Odronextamab + Lenalidomide for Lymphoma

(OLYMPIA-5 Trial)

Recruiting at 282 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must be taking: Lenalidomide

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

470 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug combination for two types of non-Hodgkin's lymphoma (NHL): follicular lymphoma (FL) and marginal zone lymphoma (MZL). The researchers aim to determine if adding the experimental drug odronextamab to lenalidomide (Revlimid) is safe and effective compared to the usual treatment, which includes rituximab. The study consists of two parts: first, assessing safety and proper dosing, then comparing the effectiveness of the new combination against the standard treatment. Individuals with FL or MZL whose cancer has returned or hasn't responded to previous treatment might be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants access to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if 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 has shown that odronextamab, when used alone, has promising safety results. In one study, 73% of patients with relapsed or refractory follicular lymphoma (FL) achieved a complete response, meaning their cancer was undetectable after treatment. This indicates that the drug is safe, as these patients tolerated it well enough to see positive results.

For lenalidomide, when combined with rituximab, studies have demonstrated it is generally safe and effective. This combination is already a standard treatment for indolent non-Hodgkin lymphoma, a type of slow-growing blood cancer. Reports confirm that patients manage the treatment well, and it is considered safe for most people.

In this trial, researchers are testing how odronextamab works with lenalidomide, a new combination. As this is a Phase 3 trial, the treatment has already passed earlier safety tests. This suggests the combination is expected to be safe, but this study will confirm its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Odronextamab and Lenalidomide for treating lymphoma because it introduces a novel mechanism compared to standard therapies. Unlike traditional treatments like Rituximab that primarily target CD20 on B-cells, Odronextamab is a bispecific antibody designed to engage CD20 on B-cells and CD3 on T-cells, potentially enhancing the immune system's ability to attack cancer cells. This dual-targeting approach could offer a more effective way to tackle resistant forms of lymphoma, providing hope for patients who have limited options. Additionally, combining Odronextamab with Lenalidomide may enhance the anti-cancer effects by modulating the immune environment, potentially leading to better outcomes than using these drugs individually.

What evidence suggests that this trial's treatments could be effective for relapsed or refractory follicular lymphoma and marginal zone lymphoma?

Research is testing the effectiveness of combining two drugs, odronextamab and lenalidomide, for treating certain types of lymphoma, specifically relapsed or refractory follicular lymphoma (FL) and marginal zone lymphoma (MZL). Participants in this trial may receive this combination, new to human trials, although earlier research suggests odronextamab may be promising for these lymphomas. Lenalidomide is known to help the immune system fight cancer cells.

Another group of participants will receive rituximab and lenalidomide, a combination that has shown improved results in patients with recurring slow-growing lymphoma. This well-established treatment has effectively helped the immune system combat cancer. The trial compares both treatment options to determine which works better for these specific types of lymphoma. ^{2 3 4 6 7}

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 people with follicular lymphoma or marginal zone lymphoma that hasn't improved or has returned after treatment. Participants must have tried at least one anti-CD20 monoclonal antibody therapy and need more treatment. They should be able to perform daily activities (ECOG 0-2) and have measurable disease via CT or MRI scans.

Inclusion Criteria

My blood counts and organ functions are within normal ranges.

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

My lymphoma is confirmed to be of a specific type and grade.

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 in combination with lenalidomide to assess safety and determine dosing for Part 2

Up to 2 years

Part 2: Randomized Controlled

Participants are randomized to receive either odronextamab with lenalidomide or rituximab with lenalidomide to compare efficacy and safety

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

• Lenalidomide
• Odronextamab
• Rituximab

Trial Overview The study tests odronextamab combined with lenalidomide against the standard rituximab plus lenalidomide in patients with certain types of Non-Hodgkin's lymphoma. Part 1 determines the safe dose; Part 2 compares effectiveness and safety between the two drug combinations.

How Is the Trial Designed?

Group I: Rituximab+Lenalidomide Experimental Treatment 2 Interventions

In part 2 only, 1:1 randomized participants with R/R lymphoma (FL and ML), will receive rituximab in combination with lenalidomide (R2) followed by lenalidomide monotherapy.

Group II: Odronextamab+Lenalidomide Experimental Treatment 2 Interventions

In part 1 (safety run-in), participants with R/R indolent lymphoma (FL and MZL), will receive odronextamab in combination with lenalidomide. In part 2, 1:1 randomized participants with indolent lymphoma (FL/MZL), will receive odronextamab in combination with lenalidomide.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone 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 lenalidomide and rituximab (LR) showed a significantly higher overall response rate (76%) compared to lenalidomide alone (53%) in patients with recurrent follicular lymphoma, indicating that LR is more effective in treating this condition.

Both treatment regimens had similar rates of severe adverse events (grade 3 to 4), but lenalidomide alone resulted in more treatment failures, suggesting that LR may provide a better balance of efficacy and tolerability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). Leonard, JP., Jung, SH., Johnson, J., et al.[2022]

Lenalidomide, especially when combined with rituximab (the 'R(2)' regimen), shows enhanced efficacy in treating indolent B-cell and mantle cell lymphomas, even in patients resistant to rituximab, while maintaining a manageable safety profile.

The most common serious side effect is asymptomatic neutropenia, which can be managed through dose adjustments, and while immune-related symptoms like rash are more frequent with the R(2) regimen, they are generally low-grade and manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. Ruan, J., Shah, B., Martin, P., et al.[2020]

In a phase II trial involving 45 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), transformed large cell lymphoma (TL), or grade 3 follicular lymphoma, the combination of lenalidomide and rituximab showed an overall response rate of 33% and a median response duration of 10.2 months.

