Relapsed/Refractory Aggressive B-Cell Lymphoma
Conditions
Keywords
B-Cell Non-Hodgkin Lymphoma (B-NHL)
Brief summary
This study is researching a combination of 2 experimental drugs, referred to as "study drugs", called odronextamab (also known as REGN1979) and cemiplimab (also known as REGN2810). The study is focused on patients who have relapse/refractory aggressive B-cell lymphoma. The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose regimen for the combination with odronextamab. This study is also looking at several other research questions, including: * What side effects may happen from taking the study drugs * How effective the study drugs are against the disease * How much study drug is in the blood at different times * Whether the body makes substances or protein called antibodies against the study drugs (that could make the drugs less effective or could lead to side effects)
Interventions
DRUGcemiplimab
Administration via intravenous (IV) infusion. The dose(s) received will be according to dose level (DL) cohort assignment, as described in the protocol.
DRUGodronextamab
Administration IV infusion. The dose(s) received will be according to DL cohort assignment, as described in the protocol.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
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-cell NHL that is either not responsive to or relapsed after at least 2 prior lines of systemic therapy, for whom treatment with an anti-CD20 antibody may be appropriate. In addition, prior treatments should at least contain an anti-CD20 antibody and an alkylating agent. 2. Must have at least 1 nodal lesion (≥1.5 cm), or at least one extranodal lesion with longest transverse diameter (LDi) greater than 1.0 cm, documented by diagnostic imaging (computed tomography \[CT\] or magnetic resonance imaging \[MRI\]). 3. Eastern Cooperative Oncology Group (ECOG) performance status ≤1 4. Adequate bone marrow and hepatic function, as defined in the protocol 5. Willing and able to comply with clinic visits and study-related procedures 6. Provide signed informed consent Key
Exclusion criteria
1. Primary central nervous system (CNS) lymphoma, or known or suspected CNS involvement by non-primary CNS NHL 2. History of or current relevant CNS pathology, as described in the protocol 3. Ongoing or recent (within 2 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for immune-mediated adverse events (iAEs) 4. Prior therapies, as described in the protocol 5. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or other uncontrolled infection 6. Cytomegalovirus infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay until the infection is well controlled. 7. Known hypersensitivity to both allopurinol and rasburicase 8. Pregnant or breastfeeding women 9. Women of childbearing potential, or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose, as defined in the protocol 10. Patients prior diagnosis of hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) Note: Other protocol-defined Inclusion/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of dose limiting toxicities (DLTs) of cemiplimab in combination with odronextamab | Up to 28 days |
| Incidence of treatment emergent adverse events (TEAEs) of cemiplimab in combination with odronextamab | Up to 18 months |
| Severity of TEAEs of cemiplimab in combination with odronextamab | Up to 18 months |
| Incidence of adverse events of special interest (AESIs) of cemiplimab in combination with odronextamab | Up to 18 months |
| Severity of AESIs of cemiplimab in combination with odronextamab | Up to 18 months |
Secondary
| Measure | Time frame |
|---|---|
| Odronextamab and cemiplimab concentrations in serum | Up to 18 months |
| Incidence of anti-drug antibodies (ADAs) to odronextamab and cemiplimab over time | Up to 18 months |
| Titer of ADAs to odronextamab and cemiplimab over time | Up to 18 months |
| Incidence of neutralizing antibodies (Nabs) to odronextamab and cemiplimab over time | Up to 18 months |
| Titer of Nabs to odronextamab and cemiplimab over time | Up to 18 months |
| Overall response rate as assessed by investigator | Up to 18 months |
| Complete response (CR) rate as assessed by investigator | Up to 18 months |
| Duration of response as assessed by investigator | Up to 18 months |
Countries
Austria, Germany, Israel, Poland, Spain, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed