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RecruitingInterventionalPhase 3

A Phase 3, Open Label, Randomized Study to Compare the Efficacy and Safety of Odronextamab (REGN1979), an Anti-CD20 x Anti-CD3 Bispecific Antibody, in Combination With Lenalidomide Versus Rituximab in Combination With Lenalidomide in Relapsed/Refractory Participants With Follicular Lymphoma and Marginal Zone Lymphoma (OLYMPIA-5)

NCT ID: NCT06149286Sponsor: Regeneron PharmaceuticalsLast updated: 2026-05-06

Summary

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 well 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 relapsed/refractory 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

Arms & interventions

  • DrugOdronextamab

    Administered per the protocol

  • DrugLenalidomide

    Administered per the protocol

  • DrugRituximab

    Administered per the protocol

Outcome measures

Primary

  • Incidence of Dose Limiting Toxicities (DLTs) for odronextamab in combination with lenalidomide

    Part 1

    Time frame: Up to 35 days

  • Incidence of Treatment Emergent Adverse Events (TEAEs) for odronextamab in combination with lenalidomide

    Part 1

    Time frame: Up to 2 years

  • Severity of TEAEs for odronextamab in combination with lenalidomide

    Part 1

    Time frame: Up to 2 years

  • Progression-Free Survival (PFS) as assessed by Independent Central Review (ICR) in participants with R/R FL and participants with indolent lymphoma

    Part 2

    Time frame: Up to 5 years

Secondary

  • Odronextamab concentrations in serum

    Time frame: Up to 30 months

  • Incidence of Anti-drug Antibodies (ADA) to odronextamab

    Time frame: Up to 30 months

  • Magnitude of ADAs to odronextamab

    Time frame: Up to 30 months

  • Best Overall Response (BOR) as assessed by investigator review

    Time frame: Up to 30 months

  • Duration of Response (DOR) as assessed by investigator review

    Time frame: Up to 5 years

  • PFS as assessed by investigator review

    Time frame: Up to 5 years

  • Complete Response (CR) as assessed by ICR

    Time frame: Up to 30 months

  • BOR as assessed by ICR

    Time frame: Up to 30 months

  • Overall Survival (OS)

    Time frame: Up to 5 years

  • Event Free Survival (EFS) as assessed by ICR

    Time frame: Up to 5 years

  • EFS as assessed by local investigator review

    Time frame: Up to 5 years

  • DOR as assessed by ICR

    Time frame: Up to 5 years

  • Time To Next anti-lymphoma Treatment (TTNT)

    Time frame: Up to 5 years

  • Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2

    Time frame: Up to 2 years

  • Severity of TEAEs for odronextamab in combination with lenalidomide versus R2

    Time frame: Up to 2 years

  • Overall change in patient reported outcomes (PROs) as measured by scores of European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQC30)

    Time frame: Up to 5 years

  • Overall change in PROs as measured by scores of Functional Assessment of Cancer Therapy-Lymphoma Subscale (FACT-LymS)

    Time frame: Up to 5 years

  • Overall change in PROs as measured by scores of EuroQoL 5 Dimensions 5 Levels (EQ-5D-5L)

    Time frame: Up to 5 years

  • Change from first assessment in Patient Global Impression on Severity (PGIS)

    Time frame: Up to 5 years

  • Change from first assessment in Patient Global Impression on Change (PGIC)

    Time frame: Up to 5 years

  • Change from first assessment in the Global Population item 5 (GP5) items of the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire

    Time frame: Up to 5 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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, as described in the protocol. 2. Must have refractory disease or relapsed after at least 1 prior line (with a duration of at least 2 cycles) of systemic chemo-immunotherapy or immunotherapy. Prior systemic therapy should have included at least one anti-Cluster of Differentiation 20 (CD20) monoclonal antibody and participant should meet indication for treatment, as described in the protocol. 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, as described in the protocol. 6. All study participants must: 1. Have an understanding that lenalidomide could have a potential teratogenic risk. 2. Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide. 3. Agree not to share study medication with another person. 4. Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide. 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, as described in the protocol. 2. Participants with current or past histological evidence of 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 (inclusion diagnosis) 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. as described in the protocol. 7. Active infection as defined in the protocol. Note: Other protocol-defined Inclusion/Exclusion criteria apply

Study locations (8)

David Geffen School of Medicine at UCLA

Los Angeles, California, 90095

Recruiting

Boca Raton Clinical Research (BRCR) Global

Plantation, Florida, 33322

Recruiting

Indiana University and Comprehensive Cancer Center

Indianapolis, Indiana, 46202

Recruiting

Hattiesburg Clinic

Hattiesburg, Mississippi, 39401

Recruiting

Dartmouth Cancer Center

Lebanon, New Hampshire, 03756

Recruiting

Stony Brook University Hospital

Stony Brook, New York, 11794

Recruiting

Clinical Research Alliance Inc

Westbury, New York, 11590

Withdrawn

Prohealth Care Inc

Waukesha, Wisconsin, 53188

Recruiting