BeiGene, Ltd. announced the presentation of new clinical data at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, underscoring its leadership in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) through continued clinical success with BRUKINSA (zanubrutinib) and promising advancements in its pipeline assets. Long-term follow-up results from the ongoing Phase 3 SEQUOIA study presented during ASH, which were simultaneously published in the Journal of Clinical Oncology, reaffirm BRUKINSA?s durable efficacy and differentiated safety profile across diverse CLL patient populations, including those with high-risk features. Additional findings spotlight the promising potential of BeiGene?s BTK-targeted chimeric degradation activation compound (CDAC), BGB-16673, which has shown rapid and deep responses in B-cell malignancies in phase 1/2 clinical trials.

BeiGene is also developing a next-generation BCL2 inhibitor, sonrotoclax, aiming to improve the safety profile and feasibility of use for this class of drugs and deliver deeper and more durable responses. Together, these advancements reflect BeiGene?s comprehensive approach to addressing the complexities of CLL and its commitment to reshaping the treatment landscape for B-cell malignancies. With a median follow-up of 61.2 months, data from the SEQUOIA study of patients with treatment-naïve CLL/SLL demonstrated that treatment with 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 (BR).

At 54 months, 80.1% of patients who received BRUKINSA remained progression-free (95% CI, 74.3, 84.7) while only 44.6% of patients who received BR remained progression-free (95% CI, 37.6, 51.3). At 60 months, PFS rates were 75.8% (95% CI, 69.0, 81.3) and 40.1% (95% CI, 32.7, 47.3) for BRUKINSA and BR, respectively. Notably, for patients in the study with unmutated IGHV, a prognostic biomarker that indicates a patient?s CLL may be more aggressive, treatment with BRUKINSA reduced the risk of progression or death by 79% compared to BR (HR, 0.21; 95% CI, 0.14-0.33; P<.0001).

The safety profile of BRUKINSA was consistent with the results of prior studies, and no new safety signals were identified. Grade =3 treatment-emergent adverse events of interest (AEIs) with BRUKINSA and BR included infection (30.0% and 22.5%, respectively), neutropenia (12.5%; 51.1%), bleeding (7.5%; 1.8%), thrombocytopenia (2.5%; 8.4%), and anemia (0.8%; 2.6%). Rates of atrial fibrillation were 7.1% with BRUKINSA and 3.5% with BR.

The rate of discontinuation due to AEs was 20% in the BRUKINSA arm; 13% of patients discontinued BR early due AEs.(Abstract 3249). In addition to BRUKINSA, BeiGene is advancing a robust pipeline to address the needs of CLL patients, including: Sonrotoclax (BCL2 Inhibitor): Presented data from the Phase 1/1b study (NCT04277637) demonstrated sonrotoclax, in combination with BRUKINSA, was generally well-tolerated and no cases of tumor lysis syndrome (TLS) were reported in patients with treatment-naïve CLL/SLL. Grade =3 treatment-emergent adverse events (TEAEs) occurred in 49.6% of patients, with the most common (=20%) being neutropenia (24% in 160mg cohort; 23% in 320mg cohort).

With a median follow-up of 19.4 months (0.4?33.3 months), the combination achieved a 99% overall response rate (ORR), including in patients with high-risk features (51% had unmutated IGHV, 20% had TP53 mutation, and 9% had del(17p)). High and early rates of undetectable minimal residual disease (uMRD) were seen by week 24 of combination therapy, with responses continuing to deepen with time through week 48. Best uMRD rate was achieved in 92% of patients (n=112).

At a median follow-up of over a year and a half, no progression has been observed in the 320 mg dose cohort. These data support continued evaluation of this combination in the ongoing registrational Phase 3 fixed-duration CELESTIAL-TNCLL study (NCT06073821) (Abstract 1012); BGB-16673 (BTK CDAC): Data from the Phase 1/2 CaDAnCe-101 CLL study (NCT05006716) demonstrated that treatment with BGB-16673 was generally well tolerated in this heavily pretreated population of patients. Promising antitumor activity was observed in patients with high-risk features, including in patients with BTK inhibitor-resistant mutations and those previously exposed to covalent BTK inhibitors, noncovalent BTK inhibitors, and BCL2 inhibitors.

No atrial fibrillation was observed in either the CLL/SLL or WM cohorts. From the cohort of CLL/SLL patients, BGB-16673 demonstrated an ORR of 94% at the 200mg dose. Furthermore, amongst all doses delivered, 2 patients achieved a complete remission/complete remission with incomplete count recovery (CR/CRi).

Grade =3 TEAEs were reported in 57% of patients. The most common grade =3 TEAEs (=10%) were neutropenia/neutrophil count decreased (20%) and pneumonia (10%). (Abstract 885).

From the cohort of Waldenström's macroglobulinemia patients, BGB-16673 demonstrated a 93% disease control rate (DCR) and 26% very good partial response (VGPR). Grade =3 TEAEs were reported in 45% of patients. The most common grade =3 TEAE (=20%) was neutropenia/neutrophil count decreased.