Recruiting
Phase 3

Odronextamab & Rituximab

Sponsor:

Regeneron Pharmaceuticals

Code:

NCT06149286

Conditions

Relapsed/Refractory Follicular Lymphoma

Relapsed/Refractory Marginal Zone Lymphoma (R/R MZL)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Odronextamab

Lenalidomide

Rituximab

Study Details

Brief 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

Conditions

Relapsed/Refractory Follicular Lymphoma

Relapsed/Refractory Marginal Zone Lymphoma (R/R MZL)

Study ID

NCT06149286

Start date

Dec 28, 2023

Status verified date

Aug, 2026

Completion date

Apr 30, 2031

Anticipated

Primary completion date

Apr 30, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

580 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Odronextamab+Lenalidomide

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 R/R FL and MZL, will receive odronextamab in combination with lenalidomide.

experimental: Rituximab+Lenalidomide

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

Interventions

Odronextamab

Administered per the protocol

Lenalidomide

Administered per the protocol

Rituximab

Administered per the protocol

Primary outcome measure

  • Incidence of Dose Limiting Toxicities (DLTs) for odronextamab in combination with lenalidomide [ Time Frame: Up to 35 days ]
  • Incidence of Treatment Emergent Adverse Events (TEAEs) for odronextamab in combination with lenalidomide [ Time Frame: Up to 2 years ]
  • Severity of TEAEs for odronextamab in combination with lenalidomide [ Time Frame: Up to 2 years ]
  • Progression-Free Survival (PFS) as assessed by Independent Central Review (ICR) [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Clinical Trials Administrator

844-734-6643clinicaltrials@regeneron.com

Locations

David Geffen School of Medicine at UCLA

Recruiting

Los Angeles, California, United States, 90095

Boca Raton Clinical Research (BRCR) Global

Recruiting

Plantation, Florida, United States, 33322

Indiana University and Comprehensive Cancer Center

Recruiting

Indianapolis, Indiana, United States, 46202

Hattiesburg Clinic

Recruiting

Hattiesburg, Mississippi, United States, 39401

Dartmouth Cancer Center

Recruiting

Lebanon, New Hampshire, United States, 03756

Stony Brook University Hospital

Recruiting

Stony Brook, New York, United States, 11794

Prohealth Care Inc

Recruiting

Waukesha, Wisconsin, United States, 53188

More Information

Sponsor

Regeneron Pharmaceuticals

Last update posted

Aug 14, 2026

Last verified

Aug, 2026

Keywords

  • Relapsed/Refractory Follicular Lymphoma
  • Relapsed/Refractory Marginal Zone Lymphoma
  • Non-Hodgkin lymphomas
  • Indolent lymphomas
  • Odronextamab

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Regeneron Pharmaceuticals on 2026-08-14.