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

Not currently recruiting at 94 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: BeiGene

Must not be taking: Bcl-2 inhibitors

Disqualifiers: CNS involvement, Plasma cell neoplasm, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and optimal dosage of a new treatment for certain B-cell lymphomas, which are types of blood cancers. It tests BGB-11417 (also known as Sonrotoclax) both alone and in combination with other drugs like zanubrutinib and obinutuzumab. The trial is open to individuals with specific types of lymphoma, such as non-Hodgkin lymphoma or chronic lymphocytic leukemia, that have not responded to previous treatments. Participants should have active disease symptoms affecting their daily life and have already tried at least one other therapy. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Will I have to stop taking my current medications?

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 shows that BGB-11417, also known as sonrotoclax, targets specific proteins in cancer cells to inhibit their growth. It is over ten times more powerful than venetoclax, another drug with similar uses.

Early findings suggest that BGB-11417 is generally well-tolerated, with serious side effects being uncommon. However, more information is needed to fully understand all possible side effects, as this is early research.

When combined with zanubrutinib, a drug that blocks a protein aiding cancer cell growth, BGB-11417 continues to show promise. Zanubrutinib has been studied before and is generally considered safe for humans. Researchers are testing these drugs together to assess their combined effectiveness and safety.

While initial safety data looks promising, ongoing studies are crucial to confirm these results. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for B-cell lymphoma because they offer a unique approach compared to existing options like chemotherapy and monoclonal antibodies. Sonrotoclax is a novel oral treatment that targets specific proteins to trigger cancer cell death, which could potentially offer better precision and fewer side effects. When combined with zanubrutinib, a targeted therapy known for inhibiting a protein critical for cancer cell survival, these treatments aim to enhance efficacy and safety. This combination approach seeks to improve outcomes for patients with different types of B-cell lymphomas, including those who have not responded to other treatments.

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

Research has shown that BGB-11417, also known as sonrotoclax, is a strong Bcl-2 inhibitor, blocking a protein that cancer cells need to survive. In studies with patients whose chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) returned or did not respond to treatment, sonrotoclax showed promising results even at lower doses. In this trial, some participants will receive sonrotoclax as monotherapy, while others will receive it with zanubrutinib, a drug targeting another cancer-related protein. The combination has been effective in treating B-cell cancers and might help stop cancer cells from growing and spreading. These findings suggest that both sonrotoclax alone and with zanubrutinib could offer new hope for treating B-cell lymphomas. ^{1 2 3 5 6}

Who Is on the Research Team?

Study Director

Principal Investigator

BeiGene

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation and Expansion

Participants receive BGB-11417 monotherapy and in combination with zanubrutinib and obinutuzumab to determine safety, tolerability, and define the maximum tolerated dose

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BGB-11417

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

In a phase 2 trial involving 39 patients with treatment-naive chronic lymphocytic leukaemia or small lymphocytic lymphoma, the combination therapy of zanubrutinib, obinutuzumab, and venetoclax (BOVen) achieved an impressive 89% rate of undetectable minimal residual disease (MRD) in both blood and bone marrow after a median treatment duration of 10 months.

The BOVen regimen was well tolerated, with the most common side effects being thrombocytopenia and neutropenia, and it supports the idea of using MRD as a biomarker to guide treatment duration, potentially allowing for earlier therapy discontinuation.

NCBI (Pubmed)

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. Soumerai, JD., Mato, AR., Dogan, A., 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 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 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]

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 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]

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 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 III ALPINE trial, zanubrutinib, a second-generation BTK inhibitor, demonstrated superior efficacy compared to ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Zanubrutinib not only showed a better safety profile but also significantly improved progression-free survival for patients, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04277637

NCT04277637 | Study of Bcl-2 Inhibitor Sonrotoclax (BGB- ... The purpose of this study is to determine the safety, tolerability; and to define the maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D); and ...

2. beonemedinfo.com beonemedinfo.com/CongressDocuments/Zhang_BGB-11417-101_nHL-WM_CSCO_Abstract_2024.pdf

CSCO 2024 A phase 1 study with the novel B-cell ... BGB-11417 is a highly selective Bcl-2 inhibitor with potency >10 times that of venetoclax in biochemical assays. BGB-11417 has favorable pharmacokinetics and a ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06859008

Study Details | NCT06859008 | Zanubrutinib in ... Zanubrutinib, a type of tyrosine kinase inhibitor, blocks a protein called Bruton tyrosine kinase (BTK), which may help keep cancer cells from growing.

4. beonemedinfo.com beonemedinfo.com/CongressDocuments/Gui%C3%A8ze_BGB-11417-101_SFH_Presentation_2023.pdf

BGB-11417 (Bcl-2 Inhibitor) Monotherapy or Combination ... CLL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; MCL, mantle cell lymphoma; MZL, marginal zone lymphoma ...

5. trialx.com trialx.com/clinical-trials/listings/316393/zanubrutinib-in-combination-with-sonrotoclax-for-the-treatment-of-underrepresented-ethnic-and-racial-minorities-with-relapsed-or-refractory-b-cell-non-hodgkin-lymphoma/

Zanubrutinib in Combination With Sonrotoclax for the Treatment ... Zanubrutinib and sonrotoclax have been shown to be an effective treatment for B-cell cancers. Giving zanubrutinib in combination with sonrotoclax may be ...

6. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(22)01326-X/fulltext

CLL-118 A Phase 1 Study With the Novel B-Cell ... BGB-11417-101 (NCT04277637) is an ongoing, first-in-human, phase 1/1b dose-escalation/expansion study evaluating the safety, tolerability, maximum tolerated ...