BeiGene Highlights Growing Portfolio and Pipeline Targeting Hematologic Malignancies at European Hematology Association 2022 Congress

BeiGene , a global, science-driven biotechnology company focused on developing innovative and affordable medicines to improve treatment outcomes and access for patients worldwide, presents data from its hematology portfolio at the European Hematology Association (EHA) 2022 Hybrid Congress being held June 9-12, 2022, in Vienna, Austria.

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“We are seeing our promising early pipeline beginning to mature as a result of our deep expertise in developing treatments for hematologic malignancies, and we’re pleased to present positive proof-of-concept data from two studies with our BCL2 inhibitor, BGB-11417, at this important hematology meeting.”

“Our data presentations at EHA build a more complete picture of the potential for our BTK inhibitor zanubrutinib across a number of hematologic malignancies, with positive clinical results from ROSEWOOD in follicular lymphoma, long-term efficacy and safety results from ASPEN, as well as patient-reported outcomes from ALPINE and SEQUIOA.” said Lai Wang, Ph.D., Global Head of R&D at BeiGene. “We are seeing our promising early pipeline beginning to mature as a result of our deep expertise in developing treatments for hematologic malignancies, and we’re pleased to present positive proof-of-concept data from two studies with our BCL2 inhibitor, BGB-11417, at this important hematology meeting.”

Highlights from the broad clinical program for zanubrutinib (BRUKINSA) presented at EHA include:

• ASPEN: Long-term safety and efficacy results from the Phase 3 ASPEN trial of zanubrutinib versus ibrutinib in patients with Waldenström macroglobulinemia (WM) showed that, at a median follow up of 43 months, zanubrutinib continued to demonstrate clinically meaningful efficacy and a tolerable safety profile in patients with WM.
• ROSEWOOD: The Phase 2 ROSEWOOD trial of zanubrutinib plus obinutuzumab versus (vs.) obinutuzumab monotherapy in patients with relapsed/refractory (R/R) follicular lymphoma met its primary endpoint of overall response rate (ORR) and was generally well-tolerated, with safety results consistent with previous studies of both medicines.
• ALPINE: In the head-to-head ALPINE trial of zanubrutinib versus ibrutinib in patients with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), those who received zanubrutinib monotherapy reported improvements in key health-related quality of life (HRQoL) endpoints compared with patients who received ibrutinib monotherapy.
• SEQUOIA: In the SEQUOIA trial of zanubrutinib vs. bendamustine plus rituximab (BR), zanubrutinib was associated with significant improvements in HRQoL in patients with treatment-naïve (TN) CLL/SLL without del(17p), as indicated by patient reported outcome (PRO) endpoints.

The ROSEWOOD and ASPEN study findings were presented at the American Society of Cancer Oncology (ASCO) Annual Meeting in June 2022.

BeiGene also presented two posters from proof-of-concept studies of BGB-11417, a highly selective investigational BCL2 inhibitor in CLL, non-Hodgkin’s lymphoma and acute myeloid leukemia (AML).

• Preliminary data from an ongoing Phase 1/1b dose-escalation and expansion study evaluating the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose of oral BGB-11417 as monotherapy or in combination with zanubrutinib, in patients with B-cell malignancies, showed promising efficacy potential for BGB-11417 and an improved safety profile, particularly in combination cohorts.
• Preliminary data from an ongoing Phase 1b/2 global, multi-center dose escalation and expansion study evaluating BGB-11417 plus azacytidine in patients with AML demonstrated the combination to be generally well-tolerated with the majority of complete responses observed by the end of Cycle 1.

Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients with Relapsed or Refractory Follicular Lymphoma: Primary Analysis of the Phase 2 Randomized ROSEWOOD Trial
Abstract Number: S205

The ROSEWOOD trial met its primary endpoint, with a 68.3% ORR in the zanubrutinib plus obinutuzumab arm versus 45.8% in the obinutuzumab arm (p = 0.0017) and median follow-up of 12.5 months. Zanubrutinib plus obinutuzumab was generally well-tolerated, with safety results consistent with previous studies of both medicines.

• Zanubrutinib plus obinutuzumab was associated with a deep and durable response, with a complete response (CR) rate of 37.2% compared to 19.4% for obinutuzumab alone; 18-month duration of response rate was 70.9% in the zanubrutinib plus obinutuzumab arm versus 54.6% in the obinutuzumab arm.
• Time to next anti-lymphoma treatment was significantly prolonged in the zanubrutinib plus obinutuzumab arm (HR 0.37 [95% CI, 0.23, 0.60].
• Median progression-free survival was 27.4 months in the zanubrutinib plus obinutuzumab arm compared to 11.2 months in the obinutuzumab arm (HR: 0.51 [95% CI, 0.32, -0.81]).
• The most common adverse events in the zanubrutinib plus obinutuzumab arm were thrombocytopenia or platelet count decreased (34.3% any grade; 14% grade ≥ 3) and neutrophil count decreased or neutropenia (27.3% any grade; 22.4% grade ≥ 3); other adverse events were similar between the two arms.
• Infusion-related reactions were more frequent in the obinutuzumab monotherapy arm.

ASPEN: Long-term Follow-up Results of a Phase 3 Randomized Trial of Zanubrutinib vs. Versus Ibrutinib in Patients with Waldenström Macroglobulinemia (WM)
Abstract Number: P1161

With a median follow-up of 43 months, zanubrutinib continued to demonstrate a clinically meaningful efficacy and tolerable safety profile in patients with WM.

