BGB-11417 for Mantle Cell Lymphoma

Recruiting at 129 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

126 Participants Needed

Trial Summary

What is the purpose of this trial?

The study consists of two parts. Part 1 determines the safety and tolerability of BGB-11417 (sonrotoclax) monotherapy, the maximum tolerated dose, and the recommended Phase 2 dose of BGB-11417 monotherapy for relapsed or refractory mantle cell lymphoma. Part 2 evaluates efficacy of BGB-11417 monotherapy at the recommended Phase 2 dose with recommended ramp-up schedule from Part 1.

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-11417, Sonrotoclax, for treating Mantle Cell Lymphoma?

Research shows that venetoclax, a drug similar to BGB-11417, has been effective in treating mantle cell lymphoma, with studies reporting overall response rates of up to 50% in relapsed patients. Additionally, combining venetoclax with other treatments has shown high response rates, suggesting potential effectiveness for similar drugs like BGB-11417. ^{1 2 3 4 5}

What is known about the safety of BGB-11417 (Sonrotoclax) in humans?

There is no specific safety data available for BGB-11417 (Sonrotoclax) in the provided research articles. However, similar drugs like venetoclax, which also target BCL-2, have been generally well tolerated in clinical trials, with common side effects including nausea, diarrhea, and blood-related issues like anemia and neutropenia (low white blood cell count). ^{1 3 6 7 8}

How is the drug BGB-11417 (Sonrotoclax) different from other treatments for mantle cell lymphoma?

BGB-11417 (Sonrotoclax) is unique because it targets BCL2, a protein that helps cancer cells survive, similar to venetoclax, but may offer a different approach or improved effectiveness in overcoming resistance seen with other BCL2 inhibitors. ^{1 3 9 10 11}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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 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 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]

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 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]

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]

References

1. United States 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. [2023]

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

Adding venetoclax to lenalidomide and rituximab is safe and effective in patients with untreated mantle cell lymphoma. [2023]

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

Cotargeting of BCL2 with Venetoclax and MCL1 with S63845 Is Synthetically Lethal In Vivo in Relapsed Mantle Cell Lymphoma. [2020]

4. United States 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. [2020]

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

Brexucabtagene Autoleucel: A Novel Chimeric Antigen Receptor T-cell Therapy for the Treatment of Mantle Cell Lymphoma. [2022]

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

Phase I First-in-Human Study of Venetoclax in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma. [2018]

7. Switzerland 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Venetoclax for the treatment of chronic lymphocytic leukemia. [2022]

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

Acalabrutinib for mantle cell lymphoma. [2021]

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

Targeting Refractory Mantle Cell Lymphoma for Imaging and Therapy Using C-X-C Chemokine Receptor Type 4 Radioligands. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study. [2021]