BGB-11417 for Mantle Cell Lymphoma

Not currently recruiting at 156 trial locations

Overseen By BeiGene

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BeiGene

Must not be taking: BCL-2 inhibitors

Disqualifiers: CNS involvement, Prior malignancy, Cardiovascular disease, 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 tests a new treatment called BGB-11417 (Sonrotoclax) for individuals with mantle cell lymphoma (MCL), a type of blood cancer, who have not responded to other treatments. The first part of the study determines the treatment's safety and identifies the optimal dose. The second part evaluates the treatment's effectiveness at that dose. Individuals diagnosed with MCL, who have tried other treatments and still have measurable disease, might be suitable candidates. As a Phase 1/Phase 2 trial, this study aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to be among the first to benefit from this new therapy.

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 BGB-11417 is likely to be safe for humans?

Research shows that sonrotoclax, the treatment under study, is generally safe for patients with mantle cell lymphoma. Earlier studies indicated that patients experienced manageable side effects, which were not severe enough to discontinue treatment. Overall, the treatment proved safe for most participants. Prospective participants should consult a doctor if they have concerns about joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for mantle cell lymphoma, like chemotherapy and targeted therapies, focus on killing cancer cells or inhibiting specific proteins that help cancer grow. But BGB-11417 is unique because it uses a novel mechanism to target these cancer cells more precisely. Researchers are excited about BGB-11417 because it offers a new approach by potentially disrupting the cancer cell's internal processes more effectively, which could lead to better outcomes and fewer side effects. This innovation makes it a promising option for patients who might not respond well to existing treatments.

What evidence suggests that BGB-11417 might be an effective treatment for mantle cell lymphoma?

Research has shown that sonrotoclax, also known as BGB-11417, yields promising results for treating relapsed or refractory mantle cell lymphoma. Studies have reported a high overall response rate, with many patients experiencing a reduction or disappearance of their cancer. The treatment is generally well-tolerated, with manageable side effects. In this trial, participants will receive sonrotoclax alone, which improved patients' response to treatment in previous studies. This suggests that sonrotoclax could be an effective option for those battling this type of lymphoma. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people with a confirmed diagnosis of mantle cell lymphoma (MCL) who have relapsed or are not responding to treatment. They must have measurable disease, previous treatments including CD20-based therapy and BTK inhibitors, and be in fairly good health based on ECOG status. People can't join if they've had certain recent transplants, active severe infections, cardiovascular issues, prior Bcl-2 inhibitor use like venetoclax, or other cancers within the last 3 years.

Inclusion Criteria

My organs are working well.

My diagnosis of mantle cell lymphoma is confirmed by tissue analysis.

My condition has returned or didn't respond to treatment.

Exclusion Criteria

I have a serious heart condition.

I am currently being treated for a serious infection.

My lymphoma 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

Part 1: Safety and Tolerability

Determines the safety and tolerability of BGB-11417 monotherapy, the maximum tolerated dose, and the recommended Phase 2 dose

Duration not specified

Part 2: Efficacy Evaluation

Evaluates efficacy of BGB-11417 monotherapy at the recommended Phase 2 dose with recommended ramp-up schedule from Part 1

Up to 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BGB-11417

Trial Overview The study tests BGB-11417 as a single agent for MCL that's come back or isn't getting better after treatment. It has two parts: first finding the safest dose and then checking how well it works at that dose against MCL.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

Participants will receive sonrotoclax

Who Is Running the Clinical Trial?

BeiGene

Lead Sponsor

Trials

216

Recruited

32,500+

Published Research Related to This Trial

In a multicenter study of 28 patients with untreated mantle cell lymphoma (MCL), the combination of lenalidomide, rituximab, and venetoclax demonstrated a high overall response rate of 96% and a complete response rate of 86%, indicating strong efficacy for this treatment regimen.

The treatment was found to be safe, with no dose-limiting toxicities reported, although common side effects included neutropenia and thrombocytopenia, suggesting that this combination could be a promising option for patients who are ineligible for transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. Phillips, TJ., Bond, D., Takiar, R., et al.[2023]

Venetoclax is an effective treatment for chronic lymphocytic leukemia (CLL) patients with 17p deletion, showing high efficacy as a single agent in relapsed/refractory cases, including those with high-risk features.

The drug is generally safe, with neutropenia being the most common serious side effect, and the risk of tumor lysis syndrome can be managed through careful dosing and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of chronic lymphocytic leukemia. Gentile, M., Petrungaro, A., Uccello, G., et al.[2022]

Acalabrutinib, an oral Bruton tyrosine kinase inhibitor, has shown an impressive overall response rate of 81% in patients with relapsed mantle cell lymphoma (MCL), indicating its efficacy as a treatment option.

