BGB-16673 Combination for B-Cell Lymphoma

Recruiting at 52 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

Must not be taking: Bcl-2 inhibitors

Disqualifiers: Treatment-naive, Brain metastasis, others

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to measure the safety, preliminary antitumor activity, pharmacokinetics, and pharmacodynamics with BGB-16673 in combination with other agents in participants with relapsed or refractory (R/R) B-cell malignancies. This study is structured as a master protocol with separate substudies. This study currently includes four substudies, and more substudies may be added as other combination agents are identified.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug BGB-16673 Combination for B-Cell Lymphoma?

Zanubrutinib, a component of the BGB-16673 combination, has shown effectiveness in treating B-cell lymphoma, particularly in relapsed and refractory cases, by providing deep and sustained remissions. Additionally, in a study with chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL) patients, zanubrutinib combined with obinutuzumab showed high response rates, indicating its potential effectiveness in similar conditions. ^{1 2 3 4 5}

What safety data exists for the treatment Zanubrutinib (BGB-3111) in humans?

Zanubrutinib, a treatment for B-cell lymphoma, has been generally well tolerated in clinical trials. Common side effects include infections, low white blood cell counts (neutropenia), bruising, cough, diarrhea, and fatigue. Serious side effects were rare, and the treatment was considered safe for most patients. ^{3 4 6 7 8}

What makes the BGB-16673 combination drug unique for treating B-cell lymphoma?

The BGB-16673 combination drug is unique because it includes zanubrutinib, a highly selective Bruton tyrosine kinase (BTK) inhibitor, which has shown promising results in achieving deep and sustained remissions in relapsed and refractory B-cell lymphomas. This combination leverages targeted therapy, which is a more precise approach compared to traditional treatments, potentially offering better outcomes for patients with difficult-to-treat lymphomas. ^{1 3 7 9 10}

Research Team

Study Director

Principal Investigator

BeiGene

Eligibility Criteria

This trial is for adults with B-cell malignancies that have come back or didn't respond to treatment. They should not have tried Bruton tyrosine kinase inhibitors, or if they did, stopped without disease progression. Participants need a confirmed diagnosis, be relatively active (ECOG 0-2), and have organs working well. They must understand the study and agree to its rules, including birth control measures.

Inclusion Criteria

I can sign and follow the informed consent form for the trial.

I have a confirmed relapsed or refractory B-cell cancer.

My cancer can be measured by medical tests.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Sequential cohorts of increasing dose level combinations of BGB-16673 and other agents are evaluated in participants with selected B-cell malignancies

Up to approximately 3 years

Safety Expansion

Cohorts of select dose level combinations of BGB-16673 and other agents are evaluated for safety in participants with selected B-cell malignancies

Up to approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• BGB-16673
• Sonrotoclax
• Zanubrutinib

Trial Overview The trial tests BGB-16673 combined with other drugs in people with relapsed/refractory B-cell cancers. It's organized into substudies within a master protocol; initially featuring two substudies but may include more later on. The focus is on safety, cancer-fighting ability, how the body processes the drugs (pharmacokinetics), and their effects on the body (pharmacodynamics).

Participant Groups

Group I: Substudy 4 Part 1b: Safety Expansion Experimental Treatment 3 Interventions

Cohorts of select dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies.

Group II: Substudy 4 Part 1a: Dose Escalation Experimental Treatment 3 Interventions

Sequential cohorts of increasing dose level combinations of BGB-16673 and glofitamab will be evaluated in participants with selected B-cell malignancies. Participants will receive obinutuzumab as pretreatment prior to the start of combination treatment.

Group III: Substudy 3 Part 1b: Safety Expansion Experimental Treatment 2 Interventions

Cohorts of select dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies.

Group IV: Substudy 3 Part 1a: Dose Escalation Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose level combinations of BGB-16673 and mosunetuzumab will be evaluated in participants with selected B-cell malignancies.

Group V: Substudy 2 Part 1b: Safety Expansion Experimental Treatment 2 Interventions

Cohorts of select dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies.

Group VI: Substudy 2 Part 1a: Dose Escalation Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose level combinations of BGB-16673 and zanubrutinib will be evaluated in participants with selected B-cell malignancies.

Group VII: Substudy 1 Part 1b: Safety Expansion Experimental Treatment 2 Interventions

Cohorts of select dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies.

Group VIII: Substudy 1 Part 1a: Dose Escalation Experimental Treatment 2 Interventions

Sequential cohorts of increasing dose level combinations of BGB-16673 and sonrotoclax will be evaluated in participants with selected B-cell malignancies.

BGB-16673 is already approved in United States for the following indications:

Approved in United States as BGB-16673 for:

• Relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) following 2 or more prior lines of therapy including a BTK inhibitor and a BCL-2 inhibitor

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Findings from Research

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 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]

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, 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]

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, a selective BTK inhibitor, was well-tolerated in a phase 1 study with 144 patients, showing no dose-limiting toxicities and achieving over 95% BTK occupancy in blood cells at all tested doses.

In patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), zanubrutinib demonstrated a remarkable overall response rate of 96.2% and a 100% estimated progression-free survival at 12 months, indicating strong efficacy with low major toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Tam, CS., Trotman, J., Opat, S., et al.[2021]

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, 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]

Zanubrutinib, a Bruton's tyrosine kinase inhibitor, is primarily metabolized by the CYP3A enzyme, as shown by significant changes in its pharmacokinetics when coadministered with rifampin (a CYP3A inducer) and itraconazole (a CYP3A inhibitor).

The study demonstrated that the pharmacokinetics of zanubrutinib were consistent across Asian and non-Asian subjects, indicating that no dose adjustments are needed based on ethnicity, and the drug was well tolerated in participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects. Mu, S., Tang, Z., Novotny, W., 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]

References

1. 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]

2. 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]

3. China pubmed.ncbi.nlm.nih.gov

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

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

Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. [2021]

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

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

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. Germany pubmed.ncbi.nlm.nih.gov

Effect of rifampin and itraconazole on the pharmacokinetics of zanubrutinib (a Bruton's tyrosine kinase inhibitor) in Asian and non-Asian healthy subjects. [2022]

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

Zanubrutinib: First Approval. [2020]