Zanubrutinib + Tislelizumab for B-Cell Lymphoma

Not currently recruiting at 236 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the long-term safety of zanubrutinib, a cancer drug, either alone or with tislelizumab, in people with B-cell lymphoma. The researchers aim to assess the safety of these treatments over time for those who participated in a previous zanubrutinib study. It suits individuals already using zanubrutinib or who have been part of a related study and wish to continue treatment. Participants should not have serious heart issues or active infections and must meet specific health criteria, such as having healthy blood counts. As a Phase 3 trial, this study is the final step before FDA approval, allowing participants to contribute to the potential availability of these treatments.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of zanubrutinib and tislelizumab is generally safe for people with B-cell cancers. Previous studies found that patients tolerated this combination well, with positive responses. While some side effects occurred, they were mostly manageable.

Studies have shown that zanubrutinib alone is safer compared to similar treatments, particularly with fewer serious bleeding events. This suggests that zanubrutinib, both alone and with tislelizumab, is generally well-tolerated in people with B-cell cancers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Zanubrutinib and Tislelizumab for B-cell lymphoma because they offer a fresh approach to treatment. Zanubrutinib is a Bruton’s tyrosine kinase (BTK) inhibitor, which means it targets and blocks a specific protein that helps cancer cells grow, potentially leading to more effective control of the disease. Tislelizumab is an anti-PD-1 antibody, which helps the immune system recognize and attack cancer cells. This combination could provide a powerful one-two punch, offering an alternative to traditional chemotherapy and potentially improving outcomes for patients with B-cell lymphoma.

What evidence suggests that this trial's treatments could be effective for B-cell lymphoma?

Research has shown that combining zanubrutinib and tislelizumab can be a promising treatment for certain B-cell lymphomas. For instance, in cases like Richter transformation, this combination resulted in 74.7% of patients being alive one year after starting treatment, indicating many patients survived for at least a year. Another study found that this combination might benefit patients who previously received CAR T-cell therapy, a type of cancer treatment. In this trial, some participants will receive the combination of zanubrutinib and tislelizumab, while others will receive zanubrutinib alone. Zanubrutinib alone has also been effective, providing strong disease control for patients whose conditions returned or didn't respond to other treatments, with 72.9% of patients experiencing benefits for two years. These findings suggest that both the combination and zanubrutinib alone could benefit people with B-cell lymphomas. ^{1 6 7 8 9}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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, 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]

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]

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]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/7/22/6801/497772/Safety-and-efficacy-of-zanubrutinib-in-relapsed

Safety and efficacy of zanubrutinib in relapsed/refractory ... Key Points. With longer follow-up, zanubrutinib showed durable disease control (2-year DOR rate of 72.9%) in patients with R/R MZL.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10557885/

Long‐term outcomes of second‐line versus later ... Zanubrutinib in second‐line treatment was associated with significantly improved OS compared with later‐line treatment of R/R MCL. Keywords: ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2468294225000401

Efficacy and safety of zanubrutinib combined with chimeric ... Zanubrutinib combined with CAR T-cell therapy offers an effective treatment option for patients with R/R DLBCL, enhancing response rates and survival.

4. nature.com nature.com/articles/s41408-023-00902-x

Zanubrutinib: past, present, and future | Blood Cancer ... Pooled data from 10 clinical trials in B-cell malignancies, including 1550 patients treated with zanubrutinib, showed low treatment ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2211582

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic ... Zanubrutinib has been shown to have high (>90%) steady-state BTK inhibitor occupancy in peripheral-blood mononuclear cells and lymph nodes.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10679804/

Safety and efficacy of zanubrutinib in relapsed/refractory ... With longer follow-up, zanubrutinib showed durable disease control (2-year DOR rate of 72.9%) in patients with R/R MZL.

7. haematologica.org haematologica.org/article/view/haematol.2023.283846

<i>post-hoc</i> analysis of a large clinical trial safety ... In the comparative analysis, zanubrutinib exhibited a more favorable safety profile than ibrutinib, as demonstrated by the longer median ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02343120

NCT02343120 | Study of the Safety and Pharmacokinetics ... This study evaluated the safety, tolerability, pharmacokinetic profile and efficacy of BGB-3111 in participants with B-cell lymphoid malignancies.

9. brukinsahcp.com brukinsahcp.com/wm/safety/

BRUKINSA® (zanubrutinib) Safety in WM | HCPs Grade 3 or higher hemorrhage including intracranial and gastrointestinal hemorrhage, hematuria, and hemothorax was reported in 3.8% of patients treated with ...