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NCT Number: NCT06149286

A Trial to Find Out if Odronextamab Combined With Lenalidomide is Safe and Works Better Than Rituximab Combined With Lenalidomide in Adult Participants With Follicular Lymphoma and Marginal Zone Lymphoma

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

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Key information

Conditions

Relapsed/Refractory Follicular Lymphoma Disease Attributes Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, B-Cell, Marginal Zone Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Recurrence Relapsed/Refractory Marginal Zone Lymphoma (R/R MZL)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Liverpool Hospital, Liverpool, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Key Inclusion Criteria:

  • 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.
  • 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.
  • Have measurable disease on cross sectional imaging documented by diagnostic Computed Tomography [CT], or Magnetic Resonance Imaging [MRI] imaging, as described in the protocol.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate hematologic and organ function, as described in the protocol.
  • All study participants must:
  • Have an understanding that lenalidomide could have a potential teratogenic risk.
  • Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of lenalidomide.
  • Agree not to share study medication with another person.
  • Agree to be counseled about pregnancy precautions and risk of fetal exposure associated with lenalidomide.

Key Exclusion Criteria:

  • 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.
  • 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.
  • History of or current relevant CNS pathology, as described in the protocol.
  • 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.
  • 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.
  • Allergy/hypersensitivity to study drugs or excipients. as described in the protocol.
  • Active infection as defined in the protocol.

Note: Other protocol-defined Inclusion/Exclusion criteria apply

Treatment and study plan

Odronextamab

Drug

Administered per the protocol

Other names: REGN1979, Ordspono

Lenalidomide

Drug

Administered per the protocol

Other names: REVLIMID

Rituximab

Drug

Administered per the protocol

Other names: Rituxan

Primary outcomes

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

    Time frame: Up to 35 days

    Part 1

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

    Time frame: Up to 2 years

    Part 1

  3. Severity of TEAEs for odronextamab in combination with lenalidomide

    Time frame: Up to 2 years

    Part 1

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

    Time frame: Up to 5 years

    Part 2

Secondary outcomes

  1. Odronextamab concentrations in serum

    Time frame: Up to 30 months

    Part 1 and Part 2

  2. Incidence of Anti-drug Antibodies (ADA) to odronextamab

    Time frame: Up to 30 months

    Part 1 and Part 2

  3. Magnitude of ADAs to odronextamab

    Time frame: Up to 30 months

    Part 1 and Part 2

  4. Best Overall Response (BOR) as assessed by investigator review

    Time frame: Up to 30 months

    Part 1 and Part 2

  5. Duration of Response (DOR) as assessed by investigator review

    Time frame: Up to 5 years

    Part 1 and Part 2

  6. PFS as assessed by investigator review

    Time frame: Up to 5 years

    Part 1 and Part 2

  7. Complete Response (CR) as assessed by ICR

    Time frame: Up to 30 months

    Part 2

  8. BOR as assessed by ICR

    Time frame: Up to 30 months

    Part 2

  9. Overall Survival (OS)

    Time frame: Up to 5 years

    Part 2

  10. Event Free Survival (EFS) as assessed by ICR

    Time frame: Up to 5 years

    Part 2

  11. EFS as assessed by local investigator review

    Time frame: Up to 5 years

    Part 2

  12. DOR as assessed by ICR

    Time frame: Up to 5 years

    Part 2

  13. Time To Next anti-lymphoma Treatment (TTNT)

    Time frame: Up to 5 years

    Part 2

  14. Incidence of TEAEs for odronextamab in combination with lenalidomide versus R2

    Time frame: Up to 2 years

    Part 2

  15. Severity of TEAEs for odronextamab in combination with lenalidomide versus R2

    Time frame: Up to 2 years

    Part 2

  16. 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

    Part 2 The EORTC QLQ-C30 includes 5 functional scales (physical, role, cognitive, emotional and social functioning), 3 symptom scales (fatigue, pain and nausea/vomiting), a global health status (GHS)/QoL scale, and six single items (constipation, diarrhea, insomnia, shortness of breath, appetite loss and financial difficulties). For the functioning scales and global health status/QoL, scores range from 1 = "very poor" to 7 = "excellent" with higher scores indicate better functioning; for the symptom scales, scores range from 1 = "not at all" to 4 = "very much" higher scores indicate higher symptom burden.

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

    Time frame: Up to 5 years

    Part 2 The FACT-Lym lymphoma subscale (LymS) includes 15 items to assess NHL-related symptoms and concerns. All questions are answered on a 5-point scale ranging from "not at all" (0) to "very much" (4). Higher scores are associated with a worse quality of life.

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

    Time frame: Up to 5 years

    Part 2 The EQ-5D-5L consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-5L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: "no problems", "slight problems", "moderate problems", "severe problems" and "extreme problems". The EQ VAS records the participant's self-rated health on a vertical visual analogue scale where the endpoints are labeled "Best imaginable health state" and "Worst imaginable health state".

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

    Time frame: Up to 5 years

    Part 2 The PGIS includes a single-item to assess how a patient perceives the overall severity of cancer symptoms over the past 7 days. Patients will choose the response that best describes the severity of their overall cancer symptoms with options on a 5-point scale ranging from 1 (No symptoms) to 4 (Very Severe).

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

    Time frame: Up to 5 years

    Part 2 The PGIC item includes a single-item to assess how a patient perceives their overall change in health status since the start of study treatment. Patients will choose from response options on a 7-point scale ranging from 1 (Much Better) to 7 (Much worse); 1- Much Better, 2-Moderately Better, 3-A Little Better, 4-About the Same, 5-A Little Worse, 6-Moderately Worse, 7-Much Worse.

  21. 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

    Part 2 A single item (GP5) of the validated FACT-G questionnaire will be used to assess from the participant perspective the overall impact of treatment side-effect. The question item is on a 5-point scale ranging from "not at all" (0) to "very much" (4).

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Trials Administrator

CONTACT

[email protected]

844-734-6643

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study title

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)

Acronym: OLYMPIA-5

Important dates

Study start
2023
Primary completion
2029
Study completion
2029
First posted
Nov 28, 2023
Registry last updated
May 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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