Odronextamab + Chemotherapy for B-Cell Lymphoma

(OLYMPIA-3 Trial)

Recruiting in Palo Alto (17 mi)

+189 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Systemic anti-lymphoma therapy

Disqualifiers: CNS lymphoma, Active malignancy, Infections, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called odronextamab with chemotherapy for patients with a type of lymphoma that hasn't been treated before, has come back, or hasn't responded to treatment. The study will check if this combination is safe and effective compared to the current standard treatment. Researchers will also look at side effects, how the drug behaves in the body, and its impact on daily life.

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.

What data supports the effectiveness of the drug Odronextamab + Chemotherapy for B-Cell Lymphoma?

Research shows that combining rituximab with chemotherapy drugs like cyclophosphamide, doxorubicin, vincristine, and prednisone (known as R-CHOP) is effective for treating aggressive B-cell lymphoma. Adding rituximab to similar chemotherapy regimens has shown improved outcomes in various studies, suggesting potential benefits for the combination of Odronextamab with these chemotherapy drugs. ^{1 2 3 4 5}

Is the combination of Odronextamab and chemotherapy safe for treating B-cell lymphoma?

The combination of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has been used in treating B-cell lymphoma, but it can cause severe side effects. Safety data from studies show that while these treatments can be effective, they also carry a risk of serious adverse reactions, so careful monitoring is necessary. ^{6 7 8 9 10}

What makes the drug odronextamab combined with chemotherapy unique for treating B-cell lymphoma?

Odronextamab is a novel bispecific antibody that targets both CD3 on T cells and CD20 on B cells, which helps the immune system attack cancer cells more effectively. This mechanism is different from traditional treatments like rituximab, which only targets CD20, and it shows promise in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. ^{3 6 9 11 12}

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cyclophosphamide (Alkylating agents)
• Doxorubicin (Anti-tumor antibiotic)
• Odronextamab (Monoclonal Antibodies)
• Prednisone/Prednisolone (Anti-metabolites)
• Rituximab (Monoclonal Antibodies)
• Vincristine (Vinca alkaloids)

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.

Participant Groups

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

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

David Geffen School of Medicine at UCLA Los Angeles, CA

University Hospitals Cleveland Medical Center Cleveland, OH

Duke University Medical Center Durham, NC

Stony Brook University Hospital Stony Brook, NY

More Trial Locations

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals Lead Sponsor

References

1. Italy pubmed.ncbi.nlm.nih.gov

Clinical experience with biweekly CHOP plus rituximab chemoimmunotherapy for the treatment of aggressive B-cell non-Hodgkin lymphoma. [2021] The results of CHOP-21 (cyclophosphamide, doxorubicin, vincristine and prednisone given every 21 days) for the treatment of aggressive B-cell lymphoma have recently been improved by the addition of rituximab and by increasing the dose density. R-CHOP-14 combines these two approaches.

2. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and toxicity of PACEBOM chemotherapy in relapsed/refractory aggressive lymphoma in the rituximab era. [2018] Relapsed/refractory (R/R) aggressive lymphoma outcomes are poor. There is no standard treatment. PACEBOM (prednisolone, doxorubicin, cyclophosphamide, etoposide, bleomycin, vincristine and methotrexate) has shown efficacy for several lymphoma subtypes in published reports. We evaluate PACEBOM+/-rituximab for R/R aggressive lymphomas in this millennium.

3. England 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. [2022] CODOX-M/IVAC (cyclophosphamide, vincristine, doxorubicin-methatrexate/ifusamide, etoposide, cytarabine) chemotherapy is commonly used to treat Burkitt lymphoma and in the HIV-negative population. Rituximab is often added with suggested survival benefits. Concerns over increased toxicity in an already immunocompromized population have prevented its routine addition in people living with HIV (PLWH). This study evaluated the effect on treatment-related toxicity and efficacy of adding rituximab to CODOX-M/IVAC chemotherapy in PLWH.

4. United States 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. [2021] Alliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.

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

Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma. [2022] R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is standard care for aggressive B-cell lymphoma. A prospective trial was conducted to investigate the role of additive radiotherapy (RT) to bulky and extralymphatic disease.

