BeiGene Presents Long-Term Efficacy and Safety Results from Three Pivotal Trials of BRUKINSA® (Zanubrutinib) and Tislelizumab at EHA2021
BRUKINSA demonstrated long-term clinical benefits and tolerability in patients with mantle cell lymphoma and chronic lymphocytic leukemia at extended follow-up of nearly three years
Tislelizumab achieved deep and durable responses in classical Hodgkin’s lymphoma with a median progression-free survival of 32 months and no new safety signals at 34-month follow-up
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“We are excited to see the long-term clinical benefits tislelizumab and BRUKINSA provided for patients in these pivotal trials, which supported the approvals in the relapsed or refractory setting of cHL and CLL or SLL in
Long-Term Follow-up Results of Tislelizumab in R/R cHL
Oral presentation; Abstract code: S207
The 34-month follow-up results from the single-arm, multicenter, pivotal Phase 2 trial (NCT03209973) demonstrated that tislelizumab was active and generally well-tolerated as a treatment for patients with R/R cHL. Results from this pivotal Phase 2 trial supported the conditional approval of tislelizumab for the treatment of patients with cHL who received at least two prior therapies in
“Despite the progress made by previous checkpoint inhibitors in R/R cHL treatment, only a minority of patients can achieve a CR,” said
With a median follow-up time of 34 months, tislelizumab demonstrated deep and durable responses in patients with R/R cHL across all patient subgroups. The IRC-assessed overall response rate (ORR) was 87.1% (95% CI: 77.0, 93.9) and the complete response (CR) rate was 67.1% (95% CI: 54.9, 77.9). The median progression-free survival (PFS) was 31.5 months (95% CI: 16.53, not estimable [NE]), and the PFS rate at 24 months and 36 months was 55.4% (95% CI: 42.2, 66.8) and 40.8% (95% CI: 25.2, 55.8), respectively. The median overall survival (OS) was not reached, and the OS rate at 24 months and 36 months was 93.9% (95% CI: 84.5, 97.7) and 84.8% (95% CI: 70.5, 92.6), respectively.
Tislelizumab remained generally well-tolerated with long-term exposure. Most adverse events were Grade 1-2 and no new safety signals were identified. Treatment-emergent adverse events (TEAEs) of any grade were reported in 97.1% of patients, and Grade ≥3 TEAEs occurred in 41.4% of patients. Treatment discontinuation due to TEAEs occurred in 8.6% of patients.
Long-Term Follow-up Results of BRUKINSA in R/R MCL
Poster; Abstract code: EP789
The 35-month follow-up results from the single-arm, open-label, multicenter pivotal Phase 2 trial (NCT03206970) demonstrated BRUKINSA’s long-term benefit and tolerability for patients with R/R MCL. Results from this pivotal Phase 2 trial were part of the data package that supported the accelerated approval of BRUKINSA in this indication in the
“With nearly three years of patient follow-up, BRUKINSA sustained a high response rate in patients with R/R MCL, and the safety profile remained largely unchanged with longer treatment exposure,” said
With a median follow-up time of 35.3 months and a median duration of exposure of 27.6 months, BRUKINSA demonstrated high, deep, and sustained efficacy in patients with R/R MCL, and responses were generally consistent across patient subgroups. The investigator-assessed ORR was 83.7% (95% CI: 74.2, 90.8), including 67 patients who achieved a CR (77.9%). The median PFS was 33.0 months (95% CI: 19.4, NE) and the estimated 36-month PFS rate was 47.6% (95% CI: 36.2, 58.1).
In long-term follow-up, the safety profile of BRUKINSA largely remained the same. Most adverse events occurred during the early stage of BRUKINSA treatment, with no additional dose reduction, treatment discontinuation, or death due to TEAEs. Grade ≥3 TEAEs occurred in 50.0% of patients.
Long-Term Follow-up Results of BRUKINSA in R/R CLL or SLL
Poster; Abstract code: EP639
Based on the 34-month follow-up results from the single-arm, open-label, multicenter pivotal Phase 2 trial (NCT03206918), BRUKINSA continued to demonstrate deep and durable responses in patients with R/R CLL, regardless of subgroup characteristics, and was well-tolerated with no new safety signals identified. Results from this pivotal Phase 2 trial supported the conditional approval of BRUKINSA in
“With an additional 19-month follow-up time, BRUKINSA continued to demonstrate promising efficacy and tolerability, as deeper responses were observed in more patients and no new safety signals were identified,”
After a median follow-up time of 34 months, responses to BRUKINSA increased and deepened over time and were consistent across all subgroups. The IRC-assessed ORR was 87.9%, including six patients who achieved a CR (6.6%), 63 patients who achieved a PR (69.2%), and 11 patients who achieved a PR with lymphocytosis (PR-L; 12.1%).
With a longer follow-up, BRUKINSA continued to be generally well-tolerated in patients with R/R CLL, similar to the previously reported data, with no new safety signals identified. TEAEs of any grade were reported in all patients (100%), and Grade ≥3 TEAEs occurred in 83.5% of patients. Treatment discontinuation due to TEAEs occurred in 15.4% of patients and fatal TEAEs occurred in 6.6% of patients.
To learn more about BeiGene’s research and development and activities around EHA2021, please visit https://beigenemedical.eu.
BeiGene EHA2021 Investor Conference Call and Webcast Information
A live webcast of the conference call can be accessed from the investors section of BeiGene’s website at http://ir.beigene.com or http://hkexir.beigene.com. An archived replay will be available two hours after the event for 90 days.
