Odronextamab for Lymphoma

(ELM-1 Trial)

No longer recruiting at 23 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must be taking: Anti-CD20 antibody

Must not be taking: Standard chemotherapy, Radiotherapy

Disqualifiers: CNS lymphoma, HIV, Hepatitis, others

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

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of odronextamab for individuals with certain types of lymphoma, a blood cancer affecting lymph nodes. The researchers aim to determine the optimal dose and effectiveness of the treatment when administered either through an IV or as an injection under the skin. Candidates for this trial have a CD20+ B-cell cancer, such as B-NHL, and have not responded to previous treatments. Participants should have tried at least two other treatments and must have a measurable tumor. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had standard anti-lymphoma chemotherapy or radiotherapy within 28 days before starting the study drug.

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

Research has shown that odronextamab is generally well-tolerated for treating certain types of lymphoma. In studies involving patients with Diffuse Large B-Cell Lymphoma (DLBCL) that returned or did not respond to other treatments, the results were promising. Most side effects were manageable with additional care, although one report noted a serious reaction called cytokine release syndrome in a patient following a specific treatment plan.

For patients with relapsed or refractory Follicular Lymphoma (FL), odronextamab also appeared safe. The treatment proved effective for many patients, leading to high rates of complete response, meaning the cancer was no longer detectable. Again, most side effects were manageable.

Both studies suggest that odronextamab can be safe for people with these types of lymphoma, although monitoring for side effects remains important. This supports the growing evidence that this treatment can be a viable option with appropriate care. ^{1 2 3 4 5}

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

Researchers are excited about Odronextamab for treating lymphoma because it represents a new approach compared to existing treatments like chemotherapy, radiation, and CAR-T cell therapy. Odronextamab is a bispecific antibody that uniquely targets both CD20 on B-cells and CD3 on T-cells, effectively bringing them together to trigger an immune response against the cancer cells. This targeted mechanism offers a promising new way to treat lymphoma, particularly diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL), potentially with fewer side effects and improved outcomes.

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

Research has shown that odronextamab, which participants in this trial may receive, may help treat diffuse large B-cell lymphoma (DLBCL), especially in patients who haven't improved with CAR-T therapy. In one study, 48% of these patients responded to the treatment, and 32% experienced a complete response, meaning their cancer disappeared. For follicular lymphoma (FL), odronextamab achieved an 80% response rate, with 73% of patients experiencing a complete response, and these effects lasted up to 23 months on average. These findings suggest that odronextamab could effectively treat both DLBCL and FL, offering hope to patients with these challenging conditions. ^{1 2 3 5 6}

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 people with certain B-cell blood cancers (like lymphoma or leukemia) that haven't responded to previous treatments. Participants must have good bone marrow function, a specific performance status, and measurable cancer lesions. They can't join if they've had recent chemotherapy, CNS issues, HIV/HBV/HCV infections, or live vaccinations within the last month.

Inclusion Criteria

I have a tumor larger than 1.5 cm that can be measured by a scan.

I am willing to have a biopsy if my doctor thinks it's safe.

I have FL grade 1-3a or DLBCL and have had at least 2 treatments including an anti-CD20 antibody and an alkylating agent.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy for lymphoma in the last 28 days.

I do not have HIV, HBV, HCV, or CMV infections.

I have hepatitis B but it's under control and I'm on antiviral therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Odronextamab is administered intravenously with a dose escalation and dose expansion phase for B-NHL and CLL

24 months

Treatment Part B

Odronextamab is administered subcutaneously with a dose finding and dose expansion phase for B-NHL

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

48 months

What Are the Treatments Tested in This Trial?

Interventions

• Odronextamab

Trial Overview The study tests Odronextamab at various doses in two parts: Part A uses IV administration for dose escalation/expansion in B-NHL and CLL patients; Part B explores subcutaneous administration for dose finding/expansion specifically in B-NHL patients.

How Is the Trial Designed?

Group I: Part A Experimental Treatment 1 Intervention

DLBCL post CAR-T

Group II: 2N Part B Experimental Treatment 1 Intervention

DLBCL

Group III: 1N Part B Experimental Treatment 1 Intervention

FL

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]

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]

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]

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 III study involving 491 patients with diffuse large B-cell lymphoma, the more intensive treatment regimen DA-EPOCH-R did not show a statistically significant improvement in progression-free survival (PFS) or overall survival (OS) compared to the standard R-CHOP regimen, with 2-year PFS rates of 78.9% for DA-EPOCH-R and 75.5% for R-CHOP.

DA-EPOCH-R was associated with a higher incidence of severe adverse events, including infections and febrile neutropenia, indicating that while it is a more intensive treatment, it does not provide additional survival benefits and carries greater risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Bartlett, NL., Wilson, WH., Jung, SH., et al.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/145/14/1498/534869/Odronextamab-monotherapy-in-R-R-DLBCL-after

Odronextamab monotherapy in R/R DLBCL after progression ... In patients with diffuse large B-cell lymphoma progressing after CAR-T therapy, odronextamab showed a 48% ORR and 32% CR rate. Odronextamab had ...

2. 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.

3. 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.

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3118/532985/Long-Term-Efficacy-and-Safety-of-Odronextamab-in

Long-Term Efficacy and Safety of Odronextamab in Relapsed ... Importantly, continued treatment with odronextamab demonstrated no detrimental effects on survival outcomes over a longer follow-up period.

5. onclive.com onclive.com/view/elm-2-data-display-long-term-efficacy-and-safety-of-odronextamab-in-r-r-follicular-lymphoma

ELM-2 Data Display Long-Term Efficacy and Safety of ... Long-term efficacy and safety data with odronextamab (Ordspono) in heavily pretreated patients with relapsed/refractory follicular lymphoma demonstrate deep ...

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

Safety and efficacy of odronextamab in patients with ... Grade ≥3 cytokine release syndrome was seen in one patient with the optimized step-up regimen, and safety was generally manageable with ...