6. England pubmed.ncbi.nlm.nih.gov

Infectious diseases and immunological markers associated with patients with non-Hodgkin lymphoma treated with rituximab. [2019] The use of rituximab (RTX) is increasing, even in developing countries. It has become the first-line therapy or adjuvant to chemotherapy (CHOP; cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone) for various diseases, including B cell lymphoma and autoimmune diseases.

7. China 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. [2023] To compare the efficacy and safety of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin plus rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in Waldeyer's ring diffuse large B-cell lymphoma (WR-DLBCL) at a single institution.

8. Greece pubmed.ncbi.nlm.nih.gov

Evaluation of Medication Instruction Sheets for Patients Undergoing R-CHOP Therapy in Non-Hodgkin's Lymphoma. [2022] High-dose chemotherapy is frequently administered to patients with hematologic malignancies, thereby causing severe adverse drug reactions (ADRs) at a relatively high frequency. To precisely monitor ADRs, we developed a medication instruction sheet (MIS) for patients who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) combination therapy for non-Hodgkin's lymphoma (NHL). Herein, we evaluated the usefulness of the MIS for managing ADRs in patients who received R-CHOP therapy.

9. United States 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. [2022] Improved outcomes have recently been reported for rituximab (R) plus rituximab plus infusional etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH) chemotherapy in patients with human immunodeficiency virus (HIV)-associated, aggressive B-cell, non-Hodgkin lymphoma (NHL). The objective of the current analysis was to assess whether patient selection or other factors contributed to this improvement and to identify patients who are at the greatest risk for lethal toxicity.

10. United States 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. [2015] To evaluate the safety and efficacy of a modified version of cyclophosphamide, doxorubicin, vincristine, prednisone (pirarubicin, cyclophosphamide, vincristine, and prednisone [THP-COP]) plus radiotherapy for early-stage aggressive non-Hodgkin's lymphoma of the head and neck.

11. England pubmed.ncbi.nlm.nih.gov

Novel CD20 monoclonal antibodies for lymphoma therapy. [2022] Rituximab (RTX), a monoclonal antibody (mAb) against CD20, has been widely used for lymphoma therapy. RTX in combination with cyclophosphamide /doxorubicin /vincristine /prednisone (R-CHOP) remains the standard frontline regimen for diffuse large B-cell lymphoma. However, suboptimal response and /or resistance to rituximab have remained a challenge in the therapy of B-cell non-Hodgkin's lymphoma (NHL). Novel agents are under active clinical trials. This review will summarize the latest development in new mAbs against CD20, which include second-generation mAbs, ofatumumab, veltuzumab (IMMU-106), ocrelizumab (PRO70769), and third-generation mAbs, AME-133v (ocaratuzumab), PRO131921 and GA101 (obinutumumab).

12. 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] Odronextamab is a fully-human IgG4-based CD20xCD3 bispecific antibody that binds to CD3 on T cells and CD20 on B cells, triggering T-cell-mediated cytotoxicity independent of T-cell-receptor recognition. Adequate safety, tolerability, and encouraging durable complete responses have been observed in an ongoing first-in-human (FIH) study of odronextamab in patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL; NCT02290951). We retrospectively evaluated the pharmacokinetic, pharmacodynamic, and antitumor characteristics of odronextamab in a series of in vitro/in vivo preclinical experiments, to assess their translational value to inform dose escalation for the FIH study. Half-maximal effective concentration values from in vitro cytokine release assays (range: 0.05-0.08 mg/L) provided a reasonable estimate of odronextamab concentrations in patients associated with cytokine release at a 0.5 mg dose (maximum serum concentration: 0.081 mg/L) on week 1/day 1, which could therefore be used to determine the week 1 clinical dose. Odronextamab concentrations resulting in 100% inhibition of tumor growth in a Raji xenograft tumor mouse model (1-10 mg/L) were useful to predict efficacious concentrations in patients and inform dose-escalation strategy. Although predicted human pharmacokinetic parameters derived from monkey data overestimated projected odronextamab exposure, they provided a conservative estimate for FIH starting doses. With step-up dosing, the highest-tested weekly odronextamab dose in patients (320 mg) exceeded the 1 mg/kg single dose in monkeys without step-up dosing. In conclusion, combination of odronextamab in vitro cytokine data, efficacious concentration data from mouse tumor models, and pharmacokinetic evaluations in monkeys has translational value to inform odronextamab FIH study design in patients with R/R B-NHL.