Odronextamab + Chemotherapy for B-Cell Lymphoma

(OLYMPIA-3 Trial)

Not currently recruiting at 230 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Systemic anti-lymphoma therapy

Disqualifiers: CNS lymphoma, Active malignancy, Infections, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, odronextamab (an experimental treatment), alongside chemotherapy to evaluate its effectiveness for people with diffuse large B-cell lymphoma (DLBCL), a type of blood cancer. It targets individuals who have not yet received treatment or whose cancer has returned or resisted previous treatments. The study compares this new combination to the current standard treatment, which includes rituximab. Participants with measurable disease, meaning noticeable tumors, may be suitable for this trial. The study also examines side effects and the drug's impact on daily life. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that any other therapy or investigational treatment should not be taken within 28 days before starting the study treatment. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown promising results for odronextamab in patients with diffuse large B-cell lymphoma (DLBCL). Research indicates that odronextamab, when used alone, exhibits strong antitumor activity, effectively fighting cancer cells.

For safety, odronextamab has been tested in patients whose cancer returned or didn't respond to other treatments. Results showed it was generally well-tolerated, though some patients experienced side effects like fever, tiredness, and low blood cell counts, which are common with cancer treatments.

In ongoing research, odronextamab is combined with chemotherapy, aiming to improve effectiveness and explore any new side effects. Since this study is in a later phase, earlier tests have shown the treatment to be reasonably safe for further testing.

Overall, odronextamab has shown potential, but like any treatment, it may cause side effects. Clinical trial participants are closely monitored to manage these risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for B-cell lymphoma?

Unlike the standard treatment for B-cell lymphoma, which typically includes a regimen known as R-CHOP (Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone), Odronextamab offers a novel approach by harnessing its unique mechanism as a bispecific antibody. This means it can simultaneously bind to cancer cells and T-cells, potentially enhancing the immune system's ability to attack the lymphoma cells more effectively. Researchers are excited about Odronextamab because it could offer a more direct and potent immune-mediated attack on the cancer, potentially leading to better outcomes for patients.

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

Research has shown that odronextamab, when used alone, produces promising results in treating diffuse large B-cell lymphoma (DLBCL) that has returned or resisted other treatments. Earlier studies demonstrated that patients responded well to odronextamab, even when other treatments had failed. In this trial, participants will receive either a combination of odronextamab with chemotherapy, known as Odro-CHOP, or Rituximab with chemotherapy, known as R-CHOP. Although detailed information from the current combination study is not yet available, the expectation is that odronextamab will enhance the effectiveness of chemotherapy. Notably, the side effects of odronextamab have been manageable with proper care, suggesting it could be a promising option for individuals with DLBCL. ^{1 2 3 4 6}

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 adults with a life expectancy of at least 12 months who have either not been treated for diffuse large B-cell lymphoma (DLBCL), or whose DLBCL has relapsed or not responded to treatment. They should have measurable disease, be reasonably fit (ECOG ≤2), and their organs must function well. People with another active cancer, severe medical conditions, recent major surgery, organ transplants, certain infections like COVID-19 or hepatitis, CNS involvement by lymphoma, prior anti-lymphoma therapy or allergies to study drugs cannot join.

Inclusion Criteria

I have at least one measurable cancer lesion.

My DLBCL is considered high-risk based on the IPI score.

My lymphoma is CD20+ DLBCL and either untreated or has come back.

Exclusion Criteria

I do not have any active infections, including COVID-19, HIV, hepatitis B or C, or CMV.

I am not allergic to the drugs used in this study.

