Clinical results from next-generation investigational therapies demonstrate potential for deep, durable responses that support the advancement of pivotal studies and future regulatory filings
Phase 1 study of BCL2 inhibitor sonrotoclax plus BRUKINSA® elicited deep responses – 96% ORR in R/R CLL and 79% ORR in R/R MCL patients – with no new safety signals in the latest results
BTK degrader BGB-16673 shows strong early results in hard-to-treat populations
BeOne Medicines Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company, will present new clinical data from three cornerstone hematology assets at the European Hematology Association (EHA) Congress. Four oral presentations highlight the promising clinical activity of BeOne’s next-generation BCL2 inhibitor sonrotoclax, BTK protein degrader BGB-16673, and the backbone of our hematology franchise, BTK inhibitor BRUKINSA (zanubrutinib), which has the broadest label globally of any approved BTK inhibitor. These data reinforce the company’s strategic vision to redefine the standard of care for B-cell malignancies.
“The data presented at EHA 2025 underscore the strength of BeOne’s comprehensive hematology pipeline, built on the success of BRUKINSA, the only BTK inhibitor to demonstrate superior progression-free survival over ibrutinib in a Phase 3 trial,1” said Lai Wang, Ph.D. Global Head of R&D at BeOne. “With our potentially best-in-class BCL2 inhibitor, sonrotoclax, and first-in-class BTK degrader, BGB-16673, we are advancing innovative therapies aimed at addressing resistance mechanisms and improving outcomes for patients with B-cell malignancies.”
The data presented at EHA 2025 support the ongoing advancement of sonrotoclax and BGB-16673 into Phase 3 studies and lay the groundwork for BeOne’s first regulatory submissions for these programs. The company’s integrated development approach—anchored in differentiated mechanisms and translational science—positions its programs to address key areas of unmet need in hematologic oncology.
“While existing therapies have improved outcomes in CLL and related malignancies, many patients still relapse or develop resistance and continue to face limited options,” said Stephan Stilgenbauer, Professor of Medicine and Medical Director of the Comprehensive Cancer Center Ulm (CCCU), Head of the Early Clinical Trials Unit (ECTU), and Head of the Division of CLL Dept. of Internal Medicine III at Ulm University. “The updated data presented at EHA underscore the potential of novel approaches, including BTK degradation and BCL2-based combinations, to overcome known mechanisms of resistance and expand treatment options for patients.”
Sonrotoclax + BRUKINSA Demonstrates Deep Responses in CLL and MCL
BeOne’s data will highlight the emerging potential of its next-generation assets to address the unmet needs of patients with B-cell malignancies.
Updated results from Phase 1 studies evaluating sonrotoclax in combination with BRUKINSA in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and with R/R mantle cell lymphoma (MCL) demonstrated consistent, deep responses and a manageable safety profile. Sonrotoclax is well-positioned to improve key aspects of the BCL2 inhibitor class and has demonstrated robust and durable antitumor activity and a tolerable safety profile across all dose levels.
- R/R CLL/SLL (Oral Presentation S159):
- Overall response rate (ORR): 96%; complete response (CR): 52% across all dose levels
- Undetectable minimal residual disease (uMRD) was achieved in 82% of patients overall, with responses deepening over time
- No tumor lysis syndrome (TLS) or febrile neutropenia observed
- R/R MCL (Oral Presentation S234):
- ORR: 79%; CR rate: 66%, with 84% of responders in ongoing response at data cutoff
- No TLS or atrial fibrillation/flutter reported; the most common grade ≥3 adverse event was neutropenia (19.6%)
Robust Early Results in CLL and WM with Potentially First-in-Class BTK Degrader
As the most clinically advanced BTK degrader, BGB-16673 continues to show potential in patients with various hematological malignancies. Updated data from the ongoing Phase 1 CaDAnCe-101 study of BGB-16673 in R/R CLL/SLL and R/R Waldenström macroglobulinemia (WM) showed substantial antitumor activity and a tolerable safety profile across heavily pretreated populations.
- R/R CLL/SLL (Oral Presentation S158):
- ORR: 84.8% across all dose levels and 93.8% at the recommended phase 2 dose of 200mg
- Patients were heavily pretreated, with most previously treated with BTK and BCL2 inhibitors. The median number of prior therapies was four. Responses deepened over time
- Grade ≥3 adverse events included neutropenia (24%) and pneumonia (11%); no reported deaths were attributed to study drug
- R/R Waldenström Macroglobulinemia (Oral Presentation S231):
- ORR: 84.4%; major response rate: 75.0%; very good partial response rate (VGPR): 31.3%
- Rapid onset of response (median: 1.0 month), with continued deepening over time
- Efficacy observed across genetic backgrounds and prior BTKi exposure
- Most common grade ≥3 TEAE was neutropenia/neutrophil count decreased (31%); no reported atrial fibrillation or febrile neutropenia.
BRUKINSA Monotherapy Showed Sustained OS and PFS Benefit
Data from Arm D of the SEQUOIA Phase 3 trial will also be presented at the meeting (Abstract PS1566), demonstrating that treatment with BRUKINSA plus venetoclax has the potential to drive progression-free survival and overall deep and durable responses across the frontline CLL patient spectrum, including patients with high-risk mutational status. SEQUOIA Arm D investigated BRUKINSA plus venetoclax in 114 patients with treatment-naïve (TN) CLL / SLL with or without del(17p) and/or TP53 high-risk mutations. At a median follow-up of 31.2 months, the combination induced a high 24-month progression-free survival (PFS) rate of 92% (95% CI, 85-96%) and an impressive overall response rate (ORR) of 97%. The 24-month overall survival (OS) rate was 96% (95% CI, 90%-98%). Notably, these benefits were observed regardless of del(17p)/TP53 mutational status. The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.
Arm C of the SEQUOIA study investigated BRUKINSA monotherapy in patients with TN CLL / SLL and del(17p) mutations, representing the largest prospective cohort of CLL/SLL patients with del(17p), will be presented at EHA (Abstract: PS1565). At a median follow-up of over 5.5 years (65.8 months), most patients remained progression-free. Notably, at 60 months, 72.2% of patients who received BRUKINSA remained progression-free (95% CI, 62.4, 79.8). When adjusted for the impact of the COVID-19 pandemic, 73.0% of patients in the cohort remained progression-free (95% CI, 63.3, 80.6) at 60 months. The 60-month OS rate was 85.1% (95% CI, 76.9, 90.6) and 87.0% (95% CI, 79.0, 92.1) when adjusted for COVID-19. At the time of data cut-off, the ORR was 97.3%, and 62.2% of patients were still receiving treatment with BRUKINSA. The safety profile of BRUKINSA was consistent with the results of prior studies with no new safety signals identified.
BeOne will host an investor R&D Day on June 26 at 8:30 am ET covering our deep and broad global innovation pipeline and platforms, as well as the Company’s vision, differentiated capabilities, and value creation drivers. The live webcast can be accessed from the investors section of BeOne’s website at https://ir.beonemedicines.com/, https://hkexir.beonemedicines.com/, or https://sseir.beonemedicines.com/. An archived replay will be available to investors for 90 days following the event.
