A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Participants With Aggressive B-cell Non-Hodgkin Lymphomas

Study Overview
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Brief Summary
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The study is researching an experimental drug called REGN5837 in combination with another experimental drug, odronextamab. The aim of the study is to see how safe and tolerable the study drugs are, and to define the recommended dose for phase 2 for the combination. The study is focused on patients with relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs). 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 your 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) To find out how well the study drugs work against relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs)

Official Title
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A Phase 1 Study to Assess Safety and Tolerability of REGN5837, an Anti-CD22 x Anti-CD28 Costimulatory Bispecific Monoclonal Antibody, in Combination With Odronextamab, an Anti-CD20 x Anti-CD3 Bispecific Monoclonal Antibody, in Patients With Aggressive B-Cell Non-Hodgkin Lymphomas (ATHENA-1)

Conditions
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B-cell Non-Hodgkins Lymphoma (B-NHL)

Intervention / Treatment
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* Drug: Odronextamab
* Drug: REGN5837


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: 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. Measurable disease on cross sectional imaging as defined in the protocol Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate bone marrow, renal and hepatic function as defined in the protocol 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: Prior treatments with allogeneic stem cell transplantation or solid organ transplantation, treatment with anti-CD20 x anti- CD3 bispecific antibody, such as odronextamab Diagnosis of mantle cell lymphoma (MCL) Primary central nervous system (CNS) lymphoma or known involvement by non-primary CNS lymphoma 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 Standard radiotherapy within 14 days of first administration of study drug. Continuous systemic corticosteroid treatment with more than 10 mg per day of prednisone or corticosteroid equivalent within 72 hours of start of odronextamab Co-morbid conditions, as described in the protocol Infections, as described in the protocol Allergy/hypersensitivity: Known hypersensitivity to both allopurinol and rasburicase NOTE: Other protocol defined 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Odronextamab and REGN5837<br>Odronextamab and REGN5837 will be administered by IV infusion using a step-up dosing schedule. | Drug: Odronextamab<br>* Odronextamab will be administered by IV infusion<br>* Other names: REGN1979;Drug: REGN5837<br>* REGN5837 will be administered by IV infusion<br>|

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 REGN5837 in combination with odronextamab | 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). | From Cycle 2, Day 15 to Cycle 4, Day 7 (each induction cycle is 21 days) | 
| Incidence of treatment-emergent adverse events (TEAEs) of REGN5837 in combination with odronextamab | 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. | From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years | 
| Severity of TEAEs of REGN5837 in combination with odronextamab | 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. | From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years | 
| Incidence of adverse events of special interest (AESIs) of REGN5837 in combination with odronextamab | 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. | From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years | 
| Severity of AESIs of REGN5837 in combination with odronextamab | 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. | From dose 1 of study treatment, until the date of progression, assessed up to study completion, approximatively 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Incidence of anti-drug antibodies (ADAs) to REGN5837 |  | Up to 90 days post last study drug administration | 
| Incidence of ADAs to odronextamab |  | Up to 90 days post last study drug administration | 
| Titer of ADAs to REGN5837 |  | Up to 90 days post last study drug administration | 
| Titer of ADAs to odronextamab |  | Up to 90 days post last study drug administration | 
| Overall response rate (ORR) according to the Lugano Classification of response | 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. | Through study completion, an average of approximately 5 years | 
| Complete response (CR) rate according to the Lugano Classification of response | 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. | Through study completion, an average of approximately 5 years | 
| Progression free survival (PFS) according to the Lugano Classification of response | 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. | Through study completion, an average of approximately 5 years | 
| Overall survival (OS) | OS is measured from the start of study treatment until death due to any cause. | Through study completion, an average of approximately 5 years | 
| Duration of Response (DoR) according to the Lugano Classification of response | 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. | Through study completion, an average of approximately 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aggressive B-Cell Non-Hodgkin Lymphomas