Epcoritamab, Rituximab, Gemcitabine and Oxaliplatin (R-GemOx) as Salvage Therapy Before Autologous Stem Cell Transplant for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Recruiting now · Phase 2

Conditions studied: Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified, Recurrent Primary Mediastinal Large B-Cell Lymphoma, Recurrent Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma, Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified, Refractory Primary Mediastinal Large B-Cell Lymphoma, Refractory Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

In brief

This phase II trial tests how well epcoritamab in combination with rituximab, gemcitabine and oxaliplatin (R-GemOx) works as treatment given after the cancer has not responded to other treatments (salvage therapy) before autologous stem cell transplant in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Epcoritamab is a so-called bispecific antibody, a molecule that can bind simultaneously to two different receptors (proteins present on the cell surface). Epcoritamab binds to a receptor called CD3 with one part of the antibody and to a receptor called CD20 with another part of the antibody. CD3 is expressed on T cells, which are important cells of the immune system that help the body fight cancers and infections. CD20 is expressed on the surface of DLBCL cells. By simultaneous binding to CD3 and CD20, epcoritamab brings T cells and DLBCL cells close together and activates the T cells to kill the lymphoma cells. Rituximab is a so-called monoclonal antibody, a molecule that binds to a single receptor. Like epcoritamab, rituximab binds to CD20. After binding to CD20, rituximab activates the immune system to kill the lymphoma cell through several different mechanisms. Gemcitabine is a chemotherapy drug that blocks the cells from making DNA and may kill cancer cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's DNA and may kill cancer cells. Giving epcoritamab-R-GemOx as therapy before an autologous stem cell transplant may help kill cancer cells in the body and help make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow.

Key facts

Study ID: NCT07365306
Run by: City of Hope Medical Center
People needed: 43
Starts: 2026-04-15
Expected to finish: 2029-10-15
Last updated by the study team: 2026-04-24

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

Documented informed consent of the participant and/or legally authorized representative.
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
If unavailable, exceptions may be granted with study principal investigator (PI) approval
Age: ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) ≤ 2
Histologically confirmed diagnosis of DLBCL, not-otherwise specified (NOS), transformation of indolent B-cell lymphoma, High grade B-cell lymphoma (HGBCL), NOS, primary mediastinal large B-cell lymphoma (PMBCL)
Biopsy-proven relapsed or refractory disease after 1 prior line of chemoimmunotherapy and:
CAR-naïve patients (Cohort 1)
If primary refractory, or relapsed within 12 months and are ineligible for or are unwilling to undergo CD19-directed CAR-T cell therapy
If relapsed beyond 12 months
CAR-experienced patients (Cohort 2)
If relapsed or refractory to CD19-directed CAR T cell therapy
Measurable disease on computed tomography (CT) scan, defined as a nodal site greater than 1.5 cm in the longest axis or an extranodal site greater than 1.0 cm in the longest axis AND baseline fluorodeoxyglucose-positron emission tomography (FDG-PET) must demonstrate positive lesion compatible with CT defined anatomical tumor sites
Considered eligible for high-dose chemotherapy followed by ASCT
Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
Positive for CD20 by immunohistochemistry
Without bone marrow involvement: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3
NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
Without bone marrow involvement: Platelets ≥ 100,000/mm\^3. With bone marrow involvement: Platelets ≥ 75,000/mm\^3
NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
Hemoglobin ≥ 8g/dL
NOTE: Red blood cell transfusions are not permitted within 14 days of hemoglobin assessment unless cytopenia is secondary to disease involvement
Total bilirubin ≤ 1.5 X upper limit of normal (ULN)
If hepatic involvement by lymphoma, or Gilbert's disease: ≤ 3 X ULN

You may not qualify if…

Autologous or allogeneic stem cell transplant within 1 year prior to day 1 of study therapy
Chemotherapy, biological therapy, immunotherapy within 21 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of study therapy other than a single cycle of R-GemOx
Has received or plans to receive radiotherapy except for palliative radiation to non-target lesions or major surgery within 4 weeks prior day 1 of study therapy
Prior solid organ transplantation
Vaccination with live vaccines within 4 weeks of the first dose of study drug or is expected to need any live vaccination during study participation including at least 3 months following the last dose of study treatment.
COVID-19 non-replicating adenoviral vaccines are permitted with a minimum period of 3 days between the vaccine and a dose of study treatment
Active medication use known to decrease T-cell numbers or activity or other concurrent immunosuppressive medication within 5 half-lives or 28 days, whichever is longer, prior to randomization except for up to 20 mg prednisone daily or equivalent
Known active central nervous system (CNS) involvement by lymphoma, including leptomeningeal involvement
Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia, or New York Heart Association (NYHA) heart failure class III-IV, or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of screening
Clinically significant liver disease, including active hepatitis, current alcohol abuse, or cirrhosis
History of severe allergic or anaphylactic reactions to anti CD20 monoclonal or bi-specific antibody therapy, or known significant allergy or intolerance to any component or excipient constituents of the study treatment (and their excipients) and/or other products in the same class
Clinically significant uncontrolled illness
Active uncontrolled infection requiring systemic antibiotics
Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) within 2 weeks prior to first dose of study treatment
Current seizure disorder requiring therapy
Peripheral (sensory) neuropathy grade > 1 with the exception of neuropathy related directly to lymphoma (e.g., nerve compression from tumor)
Other active malignancy. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Recent major surgery (within 4 weeks) prior to start of study therapy, other than for diagnosis
Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients with past HBV infection (defined as negative HBV surface antigen [HBsAg] and positive hepatitis B core antibody [HBcAb]) are eligible if HBV DNA is undetectable. Patients who are positive for HCV antibody are eligible if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA). Testing to be done only in patients suspected of having infections or exposures
Known active human immunodeficiency virus (HIV) infection. Subjects who have an undetectable or unquantifiable HIV viral load with CD4 > 200 and are on highly active antiretroviral therapy (HAART) medication are allowed. Testing to be done only in patients suspected of having infections or exposures
Active (symptomatic) cytomegalovirus (CMV) disease
Active tuberculosis (TB) or history of completed treatment for active TB within the past 12 months
History of or current progressive multifocal leukoencephalopathy (PML)
Toxicities from prior anticancer therapy that have not resolved to Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0) grade 0 or 1, with the exception of alopecia
Females only: Pregnant or breastfeeding

Where it is running

City of Hope Medical Center — Duarte, California, United States (enrolling)
City of Hope Atlanta Cancer Center — Newnan, Georgia, United States
City of Hope at Chicago — Zion, Illinois, United States

Full record on ClinicalTrials.gov

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