A Study to Learn How Safe and Tolerable Odronextamab and Cemiplimab Are in Adult Patients With B-cell Malignancies

Study Overview
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Brief Summary
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The 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 of combination 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 your disease How much study drug is in your 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)

Official Title
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A Phase 1 Study to Assess Safety and Tolerability of Odronextamab (REGN1979) an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, and Cemiplimab (REGN2810), an Anti-Programmed Death-1 Monoclonal Antibody in Patients With B-Cell Malignancies (CLIO-1)

Conditions
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Relapsed/Refractory Aggressive B-Cell Lymphoma

Intervention / Treatment
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* Drug: cemiplimab
* Drug: odronextamab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Have documented CD20+ aggresive 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. Must have at least 1 nodal lesion (≥1.5 cm), or at least one extranodal lesion with LDi greater than 1.0 cm, documented by diagnostic imaging (computed tomography [CT] or magnetic resonance imaging [MRI]). Eastern Cooperative Oncology Group (ECOG) performance status ≤1 Adequate bone marrow and hepatic function, as defined in the protocol Willing and able to comply with clinic visits and study-related procedures Provide signed informed consent Key Exclusion Criteria: Primary central nervous system (CNS) lymphoma, or known or suspected CNS involvement by nonprimary CNS NHL History of or current relevant CNS pathology 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) Prior therapies, as described in the protocol Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection or other uncontrolled infection Cytomegalovirus infection as noted by detectable levels on peripheral blood polymerase chain reaction (PCR) assay until the infection is well controlled. Known hypersensitivity to both allopurinol and rasburicase Pregnant or breastfeeding women 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 Note: Other protocol Inclusion/Exclusion criteria apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation phase<br>Safety assessment of odronextamab in combination with cemiplimab and selection of recommended phase 2 dose (RP2D) regimen(s) for the combination of odronextamab and cemiplimab. | Drug: cemiplimab<br>* Administration via intravenous (IV) infusion. The dose(s) received will be according to dose level (DL) cohort assignment, as described in the protocol.<br>* Other names: Libtayo;Drug: odronextamab<br>* Administration IV infusion. The dose(s) received will be according to DL cohort assignment, as described in the protocol.<br>* Other names: REGN1979;|
| Experimental: Dose expansion phase<br>RP2D administration of the combination treatment. | Drug: cemiplimab<br>* Administration via intravenous (IV) infusion. The dose(s) received will be according to dose level (DL) cohort assignment, as described in the protocol.<br>* Other names: Libtayo;Drug: odronextamab<br>* Administration IV infusion. The dose(s) received will be according to DL cohort assignment, as described in the protocol.<br>* Other names: REGN1979;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | 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 |