BGB-16673 Combination for B-Cell Lymphoma

Recruiting at 64 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, BGB-16673, combined with other medications to evaluate its safety and effectiveness in treating B-cell lymphoma that has returned or is unresponsive to treatment. Researchers aim to determine if this combination can slow cancer cell growth and how the body processes the drugs. The study includes different groups, each testing various drug combinations to identify the most effective one. Individuals with relapsed or hard-to-treat B-cell lymphoma who have noticeable symptoms might be suitable for this trial. As a Phase 1/Phase 2 trial, the study focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

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.

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

Research has shown that BGB-16673, when combined with other treatments, holds promise for patients with certain B-cell cancers that have returned or are difficult to treat. The FDA has fast-tracked BGB-16673 for some conditions, indicating potential benefits and a reasonable safety record in earlier studies.

When used with zanubrutinib, early results have shown positive responses in patients with chronic lymphocytic leukemia (CLL) and other treatment-resistant B-cell cancers. This combination is undergoing further study to evaluate its efficacy and safety.

Combined with sonrotoclax, BGB-16673 continues to yield promising results, with patients responding well and safety being closely monitored in ongoing studies.

For combinations with mosunetuzumab and glofitamab, both are being tested for safety and effectiveness in treating similar B-cell cancers. Initial reports suggest these combinations are safe and effective for patients whose cancers have returned or did not respond to previous treatments.

As this is a Phase 1/2 trial, the primary goal is to ensure safety and determine the optimal dose. This phase represents an early step in clinical research, so while results are promising, more data is needed to fully understand safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BGB-16673 and its combination treatments for B-cell lymphoma because they offer unique mechanisms of action compared to standard therapies like chemotherapy or monoclonal antibodies alone. BGB-16673 is a potent BTK inhibitor, which specifically targets and blocks the Bruton's tyrosine kinase (BTK) pathway, crucial in the survival and proliferation of B-cell malignancies. The combinations with sonrotoclax, zanubrutinib, and other agents enhance this effect by attacking cancer cells through different pathways simultaneously, potentially leading to more effective results. Unlike traditional treatments, these combinations may offer a more targeted approach with the possibility of fewer side effects and improved 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 BGB-16673, when combined with other treatments, may aid in treating certain B-cell cancers that are recurrent or difficult to treat. Studies have found that BGB-16673 significantly reduces levels of a protein called BTK, which plays a key role in some B-cell cancers. For instance, some patients with a slow-growing type of non-Hodgkin lymphoma experienced complete recovery within a few months. In this trial, participants will receive different combinations of BGB-16673 with other drugs. One arm will evaluate BGB-16673 combined with zanubrutinib, which the FDA has prioritized for treating advanced chronic lymphocytic leukemia and small lymphocytic lymphoma due to its potential benefits. Other arms will test combinations with sonrotoclax and mosunetuzumab for safety and effectiveness, with early results showing promise. These combinations remain under study, but initial findings are encouraging for those with B-cell cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

BeOne Medicines

Lead Sponsor

Published Research Related to This Trial

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 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]

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 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 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, 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]

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]

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]

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This new study will check how safe and helpful a potential anticancer drug called BGB-16673 is in participants with R/R B-cell malignancies when it is given in ...

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A drug, BGB-16673, in combination with other ...

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BTK Degrader BGB-16673 Shows Durable Efficacy in ...

Complete responses were observed in one FL patient (time to CR: 3.3 months) and two MZL patients (time to CR: 3.6 and 13.7 months). Responses ...

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clinicaltrials.eu

clinicaltrials.eu/inn/bgb-16673/

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BGB-16673 is primarily being studied for B-cell malignancies (blood cancers), including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL) ...

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This new study will check how safe and helpful a potential anticancer drug called BGB-16673 is in participants with R/R B-cell malignancies when it is given in ...

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