I do not have severe nerve damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1A

Dose escalation to determine the safety and tolerability of odronextamab in combination with chemotherapy

Up to 35 days

Treatment Part 1B

Randomized exploration of odronextamab regimens for dose optimization

Up to 22 weeks

Treatment Part 2

Comparison of odronextamab with chemotherapy versus rituximab with chemotherapy

Up to 22 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Doxorubicin
• Odronextamab
• Prednisone/Prednisolone
• Rituximab
• Vincristine

Trial Overview The trial compares the effectiveness and safety of an experimental drug called odronextamab combined with chemotherapy versus rituximab combined with chemotherapy in patients with previously untreated DLBCL. It's divided into parts: early phases determine the best dose and schedule of odronextamab; later phase tests its efficacy against standard care rituximab.

How Is the Trial Designed?

Group I: Odronextamab + CHOP Experimental Treatment 5 Interventions

Part 1, includes dose escalation (Part 1A), and randomized exploration of 2 regimens of odronextamab -cyclophosphamide, doxorubicin, vincristine, prednisone (Odro-CHOP) dose optimization (Part 1B).

Group II: Rituximab + CHOP Active Control 5 Interventions

Part 2 is the randomized controlled portion, participants will receive either Odro-CHOP or R-CHOP.

Cyclophosphamide is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• 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

The combination of biweekly THP-COP chemotherapy and radiotherapy resulted in a high 5-year overall survival rate of 89% and a cause-specific survival rate of 90% in 41 patients with early-stage non-Hodgkin's lymphoma.

Despite some patients experiencing grade 4 neutropenia (12%), the treatment was well-tolerated, with 93% of patients completing the chemotherapy as scheduled, indicating that this regimen is both feasible and effective for low-risk cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pilot study of modified version of CHOP plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck. Nishioka, T., Tsuchiya, K., Nishioka, S., et al.[2015]

In a study of 50 patients treated with R-CHOP-14 for aggressive B-cell lymphoma, 82% achieved a complete or improved response, indicating high efficacy of this treatment regimen.

Despite its effectiveness, R-CHOP-14 was associated with significant toxicities, including grade 3-4 neutropenia in 32% of patients and peripheral neuropathy in 45%, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. Aguiar Bujanda, D., Aguiar Morales, J., Bohn Sarmiento, U., et al.[2021]

In a study of 115 patients with Waldeyer's ring diffuse large B-cell lymphoma, those treated with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) showed significantly better progression-free survival (PFS) and overall survival (OS) compared to those receiving standard R-CHOP treatment, with 2-year PFS rates of 90.1% versus 80.5%.

The DA-EPOCH-R treatment was associated with fewer deaths (2 out of 42 patients) compared to R-CHOP (9 out of 42 patients) during a median follow-up of 45 months, while both treatments had similar clinical responses and treatment-related toxicities, indicating that DA-EPOCH-R is a safer and more effective option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-adjusted EPOCH-R vs. R-CHOP in frontline management of Waldeyer's ring diffuse large B-cell lymphoma: a retrospective study from a single institution. Liang, Y., Liu, X., Yang, J., et al.[2023]

In a pooled analysis of 150 patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma, those treated with R-EPOCH showed significantly better event-free survival (EFS) and overall survival (OS) compared to those receiving R-CHOP, particularly in patients with a CD4 count ≥100/μL.

Patients with CD4 counts <50/μL experienced a much higher rate of treatment-related deaths (37% vs 6%), indicating that lower immune function increases the risk of lethal toxicity during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of AIDS malignancy consortium trials evaluating rituximab plus CHOP or infusional EPOCH chemotherapy in HIV-associated non-Hodgkin lymphoma. Barta, SK., Lee, JY., Kaplan, LD., et al.[2022]

In a study of seven patients with non-Hodgkin lymphoma treated with rituximab (RTX) and chemotherapy, there was a significant reduction in their ability to mount an immune response to vaccines, indicating increased susceptibility to infections.

The introduction of intravenous immunoglobulin (IVIg) therapy was crucial for managing recurrent infections, such as pneumonia and sinusitis, highlighting the importance of monitoring and addressing hypogammaglobulinemia in patients undergoing RTX treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. de Souza, KJ., Ferro, RS., Prestes-Carneiro, LE., et al.[2019]

The medication instruction sheet (MIS) developed for patients receiving R-CHOP therapy effectively predicted 71% of adverse drug reactions (ADRs) during the treatment period, demonstrating its usefulness in managing these reactions.

