BMS-986458 + Rituximab for Non-Hodgkin Lymphoma

Recruiting at 41 trial locations

Overseen By First line of the email MUST contain the NCT# and Site#

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Bristol-Myers Squibb

Must not be taking: Cereblon-modulating, CAR-T

Disqualifiers: ECOG ≥ 2, CNS involvement, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

308 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new treatment, BMS-986458, for individuals with non-Hodgkin lymphoma that hasn't responded to other treatments. The study examines how well this drug works alone and in combination with other anti-lymphoma medications, such as Rituximab. Individuals who have undergone at least two prior treatments for non-Hodgkin lymphoma and have noticeable disease on scans may be suitable for this trial. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial group, offering participants a chance to contribute to early-stage development and potentially benefit from a new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot have had certain treatments like CAR-T or radiotherapy recently. It's best to discuss your specific medications with the trial team.

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

Research has shown that BMS-986458 is generally well-tolerated. In previous studies, the most common side effects included mild joint pain (19.4%) and tiredness. These are low-grade side effects, meaning they are not severe. BMS-986458 works by breaking down a protein called BCL6, which helps certain lymphoma cells survive.

When combined with Rituximab, another drug for blood cancers, BMS-986458 also shows promise. Rituximab is widely used and generally safe, though it can cause mild allergic reactions during infusion.

Overall, researchers are carefully studying this treatment combination to ensure it is safe and effective for people with relapsed or hard-to-treat non-Hodgkin lymphoma. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about BMS-986458 for treating Non-Hodgkin Lymphoma because it represents a fresh approach compared to the standard treatments like Rituximab, CHOP therapy, or targeted therapies such as ibrutinib. BMS-986458 is unique as it introduces a new active ingredient that could potentially enhance the immune system's ability to fight cancer cells. This investigational drug is being tested both as a single agent and in combination with Rituximab, offering a novel mechanism of action that could lead to improved outcomes. Its combination with Rituximab, a well-known monoclonal antibody, could potentially result in a synergistic effect, enhancing the overall effectiveness against the lymphoma.

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

Research has shown that BMS-986458 could effectively treat non-Hodgkin lymphoma. It breaks down a protein called BCL6, which helps lymphoma cells survive and grow. In studies, BMS-986458 demonstrated strong anti-tumor effects in 80% of tested cell lines and patient samples with BCL6. In this trial, some participants will receive BMS-986458 alone, while others will receive it with Rituximab. Early trials with patients who had undergone many previous treatments showed promising results for the combination, supporting further research. This combination aims to enhance the treatment's effectiveness by attacking the lymphoma in different ways. ^{1 2 4 6 7}

Who Is on the Research Team?

Bristol-Myers Squibb

Principal Investigator

Bristol-Myers Squibb

Are You a Good Fit for This Trial?

This trial is for people with Non-Hodgkin Lymphoma who have tried at least two prior treatments. They must have a type of lymphoma that shows up on certain body scans and agree to follow a pregnancy prevention plan.

Inclusion Criteria

I have had at least 2 treatments for my lymphoma, including chemotherapy with rituximab.

I have follicular lymphoma, not type 3b, and have had at least 2 prior treatments.

Participants must accept and follow pregnancy prevention plan.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BMS-986458 as a single agent or in combination with anti-lymphoma agents

12 weeks

Bi-weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BMS-986458
• Rituximab

Trial Overview The study tests BMS-986458, both alone and combined with other anti-lymphoma drugs like Rituximab, to see how safe it is and if it works against relapsed/refractory non-Hodgkin Lymphoma.

How Is the Trial Designed?

Group I: Part B2 Experimental Treatment 4 Interventions

Combination Treatment

Group II: Part B1 Experimental Treatment 1 Intervention

Single Agent

Group III: Part A2 Experimental Treatment 4 Interventions

Combination Treatment

Group IV: Part A1 Experimental Treatment 1 Intervention

Single Agent

Who Is Running the Clinical Trial?

Bristol-Myers Squibb

Lead Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Published Research Related to This Trial

Rituximab combined with Bruton tyrosine kinase inhibitors (BTKis) shows potential efficacy in treating elderly patients with diffuse large B-cell lymphoma (DLBCL), based on a case study of two patients.

The treatment involved an initial two courses of the R-miniCHOP chemotherapy regimen followed by the combination therapy, suggesting a new strategy for managing DLBCL in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab combined with Bruton tyrosine kinase inhibitor to treat elderly diffuse large B-cell lymphoma patients: Two case reports. Zhang, CJ., Zhao, ML.[2023]

The LYM-2034 phase 2 trial involved 164 patients with non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL), comparing the efficacy of two treatment regimens: R-CHOP and VR-CAP.

The study highlights the heterogeneity of DLBCL, suggesting that different subtypes may require tailored treatment approaches, as evidenced by the comparison of traditional chemotherapy (R-CHOP) with the addition of bortezomib (VR-CAP).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subtype-specific therapy for DLBCL: are we there yet? Khan, N., Fisher, RI.[2021]

In patients with diffuse large B-cell lymphoma (DLBCL) who are Bcl-6 negative, the addition of rituximab (R) to standard CHOP chemotherapy significantly improves failure-free survival (76% vs. 9%) and overall survival (79% vs. 17%).

For Bcl-6 positive patients, there was no significant difference in treatment outcomes between R-CHOP and CHOP alone, indicating that the benefit of rituximab may be limited to those without Bcl-6 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic significance of Bcl-6 protein expression in DLBCL treated with CHOP or R-CHOP: a prospective correlative study. Winter, JN., Weller, EA., Horning, SJ., et al.[2021]

Rituximab is the first monoclonal antibody approved for treating B-cell lymphomas, showing significant effectiveness in conditions like follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma.

The combination of rituximab with standard chemotherapy agents (cyclophosphamide, doxorubicin, vincristine, and prednisone) has achieved the highest efficacy reported for treating diffuse large B-cell lymphoma and follicular lymphoma, while maintaining low toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evolving role of rituximab in the treatment of patients with non-Hodgkin's lymphoma. Traullé, C., Coiffier, BB.[2015]

In a study of 824 young patients with good-prognosis diffuse large-B-cell lymphoma, adding rituximab to CHOP-like chemotherapy significantly improved 3-year event-free survival (79% vs 59%) and overall survival (93% vs 84%).

The study identified two prognostic subgroups based on treatment response and disease characteristics, allowing for a more tailored therapeutic approach without increasing the frequency of adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised controlled trial by the MabThera International Trial (MInT) Group. Pfreundschuh, M., Trümper, L., Osterborg, A., et al.[2022]

In a phase 1 study involving 20 patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL), bortezomib could be safely added to the standard R-CHOP chemotherapy regimen at a dose of 1.3 mg/m2, with acceptable levels of toxicity.

The treatment showed promising efficacy, with a 95% complete response rate among evaluable patients and a 4-year overall survival rate of 75%, indicating that this combination could be a viable option for patients with these types of lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma. Furman, RR., Martin, P., Ruan, J., et al.[2022]

Combining rituximab, a monoclonal antibody, with antisense oligonucleotides (AS-ODNs) that down-regulate the antiapoptotic protein BCL-2 significantly enhances apoptosis in B-cell lymphoma cells and improves therapeutic outcomes, as shown in vitro with DoHH2 cells and in vivo in mouse models.

This combination therapy not only prolongs survival in mice with human lymphoma but also shows potential for curative effects with higher and repeated doses, suggesting a promising avenue for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced efficacy of therapy with antisense BCL-2 oligonucleotides plus anti-CD20 monoclonal antibody in scid mouse/human lymphoma xenografts. Smith, MR., Jin, F., Joshi, I.[2020]

Patients with diffuse large B-cell lymphomas that have genetic alterations in MYC, BCL2, and/or BCL6 tend to have poorer outcomes with standard RCHOP chemotherapy, leading to the suggestion of more intense treatment regimens.

There is currently insufficient evidence to recommend consolidative stem cell transplants for these patients, highlighting the need for collaborative clinical trials to determine the best treatment strategies for this high-risk group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6: Double hit and triple hit lymphomas and double expressing lymphoma. Rosenthal, A., Younes, A.[2018]

In a study of 567 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) treated with rituximab-CHOP (RCHOP), bone marrow (BM) involvement was found in 8.5% of cases and significantly worsened overall survival (OS) and event-free survival (EFS) rates.

