Odronextamab for Large B-Cell Lymphoma

Overseen By Mengyang Di, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Washington

Must not be taking: Immunosuppressives, Corticosteroids, Biologics, others

Disqualifiers: Brain metastases, Seizure disorder, Active infection, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 12 months

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of odronextamab as a bridging therapy for individuals with large B-cell lymphoma that has recurred or not responded to treatment. Odronextamab is designed to help the immune system identify and attack cancer cells. The trial aims to determine if administering odronextamab before CAR-T cell therapy can better control the disease and improve the chances of successful treatment. Suitable candidates have large B-cell lymphoma that did not respond to prior treatment and have already received an anti-CD20 antibody. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot receive certain treatments like standard chemotherapy, radiotherapy, or specific biologic agents within 2 weeks before starting the study drug. It's best to discuss your current medications with the trial team.

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

Research has shown that odronextamab demonstrates promising safety results from earlier studies. In patients with certain types of large B-cell lymphomas that have returned or are not responding to treatment, odronextamab was generally well-tolerated. Most side effects were manageable with additional treatments that controlled symptoms. Importantly, long-term studies found no negative effects on survival, suggesting that odronextamab can be used safely over time. Prospective participants in a trial with odronextamab may find these findings reassuring regarding its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for large B-cell lymphoma, which often include chemotherapy and immunotherapy, odronextamab is a bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells. This dual targeting helps recruit the body's T-cells to directly attack the cancerous B-cells, potentially leading to a more direct and effective immune response. Researchers are excited about odronextamab because its mechanism may offer a more precise treatment option with the potential for fewer side effects compared to traditional therapies. Additionally, the unique dosing schedule of odronextamab might enhance its effectiveness while potentially improving the patient's quality of life.

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

Studies have shown that odronextamab, the investigational treatment in this trial, effectively treats patients with hard-to-treat large B-cell lymphoma. It helps the body's immune cells, called T-cells, connect to and attack cancer cells. Research indicates that odronextamab shows promise for patients who have not responded to other treatments. In these studies, many patients experienced a significant decrease in their cancer. The treatment generally causes mild side effects, making it safe to manage. Overall, odronextamab appears to be a hopeful option for those with relapsed or stubborn large B-cell lymphoma. ^{1 2 4 5 6}

Who Is on the Research Team?

Mengyang Di, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

This trial is for patients with large B-cell lymphomas that have either relapsed or are refractory. Candidates should be planning to receive CAR-T cell therapy and need a treatment option to control their disease before undergoing leukapheresis.

Inclusion Criteria

Negative pregnancy test for WOCBP

Willingness to use contraception

My diagnosis is large B cell lymphoma.

Exclusion Criteria

I have received a stem cell transplant from a donor.

I haven't taken immunosuppressive drugs in the last 2 weeks.

Known hypersensitivity to certain medications

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive odronextamab intravenously with a step-up dosing schedule during cycle 1, followed by regular dosing in cycles 2-4 and every other week thereafter

Up to 12 months

Multiple visits for IV administration

Leukapheresis and CAR-T Infusion

Patients undergo leukapheresis followed by lymphodepletion and CAR-T infusion per standard of care

After 2 cycles of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment, including PET/CT scans and other assessments

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Odronextamab

Trial Overview

The trial is testing odronextamab as a 'bridging therapy' before CAR-T cell therapy in patients with certain types of B-cell lymphoma. The goal is to see if it can prevent cancer progression and improve the success rate of subsequent CAR-T treatment.

How Is the Trial Designed?

Group I: Treatment (odronextamab) Experimental Treatment 11 Interventions

Patients receive odronextamab IV based on the following schedules: * Step-up dosing during cycle 1: 0.2 mg on C1D1, 0.5 mg on C1D2, 2 mg on C1D8 and C1D9, respectively, and 10 mg on C1D15 and C1D16, respectively (0.7/4/20 regimen). * Dosing during cycles 2-4: Odron will be given at 160 mg weekly. * Once every other week at 320 mg of remaining cycles. Please see the Detailed Description for additional information.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Regeneron Pharmaceuticals

Industry 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, 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, 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]

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]

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]

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%201/3118/532985/Long-Term-Efficacy-and-Safety-of-Odronextamab-in

Long-Term Efficacy and Safety of Odronextamab in Relapsed ...

Odronextamab, a novel, investigational, CD20×CD3 bispecific antibody, has demonstrated compelling efficacy and a generally manageable safety profile in heavily ...

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.

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 ...

5.

ash.confex.com

ash.confex.com/ash/2024/webprogram/Paper199980.html

Paper: Long-Term Efficacy and Safety of Odronextamab in ...

Here, we report long-term efficacy and safety data for odronextamab from a pooled analysis of the DLBCL post–CAR-T cohort in the ELM-1 study (NCT02290951), ...

6.

annalsofoncology.org

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

Safety and efficacy of odronextamab in patients with ...

Highlights. •. Outcomes for patients with follicular lymphoma (FL) worsen with each relapse, representing a clear medical unmet need.