• Exploratory analyses showed a consistent trend of deeper, earlier, and more durable responses (CR+VGPR) compared with ibrutinib over time.
• Median time to CR+VGPR was shorter for zanubrutinib: 6.7 months (range, 1.9-42.0) vs ibrutinib: 16.6 months (range, 2.0-49.9).
• Over the follow-up period, patients receiving zanubrutinib had fewer adverse events leading to death, treatment discontinuation, and dose reduction as compared with ibrutinib.
• The prevalence of atrial fibrillation, hypertension, and bleeding were lower in the zanubrutinib arm at all time intervals; neutropenia occurred early, and prevalence decreased over time for patients receiving zanubrutinib.

Health-related Quality of Life Outcomes Associated with Zanubrutinib vs Ibrutinib Monotherapy in Patients with Relapsed/Refractory (R/R) CLL/SLL: Results from The Randomized Phase 3 ALPINE Trial
Abstract Number: P663

In the Phase 3 open-label ALPINE trial, HRQoL was examined at key cycles (7 and 13; corresponding to 6 and 12 months of treatment, respectively). PRO endpoints included global health status (GHS), physical and role functions, and fatigue, pain, diarrhea, and nausea/vomiting.

• Adjusted completion rates for PROs were high (>85%) in both arms at Cycles 7 and 13.
• Estimated mean treatment differences and 95% CI in key PRO endpoints demonstrated treatment differences, in favor of zanubrutinib, in GHS, physical functioning, and fatigue in Cycle 7, and diarrhea in Cycle 13.
• Mean change from baseline showed greater improvement with zanubrutinib compared with ibrutinib at both Cycle 7 and Cycle 13.

Patient-Reported Outcomes from a Phase 3 Randomized Study of Zanubrutinib Versus Bendamustine Plus Rituximab (BR) in Patients with Treatment-naïve (TN) CLL/SLL
Abstract Number: P662

PROs were secondary endpoints in the Phase 3, open-label,SEQUOIA trial of zanubrutinib (n=241) versus bendamustine plus BR (n=238) in adult patients with TN CLL/SLL without del(17p) and were assessed using the EORTC QLQ-C30, and EQ-5D-5L VAS. The PRO endpoints included GHS, physical and role functions, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting measured at critical clinical cycles of Weeks 12 and 24.

• Across all patients, adjusted completion rates for PROs were high (80%) at Weeks 12 and 24.
• Patients treated with zanubrutinib experienced greater improvements in HRQoL at Weeks 12 and 24 compared with patients who received BR.
• By Week 24, improvements were observed with zanubrutinib vs. BR in GHS, physical functioning, role functioning as well as greater reductions in diarrhea, fatigue, and nausea/vomiting.
• Comparable improvements from baseline between zanubrutinib and BR in the health status were observed at Weeks 12 and 24, respectively.

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A Phase 1 Study with the Novel B-Cell Lymphoma 2 Inhibitor BGB-11417 as Monotherapy or in Combination with Zanubrutinib in Patients with B-cell Malignancies: Preliminary Data
Abstract Number: P687

This ongoing first-in-human Phase 1/1b dose-escalation and expansion study evaluated the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose of oral BGB-11417, a highly selective investigational inhibitor of BCL2, as monotherapy (n=34) or in combination with zanubrutinib (n=44), in patients with B-cell malignancies.

Early phase 1 results suggested that BGB-11417 monotherapy and combination with zanubrutinib is generally well-tolerated in patients with CLL or NHL at the dose levels tested:

• Dose escalation concluded for monotherapy patients with NHL, with 1 dose limiting toxicity (DLT) seen and no MTD reached at doses as high as 640mg; 1 DLT was seen in monotherapy patients with CLL.
• Transient neutropenia was the most frequent grade ≥3 AE; risk of TLS appears limited and manageable.

Dose escalation was completed for Cohort 1A, with no MTD reached through 640mg and only 1 DLT of grade 3 febrile neutropenia was seen at 160 mg Although dose escalation has not yet been completed for the other cohorts and the follow up is limited, responses were observed at the preliminary dose levels:

• A reduction in ALC was noted among all patients with CLL during ramp-up, with reduction in lymphocytes noted at dose levels as low as 1 mg. Four of six R/R CLL/SLL patients receiving BGB-11417 and zanubrutinib achieved PR-L or better across dose levels ranging from 40 – 320 mg.

Preliminary Safety and Efficacy of BGB-11417, a Potent and Selective B-Cell Lymphoma 2 (BCL2) Inhibitor, in Patients with Acute Myeloid Leukemia
Abstract Number: P590

This ongoing Phase 1b/2, global, multi-center, dose-escalation and expansion study evaluated the combination of BGB-11417 and azacitidine in patients (n=31) with acute myeloid leukemia (TN unfit for intensive chemotherapy or R/R). Preliminary results showed that the 10-day regimen of BGB-11417 in 28-day cycle plus 7-day azacytidine was generally well-tolerated and active across the three dose levels tested (40, 80, 160 mg):

• 58% TN and 55% R/R patients with AML met CR+CRh criteria.
• Most CRs (7 of 11) were achieved by the end of cycle 1.
• Five of 13 evaluable CR/CRi achieved minimal residual disease negativity.
• Neutropenia was the most common grade ≥3 AE (54.8%) and was manageable with growth factor support and dose modification.
• DLTs of grade 4 neutropenia/thrombocytopenia occurred in two patients; safety stopping criteria were not met.
• Higher dose and different dosing scheduling are being explored.

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