Epcoritamab With Dose Adjusted Etoposide, Cyclophosphamide, Vincristine, Doxorubicin, Prednisone and Rituximab (EPOCH-R) for the Treatment of Aggressive B-Cell Non-Hodgkin Lymphoma
A Pilot Study of Epcoritamab With Dose Adjusted Etoposide, Cyclophosphamide, Vincristine, Doxorubicin, Prednisone and Rituximab (EPOCH-R) for Upfront Treatment of Aggressive B-Cell Non-Hodgkin Lymphomas
3 other identifiers
interventional
18
1 country
1
Brief Summary
This phase II trial tests the safety, best dose, and effectiveness of epcoritamab when given with etoposide, cyclophosphamide, vincristine, doxorubicin, prednisone and rituximab (EPOCH-R) for the treatment of patients with aggressive B-cell non-Hodgkin lymphoma. Epcoritamab is a bispecific antibody that can bind to two different antigens at the same time. Epcoritamab binds to CD3, a T-cell surface antigen, and CD20 (a tumor-associated antigen that is expressed on B-cells during most stages of B-cell development and is often overexpressed in B-cell cancers) and may interfere with the ability of cancer cells to grow and spread. Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Doxorubicin is in a class of medications called anthracyclines. Doxorubicin damages the cell's DNA and may kill cancer cells. It also blocks a certain enzyme needed for cell division and DNA repair. Prednisone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. The EPOCH-R is administrated as the standard of care treatment. This may help the immune system kill cancer cells. Giving epcoritamab with EPOCH-R may be safe, tolerable, and effective in treating patients with aggressive B-cell non-Hodgkin lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Dec 2025
Typical duration for phase_2
1 active site
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 23, 2025
CompletedFirst Posted
Study publicly available on registry
July 31, 2025
CompletedStudy Start
First participant enrolled
December 7, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 31, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
May 31, 2030
April 23, 2026
April 1, 2026
4.5 years
July 23, 2025
April 21, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Incidence of adverse events
Using Common Terminology Criteria for Adverse Events version 5.0. Estimate safety and tolerability of combining epcoritamab with dose adjusted etoposide, cyclophosphamide, vincristine, doxorubicin, prednisone and rituximab.
From the time of a subject signing consent, up until prior to Cycle 3 Day 1 (up to 42 days from Cycle 1 Day 1) or off study visit, whichever occurs earlier
Secondary Outcomes (3)
Percentage of patients that achieve a complete remission (CR) following study treatment
From the time of a subject signing consent, up until off study visit or end of treatment (Up to 18 weeks)
Progression free survival (PFS)
Up to 5 years
Overall survival (OS)
Up to 5 years
Study Arms (1)
Treatment (Epcoritamab and EPOCH-R)
EXPERIMENTALPatients receive rituximab IV on day 1, prednisone PO BID on days 1-5, etoposide IV and doxorubicin on days 1-4 and cyclophosphamide IV on day 5 of each cycle. Patients also receive epcoritamab SC on days 8 and 15 of cycle 1, days 1, 8 and 15 of cycles 2-4 and day 1 of cycles 5-6. Cycles repeat every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MUGA scan or echocardiography during screening and receive fludeoxyglucose and undergo PET scan, CT scan, bone marrow biopsy and aspirate (if needed), and blood sample collection throughout the study.
