B-cell Non-Hodgkins Lymphoma (B-NHL)
Conditions
Keywords
Aggressive B-Cell Non-Hodgkin Lymphomas, Relapsed or Refractory
Brief summary
This study is researching an experimental drug called REGN5837 in combination with another drug, odronextamab (called "study drug\[s\]"), in patients with relapsed or refractory aggressive B-cell Non-Hodgkin Lymphomas (B-NHLs). The study has 2 parts. The aim of the first part (dose escalation) is to find a safe dose of REGN5837 when given in combination with odronextamab. The goal of the second part (dose expansion) is to use the REGN5837 drug dose found in the first part to see how well REGN5837 in combination with odronextamab works. The study is looking at several other research questions, including: * What side effects may happen from taking the study drugs * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drugs (that could make the drugs less effective or could lead to side effects)
Interventions
DRUGOdronextamab
Administered per the protocol
DRUGREGN5837
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Have documented CD20+ aggressive B-NHL, with disease that has progressed after at least 2 lines of systemic therapy containing an anti-CD20 antibody and an alkylating agent, as described in the protocol. 2. Measurable disease on cross sectional imaging as defined in the protocol 3. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 4. Adequate bone marrow, renal and hepatic function as defined in the protocol 5. Availability of tumor tissue for submission to central laboratory is required for study enrollment. Archival tumor tissue for histological assessment prior to enrollment is allowed 6. During dose expansion phase of the study, participant should be willing to undergo mandatory tumor biopsies, if in the opinion of the investigator, the participant has an accessible lesion that can be biopsied without significant risk to the participant. Key
Exclusion criteria
1. Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab 2. Diagnosis of Mantle Cell Lymphoma (MCL) 3. Primary Central Nervous System (CNS) lymphoma or known involvement by non-primary CNS lymphoma, as described in the protocol 4. Treatment with any systemic anti-lymphoma therapy within 5 half-lives or within 14 days prior to first administration of study drug, whichever is shorter, as described in the protocol 5. Standard radiotherapy within 14 days of first administration of study drug, as described in the protocol 6. Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab 7. Co-morbid conditions, as described in the protocol 8. Infections, as described in the protocol 9. Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicase NOTE: Other protocol defined inclusion /
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab | From Cycle 2, Day 1 to Cycle 2, Day 21 (each induction cycle is 21 days) | A DLT is defined as any non-haematologic and haematologic toxicity, as defined in the protocol, unless the event is clearly attributable to the underlying disease or to an extraneous cause (including concomitant medications). |
| Incidence of Treatment-Emergent Adverse Events (TEAEs) of REGN5837 in combination with odronextamab | Up to approximatively 5 years | Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period. |
| Severity of TEAEs of REGN5837 in combination with odronextamab | Up to approximatively 5 years | Treatment-emergent adverse events (TEAEs) are defined as those AEs that newly occurred or worsened during the on-treatment period and any treatment-related serious adverse events (SAEs) that occurred during the post-treatment period. |
| Incidence of Adverse Events of Special Interest (AESIs) of REGN5837 in combination with odronextamab | Up to approximatively 5 years | An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. |
| Severity of AESIs of REGN5837 in combination with odronextamab | Up to approximatively 5 years | An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Concentrations of REGN5837 in the serum | Up to 90 days post last study drug administration | — |
| Concentrations of odronextamab in the serum | Up to 90 days post last study drug administration | — |
| Occurrence of Anti-Drug Antibodies (ADAs) to REGN5837 | Up to 90 days post last study drug administration | — |
| Occurrence of ADAs to odronextamab | Up to 90 days post last study drug administration | — |
| Magnitude of ADAs to REGN5837 | Up to 90 days post last study drug administration | — |
| Magnitude of ADAs to odronextamab | Up to 90 days post last study drug administration | — |
| Objective Response Rate (ORR) according to the Lugano Classification of response | Up to approximatively 5 years | The ORR is defined as the proportion of patients who achieve a best overall response CR or PR during or following study treatment according to the Lugano Classification based on local investigator review. |
| Complete Response (CR) according to the Lugano Classification of response | Up to approximatively 5 years | The CR rate is defined as the proportion of patients who achieve a best overall response CR during or following study treatment according to the Lugano Classification based on local investigator review. |
| Overall Survival (OS) | Up to approximatively 5 years | OS is measured from the start of study treatment until death due to any cause. |
| Progression Free Survival (PFS) according to the Lugano Classification of response | Up to approximatively 5 years | PFS is defined as the time from the start of study treatment until the first date of progressive disease, or death due to any cause, whichever occurs first, based on local investigator review. |
| Duration of Response (DoR) according to the Lugano Classification of response | Up to approximatively 5 years | DOR is defined for responders (patients with a best overall response of CR or PR). It is the time from the date of the first documented CR or PR until the date of the first date of progressive disease, or death due to any cause, whichever occurs first, based on local investigator review. |
Countries
France, Netherlands, Spain, United Kingdom, United States
Contacts
CONTACTClinical Trials Administrator
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed