Epcoritamab in Combination With R-CHOP for Patients With Aggressive Non-Hodgkin Lymphoma

NCT07588698 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 252526
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

A Phase II, open-label, two-arm, multicenter study evaluating the combination of epcoritamab with R-CHOP chemotherapy in patients with newly diagnosed, aggressive B-cell non-Hodgkin lymphoma.

Conditions

Non-Hodgkin's B-cell Lymphoma; Lymphoma Non-Hodgkin; Diffuse Large B-Cell Lymphoma (DLBCL)

Keywords

Newly diagnosed B-cell lymphoma patients; Combination immunotherapy chemotherapy; epcoritamab R-CHOP lymphoma trial

Outcome Measures

Primary Outcomes (1)

• Cytokine Release Syndrome (CRS) Rate

  The cytokine release syndrome (CRS) rate is defined as the incidence of CRS of any grade during Cycle 2, graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. The proportion and corresponding 95% confidence interval will be reported.

  Up to day 42

Secondary Outcomes (5)

• Proportion of Participants with Treatment-emergent Adverse Events

  Up to 60 days after treatment

• Overall Response (OR)

  Up to 2 years

• Duration of Overall Response

  Up to 2 years

• Median Progression-Free Survival (PFS)

  Up to 2 years

• Median Overall Survival (OS)

  Up to 2 years.

Study Arms (2)

Arm A: Treatment with Standard Dexamethasone (First 6 participants)

EXPERIMENTAL

Participants will receive 8 cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone (R-CHOP) chemotherapy combined with epcoritamab. A standard dose of dexamethasone is given in Cycle 2. Treatment includes six 21-day cycles: Cycle 1 consists of R-CHOP alone; Cycles 2-5 include R-CHOP on Day 1 with epcoritamab on Days 1, 8, and 15. In Cycle 2, dexamethasone is given on epcoritamab treatment days and for 3 subsequent days. In Cycle 6, both R-CHOP and epcoritamab are given on Day 1 only. This is followed by two 28-day consolidation cycles (Cycles 7-8) with epcoritamab on Day 1. Safety follow-up occurs at Week 8 and every 3 months for up to one year. Participants who discontinue due to adverse events will be followed until improvement or stabilization, or until new therapy begins, whichever occurs first.

Drug: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone (R-CHOP); Drug: Epcoritamab; Drug: Dexamethasone; Procedure: Positron Emission Tomography (PET); Procedure: Blood specimen collection; Behavioral: Questionnaires; Procedure: Computerized tomography (CT)

Arm B: Treatment with Modified Dexamethasone

EXPERIMENTAL

Participants will receive 8 cycles of rituximab, cyclophosphamide, hydroxydaunorubicin, oncovin, prednisolone (R-CHOP) chemotherapy combined with epcoritamab. A modified dose of dexamethasone will be given in Cycle 2. Treatment includes six 21-day cycles: Cycle 1 consists of R-CHOP alone; Cycles 2-5 include R-CHOP on Day 1 with epcoritamab on Days 1, 8, and 15. In Cycle 2, dexamethasone is administered on epcoritamab treatment days and the following day. In Cycle 6, both R-CHOP and epcoritamab are given on Day 1 only. This is followed by two 28-day consolidation cycles (Cycles 7-8) with epcoritamab on Day 1. Safety follow-up occurs at Week 8 and every 3 months for up to one year. Participants who discontinue due to adverse events will be followed until improvement or stabilization, or until new therapy begins, whichever occurs first.

Drug: Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone (R-CHOP); Drug: Epcoritamab; Drug: Dexamethasone; Procedure: Positron Emission Tomography (PET); Procedure: Blood specimen collection; Behavioral: Questionnaires; Procedure: Computerized tomography (CT)

Interventions

Rituximab, Cyclophosphamide, Hydroxydaunorubicin, Oncovin, Prednisolone (R-CHOP) DRUG

Given orally and intravenously (IV)

Also known as: R-CHOP-21

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Epcoritamab DRUG

Given subcutaneously (SC)

Also known as: EPKINLY, epcoritamab-bysp

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Dexamethasone DRUG

Given orally

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Positron Emission Tomography (PET) PROCEDURE

Undergo imaging

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Blood specimen collection PROCEDURE

Perform Blood work

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Questionnaires BEHAVIORAL

Participants complete European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Computerized tomography (CT) PROCEDURE

Undergo Imaging

Arm A: Treatment with Standard Dexamethasone (First 6 participants); Arm B: Treatment with Modified Dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have confirmed CD20-positive aggressive B-cell lymphoma, including de novo or transformed diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement; primary mediastinal large B-cell lymphoma (PMBCL); T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL); Epstein-Barr virus-positive DLBCL, NOS; or follicular lymphoma grade 3b.
• Measurable disease per Lugano 2014 criteria.
• No prior therapy for DLBCL or FL G3B other than corticosteroids or palliative radiotherapy. Of note, a cycle of anthracycline-containing regimen (given as standard of care prior to study enrollment) is allowed, provided that patients will receive a total of six cycles of chemotherapy as part of their treatment plan. Patients who received one cycle of an anthracycline-containing regimen prior to enrollment will proceed directly to Cycle 2 on study.
• Age ≥18 years
• Participants must have an International Prognostic Index (IPI) score of 2-5.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Demonstrates adequate organ function as defined below:
• Adequate bone marrow function:
• absolute neutrophil count platelets
• × 10⁹/Litre (L) (with growth factor use allowed)
• × 10⁹/L
• Exceptions:
• Patients may be enrolled despite not meeting the thresholds above if either of the following applies, provided the Absolute Neutrophil Count (ANC) is ≥0.75 × 10⁹/L:
• The patient has received one prior cycle of chemotherapy off study, and cytopenias at Cycle 2, Day 1 of protocol therapy are believed to be due to recent chemotherapy, provided there is evidence of marrow recovery and no other contraindications.
• The patient has documented bone marrow involvement by lymphoma, and cytopenias are believed to be disease-related rather than indicative of poor marrow reserve or unrelated pathology. In such cases, enrollment is permitted at the discretion of the investigator if the patient is otherwise eligible and deemed safe to proceed.

You may not qualify if:

• History of severe allergic or anaphylactic reactions to anti-CD20 mAb therapy or known allergy or intolerance to any component or excipient of epcoritamab.
• Any prior treatment with a bispecific antibody targeting CD3 and CD20.
• Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to the first dose of epcoritamab.
• Requiring immunosuppressive therapy for an ongoing baseline medical condition. For corticosteroids, prednisolone \>10 mg daily (or equivalent) qualifies as immunosuppressive and thus be excluded for this use. Note: corticosteroids at any dose are permitted for control of lymphoma related symptoms, including during screening, and for any adverse events (AE) management during study.
• Vaccination with live vaccines within 28 days prior to the first dose of epcoritamab.
• Clinically significant cardiovascular disease, including:
• Myocardial infarction within 6 months prior to the first dose of epcoritamab, or unstable or uncontrolled disease/condition related to or affecting cardiac function (eg, unstable angina, congestive heart failure New York Heart Association Class III-IV), cardiac arrhythmia (NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5 Grade 3 or higher), or clinically significant electrocardiogram (ECG) abnormalities
• Screening 12-lead ECG showing a baseline QT Corrected for Heart Rate using Fridericia's Formula (QTcF) \>470 msec
• Stroke within 6 months prior to first epcoritamab dose
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at trial enrolment or significant infections within 2 weeks prior to the first dose of epcoritamab.
• Active hepatitis B Virus (HBV) (Deoxyribonucleic Acid Polymerase Chain Reaction (DNA PCR) -positive) or hepatitis C (Ribonucleic Acid Polymerase Chain Reaction (RNA PCR) -positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy. Subjects who received treatment for Hepatitis C Virus (HCV) that was intended to eradicate the virus may participate if hepatitis C Ribonucleic acid (RNA) levels are undetectable.
• Cervical carcinoma of Stage 1B or less
• Non-invasive basal cell or squamous cell skin carcinoma
• Non-invasive, superficial bladder cancer
• Prostate cancer with a current Prostate-Specific Antigen (PSA) level \< 0.1 ng/milliliter (mL)

Sponsors & Collaborators

• Mwanasha Merrill, MD: lead

Study Sites (2)

Zuckerberg San Francisco General

San Francisco, California, 94110, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse

Interventions

Rituximab; Cyclophosphamide; Doxorubicin; Vincristine; Prednisolone; Dexamethasone; Magnetic Resonance Spectroscopy; Blood Specimen Collection; Surveys and Questionnaires

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Data Collection; Epidemiologic Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• Mwanasha Merrill, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

UCSF Hematopoietic Malignancies Clinical Trial Recruitment

CONTACT

877-827-3222; HDFCCC.Heme@ucsf.edu

Clinical Trial Recruitment

CONTACT

cancertrials@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: May 7, 2026
• First Posted: May 15, 2026
• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2029
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)