Odronextamab for B-Cell Lymphoma

(ELM-2 Trial)

Not currently recruiting at 331 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Systemic corticosteroids

Disqualifiers: CNS lymphoma, Recent anti-lymphoma therapy, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called odronextamab to evaluate its effectiveness in treating B-cell non-Hodgkin's lymphoma (B-NHL), a type of blood cancer. The main goals are to determine if odronextamab can kill cancer cells and to identify any side effects. The study includes different groups for specific kinds of B-NHL, such as follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, and marginal zone lymphoma. It suits those with a form of B-NHL that hasn't responded to previous treatments and who need further systemic therapy. 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 requires that you have not received any systemic anti-lymphoma therapy within 5 half-lives or 28 days before starting the study drug, whichever is shorter. This means you may need to stop certain medications before joining the trial, but the protocol does not specify all medications.

Is there any evidence suggesting that odronextamab is likely to be safe for humans?

Research shows that odronextamab, a type of antibody treatment, has been tested for safety in patients with various forms of B-cell non-Hodgkin's lymphoma. Earlier studies found that odronextamab generally causes side effects manageable with standard medical care. For instance, patients with diffuse large B-cell lymphoma (a type of B-NHL) tolerated the treatment well with supportive care.

While some side effects might occur, doctors can usually manage them. So far, studies have not identified any unexpected or serious issues that raise major safety concerns. Each person's experience can differ, so discussing any concerns with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for B-cell lymphoma?

Odronextamab is unique because it targets CD20 and CD3, harnessing the body's own immune system to attack B-cell lymphomas directly. Unlike standard treatments like chemotherapy and rituximab, which broadly affect rapidly dividing cells or target CD20 alone, odronextamab's bispecific antibody design allows for a more precise attack on cancer cells. Researchers are excited about odronextamab because it has the potential to offer a more targeted and effective treatment with possibly fewer side effects compared to traditional therapies. This innovative approach could lead to improved outcomes for patients with various types of B-cell lymphomas.

What evidence suggests that odronextamab might be an effective treatment for B-cell lymphoma?

Research has shown that odronextamab, a special type of antibody, shows promise in treating B-cell non-Hodgkin's lymphoma (B-NHL). In studies, odronextamab reduced tumor size and was generally safe. It links T cells, which kill cancer, and B cells, which are cancerous, enhancing the immune system's ability to find and destroy cancer cells. Early results suggest odronextamab works well across different B-NHL types. This trial will enroll participants in different cohorts based on their specific B-NHL type, including diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). These findings encourage further research into its use for B-NHL. ^{1 3 4 6 7}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for patients with B-cell Non-Hodgkin Lymphoma who have already tried at least two other treatments, including an anti-CD20 antibody and an alkylating agent. They should be in good physical condition (ECOG status 0 or 1) and have proper organ function. People with certain types of lymphomas, uncontrolled infections like HIV or hepatitis, recent seizures, a history of neurodegenerative conditions, or those treated with CAR-T therapy are not eligible.

Inclusion Criteria

My liver, kidneys, and bone marrow are functioning well.

My doctor thinks I need treatment for my lymphoma now.

My disease can be seen and measured on a CT or MRI scan.

Exclusion Criteria

I haven't taken more than 10 mg of steroids daily in the last 3 days.

I have been treated with a therapy targeting both CD20 and CD3.

I haven't taken any lymphoma medication recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive odronextamab to assess its effectiveness in destroying cancer cells and to evaluate safety

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Assessment of patient-reported outcomes and long-term safety

Approximately 194 weeks following the first dose

What Are the Treatments Tested in This Trial?

Interventions

• Odronextamab

Trial Overview The trial is testing Odronextamab's ability to fight cancer in different subtypes of B-cell Non-Hodgkin Lymphoma by measuring the response rate to treatment. It will also look at how long patients live without their disease getting worse, overall survival time, duration of response to treatment, control over the disease progression and its safety profile.

How Is the Trial Designed?

Group I: Other B-NHL Experimental Treatment 1 Intervention

Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia \[WM\]); Patients with a current diagnosis of mixed histology of B-NHL with an aggressive component (such as concurrent FL and DLBCL) will be allowed

Group II: MZL Experimental Treatment 1 Intervention

Marginal Zone Lymphoma cohort

Group III: MCL Experimental Treatment 1 Intervention

Mantle Cell Lymphoma cohort

Group IV: FL Experimental Treatment 1 Intervention

Follicular lymphoma grade 1-3a cohort

Group V: DLBCL Experimental Treatment 1 Intervention

Diffuse large B-cell lymphoma cohort

Odronextamab is already approved in European Union for the following indications:

Approved in European Union as Ordspono for:

• Relapsed/Refractory Follicular Lymphoma
• Relapsed/Refractory Diffuse Large B-cell Lymphoma

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Published Research Related to This Trial

Odronextamab, a bispecific antibody targeting CD20 and CD3, has shown adequate safety and tolerability in an ongoing first-in-human study for patients with relapsed/refractory B-cell non-Hodgkin lymphoma, indicating its potential as a therapeutic option.

Preclinical studies demonstrated that effective concentrations of odronextamab for inhibiting tumor growth in mouse models can inform dose escalation strategies for clinical trials, suggesting a translational approach to optimize dosing in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational findings for odronextamab: From preclinical research to a first-in-human study in patients with CD20+ B-cell malignancies. Zhu, M., Olson, K., Kirshner, JR., et al.[2022]

Elranatamab is a bispecific T cell engager that targets BCMA on multiple myeloma cells, effectively activating T cells to kill these cancer cells, and has received its first approval in the USA for treating adult patients with relapsed or refractory multiple myeloma after at least four prior therapies.

