Evaluation of Odronextamab's Anti-Tumor Efficacy and Safety in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma Patients
- Trial ID
- 2024-511747-25-00
- Protocol
- R1979-ONC-1625
Trial statistics
Objectives
The primary objective of this study is to evaluate the **anti-tumor activity** of the single agent Odronextamab in patients with B-cell non-Hodgkin lymphoma (B-NHL). This is measured by the objective response rate (ORR) according to the Lugano Classification of response in malignant lymphoma and assessed by independent central review. The study focuses on specific B-NHL subgroups, including follicular lymphoma (FL) grade 1-3a, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and other B-NHL subtypes. This evaluation is clinically relevant as it aims to determine the efficacy of Odronextamab in patients who have relapsed or are refractory to previous treatments, potentially offering a new therapeutic option for these challenging cases.
Secondary objectives include: - Assessing the anti-tumor activity of Odronextamab in five disease-specific cohorts, measured by complete response (CR) rate, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR) according to the Lugano Classification. - Evaluating the safety and tolerability of Odronextamab. - Assessing the pharmacokinetics (PK) and immunogenicity of Odronextamab. - Evaluating the effect of Odronextamab on patient-reported outcomes, including health-related quality of life (HRQL), using validated instruments such as the EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L.
Participants
The clinical trial involves a total of **351 participants** diagnosed with **B-cell non-Hodgkin lymphoma (NHL)**. The study population includes both male and female subjects, with an age range that encompasses adults and older adults. Participants were selected based on their diagnosis of specific subtypes of B-NHL, including follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, and other B-NHL subtypes, all of which have relapsed or are refractory to prior systemic therapies. The trial population includes individuals with an **Eastern Cooperative Oncology Group (ECOG) performance status** of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants are required to have adequate bone marrow, hepatic, and renal function. The study does not exclude vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to assess the anti-tumor activity of the investigational drug Odronextamab in these specific patient cohorts.
Plans and Procedures
The clinical trial is designed to evaluate the **anti-tumor activity** and safety of **odronextamab**, a bispecific monoclonal antibody, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). This is a Phase 2, open-label study, categorized as a category 2 trial per EMA guidance. The trial involves multiple disease-specific cohorts, including patients with follicular lymphoma (FL) grade 1-3a, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and other B-NHL subtypes. The primary endpoint is the objective response rate (ORR) according to the Lugano Classification, assessed by independent central review. Secondary endpoints include progression-free survival, overall survival, and incidence of treatment-emergent adverse events.
The trial employs a non-randomized, open-label design, with participants receiving odronextamab as a single agent. The study is expected to run from December 2019 to December 2025, with an estimated maximum treatment period of 24 months per participant. Participants will receive odronextamab intravenously, with a maximum daily dose of 320 mg. The trial includes a screening visit to confirm eligibility, followed by regular follow-up visits to monitor response and safety. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment.
Participants are expected to be involved in the study for up to 24 months, depending on their response to treatment and overall health status. Conditions that may lead to early termination from the study include significant adverse events, disease progression, or withdrawal of consent. The trial aims to provide comprehensive data on the efficacy and safety of odronextamab in treating various subtypes of B-cell NHL, contributing to the understanding of its therapeutic potential in this patient population.
Treatment
The clinical trial involves the administration of **Odronextamab**, a **concentrate for solution for infusion**. This investigational medication is a bispecific monoclonal antibody targeting CD20 and CD3, known by its sponsor product code **REGN1979**. The pharmaceutical form is a concentrate that requires preparation into a solution for intravenous infusion. The maximum daily dose is 320 mg, with a total maximum dose of 320 mg over a treatment period of up to 24 weeks. The administration route is exclusively intravenous, and the medication is not formulated for pediatric use. The active substance, **Odronextamab**, is a protein of non-chemical origin, specifically a human IgG4-based bispecific monoclonal antibody. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments.
