BGB-11417 +/− Zanubrutinib for B-Cell Lymphoma

Recruiting at93 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: BeiGene

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called BGB-11417 alone and with two other drugs to see if they are safe and how much can be given without serious side effects. It likely targets patients with certain cancers or blood disorders.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it is common for clinical trials to have specific requirements about medications, so it's best to discuss this with the trial coordinators.

What data supports the idea that BGB-11417 +/− Zanubrutinib for B-Cell Lymphoma is an effective drug?

The available research shows that Zanubrutinib, when used for B-Cell Lymphoma, has shown deep and lasting improvements in patients, especially those whose condition has returned or not responded to other treatments. It is also noted for having a good safety profile. In comparison to other treatments like bendamustine and rituximab, Zanubrutinib has been found to be more effective for certain types of lymphoma, such as chronic lymphocytic leukemia and small lymphocytic lymphoma, with better outcomes and fewer side effects. ^{1 2 3 4 5}

What safety data is available for BGB-11417 and Zanubrutinib in B-cell lymphoma treatment?

Zanubrutinib, a selective BTK inhibitor, has been studied in various trials for B-cell lymphomas, showing a favorable safety profile. Common adverse events include neutropenia, upper respiratory tract infections, and fatigue. In a phase 1 study, zanubrutinib combined with obinutuzumab was generally well tolerated, with neutropenia being the most common grade 3/4 adverse event. In another study, zanubrutinib was well tolerated with no serious hemorrhagic events or atrial fibrillation/flutter. Overall, zanubrutinib has demonstrated good tolerability and safety in patients with B-cell lymphoid malignancies. ^{1 3 6 7 8}

Is the drug BGB-11417 (Sonrotoclax) a promising treatment for B-cell lymphoma?

The drug BGB-11417 (Sonrotoclax) is considered promising for B-cell lymphoma because it is being studied in combination with zanubrutinib, which has shown significant activity and good tolerability in treating various B-cell malignancies. Zanubrutinib is known for its effectiveness and safety, making the combination with BGB-11417 potentially beneficial. ^{1 7 9 10 11}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with certain types of B-cell lymphoma who have relapsed or didn't respond to previous treatments. They must have measurable disease, be in fair health (ECOG 0-2), and their organs must function well. People with brain involvement by lymphoma, prior Bcl-2 inhibitor treatment failure, plasma cell neoplasm, prolymphocytic leukemia, or suspected Richter's syndrome can't join.

Inclusion Criteria

I have been diagnosed with non-Hodgkin lymphoma.

My organs are working well.

-- Serum amylase ≤ 1.5 x upper limit of normal (ULN)

Exclusion Criteria

I have or am suspected to have a specific blood cancer type.

I have been treated with a Bcl-2 inhibitor for at least 2 months or my condition worsened on it.

My lymphoma/leukemia has spread to my brain or spinal cord.

Treatment Details

Interventions

• BGB-11417 (Bcl-2 Inhibitor)

Trial Overview The study tests the safety and ideal dosing of a new drug called BGB-11417 alone and combined with zanubrutinib and obinutuzumab. It aims to find the highest dose patients can take without serious side effects (MTD) and the recommended dose for future Phase 2 trials (RP2D).

Participant Groups

Group I: Sonrotoclax Monotherapy Expansion Cohorts: Part 2 Experimental Treatment 1 Intervention

Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; CLL/SLL with low tumor burden or low creatine clearance; CLL/SLL with without high tumor burden or low creatine clearance will receive oral sonrotoclax at the RP2D dose to further define the safety profile.

Group II: Sonrotoclax Monotherapy Dose Finding: Part 1 Experimental Treatment 1 Intervention

Participants with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) including follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), marginal zone lymphoma (MZL) or transformed NHL, mantle cell lymphoma (MCL); Waldenströms macroglobulinemia (WM); and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) will receive oral sonrotoclax evaluated as monotherapy.

Group III: Sonrotoclax + Zanubrutinib Combination Therapy Dose Finding: Part 3 Experimental Treatment 2 Interventions

Participants with R/R MCL, R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib.

Group IV: Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 6 Experimental Treatment 3 Interventions

Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib at an RP2D dose to further define the safety profile.

Group V: Sonrotoclax + Zanubrutinib Combination Therapy Dose Expansion: Part 4 Experimental Treatment 2 Interventions

Participants with R/R indolent NHL including FL, MZL; aggressive NHL including DLBCL, transformed NHL; R/R MCL; R/R or treatment-naïve (TN) CLL/SLL will receive oral sonrotoclax in combination with zanubrutinib at an RP2D dose to further define the safety profile.

Group VI: Sonrotoclax + Zanubrutinib Combination Therapy Dose Escalation: Part 5 Experimental Treatment 3 Interventions

Participants with treatment naïve CLL/SLL will receive oral sonrotoclax in combination with obinutuzumab without and with zanubrutinib.

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

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]

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 has been approved for treating various lymphoproliferative disorders, providing a significant option for patients who have not responded to standard therapies.

A panel of experts identified unmet clinical needs in the use of zanubrutinib for specific lymphomas, such as Waldenström macroglobulinemia, and made recommendations for future studies to optimize its use, especially for less experienced healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unmet clinical needs in the use of zanubrutinib in malignant lymphomas (Waldenström macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma): A consensus-based position paper from an ad hoc expert panel. Zinzani, PL., Mauro, FR., Tedeschi, A., et al.[2023]

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 BTK inhibitor, demonstrated a 52.3% overall response rate in 44 Chinese patients with relapsed/refractory B-cell malignancies, indicating its potential effectiveness in treating these cancers.

The treatment was generally well tolerated, with the most common adverse event being a decrease in neutrophil count, and no serious complications like tumor lysis syndrome or new malignancies reported, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A two-part, single-arm, multicentre, phase I study of zanubrutinib, a selective Bruton tyrosine kinase inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. Song, Y., Sun, M., Qi, J., et al.[2022]

In a phase 2 study involving 41 patients with relapsed or refractory non-GCB DLBCL, zanubrutinib showed a modest overall response rate of 29.3% and a complete response rate of 17.1%, indicating some effectiveness in this challenging subtype of lymphoma.

The safety profile of zanubrutinib was consistent with previous studies, with 48.8% of patients experiencing grade ≥ 3 adverse events, but no major hemorrhage or atrial fibrillation was reported, suggesting it may be a relatively safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for relapsed or refractory non-germinal center diffuse large B-cell lymphoma. Yang, H., Xiang, B., Song, Y., 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]

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]

References

1. China pubmed.ncbi.nlm.nih.gov

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

2. 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]

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

BTK Inhibitor Options Expand for CLL/SLL. [2023]

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

Zanubrutinib, obinutuzumab, and venetoclax with minimal residual disease-driven discontinuation in previously untreated patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: a multicentre, single-arm, phase 2 trial. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Unmet clinical needs in the use of zanubrutinib in malignant lymphomas (Waldenström macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma): A consensus-based position paper from an ad hoc expert panel. [2023]

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

8. England pubmed.ncbi.nlm.nih.gov

A two-part, single-arm, multicentre, phase I study of zanubrutinib, a selective Bruton tyrosine kinase inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. [2022]

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

Zanubrutinib monotherapy for relapsed or refractory non-germinal center diffuse large B-cell lymphoma. [2022]

10. 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]

11. England pubmed.ncbi.nlm.nih.gov

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