REGN5837 + Odronextamab for Aggressive B-Cell Lymphoma

(ATHENA-1 Trial)

Recruiting at 29 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two experimental drugs, REGN5837 and odronextamab, to determine their safety and effectiveness for people with aggressive B-cell lymphoma, a type of blood cancer that has returned or not responded to other treatments. The main goal is to identify the right dose for future studies and understand any side effects. The trial also examines how much of the drugs remain in the blood and whether the body produces antibodies that could affect the drugs' effectiveness. It suits individuals with this type of lymphoma who have already tried at least two other treatments without success. 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 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 there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that both REGN5837 and odronextamab remain under evaluation for safety. Detailed safety information about their combined use in people with aggressive B-cell lymphoma is not yet available.

The study is in its early stages, focusing on assessing the safety of these drugs and determining the right doses. Early results from separate studies suggest that odronextamab can be effective against certain lymphomas. However, using it with REGN5837 is a new approach, and researchers are still investigating potential side effects.

In summary, while odronextamab alone has shown some positive results, the safety of using both drugs together is still under study. Participants might experience side effects, but understanding of these is still developing. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Odronextamab and REGN5837 for treating aggressive B-cell lymphoma because they work differently from current options like chemotherapy and targeted therapies. Odronextamab is a bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells, bridging them to help the immune system attack cancer cells more effectively. Meanwhile, REGN5837 is designed to enhance the immune response further, potentially increasing the treatment's efficacy. This dual-action approach aims to improve outcomes in patients who might not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for aggressive B-cell lymphoma?

Research shows that combining the drugs REGN5837 and odronextamab, which participants in this trial will receive, may help treat aggressive B-cell lymphomas. Earlier studies found that this combination improved the ability to fight tumors and increased survival rates in animal tests of diffuse large B-cell lymphoma. The European Union has approved odronextamab alone due to its effectiveness and lasting impact in treating certain lymphomas. In previous trials, the combination treatment achieved a 51% success rate, suggesting it might work for lymphomas that have returned or are difficult to treat. These findings offer hope that this treatment could be effective for patients with aggressive B-cell lymphomas. ^{1 2 6 7 8}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428821/

PB2328: TRIAL IN PROGRESS: ATHENA-1 – A PHASE 1 ... When combined with odronextamab (signal 1), REGN5837 improved anti-tumor efficacy and survival in in vivo diffuse large B-cell lymphoma tumor models via ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05685173

NCT05685173 | A Trial to Study if REGN5837 in ... The study is researching an experimental drug called REGN5837 in combination with another experimental drug, odronextamab (called study drugs).

3. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/ordsponotm-odronextamab-approved-european-union-treatment

Ordspono™ (odronextamab) Approved in the European ... Approval of Ordspono is based on data demonstrating robust and durable responses in both relapsed/refractory follicular lymphoma and diffuse ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10961523/

Molecular assessment of intratumoral immune cell subsets ... Odronextamab is an Fc-silenced, human, CD20×CD3 bispecific antibody that targets CD20-expressing cells via T-cell-mediated cytotoxicity independent of T-cell/ ...

5. withpower.com withpower.com/trial/phase-1-lymphoma-2-2023-27719

REGN5837 + Odronextamab for Aggressive B-Cell ... The treatment showed promising efficacy, with an overall objective response rate of 51%, and particularly high response rates in patients with follicular ...

6. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/odronextamab-ash-presentations-underscore-impressive-potential

Odronextamab ASH Presentations Underscore Impressive ... Odronextamab monotherapy led to complete responses in all patients with previously untreated follicular lymphoma evaluable for efficacy.

7. trialx.com trialx.com/clinical-trials/listings/251838/a-trial-to-study-if-regn5837-in-combination-with-odronextamab-is-safe-for-adult-participants-with-aggressive-b-cell-non-hodgkin-lymphomas/

A Trial to Study if REGN5837 in Combination With ... A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Adult Participants With Aggressive B-cell Non-Hodgkin Lymphomas.

8. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/391097

A Trial to Study if REGN5837 in Combination With ... A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Adult Participants With Aggressive B-cell Non-Hodgkin Lymphomas · Eligibility Criteria.