Efficacy
The efficacy of the clinical trial involving **Odronextamab** will be assessed primarily through the **Objective Response Rate (ORR)** according to the Lugano Classification of response in malignant lymphoma. This primary endpoint will be evaluated by an independent central review for each of the five disease-specific cohorts, which include patients with follicular lymphoma (FL) grade 1-3a, diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and other B-cell non-Hodgkin lymphoma (B-NHL) subtypes. The ORR will provide a measure of the anti-tumor activity of Odronextamab as a single agent in these patient groups.
Secondary endpoints will include additional efficacy parameters such as the complete response (CR) rate, progression-free survival (PFS), overall survival (OS), duration of response (DOR), and disease control rate (DCR), all assessed according to the Lugano Classification. These will be evaluated by both independent central review and local investigator evaluation. The trial will also monitor the incidence and severity of treatment-emergent adverse events (TEAEs), pharmacokinetics of Odronextamab, including concentration levels and the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (Nab) over time. Patient-reported outcomes will be measured using validated instruments such as the EORTC QLQ-C30, FACT-Lym, and EQ-5D-3L to assess changes in quality of life scores. The trial is designed to provide comprehensive data on the efficacy and safety of Odronextamab in treating relapsed or refractory B-cell non-Hodgkin lymphoma.
Inclusion and Exclusion Criteria
Inclusion Criteria
- For the FL grade 1-3a cohort only: Central histopathologic confirmation of the FL Grade 1 to 3a diagnosis must be obtained before study enrollment. Patients with FL grade 3b are ineligible for this cohort but may be included in the "other B-NHL" cohort. Follicular lymphoma subtyping is based on the World Health Organization (WHO) classification
- Adequate bone marrow, hepatic, and renal function as defined in the protocol
- Disease-specific cohorts: Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment. FL grade 1-3a cohort: Patients with FL grade 1-3a that has relapsed after or is refractory to at least 2 prior lines of systemic therapy, as defined in the protocol
- DLBCL cohort: Patients with DLBCL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol
- MCL after BTK inhibitor therapy cohort: Patients with MCL who have relapsed or refractory disease to at least one prior line of systemic therapy and had prior treatment with a BTK inhibitor.
- MZL cohort: Patients with MZL that have relapsed or is refractory to at least 2 prior lines of systemic therapy.
- Other B-NHL cohort: Patients with B-NHL other than FL grade 1-3a, DLBCL, MCL, or MZL that has relapsed after or is refractory to at least 2 prior lines of systemic therapy as defined in the protocol. New enrollment stopped for patients with Burkitt lymphoma and Burkitt-like lymphoma.
- Patients should in the judgment of the investigator require systemic therapy for lymphoma at the time of study enrollment
- Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI)
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Other protocol-defined inclusion criteria apply
Exclusion Criteria
- Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS Non-Hodgkin Lymphoma (NHL) (suspected CNS lymphoma should be evaluated by lumbar puncture, as appropriate, in addition to the mandatory head CT or MRI).
- Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 28 days prior to first administration of study drug, whichever is shorter.
- History of allogeneic stem cell transplantation
- Criterion removed
- Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or anti-inflammatory equivalent within 72 hours of start of study drug
- History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded
- Another malignancy except B-NHL in the past 5 years, with the exception of non-melanoma skin cancer that has undergone potentially curative therapy or in situ cervical carcinoma, or any other tumor that has been deemed to be effectively treated with definitive local control and with curative intent.
- Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection; cytomegalovirus (CMV) infection as noted by detectable levels on a blood polymerase chain reaction (PCR) assay as defined in the protocol or other uncontrolled infections
- Known hypersensitivity to both allopurinol and rasburicase
- Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy
- Other protocol-defined exclusion criteria apply
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 France | Not Recruiting | 01 Dec 2019 | 41 |
 Germany | Not Recruiting | 01 Dec 2019 | 4 |
 Italy | Not Recruiting | 01 Dec 2019 | 38 |
 Poland | Not Recruiting | 01 Dec 2019 | 58 |
 Spain | Not Recruiting | 01 Dec 2019 | 59 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Odronextamab | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 320 | 24 | PRD11227893 |
Odronextamab | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 320 | 24 | PRD10211518 |
Odronextamab | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENOUS | 320 | 24 | PRD11227892 |