Odronextamab + Chemotherapy for Follicular Lymphoma

(OLYMPIA-2 Trial)

Recruiting at 228 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Disqualifiers: CNS lymphoma, High-grade lymphoma, 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

733 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new drug, odronextamab, to determine its effectiveness in treating follicular lymphoma, a type of blood cancer. The researchers aim to assess whether odronextamab combined with chemotherapy is as effective or better than the current standard treatment, rituximab with chemotherapy. The trial also evaluates the safety of the new treatment, potential side effects, and its impact on daily life. Individuals diagnosed with certain stages of untreated follicular lymphoma may be suitable candidates for this study. As a Phase 3 trial, this study 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 information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research shows that odronextamab is generally safe for patients with follicular lymphoma, a type of non-Hodgkin lymphoma. In previous studies with patients who had received many treatments, odronextamab was well-tolerated when used alone, with most side effects managed with additional care.

When tested with chemotherapy, odronextamab maintained a manageable safety profile. The early trial phases aimed to determine the optimal dose that is both effective and safe.

Although specific side effects from this combination aren't detailed, the study's progression to a later phase suggests promising earlier results. This progression indicates a positive sign for its safety in humans so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about odronextamab for follicular lymphoma because it offers a potential new way to enhance the immune system's ability to fight cancer. Unlike the standard treatment, which typically involves chemotherapy combined with drugs like rituximab, odronextamab is a bispecific antibody designed to engage T-cells, directing them specifically to target and destroy lymphoma cells. This innovative mechanism could lead to more effective and targeted treatment outcomes. Additionally, the trial is exploring different regimens of odronextamab with chemotherapy, and some variations include maintenance therapy to potentially prolong the treatment's benefits. These aspects make odronextamab a promising candidate in the fight against follicular lymphoma.

What evidence suggests that this trial's treatments could be effective for follicular lymphoma?

Research has shown that odronextamab yields promising results for treating follicular lymphoma, a type of non-Hodgkin lymphoma (NHL). In studies with patients whose cancer returned or did not respond to previous treatments, odronextamab led to high rates of complete response, meaning the cancer was undetectable after treatment. These responses were not only significant but also lasted a long time. The side effects of odronextamab were generally manageable, suggesting it could be a good option when combined with chemotherapy. In this trial, participants will be randomized to receive odronextamab with chemotherapy, either with or without maintenance, or rituximab with chemotherapy followed by rituximab maintenance. With these findings, there is hope that odronextamab can also effectively help those with newly diagnosed follicular lymphoma. ^{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?

Adults with previously untreated follicular lymphoma can join this trial. They should be able to perform daily activities (ECOG 0-2) and have a certain level of disease severity (FLIPI-1 score). Participants must not have other types of lymphomas, recent major surgeries, organ transplants, or any condition that could risk their safety in the study.

Inclusion Criteria

For Part 1B: previously untreated individuals with a FLIPI-1 score ranging from 3 to 5.

My lymphoma is CD20 positive and is either stage II bulky or stage III/IV.

I have untreated FL with a FLIPI-1 score of 3-5, or I have relapsed/refractory FL without prior R-CHOP or R-CVP treatment.

Exclusion Criteria

My lymphoma has changed into a more aggressive form.

I have lymphoma in my brain or spinal cord.

I have been diagnosed with a specific type of blood cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1A: Dose Escalation

Non-randomized dose escalation of odronextamab with chemotherapy for safety and tolerability assessment

Up to 35 days

Part 1B: Dose Optimization

Randomized exploration of odronextamab regimens with chemotherapy for dose optimization

Up to 2 years

Part 2: Randomized Controlled

Comparison of odronextamab with chemotherapy versus rituximab with chemotherapy

Up to 5 years

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 is testing odronextamab combined with chemotherapy against the standard rituximab with chemotherapy. It's divided into three parts: initial non-randomized phases to determine safe dosages and a final phase comparing effectiveness between treatments.

How Is the Trial Designed?

Group I: Odronextamab + Chemotherapy + No maintenance Experimental Treatment 2 Interventions

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy (CHOP, or CVP) without maintenance.

Group II: Odronextamab + Chemotherapy + Maintenance Experimental Treatment 2 Interventions

In Part 2, participants will be randomized 1:1:1 to receive odronextamab with chemotherapy \[CHOP, or cyclophosphamide, vincristine, and prednisone (CVP)\], followed by odronextamab monotherapy maintenance.

Group III: Odronextamab + Chemotherapy Experimental Treatment 4 Interventions

Part 1 of the study includes ordonextamab dose escalation for participants with previously untreated FL and relapsed/refractory FL (Part 1A only) followed by a randomized exploration of 2 regimens of odronextamab (Odro) and cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) with the objective of dose optimization (Part 1B) in previously untreated patients with FL.

Group IV: Rituximab + Chemotherapy Active Control 6 Interventions

In Part 2 only, participants will be randomized 1:1:1 to receive rituximab (R) with chemotherapy (CHOP), followed by rituximab monotherapy maintenance.

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 675 patients aged 65 and older with follicular lymphoma, those who received the R-CHOP treatment as their first line of therapy had significantly longer overall survival compared to those who received it as a second line treatment.

