Zanubrutinib for Lymphoma

Recruiting at 65 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BeiGene

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 0

90 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the safety of zanubrutinib (also known as BGB-3111) in chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenström macroglobulinemia, mantle cell lymphoma, or marginal zone lymphoma patients who have become intolerant of prior ibrutinib and/or acalabrutinib treatment, by comparing intolerance to adverse event profile as assessed by the recurrence and the change in severity of adverse events.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop all current medications. However, you must stop taking corticosteroids over 10 mg daily at least 5 days before starting the study drug. Also, you cannot have received anticancer therapy less than 7 days before screening or immunotherapy less than 4 weeks before screening.

What data supports the idea that Zanubrutinib for Lymphoma is an effective treatment?

The available research shows that Zanubrutinib is an effective drug for treating lymphoma. In clinical trials, it has shown excellent results in patients with chronic lymphocytic leukemia (CLL), Waldenstrom macroglobulinemia (WM), and mantle cell lymphoma (MCL). Compared to another drug, ibrutinib, Zanubrutinib has fewer side effects, like a lower risk of heart problems and bleeding. In the SEQUOIA study, Zanubrutinib was more effective than the combination of bendamustine and rituximab in patients with untreated CLL, helping them live longer without the disease getting worse. This shows that Zanubrutinib is a strong option for treating certain types of lymphoma. ^{1 2 3 4 5}

What safety data is available for Zanubrutinib (Brukinsa) in treating lymphoma?

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, has been evaluated in multiple studies for its safety profile in treating B-cell malignancies, including lymphoma. Common adverse events include upper respiratory tract infections, neutropenia, contusion, cough, diarrhea, and fatigue. Grade 3/4 adverse events like neutropenia and pneumonia have been reported. A pooled safety analysis of 779 patients showed that zanubrutinib is generally well tolerated, with manageable and mostly reversible toxicities. Serious adverse events included pneumonia and sepsis, with treatment discontinuations due to adverse events occurring in 10% of patients. Compared to ibrutinib, zanubrutinib has a lower incidence of atrial fibrillation and major bleeding events. ^{1 6 7 8 9}

Is the drug Zanubrutinib a promising treatment for lymphoma?

Yes, Zanubrutinib is a promising drug for treating lymphoma. It is highly selective and effective, showing deep and lasting remissions in some difficult-to-treat lymphomas. It has been found to be safer and better tolerated than some other treatments, with fewer side effects. It also improves survival rates in certain types of lymphoma. ^{1 2 3 6 10}

Research Team

Dih-Yih Chen, MD

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for people with certain B-cell lymphomas or leukemia who had bad reactions to previous treatments with ibrutinib or acalabrutinib. They should be relatively active (ECOG status of 0-2), have a minimum number of neutrophils and platelets, and not have severe heart problems, recent heart attacks, CNS hemorrhage, or need high doses of steroids.

Inclusion Criteria

My condition requires treatment before starting ibrutinib or acalabrutinib.

My blood tests show enough neutrophils and platelets for treatment.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I need more than 10 mg of prednisone or similar medication daily.

My condition worsened while on ibrutinib or acalabrutinib treatment.

I have serious heart issues, including recent heart attacks or unstable angina.

Treatment Details

Interventions

• Zanubrutinib

Trial Overview The study tests Zanubrutinib's safety in patients intolerant to prior BTKi treatments. It looks at whether the side effects are less severe or occur less often than before. Patients previously treated with other cancer therapies must wait specific periods before joining.

Participant Groups

Group I: Zanubrutinib Experimental Treatment 1 Intervention

Cohort 1: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with ibrutinib Cohort 2: Chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL), Waldenström macroglobulinemia (WM), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL) previously treated with acalabrutinib alone/with ibrutinib

Zanubrutinib is already approved in United States, China for the following indications:

Approved in United States as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Approved in China as Brukinsa for:

• Chronic lymphocytic leukemia (CLL)
• Small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

Zanubrutinib is a next-generation BTK inhibitor that shows improved selectivity and reduced off-target toxicities compared to ibrutinib, making it a safer option for treating B-cell malignancies.

In recent clinical trials, zanubrutinib demonstrated significant efficacy in improving progression-free survival in patients with chronic lymphocytic leukemia (CLL) and showed better safety profiles, including a lower risk of serious side effects like atrial fibrillation and major bleeding compared to ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions. Wolska-Washer, A., Robak, T.[2023]

Zanubrutinib demonstrated a high overall response rate of 95.4% in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, with treatment-naïve patients showing even better outcomes (100% response) compared to those with relapsed/refractory disease (91.0%).