Tislelizumab (BGB-A317) is a humanized IgG4 anti-PD-1 monoclonal antibody specifically designed to minimize binding to FcγR on macrophages. In pre-clinical studies, binding to FcγR on macrophages has been shown to compromise the anti-tumor activity of PD-1 antibodies through activation of antibody-dependent macrophage-mediated killing of T effector cells. Tislelizumab is the first drug from BeiGene’s immuno-oncology biologics program and is being developed internationally as a monotherapy and in combination with other therapies for the treatment of a broad array of both solid tumor and hematologic cancers.
In addition, four supplemental Biologics License Applications for tislelizumab have been accepted by the
Tislelizumab is not approved for use outside of
BRUKINSA is a small molecule inhibitor of Bruton’s tyrosine kinase (BTK) discovered by
BRUKINSA is approved in the following indications and regions:
For the treatment of mantle cell lymphoma (MCL) in adult patients who have received at least one prior therapy (
United States, November 2019)*;
For the treatment of MCL in adult patients who have received at least one prior therapy (
China, June 2020)**;
For the treatment of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) in adult patients who have received at least one prior therapy (
China, June 2020)**;
For the treatment of relapsed or refractory MCL (
United Arab Emirates, February 2021); and
For the treatment of Waldenström’s macroglobulinemia (WM) in adult patients (
Canada, March 2021).
To-date, more than 30 marketing authorization applications in multiple indications have been submitted outside of
* This indication was approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
** This indication was approved under conditional approval. Complete approval for this indication may be contingent upon results from ongoing randomized, controlled confirmatory clinical trials.
Warnings and Precautions
Fatal and serious hemorrhagic events have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher bleeding events including intracranial and gastrointestinal hemorrhage, hematuria and hemothorax have been reported in 2% of patients treated with BRUKINSA monotherapy. Bleeding events of any grade, including purpura and petechiae, occurred in 50% of patients treated with BRUKINSA monotherapy.
Bleeding events have occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Co-administration of BRUKINSA with antiplatelet or anticoagulant medications may further increase the risk of hemorrhage.
Monitor for signs and symptoms of bleeding. Discontinue BRUKINSA if intracranial hemorrhage of any grade occurs. Consider the benefit-risk of withholding BRUKINSA for 3-7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Fatal and serious infections (including bacterial, viral, or fungal) and opportunistic infections have occurred in patients with hematological malignancies treated with BRUKINSA monotherapy. Grade 3 or higher infections occurred in 23% of patients treated with BRUKINSA monotherapy. The most common Grade 3 or higher infection was pneumonia. Infections due to hepatitis B virus (HBV) reactivation have occurred.
Consider prophylaxis for herpes simplex virus, pneumocystis jiroveci pneumonia and other infections according to standard of care in patients who are at increased risk for infections. Monitor and evaluate patients for fever or other signs and symptoms of infection and treat appropriately.
Grade 3 or 4 cytopenias, including neutropenia (27%), thrombocytopenia (10%), and anemia (8%) based on laboratory measurements, were reported in patients treated with BRUKINSA monotherapy.
Monitor complete blood counts during treatment and treat using growth factor or transfusions, as needed.
Second Primary Malignancies
Second primary malignancies, including non-skin carcinoma, have occurred in 9% of patients treated with BRUKINSA monotherapy. The most frequent second primary malignancy was skin cancer (basal cell carcinoma and squamous cell carcinoma of skin), reported in 6% of patients. Advise patients to use sun protection.
Atrial fibrillation and atrial flutter have occurred in 2% of patients treated with BRUKINSA monotherapy. Patients with cardiac risk factors, hypertension, and acute infections may be at increased risk. Grade 3 or higher events were reported in 0.6% of patients treated with BRUKINSA monotherapy. Monitor signs and symptoms for atrial fibrillation and atrial flutter and manage as appropriate.
Based on findings in animals, BRUKINSA can cause fetal harm when administered to a pregnant woman. Administration of zanubrutinib to pregnant rats during the period of organogenesis caused embryo-fetal toxicity, including malformations at exposures that were 5 times higher than those reported in patients at the recommended dose of 160 mg twice daily. Advise women to avoid becoming pregnant while taking BRUKINSA and for at least 1 week after the last dose. Advise men to avoid fathering a child during treatment and for at least 1 week after the last dose. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus.
The most common adverse reactions in > 10% of patients who received BRUKINSA were neutrophil count decreased (53%), platelet count decreased (39%), upper respiratory tract infection (38%), white blood cell count decreased (30%), hemoglobin decreased (29%), rash (25%), bruising (23%), diarrhea (20%), cough (20%), musculoskeletal pain (19%), pneumonia (18%), urinary tract infection (13%), hematuria (12%), fatigue (11%), constipation (11%), and hemorrhage (10%). The most frequent serious adverse reactions were pneumonia (11%) and hemorrhage (5%).
Of the 118 patients with MCL treated with BRUKINSA, 8 (7%) patients discontinued treatment due to adverse reactions in the trials. The most frequent adverse reaction leading to treatment discontinuation was pneumonia (3.4%). One (0.8%) patient experienced an adverse reaction leading to dose reduction (hepatitis B).
CYP3A Inhibitors: When BRUKINSA is co-administered with a strong CYP3A inhibitor, reduce BRUKINSA dose to 80 mg once daily. For co-administration with a moderate CYP3A inhibitor, reduce BRUKINSA dose to 80 mg twice daily.
CYP3A Inducers: Avoid co-administration with moderate or strong CYP3A inducers.
Hepatic Impairment: The recommended dose of BRUKINSA for patients with severe hepatic impairment is 80 mg orally twice daily.
BRUKINSA is a kinase inhibitor indicated for the treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 and other federal securities laws, including statements regarding clinical benefits of tislelizumab and BRUKINSA,
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