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

Официальное название

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)

Обзор

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)

Вмешательства

• Препарат Odronextamab
  Administered per the protocol
• Препарат REGN5837
  Administered per the protocol

Первичные конечные точки

• Incidence of Dose Limiting Toxicities (DLTs) of REGN5837 in combination with odronextamab [Срок оценки: 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 [Срок оценки: Up to approximatively 5 years]
• Severity of TEAEs of REGN5837 in combination with odronextamab [Срок оценки: Up to approximatively 5 years]
• Incidence of Adverse Events of Special Interest (AESIs) of REGN5837 in combination with odronextamab [Срок оценки: Up to approximatively 5 years]
• Severity of AESIs of REGN5837 in combination with odronextamab [Срок оценки: Up to approximatively 5 years]

Вторичные конечные точки (11)

• Concentrations of REGN5837 in the serum [Срок оценки: Up to 90 days post last study drug administration]
• Concentrations of odronextamab in the serum [Срок оценки: Up to 90 days post last study drug administration]
• Occurrence of Anti-Drug Antibodies (ADAs) to REGN5837 [Срок оценки: Up to 90 days post last study drug administration]
• Occurrence of ADAs to odronextamab [Срок оценки: Up to 90 days post last study drug administration]
• Magnitude of ADAs to REGN5837 [Срок оценки: Up to 90 days post last study drug administration]
• Magnitude of ADAs to odronextamab [Срок оценки: Up to 90 days post last study drug administration]
• Objective Response Rate (ORR) according to the Lugano Classification of response [Срок оценки: Up to approximatively 5 years]
• Complete Response (CR) according to the Lugano Classification of response [Срок оценки: Up to approximatively 5 years]
• Overall Survival (OS) [Срок оценки: Up to approximatively 5 years]
• Progression Free Survival (PFS) according to the Lugano Classification of response [Срок оценки: Up to approximatively 5 years]
• Duration of Response (DoR) according to the Lugano Classification of response [Срок оценки: Up to approximatively 5 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 9 центров

• City of Hope — Duarte
• University of California Los Angeles (UCLA) Medical Center — Santa Monica
• Norton Cancer Institute — Louisville
• Massachusetts General Hospital — Boston
• Harvard Medical School - Beth Israel Deaconess Medical Center — Boston
• Rutgers Cancer Institute of New Jersey — New Brunswick
• NYU Langone Health Perlmutter Cancer Center — New York
• Icahn School of Medicine at Mount Sinai — New York
• … и ещё 1 центр

Великобритания · 4 центра

• Royal Cornwall Hospitals NHS Trust, Royal Cornwall Hospital — Truro
• Southampton General Hospital — Southampton
• Western General Hospital — Edinburgh
• The Christie NHS Foundation Trust — Manchester

Франция · 3 центра

• CHU de Bordeaux — Talence
• Hopital Saint Louis — Paris
• Gustave Roussy — Villejuif

Нидерланды · 2 центра

• Erasmus Medical Center Rotterdam — Rotterdam
• Amsterdam University Medical Centre, location AMC — Amsterdam

Испания · 2 центра

• Hospital Vall d'Hebron — Barcelona
• University Hospital and Research Institute — Madrid

Идентификаторы

NCT: NCT05685173 · R5837-ONC-2019 · 2020-005084-32 · 2022-502137-26-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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