This novel therapy is not only approved for relapsed MCL but is also being tested as a first-line treatment, highlighting its potential to improve outcomes for patients with this challenging type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acalabrutinib for mantle cell lymphoma. Witzig, TE., Inwards, D.[2021]

Venetoclax, a BCL2-targeting drug, shows promising anticancer activity in mantle cell lymphoma (MCL), but resistance mechanisms involving proapoptotic proteins BIM and NOXA complicate its effectiveness.

Combining venetoclax with the MCL1 inhibitor S63845 resulted in synthetic lethality in patient-derived xenografts of relapsed MCL, suggesting this combination could be a novel treatment strategy for patients with chemoresistant MCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma. Prukova, D., Andera, L., Nahacka, Z., et al.[2020]

In a study of 24 patients with relapsed mantle cell lymphoma (MCL) who had undergone multiple prior therapies, venetoclax treatment resulted in a 50% overall response rate and a 21% complete response rate, with a median follow-up of 17 months.

Genomic analysis revealed that resistance to venetoclax is linked to mutations in non-BCL2 genes, with specific alterations like SMARCA4 and KMT2C/D emerging after treatment progression, indicating a need for further research into combination therapies and the mechanisms of resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of venetoclax in high risk relapsed mantle cell lymphoma (MCL) - outcomes and mutation profile from venetoclax resistant MCL patients. Zhao, S., Kanagal-Shamanna, R., Navsaria, L., et al.[2020]

In a study of 57 patients with relapsed/refractory mantle cell lymphoma (MCL), lenalidomide showed a 35% overall response rate, with a median duration of response lasting 16.3 months for those who responded.

The treatment was associated with manageable side effects, primarily neutropenia (46%), thrombocytopenia (30%), and anemia (13%), indicating that lenalidomide can be an effective option for patients with advanced MCL who have undergone multiple prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. Zinzani, PL., Vose, JM., Czuczman, MS., et al.[2021]

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 the pivotal ZUMA-2 trial, brexucabtagene autoleucel (brexu-cel) showed high efficacy in treating relapsed or refractory mantle cell lymphoma, with an objective response rate of 85% and a complete response rate of 59%, even among high-risk patients.

While brexu-cel has a similar toxicity profile to other CAR T-cell therapies, it is associated with significant treatment-related adverse effects, including severe cytopenias (94%) and neurotoxicity (31%), highlighting the need for careful management by a specialized medical team.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. Anderson, MK., Torosyan, A., Halford, Z.[2022]

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]

Citations

1. ajmc.com ajmc.com/view/positive-topline-results-seen-for-sonrotoclax-in-r-r-mantle-cell-lymphoma

Positive Topline Results Seen for Sonrotoclax in R ... - AJMC Sonrotoclax showed significant efficacy in relapsed or refractory mantle cell lymphoma, achieving a high overall response rate and manageable ...

2. targetedonc.com targetedonc.com/view/promising-bcl2-inhibitor-shows-efficacy-in-relapsed-mantle-cell-lymphoma

Promising BCL2 Inhibitor Shows Efficacy in Relapsed ... Sonrotoclax achieved its primary endpoint of overall response rate in a phase 1/2 study for relapsed/refractory mantle cell lymphoma. The study ...

3. onclive.com onclive.com/view/sonrotoclax-plus-zanubrutinib-generates-durable-responses-in-r-r-mantle-cell-lymphoma

Sonrotoclax Plus Zanubrutinib Generates Durable ... Sonrotoclax combined with zanubrutinib achieved a 79% ORR and 66% CR rate in patients with relapsed/refractory MCL. No dose-limiting toxicities ...

4. cancernetwork.com cancernetwork.com/view/sonrotoclax-meets-primary-orr-end-point-in-mantle-cell-lymphoma

Sonrotoclax Meets Primary ORR End Point in Mantle Cell ... Sonrotoclax exhibited favorable efficacy and safety outcomes in adult patients with relapsed/refractory mantle cell lymphoma (MCL) following ...

5. haematologica.org haematologica.org/article/view/12767

DP003 | COMBINATION TREATMENT WITH NOVEL BCL2 ... RESULTS: As of 6 Dec 2024, 49 pts with R/R MCL were enrolled and treated (sonro 80 mg, n=6; 160 mg, n=13; 320 mg, n=25; 640 mg, n=5): 7 were in ...

6. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/3032/500125/Monotherapy-with-Second-Generation-BCL2-Inhibitor

Monotherapy with Second-Generation BCL2 Inhibitor ... A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Bcl-2 Inhibitor Bgb-11417 in Adult ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05471843

NCT05471843 | Study of BGB-11417 Monotherapy in ... The study consists of two parts. Part 1 determines the safety and tolerability of BGB-11417 (sonrotoclax) monotherapy, the maximum tolerated dose, ...