The long-term follow-up indicated that earlier treatment with zanubrutinib leads to significantly longer progression-free and overall survival, while maintaining a favorable safety profile, with serious adverse events primarily being infections and neutropenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Xu, W., Yang, S., Tam, CS., et al.[2022]

In a phase 3 study involving 590 patients with untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to bendamustine-rituximab, with a hazard ratio of 0.42, indicating a strong efficacy advantage.

Zanubrutinib demonstrated an acceptable safety profile, with fewer severe adverse events like neutropenia compared to bendamustine-rituximab, suggesting it could be a promising new treatment option for patients with CLL and SLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. Tam, CS., Brown, JR., Kahl, BS., et al.[2023]

In the phase 3 SEQUOIA trial involving adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), zanubrutinib significantly improved progression-free survival compared to the standard treatment of bendamustine plus rituximab (BR).

Patients treated with zanubrutinib reported better health-related quality-of-life outcomes at 12 and 24 weeks, including improvements in global health status, physical functioning, and reduced symptoms of diarrhea, fatigue, and nausea/vomiting compared to those receiving BR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. Ghia, P., Barnes, G., Yang, K., et al.[2023]

In a study of 27 patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of zanubrutinib and salvage chemotherapy resulted in a high overall response rate of 74.1% and a complete remission rate of 33.3%, indicating significant efficacy.

The most common severe side effects were neutropenia and thrombocytopenia, but the treatment was generally manageable, suggesting that zanubrutinib plus chemotherapy could be a viable option for R/R DLBCL patients, especially those with poor responses to initial treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma. Yuan, X., Li, X., Huang, Y., et al.[2022]

A 75-year-old patient developed a severe disseminated cryptococcal infection, leading to pneumonia and meningitis, four months after starting zanubrutinib for Waldenström's macroglobulinemia, highlighting a potential risk of serious infections associated with BTK inhibitors.

Despite initial treatment, the patient's condition worsened, resulting in septic shock and multiorgan failure, suggesting that while zanubrutinib can be effective for certain cancers, it may also compromise immune function, increasing vulnerability to invasive fungal infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fatal disseminated cryptococcal infection in a patient treated with zanubrutinib for Waldenström's macroglobulinemia. Patel, D., Sidana, M., Mdluli, X., et al.[2022]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, was found to be generally well tolerated when combined with obinutuzumab in a phase 1 study involving 81 patients with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL).

The combination therapy showed high efficacy, achieving a 100% overall response rate in treatment-naïve CLL patients and a 92% response rate in relapsed/refractory CLL patients, with a 72% response rate in relapsed/refractory FL patients over a median follow-up of 20 to 29 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. Tam, CS., Quach, H., Nicol, A., et al.[2021]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, showed a high overall response rate of 94.5% in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma carrying the del(17p) mutation, indicating its efficacy in a challenging patient population.

The treatment was well tolerated, with an estimated 18-month progression-free survival rate of 88.6% and an overall survival rate of 95.1%, although some patients experienced adverse events, including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Tam, CS., Robak, T., Ghia, P., et al.[2021]

Zanubrutinib, a selective BTK inhibitor, was evaluated in a pooled analysis of 779 patients across 6 studies, showing a generally well-tolerated safety profile with manageable and mostly reversible treatment-emergent adverse events (TEAEs).

Common nonhematologic TEAEs included upper respiratory tract infections (39%) and rash (27%), while serious adverse events like pneumonia (11%) and sepsis (2%) were noted, but the rates of atrial fibrillation and major hemorrhage were lower than those historically reported for another BTK inhibitor, ibrutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies. Tam, CS., Dimopoulos, M., Garcia-Sanz, R., et al.[2022]

Zanubrutinib is a highly selective second-generation BTK inhibitor that has shown deep and sustained remissions in patients with relapsed and refractory B-cell lymphoma, indicating its efficacy as a targeted therapy.

The drug has a favorable safety profile, making it a promising option for precision therapy in the treatment of B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Zanubrutinib in B-Cell Lymphoma --Review]. Tang, X., Zou, WR., Peng, P., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Zanubrutinib for the treatment of lymphoid malignancies: Current status and future directions. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Zanubrutinib Monotherapy for Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Zanubrutinib versus bendamustine and rituximab in untreated chronic lymphocytic leukaemia and small lymphocytic lymphoma (SEQUOIA): a randomised, controlled, phase 3 trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Zanubrutinib plus salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

A fatal disseminated cryptococcal infection in a patient treated with zanubrutinib for Waldenström's macroglobulinemia. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Zanubrutinib (BGB-3111) plus obinutuzumab in patients with chronic lymphocytic leukemia and follicular lymphoma. [2021]

8. Italy pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Pooled safety analysis of zanubrutinib monotherapy in patients with B-cell malignancies. [2022]

10. China pubmed.ncbi.nlm.nih.gov

[Clinical Application of Zanubrutinib in B-Cell Lymphoma --Review]. [2022]