Epcoritamab Plus Ibrutinib for the Treatment of Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
Phase Ib/II Trial of Epcoritamab Plus Ibrutinib in Patients With Relapsed/Refractory Aggressive B-Cell Non-Hodgkin Lymphoma
2 other identifiers
interventional
38
1 country
2
Brief Summary
This phase Ib/II trial evaluates the safety, optimal dose, and efficacy of the combination of epcoritamab and ibrutinib in treating patients with aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to two different types of receptors (proteins present on the cell surface) at the same time. The two receptors that epcoritamab binds to are called CD3 and CD20. CD3 is found on T cells, which are important cells of the immune system that help fight cancer and infections. CD20 is found on the surface of most types of aggressive B-cell non-Hodgkin lymphoma cells. By binding to both CD3 and CD20, epcoritamab brings the two cells close together so the T cells can fight and kill the lymphoma B cells. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, binds to a protein on B cells, a type of white blood cell from which the lymphoma developed. By doing this it decreases the ability of the lymphoma B cells to survive and grow. Ibrutinib may also improve the health (or fitness) of T cells thus making epcoritamab safer and/or more effective.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Apr 2025
Typical duration for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 31, 2024
CompletedFirst Posted
Study publicly available on registry
August 2, 2024
CompletedStudy Start
First participant enrolled
April 2, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 31, 2028
February 19, 2026
April 1, 2025
1.7 years
July 31, 2024
February 16, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Incidence of adverse events (AEs)
AEs will be tabulated by type and grade using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 and displayed in summary form. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.
Up to 60 days after last dose of study drug
Incidence of cytokine release syndrome (CRS)
CRS severity will be graded using American Society for Transplantation and Cellular Therapy Cytokine Release Syndrome criteria. The CRS rate will be calculated together with 95% one-sided confidence intervals among evaluable patients.
Up to 60 days after last dose of study drug
Secondary Outcomes (5)
Overall response rate (ORR)
Up to 24 months
Complete response (CR) rate
Up to cycle 12 (each cycle is 28 days)
Progression-free survival (PFS)
From the start of treatment to the time of progression or death, whichever occurs first, assessed up to 5 years
Duration of response (DOR)
Up to 5 years
Overall survival (OS)
From the start of treatment to death from any cause, assessed up to 5 years
Study Arms (1)
Treatment (epcoritamab, ibrutinib)
EXPERIMENTALPatients receive ibrutinib PO QD on days -7 to 28 of cycle 1 and on days 1 to 28 of remaining cycles, as well as epcoritamab SC on days 1, 8, 15 and 22 of cycles 1-3, days 1 and 15 of cycles 4-9, and on day 1 of remaining cycles. Treatment repeats every 28 days for up to 6 cycles of ibrutinib and up to 12 cycles of epcoritamab in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT and PET/CT throughout the study. Patients may also undergo bone marrow aspiration and biopsy on study.
