REGN5837 + Odronextamab for Aggressive B-Cell Lymphoma

(ATHENA-1 Trial)

Recruiting at 28 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Corticosteroids, others

Disqualifiers: Mantle cell lymphoma, CNS lymphoma, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

91 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking any systemic anti-lymphoma therapy within 5 half-lives or 14 days before starting the study drugs, whichever is shorter. You also need to stop continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or equivalent within 72 hours of starting odronextamab.

Is the combination of REGN5837 and Odronextamab safe for humans?

Odronextamab has shown a manageable safety profile in early human trials for aggressive B-cell lymphoma, with no severe cytokine release syndrome or neurological issues reported. REGN5837, when used alone, showed no toxicity in primate studies, and it enhances the effect of Odronextamab without additional safety concerns. ^{1 2 3 4 5}

What makes the drug combination of REGN5837 and Odronextamab unique for treating aggressive B-cell lymphoma?

The combination of REGN5837 and Odronextamab is unique because it uses two bispecific antibodies to enhance the immune system's ability to fight cancer. Odronextamab targets CD20 on B cells and CD3 on T cells, while REGN5837 targets CD22 on tumor cells and CD28 on T cells, together boosting T cell activation and antitumor activity without chemotherapy. ^{1 2 3 4 6}

What is the purpose of this trial?

The study is researching an experimental drug called REGN5837 in combination with another experimental drug, odronextamab (called "study drugs"). The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose for phase 2. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drugs (that could make the drugs less effective or could lead to side effects) * To find out how well the study drugs work against relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs)

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for people with aggressive B-cell non-Hodgkin lymphomas who've had at least two prior treatments, including an anti-CD20 antibody and an alkylating agent. They should be in good physical condition (ECOG 0 or 1) and have proper organ function. Those with certain types of lymphoma, recent other cancer treatments, high-dose steroids, or significant health risks are excluded.

Inclusion Criteria

My aggressive B-cell lymphoma has worsened despite two prior treatments including an anti-CD20 antibody and an alkylating agent.

I am willing to have a tumor biopsy if it's safe and needed for the study.

I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

I have not had a stem cell or organ transplant, nor have I been treated with odronextamab.

I have been diagnosed with mantle cell lymphoma.

I am taking more than 10 mg of prednisone or its equivalent daily.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive REGN5837 and odronextamab via IV infusion using a step-up dosing schedule

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

• Odronextamab
• REGN5837

Trial Overview The study tests the safety and tolerability of REGN5837 combined with odronextamab in patients whose disease has worsened after previous therapies. It aims to determine the right dose for future studies and assess side effects, drug levels in blood, potential immune responses to the drugs, and their effectiveness against B-NHLs.

Participant Groups

Group I: Odronextamab and REGN5837 Experimental Treatment 2 Interventions

Odronextamab and REGN5837 will be administered by IV infusion using a step-up dosing schedule.

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

Findings from Research

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]

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]

There are 7 new FDA-approved medications for treating relapsed or refractory diffuse large B cell lymphoma (DLBCL), including 5 CD19-targeted therapies, 3 of which are CAR-T cell therapies that aim for curative intent.

While these novel therapies show promise, they come with varying tolerability and financial considerations, highlighting the need for careful treatment sequencing and ongoing clinical trials for future advancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell Lymphoma. Nuvvula, S., Dahiya, S., Patel, SA.[2022]

Rituximab (RTX) is a widely used monoclonal antibody for treating diffuse large B-cell lymphoma, often combined with other drugs in the R-CHOP regimen, but some patients experience suboptimal responses or resistance.

New developments in CD20-targeting monoclonal antibodies, including second- and third-generation agents like ofatumumab and obinutumumab, are being actively researched to improve treatment outcomes for B-cell non-Hodgkin's lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. Cang, S., Mukhi, N., Wang, K., et al.[2022]

References

1. England 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. [2023]

2. England 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. [2023]

3. United States 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. [2022]

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

CD22-targeted CD28 bispecific antibody enhances antitumor efficacy of odronextamab in refractory diffuse large B cell lymphoma models. [2022]

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

The Novel Therapeutic Landscape for Relapsed/Refractory Diffuse Large B Cell Lymphoma. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]