Odronextamab + Lenalidomide for Lymphoma

(OLYMPIA-5 Trial)

Recruiting in Palo Alto (17 mi)

+203 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Regeneron Pharmaceuticals

Must be taking: Lenalidomide

Disqualifiers: CNS lymphoma, High-grade lymphoma, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called odronextamab (referred to as study drug), in combination with lenalidomide. The study is focused on participants who have one of two types of cancer: follicular lymphoma (FL) or marginal zone lymphoma (MZL) that has come back after treatment (called "relapsed"), or did not respond to treatment (called "refractory"). FL and MZL are subtypes of Non-Hodgkin 's lymphoma (NHL). This study will be made up of two parts (Part 1 not randomized, Part 2 randomized - controlled). The aim of Part 1 of the study is to see how safe and tolerable the study drug is when used in combination with lenalidomide, in participants with FL or MZL, and to determine the dose of the study drug to be used in Part 2 of this study. This combination is considered "first-in-human" as it has not been tested as a combination treatment in humans before. The aim of Part 2, of the study is to assess how the combination of the study drug and lenalidomide works compared to the combination of rituximab (called "the comparator drug") and lenalidomide. The combination of comparator drug and lenalidomide is the current standard-of care treatment for FL and/or MZL. 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 in combination with lenalidomide * 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) * The impact from the study drug on 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. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug combination of Odronextamab and Lenalidomide for lymphoma?

Research shows that Lenalidomide, when combined with Rituximab, significantly improves outcomes in patients with certain types of lymphoma, especially those who have not responded well to previous treatments. This suggests that Lenalidomide can be effective in enhancing the body's immune response against lymphoma. ^{1 2 3 4 5}

Is the combination of Odronextamab and Lenalidomide safe for treating lymphoma?

Lenalidomide, often used with rituximab, has a manageable safety profile in treating various lymphomas, with common side effects like neutropenia (low white blood cell count) and fatigue, which are generally manageable with dose adjustments. Although Odronextamab is not specifically mentioned, lenalidomide's safety in combination with other drugs like rituximab and obinutuzumab suggests it is generally well-tolerated in similar settings. ^{1 6 7 8 9}

What makes the drug combination of Odronextamab, Lenalidomide, and Rituximab unique for treating lymphoma?

This drug combination is unique because it combines Odronextamab, a novel agent, with Lenalidomide and Rituximab, which have shown effectiveness in overcoming resistance in certain lymphomas. Lenalidomide enhances the immune response, while Rituximab targets specific cancer cells, and Odronextamab may offer additional benefits by engaging the immune system in a new way. ^{1 2 10 11 12}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Lenalidomide (Other)
• Odronextamab (Monoclonal Antibodies)
• Rituximab (Monoclonal Antibodies)

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.

Participant Groups

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.

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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, 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]

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]

References

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

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

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

Combination of Lenalidomide and Rituximab Overcomes Rituximab Resistance in Patients with Indolent B-cell and Mantle Cell Lymphomas. [2022]

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

Phase II study of lenalidomide and rituximab as salvage therapy for patients with relapsed or refractory chronic lymphocytic leukemia. [2021]

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

The evolving role of lenalidomide in non-Hodgkin lymphoma. [2019]

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

A New Salvage Regimen for Aggressive Lymphomas Based on Gemcitabine, Rituximab, and Oxaliplatin Followed by Lenalidomide (GROC-Rev). [2022]

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

Clinical experience with lenalidomide alone or in combination with rituximab in indolent B-cell and mantle cell lymphomas. [2020]

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

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. [2021]

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

An open-label phase 1b study of obinutuzumab plus lenalidomide in relapsed/refractory follicular B-cell lymphoma. [2021]

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

A Noninterventional, Observational, European Post-Authorization Safety Study of Patients With Relapsed/Refractory Multiple Myeloma Treated With Lenalidomide. [2021]

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

Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance). [2022]

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

Lenalidomide in follicular lymphoma. [2021]

12. England 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. [2020]