Patients without BM involvement had a five-year OS of 76.3% and EFS of 67.5%, while those with BM involvement had much lower rates of 44.3% and 40.1%, respectively, indicating that BM involvement is a negative prognostic factor even with effective RCHOP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement. Kang, BW., Moon, JH., Chae, YS., et al.[2021]

BCL6 gene rearrangement was found in 19.5% of patients with diffuse large B-cell lymphoma and was linked to a non-germinal center B-cell immunophenotype, indicating a specific genetic profile associated with this cancer.

In patients treated with R-CHOP, there was a trend towards poorer overall survival for those with BCL6 rearrangement, suggesting that rituximab may change the impact of this genetic abnormality on patient outcomes, although further research is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlations between BCL6 rearrangement and outcome in patients with diffuse large B-cell lymphoma treated with CHOP or R-CHOP. Shustik, J., Han, G., Farinha, P., et al.[2021]

In a phase 2 trial involving 23 elderly patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the combination of oral lenalidomide and rituximab resulted in an overall response rate of 35%, with 8 patients achieving a complete response after maintenance therapy.

The treatment was generally safe, with manageable adverse effects primarily including neutropenia and thrombocytopenia, indicating that this regimen could be a viable option for elderly patients who have limited treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of lenalidomide and rituximab in elderly patients with relapsed or refractory diffuse large B-cell lymphoma: a phase 2 trial. Zinzani, PL., Pellegrini, C., Gandolfi, L., et al.[2020]

BCL6 is a key oncogene in various cancers, particularly B-cell lymphomas, and its inhibition can effectively kill lymphoma cells by blocking the recruitment of corepressor complexes that repress target genes.

BCL6 inhibitors have shown promise not only in diffuse large B-cell lymphomas but also in other cancers like leukemia and breast cancer, and their combination with other treatments has resulted in enhanced therapeutic effects, suggesting a strong potential for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Expanding Role of the BCL6 Oncoprotein as a Cancer Therapeutic Target. Cardenas, MG., Oswald, E., Yu, W., et al.[2021]

Rituximab, a monoclonal antibody, has significantly improved survival rates for patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) when used in combination with chemotherapy.

In patients with chronic lymphocytic leukaemia (CLL), rituximab-based chemoimmunotherapy has led to higher complete response and progression-free survival rates, demonstrating its efficacy in both untreated and relapsed cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rituximab for the treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukaemia. Hagemeister, F.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06090539

NCT06090539 | A Study to Assess BMS-986458 Alone and ... The purpose of this study is to evaluate the safety, tolerability, drug levels, and preliminary biological and clinical activity of BMS-986458, ...

2. news.bms.com news.bms.com/news/details/2025/Bristol-Myers-Squibb-Presents-Data-Across-Targeted-Protein-Degradation-Research-Including-CELMoD-Agents-and-BCL6-Ligand-Directed-Degrader-at-EHA-2025/default.aspx

Bristol Myers Squibb Presents Data Across Targeted ... Initial results evaluating 31 heavily pre-treated patients treated with BMS-986458 were promising and support continued development for the ...

3. mskcc.org mskcc.org/cancer-care/clinical-trials/24-050

A Phase 1 Study of BMS-986458 Alone and With ... BCL6 helps lymphoma cells survive and grow. By breaking down BCL6, BMS-986458 may slow lymphoma growth. If you join this study, you will get BMS-986458 alone or ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/429695

A Study to Assess BMS-986458 Alone and in Combination ... The purpose of this study is to evaluate the safety, tolerability, drug levels, and preliminary biological and clinical activity of ...

5. clinicaltrials.eu clinicaltrials.eu/trial/study-on-bms-986458-and-rituximab-for-patients-with-relapsed-or-refractory-non-hodgkin-lymphoma/

Study on BMS-986458 and Rituximab for Patients with ... This clinical trial investigates the safety, tolerability, and efficacy of BMS-986458, both alone and in combination with Rituximab, for patients suffering ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/957/531358/BMS-986458-a-Potential-First-in-Class-Highly

BMS-986458 a Potential First-in-Class, Highly Selective ... A potential first-in-class, highly selective, potent and well tolerated BCL6 ligand directed degrader (LDD) demonstrates multi-modal anti-tumor efficacy.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124037042

BMS-986458 a Potential First-in-Class, Highly Selective, ... BMS-986458 rapidly degrades BCL6 protein to levels that drive broad anti-tumor effects in 80% of BCL6 expressing NHL cell lines and all ex vivo patient derived ...