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

Trial Summary

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.

What data supports the effectiveness of the drug Odronextamab for treating Large B-Cell Lymphoma?

Research shows that Odronextamab, a type of antibody treatment, has helped some patients with difficult-to-treat B-cell lymphoma achieve complete responses, meaning their cancer was no longer detectable. In a study, two patients with a type of lymphoma that didn't respond to other treatments had no signs of cancer for over two years after using Odronextamab. ^{1 2 3 4 5}

Is odronextamab safe for humans?

Odronextamab has shown a manageable safety profile in early human trials for patients with relapsed or refractory B-cell non-Hodgkin lymphoma. In these studies, serious side effects like severe cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurological issues were not common. ^{1 2 3 4 6}

What makes the drug odronextamab unique for treating large B-cell lymphoma?

Odronextamab is unique because it is a bispecific antibody that targets both CD20 on B cells and CD3 on T cells, helping the body's immune system attack the cancer cells. It has shown promising results in patients who did not respond to other treatments like CAR T-cell therapy, with some achieving complete responses lasting over two years. ^{1 2 3 4 5}

What is the purpose of this trial?

This phase II trial tests the effectiveness of odronextamab given before chimeric antigen receptor T (CAR-T) cell therapy (bridging therapy) in patients with large B-cell lymphomas that have come back after a period of improvement (relapsed) or that have not responded to previous treatment (refractory). Odronextamab is a bispecific antibody that can bind to two different antigens at the same time. Odronextamab binds to CD3, a T-cell surface antigen, and CD20 (a tumor-associated antigen that is expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell cancers) and may interfere with the ability of cancer cells to grow and spread. Bridging therapy has been used to maintain disease control and to increase the chance of successful receipt of CAR-T cell therapy. However, bridging therapy is typically given after leukapheresis, which does not help prevent disease progression between the decision for CAR-T cell therapy and leukapheresis. Giving odronextamab as bridging therapy before leukapheresis may delay disease progression to allow leukapheresis and increase the likelihood of successful CAR-T cell therapy in patients with relapsed or refractory large B-cell lymphomas.

Research Team

Mengyang Di, MD, PhD

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

My diagnosis is large B cell lymphoma.

Negative pregnancy test for WOCBP

Willingness to use contraception

Exclusion Criteria

I have received a stem cell transplant from a donor.

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

My cancer has spread to my brain or spinal fluid.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

References

1. 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]

2. 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]

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022]

6. Italy 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. [2019]