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

• ClinicalTrials.gov Identifier: NCT05685173
• Recruitment Status: Recruiting
• First Posted: January 13, 2023
• Last Update Posted: April 26, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

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)

Condition or disease	Intervention/treatment	Phase
B-cell Non-Hodgkins Lymphoma (B-NHL)	Drug: Odronextamab; Drug: REGN5837	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 91 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: April 12, 2023
• Estimated Primary Completion Date: June 2, 2027
• Estimated Study Completion Date: May 16, 2029

Arms and Interventions

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 Name: REGN1979; Drug: REGN5837; REGN5837 will be administered by IV infusion

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Concentrations of REGN5837 in the serum [ Time Frame: Up to 90 days post last study drug administration ]
2. Concentrations of odronextamab in the serum [ Time Frame: Up to 90 days post last study drug administration ]
3. Incidence of anti-drug antibodies (ADAs) to REGN5837 [ Time Frame: Up to 90 days post last study drug administration ]
4. Incidence of ADAs to odronextamab [ Time Frame: Up to 90 days post last study drug administration ]
5. Titer of ADAs to REGN5837 [ Time Frame: Up to 90 days post last study drug administration ]
6. Titer of ADAs to odronextamab [ Time Frame: Up to 90 days post last study drug administration ]
7. Overall response rate (ORR) according to the Lugano Classification of response [ Time Frame: Through study completion, an average of approximately 5 years ]
   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.
8. Complete response (CR) rate according to the Lugano Classification of response [ Time Frame: Through study completion, an average of approximately 5 years ]
   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.
9. Progression free survival (PFS) according to the Lugano Classification of response [ Time Frame: Through study completion, an average of approximately 5 years ]
   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.
10. Overall survival (OS) [ Time Frame: Through study completion, an average of approximately 5 years ]
    OS is measured from the start of study treatment until death due to any cause.
11. Duration of Response (DoR) according to the Lugano Classification of response [ Time Frame: Through study completion, an average of approximately 5 years ]
    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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Locations

United States, California

City of Hope; Recruiting

Duarte, California, United States, 91010

United States, Kentucky

Norton Cancer Institute; Recruiting

Louisville, Kentucky, United States, 40241

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Medical Center (BIDMC); Recruiting

Boston, Massachusetts, United States, 02215-5400

United States, New Jersey

Rutgers Cancer Institute of New Jersey; Recruiting

New Brunswick, New Jersey, United States, 08903

United States, New York

Laura and Isaac Perlmutter Cancer Center (NYU Cancer Institute (NYUCI); Recruiting

New York, New York, United States, 10016

Icahn School of Medicine at Mount Sinai; Recruiting

New York, New York, United States, 10029

United States, Texas

University of Texas (UT) - Southwestern Medical Center; Recruiting

Dallas, Texas, United States, 75390

United Kingdom

Royal Cornwall Hospitals NHS Trust; Recruiting

Truro, Cornwall, United Kingdom, TR1 3LQ

The Christie NHS Foundation Trust; Recruiting

Withington, Manchester, United Kingdom, M20 4BQ

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05685173
• Other Study ID Numbers: R5837-ONC-2019; 2022-502137-26-00 ( Other Identifier: EUCT Number )
• First Posted: January 13, 2023
• Last Update Posted: April 26, 2024
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.

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

• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

Aggressive B-Cell Non-Hodgkin Lymphomas

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Aggression; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Aberrant Motor Behavior in Dementia; Behavioral Symptoms