A Trial to Learn if Odronextamab is Safe and Well-Tolerated and How Well it Works Compared to Rituximab Combined With Different Types of Chemotherapy for Participants With Follicular Lymphoma

Phase 3

Recruiting

• Conditions: Follicular Lymphoma (FL)
• Interventions: Drug: Odronextamab; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone/prednisolone; Drug: Bendamustine

• Registration Number: NCT06091254
• Lead Sponsor: Regeneron Pharmaceuticals

Brief Summary

This study is researching an experimental drug called odronextamab, referred to as study drug. The study is focused on participants with previously untreated follicular lymphoma (a type of non-Hodgkin lymphoma or NHL).

This study will be made up of two parts: Part 1 (non-randomized) and Part 2 (randomized - controlled).

The aim of Part 1 of the study is to see how safe and tolerable the study drug is when given alone.

The aim of Part 2 of the study is to see how the study drug works compared to rituximab (called the "comparator drug") and chemotherapy (the current standard of care for NHL). 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

* 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)

* How the study drug affects quality of life and ability to complete routine daily activities.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-13
• Study First Submitted QC: 2023-10-13
• Study First Posted: 2023-10-19
• Study Start: 2023-12-12
• Status Verified: 2024-12
• Last Update Submitted: 2025-06-24
• Last Update Posted: 2025-06-25
• Primary Completion: 2029-04-04
• Study Completion: 2029-04-04

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 478

Inclusion Criteria

1. Diagnosis of Cluster of Differentiation 20^+ (CD20^+) FL Grade 1-3a, stage II bulky or stage III / IV
2. Need for treatment as described in the protocol
3. Have measurable disease on cross-sectional imaging documented by diagnostic imaging Computed Tomography (CT) or Magnetic Resonance Imaging (MRI)
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
5. Adequate bone marrow function and hepatic function

Key

Exclusion Criteria

1. Central Nervous System (CNS) lymphoma or leptomeningeal lymphoma
2. Histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma
3. Waldenström Macroglobulinemia (WM, lymphoplasmacytic lymphoma), Grade 3b follicular lymphoma, chronic lymphocytic leukemia, or small lymphocytic lymphoma
4. Treatment with any systemic anti-lymphoma therapy
5. Infections and allergy/hypersensitivity to study drug or excipient

NOTE: Other protocol defined inclusion/exclusion criteria apply

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Odronextamab	Odronextamab	Part 1 is a safety run-in. All participants will receive odronextamab. In part 2 participants will be randomly assigned in a 1:1 ratio to receive odronextamab followed by odronextamab maintenance.
Rituximab + Investigator's Choice Chemotherapy	Rituximab	Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.
Rituximab + Investigator's Choice Chemotherapy	Doxorubicin	Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.
Rituximab + Investigator's Choice Chemotherapy	Prednisone/prednisolone	Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.
Rituximab + Investigator's Choice Chemotherapy	Bendamustine	Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.
Rituximab + Investigator's Choice Chemotherapy	Cyclophosphamide	Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.
Rituximab + Investigator's Choice Chemotherapy	Vincristine	Part 2 only, participants will be randomized 1:1 to receive rituximab in combination with chemotherapy followed by rituximab maintenance.

Primary Outcome Measures

Name	Time	Method
Incidence of dose-limiting toxicities (DLTs) for odronextamab	Up to 35 days	Part 1
Complete Response at 30 months (CR30) as assessed by independent central review	Up to 30 months	Part 2
Severity of TEAEs of odronextamab	Up to 2 years	Part 1
Incidence of treatment-emergent adverse events (TEAEs) of odronextamab	Up to 2 years	Part 1

Secondary Outcome Measures

Name	Time	Method
Titer of ADAs to odronextamab over the study duration	Up to 30 months	Part 2
Incidence of NAbs to odronextamab over the study duration	Up to 30 months	Part 2
Overall mean changes in scores of PROs, as measured by the validated instruments Patient Global Impression of Change (PGIC)	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.
Progression-free survival (PFS) as assessed by independent central review	Up to 5 years	Part 2
CR30 as assessed by local investigator	Up to 30 months	Part 2
Overall survival (OS)	Up to 5 years	Part 2
Duration of response (DOR) assessed by independent central review	Up to 5 years	Part 2
Incidence of TEAEs	Up to 2 years	Part 2
Incidence of anti-drug antibodies (ADAs) to odronextamab over the study duration	Up to 30 months	Part 1
Event-free survival (EFS) as assessed by independent central review	Up to 5 years	Part 2
PFS as assessed by the local investigator	Up to 5 years	Part 2
Odronextamab concentrations in serum during the induction period	Up to 30 months	Part 2
Incidence of ADAs to odronextamab over the study duration	Up to 30 months	Part 2
Change in score of the GP5 item in the participant population	Up to 5 years	Part 2 A single item Global Population item 5 (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).
Incidence of neutralizing antibodies (NAbs) to odronextamab over the study duration	Up to 30 months	Part 1
Overall mean change in physical function [European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC-QLQ-C30)]	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.
Objective response assessed by independent central review	Up to 30 months	Part 2
DOR assessed by local investigator	Up to 5 years	Part 2
Time to next anti-lymphoma treatment (TTNT)	Up to 5 years	Part 2
Severity of TEAEs	Up to 2 years	Part 2
Odronextamab concentrations in serum during the maintenance period	Up to 30 months	Part 2
Overall mean changes in scores of patient reported outcomes (PROs), as measured by the validated instruments EORTCQLQ- C30	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.
Overall mean changes in scores of PROs, as measured by the validated instruments EuroQol-5 Dimension-5 Level Scale (EQ-5D- 5L)	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".
EFS as assessed by the local investigator	Up to 5 years	Part 2
Objective response assessed by local investigator	Up to 30 months	Part 2
Overall mean changes in scores of PROs, as measured by the validated instruments Functional Assessment of Cancer Therapy-Lymphoma (FACT-LymS)	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.
Overall mean changes in scores of PROs, as measured by the validated instruments Patient Global Impression of Severity (PGIS)	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).
Overall mean changes in scores PROs, as measured by the validated Functional Assessment of Cancer - General (FACT-G) global population 5 (GP5) question	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).
Objective response as assessed by the investigator	Up to 30 months	Part 1
Concentrations of odronextamab in serum	Up to 30 months	Part 1

Trial Locations

Locations (187)

University of Arizona Cancer Center; 🇺🇸 Tucson, Arizona, United States

David Geffen School of Medicine at UCLA; 🇺🇸 Los Angeles, California, United States

UC Irvine Health; 🇺🇸 Orange, California, United States

Investigative Clinical Research of Indiana; 🇺🇸 Noblesville, Indiana, United States

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Hattiesburg Clinic; 🇺🇸 Hattiesburg, Mississippi, United States

Icahn School of Medicine at Mt Sinai; 🇺🇸 New York, New York, United States

Stony Brook University Hospital; 🇺🇸 Stony Brook, New York, United States

Clinical Research Alliance Inc; 🇺🇸 Westbury, New York, United States

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