This is a phase 2, open-label, multicenter study evaluating the efficacy and safety of a fixed-duration combination of epcoritamab, venetoclax, and ibrutinib (EVI) in previously untreated patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have TP53 alterations.
Patients with TP53 abnormalities, including TP53 mutation and/or 17p deletion, have a poorer prognosis and are less likely to benefit from conventional chemoimmunotherapy. Targeted therapies such as ibrutinib and venetoclax have improved outcomes in this population, but many patients eventually experience disease progression. This study investigates whether adding epcoritamab, a CD3×CD20 bispecific antibody, to the combination of ibrutinib and venetoclax can improve the depth and durability of treatment responses while using a fixed-duration treatment approach.
Participants will receive sequential treatment with ibrutinib alone, followed by ibrutinib plus venetoclax, and then the triple combination of epcoritamab, venetoclax, and ibrutinib. The study will evaluate the effectiveness of this regimen, including the achievement of deep remission, as well as its safety and tolerability in this high-risk patient population.
Participant who understood and voluntarily signed and dated an informed consent form prior to any trial-specific assessments/procedures being conducted
Must be able to adhere to the trial visit schedule and other protocol requirements
Age between ≥ 18 years and < 80 years at the time of signing the informed consent form (ICF)
Cumulative Illness Rating Score (CIRS) ≤ 6
Any prior CLL or SLL-specific therapies, even including rituximab used for autoimmune cytopenias.
Myocardial infarction within 6 months prior to ICF signature
Unstable angina within 3 months prior to ICF signature
NYHA class III or IV heart failure
The Lymphoma Academic Research Organisation
Lead sponsor
Lymphoma Study Association
Collaborator
AbbVie
Collaborator
Johnson & Johnson
Collaborator