BGB-11417 for Waldenström's Macroglobulinemia

Not currently recruiting at 84 trial locations

Overseen By Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: BeOne Medicines

Disqualifiers: CNS involvement, Aggressive lymphoma, Recent malignancies, others

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

Prior Safety Data This treatment has passed at least one previous human trial

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 tests a new treatment called sonrotoclax (BGB-11417) for individuals with Waldenström's Macroglobulinemia (WM), a type of blood cancer. Researchers aim to assess its safety and effectiveness for those whose cancer has returned or hasn't responded to other treatments, as well as for those who haven't been treated yet. Some participants will take sonrotoclax alone, while others will take it with another drug, zanubrutinib. Individuals diagnosed with WM who have had trouble with past treatments or haven't tried any treatments yet might be a good fit. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 sonrotoclax (BGB-11417) is generally safe for patients with relapsed or refractory Waldenström's Macroglobulinemia (R/R WM). Most patients in earlier studies tolerated the treatment well without serious side effects. Some experienced mild to moderate side effects, but these were uncommon.

The safety of combining sonrotoclax with zanubrutinib is still under investigation. Early research suggests this combination might also be safe with manageable side effects. This trial is in a middle stage, indicating there is enough safety information to continue testing. This usually suggests the treatment is fairly safe, but ongoing studies will provide more details. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about sonrotoclax for Waldenström's Macroglobulinemia (WM) because it targets cancer cells differently than most current treatments. While traditional therapies for WM often rely on chemotherapy or proteasome inhibitors, sonrotoclax works by inhibiting BCL-2 proteins, which help cancer cells survive. This new mechanism of action could potentially provide an effective option for patients who have become resistant or intolerant to existing therapies like BTK inhibitors or anti-CD20 antibody-based treatments. Additionally, when combined with zanubrutinib, another novel drug, sonrotoclax may offer a powerful new approach for those with previously untreated WM.

What evidence suggests that this trial's treatments could be effective for Waldenström's Macroglobulinemia?

Research has shown that sonrotoclax (BGB-11417) yields promising results for treating Waldenström's Macroglobulinemia (WM). In one study, 78.3% of patients experienced either tumor shrinkage or halted cancer growth. Additionally, most patients tolerated sonrotoclax well.

In this trial, participants in different cohorts will receive sonrotoclax either alone or with zanubrutinib. The combination with zanubrutinib is being tested in participants who have not received prior treatment, aiming to improve outcomes for people with WM. These findings suggest that sonrotoclax, both alone and with zanubrutinib, could be a strong option for treating this condition. ^{1 2 3 4 6}

Who Is on the Research Team?

Study Director

Principal Investigator

BeOne Medicines

Are You a Good Fit for This Trial?

This trial is for people with Waldenström's Macroglobulinemia who have tried other treatments that didn't work or stopped working. They should not have had any other cancers in the last two years, no brain involvement from their disease, and no recent serious infections.

Inclusion Criteria

My disease did not improve or got worse with the last treatment, or I couldn't tolerate it.

My organs are working well.

I have been diagnosed with Waldenstrom macroglobulinemia.

Exclusion Criteria

I haven't had a severe infection or needed IV antibiotics in the last 2 weeks.

My lymphoma has changed into a more aggressive form.

I have not had any other cancers in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sonrotoclax as monotherapy or in combination with zanubrutinib, depending on their cohort

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• BGB-11417

Trial Overview The study tests BGB-11417, a drug designed to block a protein called BCL2 that helps cancer cells survive. Participants are grouped into three cohorts to assess how well the drug works and its safety in those with relapsed/refractory Waldenström's Macroglobulinemia.

How Is the Trial Designed?

Group I: Cohort 4 Experimental Treatment 2 Interventions

Participants with previously untreated WM will receive sonrotoclax and zanubrutinib combination therapy for a fixed duration.

Group II: Cohort 3 Experimental Treatment 1 Intervention

Participants with R/R disease to a BTK inhibitor treatment and are unsuitable for chemoimmunotherapy will receive sonrotoclax at a standard dose, given orally once daily.

Group III: Cohort 2 Experimental Treatment 1 Intervention

Participants with R/R disease to anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor and were intolerant to BTK inhibitor will receive sonrotoclax at a standard dose, given orally once daily.

Group IV: Cohort 1 Experimental Treatment 1 Intervention

Participants with R/R disease to both Bruton tyrosine kinase (BTK) inhibitor and anti-CD20 antibody-based systemic therapy containing chemotherapy or proteasome inhibitor will receive sonrotoclax at a standard dose, given orally once daily.

Who Is Running the Clinical Trial?

