A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Adult Participants With Aggressive B-cell Non-Hodgkin Lymphomas (ATHENA-1)

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)

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)

Study Overview

• Status: Recruiting
• Conditions: B-cell Non-Hodgkins Lymphoma (B-NHL)
• Intervention / Treatment: Drug: Odronextamab; Drug: REGN5837

• Study Type: Interventional
• Enrollment (Estimated): 107
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• France
  • Paris, France, 75010
    • Recruiting
    • Hopital Saint Louis
  • New Aquitaine
    • Talence, New Aquitaine, France, 33404
      • Recruiting
      • CHU de Bordeaux
  • Île-de-France Region
    • Villejuif, Île-de-France Region, France, 94800
      • Recruiting
      • Gustave Roussy
• Netherlands
  • Amsterdam, Netherlands, 1100AZ
    • Recruiting
    • Amsterdam University Medical Centre, location AMC
  • South Holland
    • Rotterdam, South Holland, Netherlands, 3015
      • Recruiting
      • Erasmus Medical Center Rotterdam
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Vall D'Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • University Hospital and Research Institute
• United Kingdom
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LJ
      • Recruiting
      • Royal Cornwall Hospitals NHS Trust, Royal Cornwall Hospital
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Recruiting
      • Southampton General Hospital
  • Scotland
    • Edinburgh, Scotland, United Kingdom, EH4 2XU
      • Recruiting
      • Western General Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City Of Hope
    • Santa Monica, California, United States, 90404
      • Recruiting
      • University of California Los Angeles (UCLA) Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Harvard Medical School - Beth Israel Deaconess Medical Center
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School Of Medicine At Mount Sinai
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health Perlmutter Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 / exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation portion	Drug: Odronextamab; Administered per the protocol; Other Names: REGN1979; Ordspono™; Drug: REGN5837; Administered per the protocol
Experimental: Dose expansion portion	Drug: Odronextamab; Administered per the protocol; Other Names: REGN1979; Ordspono™; Drug: REGN5837; Administered per the protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 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.	Up to approximatively 5 years
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 1 to Cycle 2, Day 21 (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.	Up to 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.	Up to 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
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.	Up to approximatively 5 years
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	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.	Up to approximatively 5 years
Complete Response (CR) 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.	Up to approximatively 5 years
Overall Survival (OS)	OS is measured from the start of study treatment until death due to any cause.	Up to approximatively 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.	Up to approximatively 5 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2023
• Primary Completion (Estimated): February 16, 2029
• Study Completion (Estimated): January 13, 2030

Study Registration Dates

• First Submitted: December 14, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Actual): January 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 18, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Relapsed or Refractory; Aggressive B-Cell Non-Hodgkin Lymphomas
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Pathological Conditions, Signs and Symptoms; Recurrence
• Other Study ID Numbers: R5837-ONC-2019; 2020-005084-32 (EudraCT Number); 2022-502137-26-00 (Ctis: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

IPD Sharing Access Criteria

Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli.

Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No