Odronextamab for B-Cell Lymphoma

(ELM-2 Trial)

Recruiting in Palo Alto (17 mi)

+290 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Systemic corticosteroids

Disqualifiers: CNS lymphoma, Recent anti-lymphoma therapy, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing odronextamab, a medication that helps the immune system fight cancer, on patients with certain types of B-cell non-Hodgkin lymphoma who have not responded to previous treatments. The drug works by guiding the immune system to attack cancer cells. Odronextamab is being tested for its safety and effectiveness in patients with these types of cancer.

Will I have to stop taking my current medications?

The trial requires that you have not received any systemic anti-lymphoma therapy within 5 half-lives or 28 days before starting the study drug, whichever is shorter. This means you may need to stop certain medications before joining the trial, but the protocol does not specify all medications.

Is odronextamab safe for humans?

Odronextamab has shown a manageable safety profile in early 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 5}

What makes the drug Odronextamab unique for treating 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 immune system to directly attack and kill cancerous B-cells, which is different from traditional chemotherapy or single-target therapies. ^{6 7 8 9 10}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

This trial is for patients with B-cell Non-Hodgkin Lymphoma who have already tried at least two other treatments, including an anti-CD20 antibody and an alkylating agent. They should be in good physical condition (ECOG status 0 or 1) and have proper organ function. People with certain types of lymphomas, uncontrolled infections like HIV or hepatitis, recent seizures, a history of neurodegenerative conditions, or those treated with CAR-T therapy are not eligible.

Inclusion Criteria

My liver, kidneys, and bone marrow are functioning well.

My doctor thinks I need treatment for my lymphoma now.

My disease can be seen and measured on a CT or MRI scan.

Exclusion Criteria

I haven't taken more than 10 mg of steroids daily in the last 3 days.

I have been treated with a therapy targeting both CD20 and CD3.

I haven't taken any lymphoma medication recently.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive odronextamab to assess its effectiveness in destroying cancer cells and to evaluate safety

Up to 52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Long-term follow-up

Assessment of patient-reported outcomes and long-term safety

Approximately 194 weeks following the first dose

Treatment Details

Interventions

• Odronextamab (Monoclonal Antibodies)

Trial Overview The trial is testing Odronextamab's ability to fight cancer in different subtypes of B-cell Non-Hodgkin Lymphoma by measuring the response rate to treatment. It will also look at how long patients live without their disease getting worse, overall survival time, duration of response to treatment, control over the disease progression and its safety profile.

Participant Groups

Group I: Other B-NHL Experimental Treatment 1 Intervention

Other B-cell non-Hodgkin lymphoma cohort (excluding FL Grade 1-3a, DLBCL, MCL, MZL, Waldenström macroglobulinemia \[WM\]); Patients with a current diagnosis of mixed histology of B-NHL with an aggressive component (such as concurrent FL and DLBCL) will be allowed

Group II: MZL Experimental Treatment 1 Intervention

Marginal Zone Lymphoma cohort

Group III: MCL Experimental Treatment 1 Intervention

Mantle Cell Lymphoma cohort

Group IV: FL Experimental Treatment 1 Intervention

Follicular lymphoma grade 1-3a cohort

Group V: DLBCL Experimental Treatment 1 Intervention

Diffuse large B-cell lymphoma cohort

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, 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]

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]

Elranatamab is a bispecific T cell engager that targets BCMA on multiple myeloma cells, effectively activating T cells to kill these cancer cells, and has received its first approval in the USA for treating adult patients with relapsed or refractory multiple myeloma after at least four prior therapies.

The approval was based on the drug's response rate and durability of response, with ongoing studies required to confirm its clinical benefits, indicating a promising new option for patients with difficult-to-treat multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elranatamab: First Approval. Dhillon, S.[2023]

In a phase 3 trial involving 559 patients with relapsed or refractory multiple myeloma who had previously received lenalidomide, the combination of pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared to bortezomib and dexamethasone alone, with a median survival of 11.20 months versus 7.10 months.

While the combination treatment showed better efficacy, it also resulted in higher rates of serious adverse events, particularly neutropenia and infections, indicating that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. Richardson, PG., Oriol, A., Beksac, M., et al.[2020]

In a phase II trial involving 51 patients with relapsed/refractory multiple myeloma, plitidepsin showed limited antitumor activity, with an overall response rate of 13% when used alone, and 22% when combined with dexamethasone.

Both treatment regimens were well tolerated, with common side effects including anemia and thrombocytopenia, indicating that plitidepsin can be safely administered to patients who have already undergone extensive treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II clinical and pharmacokinetic study of plitidepsin 3-hour infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma. Mateos, MV., Cibeira, MT., Richardson, PG., et al.[2021]

Pomalidomide (POM) is an effective new treatment for relapsed and refractory multiple myeloma (RRMM), particularly in patients who have already undergone two prior therapies, including lenalidomide and bortezomib.

Clinical trials have shown that POM is safe and has multiple mechanisms of action, making it a promising option for patients who are resistant to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide in the treatment of relapsed multiple myeloma. Forsberg, PA., Mark, TM.[2020]

In a phase Ib study involving 31 patients with relapsed/refractory multiple myeloma, the combination of oprozomib, pomalidomide, and dexamethasone showed a promising overall response rate of 70.6%.

While the treatment was generally well-tolerated, common adverse events included gastrointestinal issues like diarrhea and nausea, and hematologic effects such as anemia and neutropenia, indicating that the safety profile of the oprozomib formulation needs improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oprozomib, pomalidomide, and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma. Shah, J., Usmani, S., Stadtmauer, EA., et al.[2020]

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. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Elranatamab: First Approval. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial. [2020]

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

Phase II clinical and pharmacokinetic study of plitidepsin 3-hour infusion every two weeks alone or with dexamethasone in relapsed and refractory multiple myeloma. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Pomalidomide in the treatment of relapsed multiple myeloma. [2020]

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

Oprozomib, pomalidomide, and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma. [2020]