BeOne Medicines

Lead Sponsor

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a study of 91 patients with Waldenström's macroglobulinemia, 19 exhibited various ocular impairments, including serious conditions like central retinal vein occlusion and macular detachments, highlighting the potential sight-threatening nature of these manifestations.

Treatment involving plasmapheresis followed by chemotherapy, with or without rituximab, led to significant improvements in eye health for 15 patients, demonstrating the efficacy of recent therapeutic advances in managing ocular symptoms associated with WM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Spectrum of Ocular Manifestations in Patients with Waldenström's Macroglobulinemia. Dammacco, R., Lisch, W., Kivelä, TT., et al.[2022]

A 73-year-old male with Waldenstrom's Macroglobulinemia exhibited a serous macular detachment, which was analyzed using fluorescein and indocyanine green angiography before and after chemotherapy, revealing important details about the condition.

The study suggests that the serous detachment may be linked to various factors, including toxic changes in the retinal pigment epithelium and abnormal pressure dynamics between the optic disc and surrounding spaces, highlighting the complexity of the disease's effects on the retina.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Serous detection of the neuroretina in Waldenström disease. A case report]. Feigl, B., Sill, H., Haas, A.[2015]

In a phase I trial involving 106 patients with various subtypes of non-Hodgkin lymphoma, venetoclax, a BCL-2 inhibitor, was found to be generally well tolerated, with a 44% overall response rate across different lymphoma types.

The study identified 1,200 mg as the recommended dose for future studies in follicular lymphoma and diffuse large B-cell lymphoma, while 800 mg was effective for mantle cell lymphoma, indicating varying efficacy based on lymphoma subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma. Davids, MS., Roberts, AW., Seymour, JF., et al.[2018]

In a phase 2 trial involving 45 patients with relapsed or refractory chronic lymphocytic leukaemia, 76% achieved undetectable minimal residual disease (uMRD) after a triple therapy regimen of obinutuzumab, acalabrutinib, and venetoclax, indicating promising efficacy.

Despite the high rate of uMRD, the trial did not meet the predefined activity threshold, suggesting that further research is needed to evaluate the benefits of this triple therapy compared to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obinutuzumab, acalabrutinib, and venetoclax, after an optional debulking with bendamustine in relapsed or refractory chronic lymphocytic leukaemia (CLL2-BAAG): a multicentre, open-label, phase 2 trial. Cramer, P., Fürstenau, M., Robrecht, S., et al.[2022]

Waldenstrom's macroglobulinemia (WM) is characterized by the production of monoclonal immunoglobulin M (IgM) and requires standardized diagnostic criteria, including the presence of IgM monoclonal protein and lymphoplasmacytic cells in the marrow or lymph nodes.

The establishment of uniform response criteria for WM is crucial for accurately assessing treatment responses, remission durations, and survival outcomes in clinical trials, similar to criteria used for other blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Uniform response criteria in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Weber, D., Treon, SP., Emmanouilides, C., et al.[2007]

Venetoclax, an oral BCL-2 inhibitor, shows promising efficacy for treating patients with t(11;14) plasma cell disorders, both alone and in combination with other therapies.

Despite its effectiveness, the BELLINI trial indicated an increased mortality risk primarily in patients without the t(11;14) genetic marker, highlighting the need for careful patient selection in clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How do we manage t(11;14) plasma cell disorders with venetoclax? Chakraborty, R., Bhutani, D., Lentzsch, S.[2022]

In a review of ten patients with relapsed/refractory multiple myeloma (RRMM) treated with venetoclax, the overall response rate was 78%, indicating its potential efficacy, especially in patients with the t(11;14) genetic alteration.

While venetoclax treatment showed promising results, it was associated with hematologic toxicities requiring transfusions and gastrointestinal side effects, highlighting the need for monitoring and management of these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world data on safety and efficacy of venetoclax-based regimens in relapsed/refractory t(11;14) multiple myeloma. Basali, D., Chakraborty, R., Rybicki, L., et al.[2022]

A 71-year-old patient with Waldenström's macroglobulinemia, who was resistant to standard treatments, showed rapid clinical improvement when treated with idelalisib, suggesting its potential efficacy in this context.

This case highlights idelalisib as a viable treatment option for patients with Waldenström's macroglobulinemia who cannot receive ibrutinib due to complications like renal failure or other health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Idelalisib in a patient with refractory Waldenström's macroglobulinemia complicated by anuric renal failure: a case report. D'Aveni-Piney, M., Divoux, M., Busby-Venner, H., et al.[2019]

In a study of 106 patients with relapsed/refractory non-Hodgkin lymphoma, venetoclax showed a median progression-free survival of 5.4 months and a median duration of response of 14.9 months, indicating its effectiveness as a treatment.