The treatment was well tolerated, with significant hematological toxicities observed, and patients who underwent stem cell transplantation after responding to the therapy experienced a prolonged response duration of 30.9 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral lenalidomide with rituximab in relapsed or refractory diffuse large cell, follicular and transformed lymphoma: a phase II clinical trial. Wang, M., Fowler, N., Wagner-Bartak, N., et al.[2020]

In a large observational study of 2150 patients with relapsed/refractory multiple myeloma, lenalidomide plus dexamethasone demonstrated a favorable safety profile, with lower incidence rates of neuropathy and infections compared to other treatments like bortezomib and thalidomide.

The study confirmed that lenalidomide's safety profile in a real-world setting is consistent with previous clinical trial data, with no new safety concerns identified, although it did show a higher incidence of neutropenia compared to bortezomib and thalidomide.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. Gamberi, B., Berthou, C., Hernandez, M., et al.[2021]

In a phase II study involving 59 adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL), the combination of lenalidomide and rituximab resulted in a 66% overall response rate, indicating significant efficacy as a salvage therapy.

While the treatment showed promise, it was associated with notable side effects, particularly neutropenia in 73% of patients, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. Badoux, XC., Keating, MJ., Wen, S., et al.[2021]

In the phase III AUGMENT trial, lenalidomide combined with rituximab significantly improved progression-free survival in patients with relapsed or refractory follicular lymphoma compared to placebo, showing particular benefit for elderly patients.

Lenalidomide has an acceptable safety profile, although it can cause more frequent cases of severe neutropenia, which can be managed with dosage adjustments and growth factor support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: A Review in Previously Treated Follicular Lymphoma. Blair, HA.[2021]

Lenalidomide, when used in combination with rituximab, has been shown to be an effective treatment for patients with relapsed or refractory follicular lymphoma, offering a chemotherapy-free option.

This combination therapy improves outcomes compared to using rituximab alone and may serve as a viable alternative to traditional chemoimmunotherapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in follicular lymphoma. Flowers, CR., Leonard, JP., Fowler, NH.[2021]

The combination of oral lenalidomide and obinutuzumab was found to be well tolerated and effective in treating relapsed or refractory follicular lymphoma, with a response rate of 63.2% among participants.

The study established a recommended dose of lenalidomide at 20 mg, as higher doses increased the risk of grade 3/4 neutropenia, although no maximum tolerated dose was reached during the trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma. Morschhauser, F., Salles, G., Le Gouill, S., et al.[2021]

Lenalidomide is an orally bioavailable immunomodulator that has shown significant antitumor activity in treating various types of B-cell lymphomas, including mantle cell lymphoma and diffuse large B-cell lymphoma.

The drug has a favorable safety profile and is effective both as a standalone treatment and in combination with other therapies, marking a shift from traditional chemotherapy approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolving role of lenalidomide in non-Hodgkin lymphoma. Galanina, N., Petrich, A., Nabhan, C.[2019]

Lenalidomide has shown significant efficacy in improving survival rates for patients with relapsed and refractory myeloma, especially when used alongside other treatments like bortezomib and thalidomide.

While lenalidomide is effective, it is associated with common side effects such as fatigue and thrombocytopenia, and its combination with other agents can increase the risk of blood clots, highlighting the importance of managing these adverse events for continued treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. van de Donk, NW., Görgün, G., Groen, RW., et al.[2021]

In a study of 33 patients with relapsed/refractory non-Hodgkin lymphoma, the GROC-Rev chemotherapy regimen followed by lenalidomide maintenance therapy resulted in a 61% overall response rate, with 39% achieving complete response (CR).

The treatment was generally well-tolerated, although some patients experienced significant adverse events like neutropenia and infections, highlighting the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev). Cabanillas, F., Rivera, N., Acosta, M., et al.[2022]

In a phase II trial involving 50 patients with indolent B-cell or mantle cell lymphomas who were previously resistant to rituximab, the combination of lenalidomide and rituximab resulted in a significant increase in overall response rate from 30.2% after lenalidomide alone to 62.8% after adding rituximab.

The median progression-free survival for patients receiving the lenalidomide-rituximab combination was 22.2 months, which was significantly longer than the 9.13 months observed with prior rituximab treatment, indicating that this combination can effectively overcome previous resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. Chong, EA., Ahmadi, T., Aqui, NA., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10429454/

PHASE 3 TRIAL OF ODRONEXTAMAB PLUS ... This Phase 3 trial will determine the efficacy and safety of odronextamab plus lenalidomide compared with R2 in patients with R/R FL and MZL.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.TPS7094

Phase 3 trial of odronextamab plus lenalidomide versus ... Phase 3 trial evaluating the efficacy and safety of odronextamab versus standard-of-care (SOC) therapy in relapsed/refractory (R/R) aggressive B-cell non- ...

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

Safety and efficacy of odronextamab in patients with ... Outcomes for patients with follicular lymphoma (FL) worsen with each relapse, representing a clear medical unmet need. •. Odronextamab achieved ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06149286

Study Details | NCT06149286 | A Trial to Learn if ... A Trial to Learn if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Adult Participants With ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT452188

Phase 3 trial of odronextamab plus lenalidomide versus ... Phase 3 trial of odronextamab plus lenalidomide versus rituximab plus lenalidomide in relapsed/refractory (R/R) follicular lymphoma (FL) and marginal zone ...

6. clinicaltrials.gov clinicaltrials.gov/show/NCT06149286

NCT06149286 | A Trial to Learn if Odronextamab ... A phase of research to describe clinical trials that focus on the safety of a drug. They are usually conducted with healthy volunteers, and the ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0923753424037591

Safety and efficacy of odronextamab in patients with ... Odronextamab achieved high rates of deep response with durability in R/R FL, with 73% of patients attaining complete response.