A Trial to Learn if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Marginal Zone Lymphoma (MZL); Relapsed/Refractory Follicular Lymphoma

Treatments: Drug: Rituximab; Drug: Lenalidomide; Drug: Odronextamab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06149286

R1979-ONC-22102

2022-503092-28-00 (Other Identifier)

Details and patient eligibility

About

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on patients 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 odronextamab and lenalidomide works compared to the combination of rituximab and lenalidomide, (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 your 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 your quality-of-life and ability to complete routine daily activities

Enrollment: 470 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. Local histologic confirmation of FL grade 1-3a or MZL (nodal, splenic, or extra nodal MZL) as assessed by the investigator.
2. Must have refractory disease or relapsed after at least 2 cycles of prior systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-cluster of differentiation 20 (CD20) monoclonal antibody and patient should meet indication for treatment.
3. Have measurable disease on cross sectional imaging documented by diagnostic computed tomography [CT], or magnetic resonance imaging [MRI] imaging, as described in the protocol.
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
5. Adequate hematologic and organ function.

Key Exclusion Criteria:

1. Primary central nervous system (CNS) lymphoma or known involvement (either current or prior history of CNS involvement) by non-primary CNS NHL.
2. Participants with histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma, or any histology other than FL grade 1-3a or MZL.
3. History of or current relevant CNS pathology, as described in the protocol.
4. A malignancy other than NHL unless the participant is adequately and definitively treated and is cancer free for at least 3 years, with the exception of localized prostate cancer treated with hormone therapy or local radiotherapy (ie, pellets), cervical carcinoma in situ, breast cancer in situ, or nonmelanoma skin cancer that was definitively treated.
5. Any other significant active disease or medical condition that could interfere with the conduct of the study or put the participant at significant risk, as described in the protocol.
6. Allergy/hypersensitivity to study drugs or excipients.
7. Active infection as defined in the protocol.

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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470 participants in 2 patient groups

Odronextamab+Lenalidomide

Experimental group

Description:

In part 1 (safety run-in), participants with R/R indolent lymphoma (FL and ML), 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.

Treatment:

Drug: Lenalidomide

Drug: Odronextamab

Rituximab+Lenalidomide

Experimental group

Description:

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.

Treatment:

Drug: Lenalidomide

Drug: Rituximab