Odronextamab vs Chemotherapy for Follicular Lymphoma

(OLYMPIA-1 Trial)

Recruiting at 286 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

478 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma (a type of non-Hodgkin lymphoma or NHL). This study will be made up of two parts: Part 1 (non-randomized) and Part 2 (randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when given alone. The aim of Part 2 of the study is to see how the study drug works compared to rituximab (called the "comparator drug") and chemotherapy (the current standard of care for NHL). Standard of care means the usual medication expected and used when receiving treatment for a condition. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) * How the study drug affects quality of life and ability to complete routine daily activities.

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.

What data supports the effectiveness of the drug Odronextamab compared to chemotherapy for follicular lymphoma?

Research shows that the combination of bendamustine and rituximab (R-B) is an effective treatment for follicular lymphoma, achieving similar response rates to the standard R-CHOP regimen, with a better complete remission rate. This suggests that bendamustine, a component of the chemotherapy regimen, is effective in treating follicular lymphoma. ^{1 2 3 4 5}

Is the treatment with Odronextamab and chemotherapy safe for humans?

Bendamustine, often used with rituximab for treating follicular lymphoma, has been studied for safety. Some studies show it has an acceptable safety profile, but there have been reports of serious side effects, including a 2.5% rate of fatal adverse events in some cases. ^{6 7 8 9 10}

What makes the drug Odronextamab unique for treating follicular lymphoma?

Odronextamab is a novel treatment option for follicular lymphoma that differs from traditional chemotherapy regimens like R-CHOP or R-B (rituximab plus bendamustine) by potentially offering a different mechanism of action, as it is a bispecific antibody designed to engage T-cells to target and kill cancer cells. This approach may provide an alternative for patients who do not respond well to standard chemotherapy treatments. ^{2 3 5 10 11}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

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]

References

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

The Impact of Sequence of Therapy for Older Patients With Follicular Lymphoma: SEER-Medicare Analysis. [2022]

2. Switzerland 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. [2023]

3. England 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. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin plus bendamustine and rituximab or obinutuzumab in relapsed/refractory follicular lymphoma: a phase Ib/II study. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Ongoing trials in low-grade lymphoma. [2021]

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

Bendamustine in the treatment of non-Hodgkin's lymphomas. [2021]

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

Bortezomib, bendamustine, and rituximab in patients with relapsed or refractory follicular lymphoma: the phase II VERTICAL study. [2020]

8. Poland pubmed.ncbi.nlm.nih.gov

Effectiveness of bendamustine in relapsed or refractory lymphoma cases: a Turkish Oncology Group study. [2022]

9. China pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Bendamustine in the Conditioning Regiment for Autologous Hematopoietic Stem Cell Transplantation in Patients with Lymphoma]. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Maintenance rituximab or observation after frontline treatment with bendamustine-rituximab for follicular lymphoma. [2020]

11. England 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. [2022]