The MIS accurately matched the onset timing of infusion reactions and peripheral neuropathy, although its effectiveness was lower for predicting thrombocytopenia-related ADRs, indicating areas for improvement in monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. Uchida, M., Kawai, R., Hisamitsu, R., 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 III study involving 491 patients with diffuse large B-cell lymphoma, the more intensive treatment regimen DA-EPOCH-R did not show a statistically significant improvement in progression-free survival (PFS) or overall survival (OS) compared to the standard R-CHOP regimen, with 2-year PFS rates of 78.9% for DA-EPOCH-R and 75.5% for R-CHOP.

DA-EPOCH-R was associated with a higher incidence of severe adverse events, including infections and febrile neutropenia, indicating that while it is a more intensive treatment, it does not provide additional survival benefits and carries greater risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303. Bartlett, NL., Wilson, WH., Jung, SH., et al.[2021]

In a study of 91 people living with HIV and Burkitt lymphoma, adding rituximab to CODOX-M/IVAC chemotherapy did not increase severe treatment-related toxicities, indicating it is a safe option for this population.

The addition of rituximab significantly improved both overall survival (72% vs. 55%) and progression-free survival (81% vs. 55%) compared to chemotherapy alone, suggesting it enhances treatment efficacy without added risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adding rituximab to CODOX-M/IVAC chemotherapy in the treatment of HIV-associated Burkitt lymphoma is safe when used with concurrent combination antiretroviral therapy. Alwan, F., He, A., Montoto, S., et al.[2022]

In a study of 37 patients with relapsed/refractory aggressive lymphoma, the PACEBOM regimen demonstrated an overall response rate of 65% for Diffuse Large B-Cell Lymphoma (DLBCL), 70% for T-Cell Lymphoma (TCL), and 71% for Hodgkin lymphoma, indicating its efficacy as a treatment option.

The combination of PACEBOM with rituximab showed manageable toxicity, with the most common severe side effects being neutropenia (46%) and anemia (24%), suggesting that this treatment can be safely administered to patients previously treated with rituximab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era. Tamjid, B., Mckendrick, J., Schwarer, A., et al.[2018]

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 study involving 166 patients with aggressive B-cell lymphoma, the addition of radiotherapy (RT) to the standard R-CHOP treatment significantly improved event-free survival (EFS) for those with bulky disease, indicating that RT is beneficial for this patient group.

Patients who did not receive RT had a higher risk of disease progression and lower overall survival rates, suggesting that RT effectively mitigates the risks associated with bulky disease in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. Held, G., Murawski, N., Ziepert, M., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7086

Phase 3 trial evaluating efficacy and safety of ... Phase 3 trial evaluating efficacy and safety of odronextamab plus CHOP vs rituximab plus CHOP in previously untreated diffuse large B-cell ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06091865

NCT06091865 | A Study to Compare How Well ... This study is researching an experimental drug called odronextamab, referred to as study drug, when used in combination with chemotherapy.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12003196/

Odronextamab monotherapy in patients with relapsed ... Odronextamab monotherapy in patients with relapsed/refractory diffuse large B cell lymphoma: primary efficacy and safety analysis in phase 2 ELM-2 trial

4. 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.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10428936/

PHASE 3 TRIAL EVALUATING THE EFFICACY AND SAFETY ... In the Phase 2 ELM-2 study (NCT03888105), odronextamab monotherapy demonstrated clinically important antitumor activity (objective response rate ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4486/534059/Dynamics-of-Complete-Responses-in-Patients-with

Dynamics of Complete Responses in Patients with Relapsed ... Odronextamab, an investigational CD20xCD3 bispecific antibody, for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma.