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
Single group
Ibrutinib Oral Tablet
DrugOrally once daily, administered alone during the initial treatment phase and continued in combination with venetoclax and epcoritamab according to the study treatment schedule.
Venetoclax Oral Tablet
DrugOral administration as part of the study treatment regimen, in combination with ibrutinib and subsequently with epcoritamab according to the study treatment schedule.
Epcoritamab
DrugSubcutaneous administration as part of the study treatment regimen in combination with ibrutinib and venetoclax according to the study treatment schedule
Rate of Participants Achieving Complete Remission (CR) with Undetectable Minimal Residual Disease (uMRD) in Bone Marrow
Rate of participants achieving complete remission (CR) with undetectable minimal residual disease (uMRD) in bone marrow, assessed according to 2018 iwCLL response criteria.
Bone Marrow uMRD Rate
Proportion of participants with undetectable minimal residual disease in bone marrow.
Complete Response Rate (CRR)
Proportion of participants achieving complete response according to iwCLL 2018 criteria.
Overall Response Rate (ORR)
Proportion of participants achieving complete or partial response according to iwCLL 2018 criteria.
Duration of Response
Time from first response to disease progression or death
Click on the lead sponsor to view all of their trials.
The Lymphoma Academic Research Organisation
Lead sponsor
Lymphoma Study Association
Collaborator
AbbVie
Collaborator
Johnson & Johnson
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