Interventions
Undergo CT and PET/CT
Given SC
Given PO
Undergo PET/CT
Undergo blood sample collection
Undergo bone marrow aspiration and biopsy
Undergo bone marrow aspiration and biopsy
Eligibility Criteria
You may qualify if:
- One of the following CD20+ B-cell non-Hodgkin lymphoma subtypes (note, documentation of CD20 positivity by flow cytometry and/or immunohistochemistry is based on any representative pathology report)
- Diffuse large B-cell lymphoma (DLBCL), including DLBCL, not otherwise specified (NOS); T-cell/histiocyte-rich large B-cell lymphoma; and Epstein-Barr virus-positive DLBCL, NOS
- High-grade B-cell lymphoma (HGBL) with MYC and BCL2 and/or BCL6 rearrangements (double-hit or triple-hit lymphoma) or HGBL, NOS
- Primary mediastinal B-cell lymphoma (PMBCL)
- Follicular lymphoma, grade 3b (also known as follicular large B-cell lymphoma in the 5th edition of World Health Organization \[WHO\] classification of lymphoid neoplasms)
- Patients with previously diagnosed indolent lymphoma (follicular lymphoma or marginal zone lymphoma but not lymphoplasmacytic lymphoma or small lymphocytic lymphoma/chronic lymphocytic leukemia) who have transformed to any of the above lymphoma subtypes are eligible
- Patients must have relapsed or refractory aggressive B-cell lymphoma and received prior treatment with an anthracycline in combination with an anti-CD20 monoclonal antibody:
- ≥ 2 prior systemic lymphoma treatments OR
- ≥ 1 prior systemic lymphoma treatment in patients with high-risk disease defined as primary refractory or relapsed within 12 months of completing anthracycline-based frontline treatment who are ineligible for chimeric antigen receptor (CAR) T cells per the treating physician. The reason for CAR T-cell treatment ineligibility should be documented
- Prior treatment with a BTK inhibitor is allowed if stopped due to lymphoma progression or treatment completion but not intolerance
- Prior treatment with autologous stem cell transplant (ASCT) is allowed if ≥ 100 days prior to enrollment
- Prior treatment with CAR T cells is allowed if ≥ 30 days prior to enrollment
- Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of ibrutinib or epcoritamab in patients \< 18 years of age, children are excluded from this study
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Measurable disease (defined as \> 1.5 cm in diameter) or at least one PET fludeoxyglucose F-18 (FDG) avid area of disease
- +11 more criteria
You may not qualify if:
- Prior therapy with a bispecific antibody targeting CD3 and CD20
- Prior lymphoma therapy should be completed greater than two weeks before the start of protocol therapy, except for corticosteroids used for palliation of symptoms
- Patients who require immediate cytoreductive therapy for their lymphoma per the treating physician's assessment are ineligible
- Patients with a history of allogeneic stem cell transplantation are excluded unless the transplant was \> 180 days before the first scheduled dose of ibrutinib AND the patient does not have evidence of active acute or chronic graft versus host disease AND the patient must not have taken immunosuppressive medications associated with the transplant for at least 1 month before the first scheduled dose of ibrutinib
- Ongoing systemic treatment with a strong CYP3A inhibitor or inducer. Treatment with any strong CYP3A inhibitor or inducer needs to be stopped for 5 half-lives prior to starting treatment on trial
- Major surgery within 4 weeks before the start of treatment other than surgery performed for lymphoma diagnosis
- Known active central nervous system (CNS) involvement by lymphoma. Patients who are enrolled and subsequently identified to have pathologic confirmation of CNS involvement by lymphoma may be continued on the study at the discretion of the principal investigator
- Active uncontrolled infection or infection requiring intravenous (IV) antibiotic therapy for \> 2 consecutive days within 2 weeks prior to the first dose of study drug
- Evidence of current uncontrolled or symptomatic cardiovascular conditions, including, uncontrolled cardiac arrhythmias, history of or symptomatic congestive heart failure (New York Heart Association \[NYHA\] class III or greater), unstable angina, or myocardial infarction within the past 6 months. Poorly controlled or clinically significant atherosclerotic vascular disease including angioplasty, cardiac or vascular stenting within 6 months of enrollment
- Known liver cirrhosis with moderate to severe hepatic impairment (Child-Pugh class B or C)
- Clinically significant pulmonary disease or history of bronchospasm requiring intubation, or clinically significant active interstitial lung disease or pneumonitis
- History of cerebrovascular accident or transient ischemic attack within the 6 months before day 1, cycle 1 of treatment
- Any prior history of intracranial hemorrhage
- Clinically significant known bleeding diatheses or platelet dysfunction disorders.
- Receiving treatment with coumadin/warfarin
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Yazeed Sawalhalead
- AbbViecollaborator
- Genmabcollaborator
Study Sites (2)
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Yazeed Sawalha
Ohio State University Comprehensive Cancer Center
Central Study Contacts
The Ohio State University Comprehensive Cancer Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
July 31, 2024
First Posted
August 2, 2024
Study Start
April 2, 2025
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
December 31, 2028
Last Updated
February 19, 2026
Record last verified: 2025-04