Interventions
Undergo blood sample collection
Undergo bone marrow biopsy
Undergo CT scan
Given IV
Given IV
Undergo echocardiography
Given SC
Undergo PET scan
Given PO
Given IV
Given IV
Given fludeoxyglucose
Undergo MUGA scan
Eligibility Criteria
You may qualify if:
- Untreated aggressive large-B cell lymphoma (non-Hodgkin lymphoma) with adverse features that may predict sub-optimal response to R-CHOP and in the opinion of the investigator would be treated with dose adjusted (DA)-EPOCH-R as standard of care. Subjects must be planned to receive full course (6 cycles) chemoimmunotherapy as per clinical standard of care. 1 prior cycle of chemoimmunotherapy may be allowed. Composite lymphomas are not excluded provided that the subject has not received prior systemic therapy for the indolent component and would receive DA-EPOCH-R as the standard of care regimen for the aggressive component. Eligible histologies based on 2016 World Health Organization (WHO) classification include:
- High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 translocations
- High grade B-cell lymphoma, not otherwise specified (NOS)
- Diffuse large b-cell lymphoma (DLBCL) NOS
- Primary mediastinal B-cell lymphoma
- T-cell/histiocyte-rich large-B-cell lymphoma
- Epstein Barr virus (EBV) + DLBCL, NOS
- Burkitt lymphoma
- B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma
- Be willing and able to provide written informed consent for the trial
- Be ≥ 18 years of age on day of signing informed consent
- Have measurable disease, including at least 1 nodal site measuring 1.5 cm or 1 extranodal site measuring 1.0 cm in longest dimension on CT or FDG-PET
- Have a performance status of 0-2 on the Eastern Cooperative Oncology Group (ECOG) performance scale (PS) at time of enrollment
- Left ventricular ejection fraction (LVEF) ≥ 50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO)
- Absolute neutrophil count (ANC) ≥ 1,000/μL except in cases of marrow infiltration by lymphoma
- +10 more criteria
You may not qualify if:
- Contraindication to any of the individual components of EPOCH-R, including, or history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products or if receiving an additional 6 cycles of anthracycline would place patient over the anthracycline lifetime cumulative dose (400 mg/m\^2)
- Prior systemic treatment for lymphoma. Prior radiotherapy is allowed provided that this site is not used as a measurable site to assess response
- Prior organ transplantation
- Current grade \> 1 peripheral neuropathy by clinical examination or demyelinating form of Charcot-Marie-Tooth disease
- Prior systemic therapy for indolent lymphoma
- Prior therapy for large B-cell lymphoma except for patients who require lymphoma symptom control during screening may receive steroids and/or 1 cycle of chemoimmunotherapy in the following manner:
- Up to 30 mg/day of prednisone or equivalent may be used for lymphoma symptom control during screening, including prior to finalization of staging (not included as part of pre-phase treatment). If glucocorticoid treatment is urgently required at higher doses for lymphoma symptom control prior to the start of study treatment, tumor assessments must be completed prior to initiation of \> 30-100 mg/day of prednisone or equivalent. Prednisone \> 30-100 mg/day or equivalent may be given for a maximum of 7 days as a pre-phase treatment. If patients exceed the allowed dosing of corticosteroids, patients may still be eligible for the study provided that baseline imaging is performed (or repeated) after completion of the course of higher dose of steroids. Allowed corticosteroid dosing resets from the point of imaging forward and patients who do not exceed the allowed corticosteroid dosing from the point of imaging until initiation of study treatment may enroll. A maximum of 1 cycle of chemoimmunotherapy is allowed if needed for urgent disease stabilization if patient had staging PET/CT and LVEF evaluation prior to chemoimmunotherapy; in this situation patients will receive therapy on study starting with cycle (C)1 day (D)8 epcoritamab provided the next cycle of EPOCH-R chemotherapy will not be delayed by \> 7 days. In this situation, the date of receiving the first dose of EPOCH-R is considered C1D1 of the study treatment. Labs collected prior to C1D1, in accordance with SOC for the administration of these drugs, can be used for screening purposes
- History of other malignancy that could affect compliance with the protocol or interpretation of results except with permission of the principal investigator. The following are eligible without a specific waiver:
- Patients with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study are eligible.
- Patients with any malignancy appropriately treated with curative intent and the malignancy has been in remission without treatment for ≥ 2 years prior to enrollment are eligible.
- Patients with low-grade, early-stage prostate cancer (Gleason score 6 or below, stage 1 or 2) with no requirement for therapy at any time prior to study are eligible
- Evidence of significant, uncontrolled, concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
- Recent major surgery (within 4 weeks prior to the start of cycle 1), other than for diagnosis
- History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction in the last 6 months
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) which requires systemic treatment. Patients may proceed with screening during treatment for infection, but systemic treatment must be completed by cycle 1 day 1.
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Washingtonlead
- AbbViecollaborator
Study Sites (1)
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mengyang Di, MD, PhD
Fred Hutch/University of Washington Cancer Consortium
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 23, 2025
First Posted
July 31, 2025
Study Start
December 7, 2025
Primary Completion (Estimated)
May 31, 2030
Study Completion (Estimated)
May 31, 2030
Last Updated
April 23, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share