Zanubrutinib + Tislelizumab for B-Cell Lymphoma

Recruiting at 224 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: BeiGene

Must be taking: Zanubrutinib

Must not be taking: Chemotherapy, Targeted therapy

Disqualifiers: Infection, Heart failure, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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: Unknown

Duration: Up to 5 years

500 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the long-term safety of zanubrutinib regimens in participants with B-cell malignancies who participated in a BeiGene parent study for zanubrutinib.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that certain therapies like chemotherapy, targeted therapy, and radiation therapy are not allowed during the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Zanubrutinib for B-cell lymphoma?

Zanubrutinib has shown good effectiveness and safety in treating various B-cell cancers like chronic lymphocytic leukemia and mantle cell lymphoma, with studies indicating high response rates and better tolerability compared to similar drugs. It has been effective in improving progression-free survival in patients with these conditions. ^{1 2 3 4 5}

What is the safety profile of Zanubrutinib in humans?

Zanubrutinib has been generally well tolerated in clinical trials for various B-cell lymphomas, with common side effects including infections, reduced blood cell counts, and diarrhea. Serious side effects like neutropenia (low white blood cell count) and pneumonia have been reported, but the drug is considered to have a favorable safety profile compared to similar treatments. ^{3 4 5 6 7}

What makes the drug Zanubrutinib unique for treating B-cell lymphoma?

Zanubrutinib is a next-generation drug that specifically targets Bruton's tyrosine kinase (BTK) with high selectivity, reducing side effects compared to similar drugs like ibrutinib. It is taken orally and has shown excellent efficacy and safety in treating various B-cell lymphomas, making it a promising option for patients with relapsed or refractory conditions. ^{2 3 5 8 9}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for people with B-cell malignancies who were in a previous BeiGene study. They should have stable vital signs, normal organ function, and agree to birth control if needed. It's not for those with severe heart failure, uncontrolled infections, or women who are pregnant or breastfeeding.

Inclusion Criteria

Platelets ≥ 50,000/mm3

Absolute neutrophil count ≥ 750/mm3

I am currently being treated with zanubrutinib.

Exclusion Criteria

Pregnant or lactating woman

Inability to comply with study procedures

I do not have an ongoing serious infection or one that needed IV antibiotics recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive open-label zanubrutinib, with some receiving it in combination with Tislelizumab as in the parent study

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Zanubrutinib

Trial Overview The trial tests long-term safety of Zanubrutinib alone or with Tislelizumab in patients previously enrolled in related studies. The focus is on those who may continue benefiting from Zanubrutinib after showing no progression of disease.

Participant Groups

Group I: Zanubrutinib in combination with Tislelizumab Experimental Treatment 2 Interventions

Participants to receive the combination as in the parent study (Australia Only)

Group II: Zanubrutinib (BGB-3111) Experimental Treatment 1 Intervention

All participants to receive open-label zanubrutinib

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

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]

Zanubrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, received accelerated approval in the USA on November 14, 2019, for treating adult patients with mantle cell lymphoma (MCL) who have undergone at least one prior therapy.

The approval was based on the overall response rate (ORR) observed in phase II and I/II clinical trials, highlighting its efficacy in managing B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib: First Approval. Syed, YY.[2020]

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 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, 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 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]

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]

References

1. 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]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Zanubrutinib: First Approval. [2020]

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

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

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

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

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

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

6. Italy pubmed.ncbi.nlm.nih.gov

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

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

Zanubrutinib in relapsed/refractory mantle cell lymphoma: long-term efficacy and safety results from a phase 2 study. [2022]

8. China pubmed.ncbi.nlm.nih.gov

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

9. 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]