B-cell Non-Hodgkin Lymphoma (B-NHL)
Conditions
Keywords
Relapsed B-NHL, Refractory B-NHL, NHL, Follicular lymphoma (FL), Diffuse large B-cell lymphoma (DLBCL), Mantle cell lymphoma (MCL), Marginal zone lymphoma (MZL), bispecific antibody, CD20
Brief summary
This study is researching an investigational drug, odronextamab, in adult patients B-cell non-Hodgkin's lymphoma (B-NHL). The main purpose of this study is to assess the effectiveness of odronextamab in destroying cancer cells and to learn more about the safety of odronextamab. The study is looking at several other research questions, including: * To see if odronextamab works to destroy cancer cells * Side effects that may be experienced by people taking odronextamab * How odronextamab works in the body * How much odronextamab is present in the blood
Interventions
DRUGOdronextamab
Administered by intravenous (IV) infusion
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
5 cohorts The first 68 patients in the DLBCL cohort will be randomized; the remaining patients will not be randomized
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. 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 (Swerdlow, 2017) 2. 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 Bruton's tyrosine kinase (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. 3. Measurable disease on cross sectional imaging as defined in the protocol documented by diagnostic imaging (computed tomography (CT), or magnetic resonance imaging (MRI) 4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 5. Adequate bone marrow, hepatic, and renal function as defined in the protocol Key
Exclusion criteria
1. 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) 2. 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 3. History of allogeneic stem cell transplantation, up to 12 months prior to first administration of study drug. The presence of acute or chronic graft-versus host disease (GVHD) will also be an exclusion 4. 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 5. History of neurodegenerative condition or CNS movement disorder. Patients with a history of seizure within 12 months prior to study enrollment are excluded 6. 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 7. 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 8. Known hypersensitivity to both allopurinol and rasburicase 9. Prior treatment with an anti-CD20 x anti-CD3 bispecific therapy Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR), as assessed by independent central review | Up to 52 weeks of study treatment | FL grade 1-3a/MZL |
| ORR, as assessed by independent central review | Up to 36 weeks of study treatment | DLBCL/MCL/Other B-NHL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR, as assessed by the local investigator | Up to 52 weeks of study treatment | FL/MZL |
| Complete Response (CR) Rate, as assessed by the local investigator | Up to 52 weeks of study treatment | FL grade 1-3a/MZL |
| CR rate, as assessed by independent central review | Up to 52 weeks of study treatment | FL grade 1-3a/MZL |
| CR rate, as assessed by the local investigator | Up to 36 weeks of study treatment | DLBCL/MCL/Other B-NHL |
| Progression-Free Survival (PFS), as assessed by independent central review | Approximately 194 weeks following the first dose | — |
| PFS, as assessed by the local investigator | Approximately 194 weeks following the first dose | — |
| Overall Survival (OS) | Approximately 194 weeks following the first dose | — |
| Duration Of Response (DOR), as assessed by independent central review | Approximately 194 weeks following the first dose | — |
| DOR, as assessed by the local investigator | Approximately 194 weeks following the first dose | — |
| Disease Control Rate (DCR), as assessed by independent central review | Up to 52 weeks of study treatment | FL grade 1-3a/MZL |
| DCR, as assessed by the local investigator | Up to 52 weeks of study treatment | FL grade 1-3a/MZL |
| DCR, as assessed by independent central review | Up to 36 weeks of study treatment | DLBCL/MCL/Other B-NHL |
| Incidence and severity of Treatment Emergent Adverse Events (TEAEs) | Approximately 194 weeks following the first dose | — |
| Concentration of odronextamab | 12 weeks following end of treatment | End of infusion \[EOI\]; Concentration at a specified time t \[Ct\]) |
| Incidence of Anti-Drug Antibodies (ADA) to odronextamab over time | 12 weeks following end of treatment | — |
| Titer of anti-drug antibodies to odronextamab over time | 12 weeks following end of treatment | — |
| Incidence of Neutralizing antibodies (Nab) to odronextamab over time | 12 weeks following end of treatment | — |
| Changes in scores of patient-reported outcomes as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Cancer-30 (EORTC-QLQ-C30) | Approximately 194 weeks following the first dose | The EORTC QLQ-C30 is a self-reported, 30-item generic questionnaire developed to assess 15 domains: global health status scale, five functional scales (physical, role, emotional, cognitive, and social functioning) and nine symptom scales (fatigue, nausea, vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea and financial difficulties). |
| Changes in scores of patient-reported outcomes as measured by Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) | Approximately 194 weeks following the first dose | Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS). |
| Changes in scores of patient-reported outcomes as measured by EuroQol-5 Dimensions-3 Levels (EQ-5D-3L) | Approximately 194 weeks following the first dose | The EQ-5D-3L is a standardized instrument for use as a measure of health outcome. It is a health questionnaire that consists of the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The EQ-5D-3L descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. |
Countries
Australia, Canada, China, France, Germany, Italy, Japan, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed