Odronextamab vs Chemotherapy for Follicular Lymphoma

(OLYMPIA-1 Trial)

Not currently recruiting at 378 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

Disqualifiers: CNS lymphoma, High-grade transformation, 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 explores a new drug, odronextamab, for individuals with follicular lymphoma, a type of non-Hodgkin lymphoma. In the first part, researchers will assess the safety and tolerability of odronextamab when taken alone. In the second part, they will compare it to the standard treatment of rituximab and chemotherapy to determine which is more effective. Participants must have a diagnosis of follicular lymphoma requiring treatment and measurable disease on a CT or MRI scan. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should not have had any systemic anti-lymphoma therapy, which might imply stopping certain treatments. It's best to discuss your specific medications with the trial team.

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

Research has shown that odronextamab is generally well-tolerated by patients with follicular lymphoma who have undergone previous treatments. In these studies, many patients experienced a significant reduction in their cancer. Most side effects were manageable, although some patients did experience them.

In another study involving patients who had not been treated before, odronextamab also demonstrated promising safety results. Administered on its own, the treatment produced side effects similar to those seen in patients with prior treatments. This suggests that odronextamab may be a safe option for people with follicular lymphoma, even if they are new to treatment.

Overall, the evidence indicates that odronextamab is generally safe. However, participants should be aware of potential side effects and discuss them with their healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for follicular lymphoma?

Odronextamab is unique because it is a bispecific antibody that targets both CD20 on B-cells and CD3 on T-cells, engaging the body's immune system to attack follicular lymphoma cells more directly. Unlike traditional chemotherapy, which attacks rapidly dividing cells broadly, odronextamab's targeted approach may reduce damage to healthy cells and minimize side effects. Researchers are excited about its potential to provide more effective and precise treatment by harnessing the immune system to fight the cancer, which could lead to better outcomes for patients with follicular lymphoma.

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

Research shows that odronextamab, which participants in this trial may receive, has promising results for treating follicular lymphoma. Earlier studies found that patients with this type of lymphoma, who had already tried many treatments without success, experienced high rates of complete recovery. These recoveries were not only strong but also lasted a long time, with about 54.3% of patients remaining in recovery for three years. Doctors generally managed the side effects of odronextamab effectively. This evidence suggests that odronextamab could be an effective treatment option for 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?

This trial is for adults with a type of non-Hodgkin lymphoma called follicular lymphoma, who haven't been treated before. They should have a certain level of physical fitness (ECOG 0-2) and their bone marrow and liver must be functioning well. People with CNS involvement, transformed high-grade lymphomas, or specific other conditions are excluded.

Inclusion Criteria

You need the specific treatment described in the study protocol.

My cancer can be measured on a CT or MRI scan.

My liver and bone marrow are working well.

Exclusion Criteria

My cancer is in the brain or spinal cord.

You have an infection or you are allergic to the study drug or any of its ingredients.

I am currently receiving or have received systemic therapy for lymphoma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety Run-in

Participants receive odronextamab to assess safety and tolerability

Up to 30 months

Part 2: Randomized Controlled

Participants are randomized to receive either odronextamab or 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

• Bendamustine
• Cyclophosphamide
• Doxorubicin
• Odronextamab
• Prednisone/prednisolone
• Rituximab
• Vincristine

Trial Overview The study tests odronextamab against the usual treatment combination of rituximab and chemotherapy for follicular lymphoma. It has two parts: first to check safety and tolerability, then to compare effectiveness. The study also looks at how much drug is in the blood over time, potential antibodies against it, side effects, and life quality impacts.

How Is the Trial Designed?

Group I: Odronextamab Experimental Treatment 1 Intervention

Part 1 is a safety run-in. All participants will receive odronextamab. In part 2 participants will be randomly assigned in a 1:1 ratio to receive odronextamab followed by odronextamab maintenance.

Group II: Rituximab + Investigator's Choice Chemotherapy Active Control 6 Interventions

Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.

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

Approved in United States as Treanda for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in European Union as Ribomustin for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma
• Multiple myeloma

Approved in Canada as Levact for:

• Chronic lymphocytic leukemia
• Non-Hodgkin lymphoma

Approved in Japan as Bendamustine hydrochloride for:

• Chronic lymphocytic leukemia
• Non-Hodgkin 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

In a study involving 549 patients with advanced indolent lymphoma, bendamustine plus rituximab significantly improved median progression-free survival (69.5 months) compared to R-CHOP (31.2 months), indicating it may be a more effective first-line treatment.

Bendamustine plus rituximab was better tolerated than R-CHOP, with significantly lower rates of side effects such as alopecia, hematological toxicity, infections, and peripheral neuropathy, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Rummel, MJ., Niederle, N., Maschmeyer, G., et al.[2022]

In a study of 640 newly diagnosed follicular lymphoma patients, maintenance rituximab (MR) after bendamustine and rituximab (BR) induction improved the duration of response for those who achieved partial remission, while complete remission patients did not show similar benefits.

The safety profile of MR was acceptable, with a fatal adverse event rate of 2.5% after BR, which did not significantly differ between patients receiving MR and those who did not, suggesting that MR is a safe option for patients with partial remission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. Hill, BT., Nastoupil, L., Winter, AM., et al.[2020]

Bendamustine demonstrated a high objective response rate of 74.3% in 99 patients with relapsed/refractory Hodgkin and non-Hodgkin lymphoma, indicating its efficacy as a salvage treatment after multiple lines of chemotherapy.

The most common side effects included lymphopenia, anemia, and neutropenia, with serious side effects occurring in a minority of patients, suggesting that while bendamustine is effective, monitoring for these side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. Karadurmus, N., Paydas, S., Esin, E., et al.[2022]

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 study of 145 patients with grade 3A follicular lymphoma, the combination of bendamustine and rituximab (R-B) showed a similar overall response rate to the standard R-CHOP treatment but had a better complete remission rate (87% vs. 80%).

While R-CHOP demonstrated significantly longer overall survival compared to R-B, this difference was not statistically significant after adjusting for age, suggesting both treatments are valid first-line options for this type of lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of first-line treatment with bendamustine plus rituximab versus R-CHOP for patients with follicular lymphoma grade 3A: Results of a retrospective study from the Fondazione Italiana Linfomi. Margiotta-Casaluci, G., Bigliardi, S., Cocito, F., et al.[2023]

Bendamustine has been approved for treating chronic lymphocytic leukemia and has shown good response rates with minor side effects when used alone for non-Hodgkin's lymphomas.

When combined with rituximab and other agents, bendamustine significantly improves efficacy, making it a valuable option for treating relapsed indolent non-Hodgkin's lymphomas, with less toxicity compared to traditional R-CHOP therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine in the treatment of non-Hodgkin's lymphomas. Hagemeister, F., Manoukian, G.[2021]

In the phase Ib/II GO29365 study involving 112 patients with relapsed or refractory follicular lymphoma, the combination of polatuzumab vedotin with bendamustine and rituximab (Pola-BR) showed similar PET complete response rates (69.2%) compared to bendamustine and rituximab alone (63.4%).

However, the addition of polatuzumab vedotin was associated with a higher incidence of serious adverse events and cytopenias, indicating that it does not provide a clear benefit over standard treatment regimens for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma: a phase Ib/II study. Flowers, CR., Matasar, MJ., Herrera, AF., et al.[2023]

Rituximab plus bendamustine (R-B) is less toxic and achieves similar complete remission rates compared to R-CHOP in patients with follicular lymphoma grade 3A, with 97% vs. 96% complete remissions respectively.

Patients treated with R-B experienced significantly lower relapse rates (16% vs. 41%) and longer progression-free survival (15 years vs. 11.7 years) compared to those treated with R-CHOP, making R-B a more effective first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bendamustine plus Rituximab Versus R-CHOP as First-Line Treatment for Patients with Follicular Lymphoma Grade 3A: Evidence from a Multicenter, Retrospective Study. Mondello, P., Steiner, N., Willenbacher, W., et al.[2019]

The current standard treatment for follicular lymphoma is a combination of chemotherapy and rituximab, specifically the R-CHOP regimen, which has been widely used and is effective.

Bendamustine combined with rituximab has shown excellent efficacy and tolerability in treating low-grade lymphomas, making it a promising alternative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing trials in low-grade lymphoma. Burchardt, A.[2021]

In a study involving 73 patients with relapsed or refractory follicular lymphoma, the combination of bortezomib, bendamustine, and rituximab achieved an impressive overall response rate of 88%, with 53% of patients experiencing a complete response.

The treatment demonstrated a median progression-free survival of 14.9 months, and while there were manageable toxicities, including myelosuppression, the overall safety profile was acceptable for patients undergoing this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. Fowler, N., Kahl, BS., Lee, P., et al.[2020]

Bendamustine used as a conditioning regimen for autologous stem cell transplantation in 35 lymphoma patients resulted in successful hematopoietic reconstitution, with median times of 11 days for neutrophil and 12 days for platelet engraftment, and a high overall survival rate of 90.97% at 12 and 24 months.

The treatment was associated with manageable side effects, including nausea, vomiting, and diarrhea, with no transplant-related deaths reported, indicating that bendamustine is both effective and tolerable for patients undergoing this procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma]. Fu, Y., Feng, YF., Liu, F., et al.[2023]

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 ...