The approval was based on the drug's response rate and durability of response, with ongoing studies required to confirm its clinical benefits, indicating a promising new option for patients with difficult-to-treat multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elranatamab: First Approval. Dhillon, S.[2023]

In a phase Ib study involving 31 patients with relapsed/refractory multiple myeloma, the combination of oprozomib, pomalidomide, and dexamethasone showed a promising overall response rate of 70.6%.

While the treatment was generally well-tolerated, common adverse events included gastrointestinal issues like diarrhea and nausea, and hematologic effects such as anemia and neutropenia, indicating that the safety profile of the oprozomib formulation needs improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oprozomib, pomalidomide, and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma. Shah, J., Usmani, S., Stadtmauer, EA., et al.[2020]

Odronextamab, a bispecific antibody targeting CD20 and CD3, has shown promising results in patients with relapsed/refractory B-cell non-Hodgkin lymphoma, achieving durable complete responses in two patients for over 2 years after treatment.

The treatment was well-tolerated, with no severe cytokine release syndrome or neurological adverse events reported, indicating a manageable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete responses to odronextamab in two patients with diffuse large B-cell lymphoma refractory to chimeric antigen receptor T-cell therapy. Weinstock, M., Elavalakanar, P., Bright, S., et al.[2023]

In a phase II trial involving 51 patients with relapsed/refractory multiple myeloma, plitidepsin showed limited antitumor activity, with an overall response rate of 13% when used alone, and 22% when combined with dexamethasone.

Both treatment regimens were well tolerated, with common side effects including anemia and thrombocytopenia, indicating that plitidepsin can be safely administered to patients who have already undergone extensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical and pharmacokinetic study of plitidepsin 3-hour infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma. Mateos, MV., Cibeira, MT., Richardson, PG., et al.[2021]

Odronextamab, a bispecific antibody targeting CD20 and CD3, shows early promise in treating relapsed/refractory diffuse large B cell lymphoma (DLBCL), but many patients still do not achieve complete responses.

The addition of REGN5837, which engages CD28 on T cells, significantly enhances the antitumor activity of odronextamab in preclinical models, suggesting a potential chemotherapy-free treatment strategy for DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models. Wei, J., Montalvo-Ortiz, W., Yu, L., et al.[2022]

In a phase 3 trial involving 559 patients with relapsed or refractory multiple myeloma who had previously received lenalidomide, the combination of pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared to bortezomib and dexamethasone alone, with a median survival of 11.20 months versus 7.10 months.

While the combination treatment showed better efficacy, it also resulted in higher rates of serious adverse events, particularly neutropenia and infections, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Richardson, PG., Oriol, A., Beksac, M., et al.[2020]

Odronextamab, a bispecific antibody targeting CD20 and CD3, demonstrated a manageable safety profile with no dose-limiting toxicities observed during a phase 1 trial involving 145 heavily pretreated patients with B-cell non-Hodgkin lymphoma.

The treatment showed promising efficacy, with an overall objective response rate of 51%, and particularly high response rates in patients with follicular lymphoma (91%) and in those with diffuse large B-cell lymphoma who had not received prior CAR T therapy (53%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Odronextamab, a human CD20×CD3 bispecific antibody in patients with CD20-positive B-cell malignancies (ELM-1): results from the relapsed or refractory non-Hodgkin lymphoma cohort in a single-arm, multicentre, phase 1 trial. Bannerji, R., Arnason, JE., Advani, RH., et al.[2023]

Pomalidomide (POM) is an effective new treatment for relapsed and refractory multiple myeloma (RRMM), particularly in patients who have already undergone two prior therapies, including lenalidomide and bortezomib.

Clinical trials have shown that POM is safe and has multiple mechanisms of action, making it a promising option for patients who are resistant to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide in the treatment of relapsed multiple myeloma. Forsberg, PA., Mark, TM.[2020]

In a phase II study involving 61 patients with relapsed or refractory diffuse large B-cell lymphoma, coltuximab ravtansine showed an overall response rate of 43.9%, indicating moderate efficacy in this difficult-to-treat population.

The treatment was generally well tolerated, with common side effects including fatigue (30%) and nausea (23%), and serious adverse events were relatively low, suggesting a favorable safety profile for this antibody drug conjugate.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II multicenter study of the anti-CD19 antibody drug conjugate coltuximab ravtansine (SAR3419) in patients with relapsed or refractory diffuse large B-cell lymphoma previously treated with rituximab-based immunotherapy. Trnĕný, M., Verhoef, G., Dyer, MJ., et al.[2019]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4502/534008/Efficacy-and-Safety-of-Odronextamab-in-Rare

Efficacy and Safety of Odronextamab in Rare Subtypes of ... Odronextamab, an investigational, off-the-shelf, CD20×CD3 bispecific antibody, has shown compelling efficacy and generally manageable safety in various B-NHL ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19006

Outcomes of odronextamab in non-Hodgkin lymphoma This meta-analysis shows the good efficacy of odronextamab in the NHL with a modest safety profile. However, the meta-analysis is limited by a small sample ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12003196/

Odronextamab monotherapy in patients with relapsed ... Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03888105

NCT03888105 | A Study to Assess the Anti-Tumor Activity ... This study is researching an investigational drug, odronextamab, in adult patients B-cell non-Hodgkin's lymphoma (B-NHL).

5. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)03759-1/fulltext

Safety and efficacy of odronextamab in patients with ... Odronextamab, a CD20×CD3 bispecific antibody that engages cytotoxic T cells to destroy malignant B cells, has demonstrated encouraging activity ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40097657/

primary efficacy and safety analysis in phase 2 ELM-2 trial Odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care.

7. nature.com nature.com/articles/s43018-025-00921-6

primary efficacy and safety analysis in phase 2 ELM-2 trial Odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care.