The safety profile of venetoclax was manageable, with infrequent hematologic adverse events and common nonhematologic effects like nausea and diarrhea, which decreased after the first year of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Follow-up of Patients with Relapsed or Refractory Non-Hodgkin Lymphoma Treated with Venetoclax in a Phase I, First-in-Human Study. Davids, MS., Roberts, AW., Kenkre, VP., et al.[2023]

Venetoclax is an effective and well-tolerated treatment for advanced hematological malignancies, particularly in patients with chronic lymphocytic leukemia, showing a satisfactory overall event rate of 73%.

The most common adverse events associated with venetoclax include nausea, diarrhea, and thrombocytopenia, but these are generally mild and manageable, with few cases of severe complications like tumor lysis syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Bcl-2 Inhibitor Venetoclax in Hematological Malignancy: A Systematic Review and Meta-Analysis of Clinical Trials. Li, Q., Cheng, L., Shen, K., et al.[2020]

Venetoclax, a proapoptotic drug, has shown significant clinical activity in pediatric patients with relapsed or refractory leukemias, with 5 out of 10 patients achieving hematologic complete remission (CR) in a study conducted across 11 Polish pediatric hemato-oncology centers.

The drug appears particularly effective in certain leukemia subtypes, such as poor-prognosis acute lymphoblastic leukemia (ALL) with TCF::HLF fusion, suggesting that BH3-mimetics like venetoclax could be beneficial in targeted treatments for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax Use in Paediatric Haemato-Oncology Centres in Poland: A 2022 Survey. Bobeff, K., Pastorczak, A., Urbanska, Z., et al.[2023]

In a study of 45 pediatric patients with B-cell non-Hodgkin's lymphoma, both the CCCG-97 and BFM-90 chemotherapy protocols resulted in high complete response rates (88.9%), with the CCCG-97 group achieving a slightly higher rate of 95.2%.

The 5-year event-free survival rates were comparable between the two protocols, with 76.2% for CCCG-97 and 75.0% for BFM-90, indicating that both treatment strategies are effective and have manageable toxicity, primarily myelosuppression and mucositis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of the efficacy of CCCG-97 and BFM-90 protocols in the treatment for children with mature B-cell non-Hodgkin's lymphoma]. Meng, JH., Gao, YJ., Lu, FJ., et al.[2018]

Waldenstrom macroglobulinemia (WM) primarily affects older males, with common symptoms including fatigue, weight loss, splenomegaly, and lymphadenopathy, based on a study of 15 patients followed for an average of 82 months.

While WM is currently incurable, treatments such as chemotherapy, bortezomib, and thalidomide have been shown to improve therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical analysis of 15 patients with Waldenstrom macroglobulinemia]. Hu, Y., Chen, SL., Zhong, YP., et al.[2015]

Citations

1. haematologica.org haematologica.org/article/view/12770

DP006 | UPDATED SAFETY AND EFFICACY RESULTS ... CONCLUSIONS: Sonro monotherapy is tolerable across tested doses and has encouraging antitumor activity, with ORRs of 78.3% across dose levels ...

2. beonemedinfo.com beonemedinfo.com/CongressDocuments/Garcia-Sanz_BGB-11417-101_IWWM_Presentation_2024.pdf

Safety and Efficacy Results of a Phase 1 Study of the Novel ... WM is a rare, incurable, B-cell lymphoma, and more tolerable and effective treatments are needed for patients who experience progression on standard ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/1661.1/529928/BGB-11417-203-an-Ongoing-Phase-2-Study-of

BGB-11417-203, an Ongoing, Phase 2 Study of Sonrotoclax ... Bortezomib in Combination with Ibrutinib/Rituximab Is a Highly Effective and Well Tolerated First - Line Treatment for Waldenström's ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05952037

NCT05952037 | A Study to Investigate Efficacy and Safety ... This study will test whether sonrotoclax (BGB-11417) can be used to improve outcomes in participants with Waldenström's Macroglobulinemia (WM) both when ...

5. library.ehaweb.org library.ehaweb.org/eha/2025/eha2025-congress/4160293/chan.y.cheah.updated.safety.and.efficacy.results.of.a.phase.1.study.of.the.html?f=

UPDATED SAFETY AND EFFICACY RESULTS OF A ... With a median follow-up of 22.1 months (range, 11.2-24.0), median progression-free survival was not reached (95% CI, 19.7-NE) (Figure). Nine patients had a BTK ...

6. beonemedinfo.com beonemedinfo.com/CongressDocuments/Cheah_BGB-11417-101_Mono_WM_EHA_Poster_2025.pdf

Updated Safety and Efficacy Results of a Phase 1 Study of ... CONCLUSIONS. • Sonrotoclax monotherapy was well tolerated in patients with. R/R WM and has durable antitumor activity in heavily pretreated.