completed the BRUKINSA plus venetoclax combination and continued BRUKINSA monotherapy.
- At 12 months following the combination period, peripheral blood undetectable minimal residual disease (uMRD) was maintained in 100% (18/18) of patients without del(17p) and TP53.
- At 18 months following the combination period, uMRD was maintained in 92% (22/24) of patients with del(17p) and/or TP53 mutation.
- The safety profile of BRUKINSA plus venetoclax was generally tolerable and no unexpected safety signals were identified.
- The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) now recommend zanubrutinib plus venetoclax as a preferred first-line regimen for CLL/SLL.
New patient-reported outcomes data in R/R CLL suggest BRUKINSA may offer a more manageable side effect profile. Up to six-years of follow-up data support BRUKINSA’s foundational role in CLL/SLL as the only BTK inhibitor with enduring PFS and long-term benefit over another BTK inhibitor.
ALPINE (NCT03734016) is a global, randomized, open-label, multicenter, Phase 3 study of BRUKINSA versus ibrutinib in patients with R/R CLL/SLL who received ≥1 prior systemic therapy. Highlights include:
- Symptom-based progression-free survival as a clinically relevant and patient-centric endpoint (Oral Presentation: 711)
- This study is among the first analyses of patients with CLL/SLL to demonstrate a statistically and clinically meaningful association between longitudinal symptom deterioration and disease progression using joint modeling.
- Deterioration in patient-reported fatigue, insomnia, and nausea/vomiting emerged as strong symptomatic indicators of disease progression.
- Compared with ibrutinib, patients on BRUKINSA showed reduced risk of symptom deterioration associated with earlier disease progression.
- The analysis showed that patients on BRUKINSA had lower odds of symptom worsening for nausea/vomiting, fatigue, pain, and insomnia.
- Up to six years of follow-up of patients from the BRUKINSA arm of ALPINE who continued in a long-term extension study (LTE-1; Poster Presentation: 2123)
- With up to 73.5 months of follow-up, the median PFS for all patients was a striking 52.5 months; the 60-month PFS rate was 47.3% (50.4% adjusted for COVID-19). These results redefine what is expected for this patient population.
- Among patients with del(17p), the median PFS was 49.9 months; the 60-month PFS rate was 38.2% (40.5% adjusted for COVID-19).
- With longer follow-up, the prevalence of most adverse events of special interest remained stable year-over-year.
BGB-16673 (BTK degrader) clinical data demonstrates rapid, robust and deepening responses in patients with heavily pretreated R/R CLL/SLL, including those with prior BTKi treatment and mutations that confer resistance to BTK inhibitors. (Oral Presentation: 85)
Updated results from CaDAnCe-101 (NCT05006716), an ongoing open-label, Phase 1/2 study evaluating BGB-16673 monotherapy in patients with B-cell malignancies, showed responses across R/R CLL/SLL patient types, including those who had previously been treated with BTK inhibitors, BCL2 inhibitors, noncovalent BTK inhibitors, and those with BTK inhibitor resistance mutations. Highlights include:
- With a median follow-up of 19.8 months, 54.4% of patients remain on treatment. Across all doses, ORR was 85.3% and CR/CR with incomplete count recovery (CRi) rate was 2.9% with responses deepening over time.
- In the group of patients dosed at the recommended phase 2 dose (RP2D; 200 mg QD), ORR was 94.4%.
- In the patients with prior covalent BTK inhibitor, BCL2i, and noncovalent BTK inhibitor treatment, ORR was 75.0%.
- The 12- and 18-month PFS rates were 73.5% and 65.9% respectively.
- BGB-16673 was generally well tolerated in this heavily pretreated population with no treatment-related deaths and no new toxicities identified with a median treatment duration of 13.6 months.
For more information about our presence at the 2025 ASH Annual Meeting and Exposition, please visit our meeting hub: congress.beonemedicines.com.
About Chronic Lymphocytic Leukemia
Chronic lymphocytic leukemia (CLL) is a life-threatening cancer of adults. It is a type of mature B-cell malignancy in which abnormal leukemic B lymphocytes (a type of white blood cells) arise from the bone marrow and flood peripheral blood, bone marrow, and lymphoid tissues.1,2 CLL is the most common type of leukemia in adults, accounting for about one-third of new cases.2,3
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