Clinical trial NCT05685173: A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Adult Participants With Aggressive B-cell Non-Hodgkin Lymphomas
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: B-cell Non-Hodgkins Lymphoma (B-NHL)
Keywords: Aggressive B-Cell Non-Hodgkin Lymphomas
Relapsed or Refractory
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-01-13
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The study is researching an experimental drug called REGN5837 in combination with another experimental drug, odronextamab (called "study drugs").

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.

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)
* To find out how well the study drugs work against relapsed or refractory aggressive B-cell non-Hodgkin lymphomas (B-NHLs)


Eligibility 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, 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

Primary outcomes:
measure: Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab
timeFrame: From Cycle 2, Day 15 to Cycle 4, Day 7 (each induction cycle is 21 days)
measure: Incidence of treatment-emergent adverse events (TEAEs) of REGN5837 in combination with odronextamab
timeFrame: Up to approximatively 5 years
measure: Severity of TEAEs of REGN5837 in combination with odronextamab
timeFrame: Up to approximatively 5 years
measure: Incidence of adverse events of special interest (AESIs) of REGN5837 in combination with odronextamab
timeFrame: Up to approximatively 5 years
measure: Severity of AESIs of REGN5837 in combination with odronextamab
timeFrame: Up to approximatively 5 years
Secondary outcomes:
measure: Concentrations of REGN5837 in the serum
timeFrame: Up to 90 days post last study drug administration
measure: Concentrations of odronextamab in the serum
timeFrame: Up to 90 days post last study drug administration
measure: Incidence of anti-drug antibodies (ADAs) to REGN5837 over the study duration
timeFrame: Up to 90 days post last study drug administration
measure: Incidence of ADAs to odronextamab over the study duration
timeFrame: Up to 90 days post last study drug administration
measure: Titer of ADAs to REGN5837 over the study duration
timeFrame: Up to 90 days post last study drug administration
measure: Titer of ADAs to odronextamab over the study duration
timeFrame: Up to 90 days post last study drug administration
measure: Overall response rate (ORR) according to the Lugano Classification of response
timeFrame: Up to approximatively 5 years
measure: Complete response (CR) rate according to the Lugano Classification of response
timeFrame: Up to approximatively 5 years
measure: Progression free survival (PFS) according to the Lugano Classification of response
timeFrame: Up to approximatively 5 years
measure: Overall survival (OS)
timeFrame: Up to approximatively 5 years
measure: Duration of Response (DoR) according to the Lugano Classification of response
timeFrame: Up to approximatively 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles (UCLA) Medical Center
state: California
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Harvard Medical School - Beth Israel Deaconess Medical Center
state: Massachusetts
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: New York
country: United States
facility: NYU Langone Health Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Dallas
country: United States
facility: UT Southwestern
state: Texas
city: Villejuif
country: France
facility: Gustave Roussy
state: Ile De France
city: Talence
country: France
facility: CHU de Bordeaux
state: Nouvelle Aquitaine
city: Paris
country: France
facility: Hopital Saint Louis
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Rotterdam
state: Zuid-Holland
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Centre, location AMC
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Madrid
country: Spain
facility: University Hospital and Research Institute
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital NHS Trust
state: Cornwall
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
state: Scotland
city: Manchester
country: United Kingdom
facility: The Christie
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: