BeiGene presented new clinical data at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, highlighting advancements in chronic lymphocytic leukemia (CLL) treatment. The data showcased the continued success of BRUKINSA® (zanubrutinib) and promising developments in BeiGene's pipeline assets, including sonrotoclax and BGB-16673.
BRUKINSA Demonstrates Long-Term Efficacy in Treatment-Naïve CLL
Long-term follow-up results from the Phase 3 SEQUOIA study, simultaneously published in the Journal of Clinical Oncology, reaffirmed BRUKINSA's durable efficacy and differentiated safety profile in diverse CLL patient populations. With a median follow-up of 61.2 months, BRUKINSA reduced the risk of progression or death by 71% (HR, 0.29; 95% CI, 0.21-0.40; P<.0001) compared to bendamustine-rituximab. At 54 months, 80.1% of patients receiving BRUKINSA remained progression-free, compared to 44.6% on bendamustine-rituximab. For patients with unmutated IGHV, BRUKINSA reduced the risk of progression or death by 79% compared to bendamustine-rituximab (HR, 0.21; 95% CI, 0.14-0.33; P<.0001).
"The long-term follow-up of SEQUOIA confirms the sustained efficacy of zanubrutinib over chemotherapy, regardless of IGHV status, in patients with treatment-naïve CLL," said Mazyar Shadman, M.D. M.P.H., Associate Professor at Fred Hutch Cancer Center. He also noted a deepening of responses, with a complete remission rate around 20%, higher than typical BTK inhibitors used as monotherapy. The safety profile of BRUKINSA was consistent with prior studies, with atrial fibrillation rates at 7.1% and discontinuation due to adverse events at 20%.
Sonrotoclax and BRUKINSA Combination Shows Promising Results
Data from a Phase 1/1b study (NCT04277637) demonstrated that sonrotoclax, a next-generation BCL2 inhibitor, in combination with BRUKINSA, was generally well-tolerated in treatment-naïve CLL/SLL patients. With a median follow-up of 19.4 months, the combination achieved a 99% overall response rate (ORR), including in patients with high-risk features. The best undetectable minimal residual disease (uMRD) rate was 92%. No progression was observed in the 320 mg dose cohort. These data support the ongoing Phase 3 CELESTIAL-TNCLL study (NCT06073821) evaluating this combination.
BGB-16673 Shows Potential in Treatment-Resistant CLL
Data from the Phase 1/2 CaDAnCe-101 CLL study (NCT05006716) demonstrated that BGB-16673, a BTK-targeted chimeric degradation activation compound (CDAC), was generally well-tolerated in heavily pretreated patients. Promising antitumor activity was observed, including in patients with BTK inhibitor-resistant mutations. In CLL/SLL patients, BGB-16673 demonstrated an ORR of 94% at the 200mg dose. Grade ≥3 treatment-emergent adverse events were reported in 57% of patients, with the most common being neutropenia (20%) and pneumonia (10%).