The benefit of receiving R-CHOP as a first line was particularly notable in patients aged 80 and older and those with lower histological grades (1 or 2), indicating that early treatment may be crucial for improving outcomes in these subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis. Xie, C., Li, R., Huang, X., et al.[2022]

In a long-term follow-up of 129 patients with advanced follicular lymphoma, the combination of rituximab with mitoxantrone, chlorambucil, and prednisolone (R-MCP) showed significantly improved overall survival compared to MCP alone, with 8-year survival rates of 76.1% versus 55.9%.

Patients receiving R-MCP also experienced longer progression-free survival (93.4 months) and event-free survival (89.6 months) compared to those on MCP alone, indicating that adding rituximab enhances long-term clinical outcomes for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of rituximab plus first-line mitoxantrone, chlorambucil, prednisolone and interferon-alpha as maintenance therapy in follicular lymphoma. Herold, M., Scholz, CW., Rothmann, F., et al.[2018]

In a study of 22 patients with resistant and relapsed CD20-positive follicular non-Hodgkin's lymphoma, the combination treatment of rituximab, high-dose cytarabine, oxaliplatin, and dexamethasone (R-DHAOx) resulted in a remarkable 95% complete response rate, demonstrating its efficacy as a salvage therapy.

With a median follow-up of 58.3 months, the treatment showed long-term effectiveness, with an 84% progression-free survival rate at 38.2 months, although it was associated with significant side effects like peripheral neuropathy and myelosuppression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment with rituximab, dexamethasone, high-dose cytarabine, and oxaliplatin (R-DHAOx) produces a strong long-term antitumor effect in previously treated patients with follicular non-Hodgkin's lymphoma. Machover, D., Delmas-Marsalet, B., Misra, SC., et al.[2015]

In a study of 60 patients with symptomatic or bulky follicular lymphoma, a combination of short-course chemoimmunotherapy (CHOP-R) followed by radioimmunotherapy (RIT) led to a significant increase in complete response (CR) rates, from 40% after CHOP-R to 82% after RIT, as assessed by imaging.

The study found that patients who did not achieve a complete metabolic response on PET imaging after CHOP-R had a higher risk of relapse, highlighting the importance of early PET assessment in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of short-course CHOP-R followed by 90Y-ibritumomab tiuxetan and extended rituximab in previously untreated follicular lymphoma. Jacobs, SA., Swerdlow, SH., Kant, J., et al.[2016]

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]

Stem cell transplantation can significantly improve survival in patients with follicular lymphoma (FL), but many patients are ineligible due to age or other health issues, leading to reliance on salvage chemotherapy.

Salvage chemotherapy for relapsed FL often involves highly toxic agents that can cause severe side effects, including myelosuppression, nausea, and long-term risks like secondary cancers, highlighting the need for novel therapies to reduce these toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage chemotherapy in follicular non-Hodgkin's lymphoma: focus on tolerability. Zinzani, PL.[2006]

The CHOEA-7 chemotherapy regimen, which includes cyclophosphamide, doxorubicin, vincristine, etoposide, and ara-C, has shown excellent results in treating patients with CD 20-positive non-Hodgkin's lymphoma.

Adding rituximab to the CHOEA-7 regimen (RCHOEA-7) further enhances treatment efficacy, indicating a promising approach for improving outcomes in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of dose-intense, dose-impact weekly combination chemotherapy with rituximab for patients with CD 20-positive B-cell non-Hodgkin's lymphoma]. Uzuka, Y., Saitou, Y., Saitou, K., et al.[2015]

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]

Rituximab is highly effective for treating low-grade CD20+ lymphoma, especially when combined with chemotherapy, which is the standard treatment for follicular lymphoma (FL).

The efficacy of rituximab can be enhanced by combining it with biological agents like interferon-alpha-2a, bortezomib, or lenalidomide, but more research is needed to determine the best combinations and timing of these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biological therapy doublets: pairing rituximab with interferon, lenalidomide, and other biological agents in patients with follicular lymphoma. Kimby, E.[2021]

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]

Citations

1. 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 ...

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

Safety and efficacy of odronextamab in patients with ... Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7049

Long-term follow-up of the phase 2 ELM-2 study Conclusions: With longer follow-up, odronextamab demonstrated durable responses in heavily pretreated pts with R/R FL from ELM-2, with robust ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39147364/

Safety and efficacy of odronextamab in patients with ... Conclusions: Odronextamab achieved high complete response rates with generally manageable safety in patients with heavily pretreated R/R follicular lymphoma.

5. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4502/534008/Efficacy-and-Safety-of-Odronextamab-in-Rare

Efficacy and Safety of Odronextamab in Rare Subtypes of ... Responses were durable, with 54.3% maintaining response at 3 years. The safety profile of odronextamab was generally manageable and consistent ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4411/529980/Odronextamab-Monotherapy-in-Previously-Untreated

Odronextamab Monotherapy in Previously Untreated Patients ... Here, we report safety and preliminary efficacy results for odronextamab monotherapy in pts with high-risk Grade 1-3a FL from the safety lead-in ...