A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for 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)

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)

Study Overview

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

• Study Type: Interventional
• Enrollment (Estimated): 91
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• United Kingdom
  • Cornwall
    • Truro, Cornwall, United Kingdom, TR1 3LQ
      • Recruiting
      • Royal Cornwall Hospitals NHS trust
  • Manchester
    • Withington, Manchester, United Kingdom, M20 4BQ
      • Recruiting
      • The Christie NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
  • Kentucky
    • Louisville, Kentucky, United States, 40241
      • Recruiting
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215-5400
      • Recruiting
      • Beth Israel Deaconess Medical Center (BIDMC)
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • 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
      • Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI)
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • University of Texas (UT) - Southwestern Medical Center

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.
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. 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
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
5. Standard radiotherapy within 14 days of first administration of study drug.
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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2023
• Primary Completion (Estimated): June 2, 2027
• Study Completion (Estimated): May 16, 2029

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 (Estimated): April 26, 2024
• Last Update Submitted That Met QC Criteria: April 25, 2024
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Aggressive B-Cell Non-Hodgkin Lymphomas
• Additional Relevant MeSH Terms: Behavioral Symptoms; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Aberrant Motor Behavior in Dementia; Aggression; Lymphoma; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: R5837-ONC-2019; 2022-502137-26-00 (Other Identifier: EUCT 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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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