A Trial to Study if REGN5837 in Combination With Odronextamab is Safe for Adult Participants With Aggressive B-cell Non-Hodgkin Lymphomas
- Conditions
- B-cell Non-Hodgkins Lymphoma (B-NHL)
- Interventions
- Registration Number
- NCT05685173
- Lead Sponsor
- Regeneron Pharmaceuticals
- 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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 91
- 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.
- 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
- 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
- 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
- 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, as described in the protocol
- 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
- Standard radiotherapy within 14 days of first administration of study drug, as described in the protocol
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Odronextamab and REGN5837 Odronextamab Odronextamab and REGN5837 will be administered by IV infusion using a step-up dosing schedule. Odronextamab and REGN5837 REGN5837 Odronextamab and REGN5837 will be administered by IV infusion using a step-up dosing schedule.
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab 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).
Incidence of treatment-emergent adverse events (TEAEs) of REGN5837 in combination with odronextamab Up to 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.
Severity of TEAEs of REGN5837 in combination with odronextamab Up to 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.
Incidence of adverse events of special interest (AESIs) of REGN5837 in combination with odronextamab Up to 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.
Severity of AESIs of REGN5837 in combination with odronextamab Up to 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
Name Time Method Incidence of anti-drug antibodies (ADAs) to REGN5837 over the study duration Up to 90 days post last study drug administration Incidence of ADAs to odronextamab over the study duration Up to 90 days post last study drug administration 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 Titer of ADAs to REGN5837 over the study duration Up to 90 days post last study drug administration Titer of ADAs to odronextamab over the study duration Up to 90 days post last study drug administration Overall response rate (ORR) according to the Lugano Classification of response Up to approximatively 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.
Complete response (CR) rate according to the Lugano Classification of response Up to approximatively 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.
Progression free survival (PFS) according to the Lugano Classification of response Up to approximatively 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.
Overall survival (OS) Up to approximatively 5 years OS is measured from the start of study treatment until death due to any cause.
Duration of Response (DoR) according to the Lugano Classification of response Up to approximatively 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.
Trial Locations
- Locations (20)
University Hospital and Research Institute
🇪🇸Madrid, Spain
The Christie
🇬🇧Manchester, United Kingdom
University of California Los Angeles (UCLA) Medical Center
🇺🇸Santa Monica, California, United States
Harvard Medical School - Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
UT Southwestern
🇺🇸Dallas, Texas, United States
CHU de Bordeaux
🇫🇷Talence, Nouvelle Aquitaine, France
Hopital Saint Louis
🇫🇷Paris, France
Amsterdam University Medical Centre, location AMC
🇳🇱Amsterdam, Netherlands
Royal Cornwall Hospital NHS Trust
🇬🇧Truro, Cornwall, United Kingdom
Western General Hospital
🇬🇧Edinburgh, Scotland, United Kingdom
City of Hope
🇺🇸Duarte, California, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
NYU Langone Health Perlmutter Cancer Center
🇺🇸New York, New York, United States
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
Gustave Roussy
🇫🇷Villejuif, Ile De France, France
Erasmus Medical Center Rotterdam
🇳🇱Rotterdam, Zuid-Holland, Netherlands
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
Southampton General Hospital
🇬🇧Southampton, Hampshire, United Kingdom