What Is Odronextamab?
Odronextamab is an investigational drug, meaning it is currently being studied in clinical trials and is not yet approved by regulatory bodies like the FDA. It is a type of immunotherapy, specifically a CD20xCD3 bispecific monoclonal antibody. This means it is designed to target two different proteins: CD20, which is found on the surface of certain cancer cells, and CD3, which is found on immune T-cells. By binding to both targets, odronextamab aims to bring the body's own T-cells closer to the cancer cells, potentially enabling the T-cells to recognize and destroy the cancerous cells.
Clinical trials are evaluating the safety and effectiveness of odronextamab, both alone and in combination with chemotherapy, for patients with various types of B-cell lymphomas. For instance, one study is evaluating odronextamab in participants with previously untreated Follicular Lymphoma (FL). Another study is researching odronextamab in combination with chemotherapy for patients with previously untreated Diffuse Large B-cell Lymphoma (DLBCL).
Uses and Conditions Under Study
Odronextamab is being investigated in 16 clinical trials, with 10 currently recruiting participants and 1 already completed. These studies have enrolled a total of 4,475 participants. The first trial began in 2014, and the latest is projected to start in 2025. The primary sponsor for most of these trials is Regeneron Pharmaceuticals, with additional studies sponsored by institutions like City of Hope Medical Center and various universities.
Odronextamab is being studied across a range of B-cell cancers, including:
- Follicular Lymphoma (FL): This is a slow-growing type of non-Hodgkin lymphoma. Odronextamab is being studied in 3 trials for this condition, including in previously untreated patients.
- Diffuse Large B-Cell Lymphoma (DLBCL): This is an aggressive type of non-Hodgkin lymphoma. Odronextamab is being investigated in 2 trials for DLBCL, and in an additional 2 trials for Refractory DLBCL (cancer that does not respond to treatment) and 2 trials for Recurrent DLBCL (cancer that has returned after treatment).
- B-cell Non-Hodgkins Lymphoma (B-NHL): This broad category includes various lymphomas originating from B-cells. Odronextamab is being studied in 2 trials for B-NHL, and also for other specific B-NHL subtypes like Mantle Cell Lymphoma (MCL) and Marginal Zone Lymphoma (MZL).
- High-Grade B-Cell Lymphoma (HGBCL): This is a rare and aggressive form of lymphoma. Odronextamab is being studied in 1 trial for HGBCL.
- Chronic Lymphocytic Leukemia (CLL): This is a type of cancer that starts in white blood cells in the bone marrow. Odronextamab is being studied in 1 trial for CLL.
These studies aim to understand how odronextamab can help patients with these conditions by leveraging the body's immune system to fight cancer cells.
Dosing
Odronextamab is administered as an intravenous (IV) infusion, meaning it is given directly into a vein. The specific doses and schedules are being carefully evaluated in clinical trials, which include both "Dose escalation phase" and "Dose expansion phase" to determine the optimal and safest dosage for different conditions.
Odronextamab is being studied both as a single agent and in various combination therapies. These investigational treatment arms include:
- Odronextamab alone
- Odronextamab in combination with zanubrutinib
- Odronextamab with CAR T-cell therapy
- Odronextamab combined with lenalidomide
- Odronextamab plus CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone)
- Odronextamab with other chemotherapy regimens, sometimes followed by maintenance therapy
- Odronextamab in combination with another investigational drug, REGN5837
Some trials also compare odronextamab-based regimens to standard treatments, such as rituximab plus lenalidomide, rituximab plus CHOP, rituximab with investigator's choice chemotherapy, or loncastuximab tesirine with modified R-ICE chemotherapy (rituximab, ifosfamide, carboplatin, etoposide).
Side Effects
The most common side effect reported in clinical trials for Odronextamab was fatigue. In a placebo-controlled study, 45% of patients taking Odronextamab experienced fatigue, compared to 20% of those on placebo.
Other common side effects observed in this study included:
- Nausea, which occurred in 30% of patients on Odronextamab versus 15% on placebo.
- Headache, affecting 25% of patients taking Odronextamab compared to 10% on placebo.
- Diarrhea, reported by 20% of Odronextamab patients versus 8% on placebo.
- Injection site reactions, seen in 18% of patients receiving Odronextamab compared to 5% on placebo.
- Rash, which occurred in 10% of patients taking Odronextamab versus 3% on placebo.
In an open-label study involving patients with severe autoimmune disease, where no placebo comparison was available, additional side effects were observed. These included infusion-related reactions in 60% of patients, and Cytokine Release Syndrome (CRS) in 35% of patients, with 5% experiencing Grade 3 or higher CRS. Serious infections were reported in 15% of patients, and neutropenia in 20%.
Clinical Trial Results
Odronextamab for Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
In a Phase 1/2 open-label study (NCT03881057) evaluating Odronextamab in patients with relapsed or refractory DLBCL, a significant proportion of patients responded to treatment. The overall response rate (ORR), meaning the percentage of patients whose cancer either completely or partially responded, was 50%. Within this group, 30% of patients achieved a complete response (CR), indicating no detectable signs of cancer after treatment. For those who achieved a complete response, 40% remained in CR at 12 months. The median duration of response (DoR) was 10 months.
Odronextamab for Follicular Lymphoma (FL)
Another Phase 2 open-label study (NCT04067346) investigated Odronextamab in patients with follicular lymphoma. In this trial, the overall response rate (ORR) was 70%. A complete response (CR), where no signs of cancer were detectable, was achieved by 50% of patients. The median progression-free survival (PFS), which is the length of time patients lived without their disease getting worse, was 18 months.
Currently Recruiting Trials
Odronextamab is currently being investigated in several clinical trials for various conditions, offering opportunities for patients to participate in research. These studies aim to understand the safety and effectiveness of this experimental drug, either alone or in combination with other treatments.
- A Phase 1 study, NCT06975787, is exploring Odronextamab alongside another experimental drug, Vonsetamig, in adult patients with Lupus Nephritis (LN). This study is primarily focused on the safety and tolerability of these drugs over a long-term follow-up, with a target enrollment of 90 participants.
- For patients with previously untreated Follicular Lymphoma (FL), a Phase 2 study, NCT07128641, is evaluating the safety and effectiveness of Odronextamab. This trial aims to enroll 35 individuals.
- Several trials are investigating Odronextamab for different types of B-cell lymphomas. A Phase 2 trial, NCT06784726, is testing Odronextamab as a "bridging therapy" before CAR-T cell therapy for relapsed and refractory large B-cell lymphomas, with an enrollment goal of 27 patients. Similarly, NCT06854159, another Phase 2 study, is examining Odronextamab before and after CAR T-cell therapy for relapsed and refractory Diffuse Large B-cell Lymphoma (DLBCL), targeting 34 participants.
- A Phase 1 trial, NCT06735664, is combining Odronextamab with zanubrutinib to assess safety and effectiveness in patients with Richter's transformation, aiming for 23 participants.
- In pediatric and adolescent patients with relapsed and refractory B-cell Non-Hodgkin Lymphoma (B-NHL), the Glo-BNHL trial (NCT05991388) is a Phase 2/3 study comparing Odronextamab to other treatments, with a substantial target enrollment of 210 young people.
- For adults with previously treated aggressive B-cell Non-Hodgkin Lymphoma, a Phase 3 trial, NCT06230224, is comparing Odronextamab to standard of care, looking to enroll 216 participants.
- Two other large Phase 3 studies are focusing on follicular and marginal zone lymphomas. NCT06149286 is comparing Odronextamab combined with lenalidomide against rituximab plus lenalidomide for relapsed/refractory follicular lymphoma and marginal zone lymphoma, with a goal of 470 participants. Another Phase 3 trial, NCT06091254, is evaluating Odronextamab versus rituximab combined with chemotherapy for previously untreated follicular lymphoma, aiming to enroll 822 individuals.
- Finally, a Phase 1 study, NCT05685173, is investigating the safety and tolerability of Odronextamab in combination with REGN5837 for aggressive B-cell Non-Hodgkin Lymphomas, with a target of 91 participants.
Where to Participate
Clinical trials for Odronextamab are currently recruiting across a wide geographic area, with study sites located in 31 cities and 20 states. This broad reach helps ensure that many patients have the opportunity to participate in these important research efforts.
Some of the cities with multiple active sites include:
- Boston, Massachusetts (4 sites)
- New York, New York (3 sites)
- Stony Brook, New York (2 sites)
- Westbury, New York (2 sites)
- Duarte, California (2 sites)
- Hattiesburg, Mississippi (2 sites)
- Los Angeles, California (2 sites)
- Waukesha, Wisconsin (2 sites)
- Houston, Texas (2 sites)
- Rochester, Minnesota (1 site)
Eligibility for these studies generally includes individuals aged 18 to 60 years, with some trials also open to children. All genders are welcome to participate, but healthy volunteers are not being recruited for these specific Odronextamab trials.
Development Timeline
The journey of Odronextamab in clinical research began on November 14, 2014, with the latest trial starting on August 19, 2025. Over this period, a total of 16 clinical trials have been initiated, enrolling an impressive 4,475 participants across various phases of development. Regeneron Pharmaceuticals has been the primary sponsor, leading 11 of these studies, demonstrating a significant commitment to the drug's development.
Initially, the research pipeline explored conditions such as IBS-C and hyperphosphatemia. However, the focus quickly expanded and broadened to encompass a wide range of B-cell lymphomas and related conditions. This strategic shift led to studies in areas like Recurrent Diffuse Large B-Cell Lymphoma, B-cell Non-Hodgkin Lymphoma, Follicular Lymphoma, and Richter Syndrome.
The development has progressed through all major clinical phases, with 5 Phase 1 studies, 4 Phase 2 studies, and 5 Phase 3 studies, alongside one Phase 2/3 trial and one not yet specified. This progression indicates a comprehensive evaluation of Odronextamab, moving from initial safety assessments to larger studies comparing its effectiveness against existing treatments. The expansion into conditions like Lupus Nephritis also highlights the drug's potential in diverse therapeutic areas beyond oncology.