Epcoritamab in Patients With Newly Diagnosed Marginal Zone Lymphoma (MZL)

Recruiting now · Phase 2

Conditions studied: Marginal Zone Lymphoma, Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, Splenic Marginal Zone Lymphoma, Nodal Marginal Zone Lymphoma

In brief

The purpose of this study is to assess if an investigational treatment of Epcoritamab will be beneficial for patients with Marginal Zone Lymphoma (MZL).

Key facts

Study ID

NCT06796998

Run by

Izidore Lossos, MD

People needed

25

Starts

2025-10-13

Expected to finish

2031-04-15

Last updated by the study team

2025-10-28

Who can join

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

You may qualify if…

• Men and women aged 18 years or older at the time of signing informed consent.
• Able and willing to sign the informed consent form (ICF).
• Ability to comply with the trial protocol.
• Histologically confirmed Marginal Zone Lymphoma (MZL) of Extranodal Marginal Zone Lymphoma (EMZL), Nodal Marginal Zone Lymphoma (NMZL) and Splenic Marginal Zone Lymphoma (SMZL) subtypes presenting with stage I-IV disease.
• Previously untreated participants.
• Participants with H. pylori-positive gastric EMZL who received an initial treatment with currently accepted antibiotics may be considered eligible if, after antibiotic regimen, participant has histologically confirmed MZL.
• Participants who were previously treated with localized therapy (eg, radiation or surgery) and never received systemic therapy and present with recurrent disease are eligible upon histological confirmation of MZL.
• Radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (defined as the presence of ≥1 lesion that measures >1.5 cm in the longest diameter (LDi) and ≥1.0 cm in the longest perpendicular diameter as assessed by PET/CT, CT or MRI, especially in extranodal sites, per response criteria for lymphomas (Cheson, et al., 2014). Imaging must be conducted within 6 weeks prior to the start of therapy.
• Participants with skin EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that skin lesion measures ≥1.5 cm in diameter by tape measure and is documented by photo or there are ≥2 skin lesions measuring >1 cm in diameter on the body that cannot be incorporated in one radiation field and at least one of them is histologically confirmed as MZL.
• Participants with gastric EMZL histologically confirmed and need therapy but do not have measurable disease and in which response to treatment can be assessed by multiple random gastric biopsies per Groupe d'Etude des Lymphomes de l'Adult (GELA) criteria (Ruskoné Fourmestraux, et al., 2011).
• Participants with conjunctival EMZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that conjunctival lesion measures ≥1 cm in diameter by tape measure and is documented by photo or there are multiple conjunctival lesions measuring together >1.5 cm that cannot be treated by radiation because of previous radiation therapy, contraindications to radiation and patient refusal to receive radiation therapy. At least one of these lesions needs to be histologically confirmed as MZL.
• Participants with splenic MZL who do not meet the radiographically measurable disease criteria described herein are eligible for participation provided that bone marrow (BM) infiltration of MZL is histologically confirmed.
• Participants will be asked to provide a lymph node or tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy but this is not an exclusion criteria.
• a. Participants with splenic MZL who do not have a tumor to biopsy or an archival tumor tissue sample are eligible for participation provided participant is willing to undergo a BM biopsy or provide an archival BM biopsy that was obtained before the date of the first dose of study treatment; BM sample must show histologically confirmed infiltration of MZL
• Participant should have at least one of the following criteria for treatment initiation:
• Threatened extranodal organ function, especially for extranodal MZL
• Involvement of ≥3 nodal sites, each with diameter of ≥3 cm
• Any nodal or extranodal tumor mass with a diameter of ≥5 cm
• B symptoms (fever ≥38 degrees Celsius of unclear etiology, night sweats, weight loss >10% within the prior 6 months) or other symptoms attributed to disease or specific organ involvement.
• Risk of local compressive symptoms that may result in organ compromise
• Splenomegaly >13 cm or splenic lesion without splenomegaly and needs treatments (e.g., symptoms, cytopenias [hemoglobin (HgB) <10 g/dL and platelet count ≤ 80 × 10\^9 platelets/L attributable to lymphoma bone marrow infiltration, splenomegaly or autoimmunity], >5,000 lymphoma cells/mm3).
• Threatened organ function, especially for extranodal MZL
• Leukopenia attributed to MZL (leukocytes <1,000 cells/mm3)
• Leukemia (>5,000 lymphoma cells/mm3)
• Requirement for transfusion or growth factor support attributed to lymphoma

You may not qualify if…

• Evidence of DLBCL transformation. Participants with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase (LDH), rapidly worsening disease, or frequent B-symptoms, must be ruled out for a transformation to a more aggressive disease, such as DLBCL.
• History of central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease. Participants with dural MZL are eligible.
• Concurrent or previous anticancer therapy (eg, chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, or tumor embolization).
• Treatment with systemic immunosuppressive medications, including, but not limited to, prednisone (>20 mg), azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents within 2 weeks prior to Day 1 of Cycle 1.
• Steroids that are used for treatment of allergy or other underlying condition are permissible, but not steroids started to treat lymphoma. Participants receiving corticosteroids must be at a dose level ≤20 mg/day within 7 days of the trial intervention administration.
• The use of inhaled corticosteroids is permitted
• The use of mineralocorticoids for management of orthostatic hypotension is permitted
• Single dose of dexamethasone for nausea or B symptoms is permitted
• Antibiotic treatment of H. pylori-positive gastric EMZL
• Allogeneic stem cell transplant or autologous stem cell transplant or chimeric antigen receptor (CAR) T-cell therapy for any indication
• Active graft versus host disease.
• Inadequate recovery from toxicity and/or complications from a major surgery before starting therapy.
• Current or previous other malignancy within 3 years of trial entry, except cured basal or squamous cell skin cancer, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy.
• Significant concurrent, uncontrolled medical condition, including, but not limited to, renal, hepatic, hematological, gastrointestinal (GI), endocrine, pulmonary, neurological, cerebral, or psychiatric disease.
• Chronic or current active infectious disease (including severe acute respiratory syndrome coronavirus (CoV) 2 (SARS-CoV-2)) requiring systemic antibiotics, antifungal, or antiviral treatment or any major episode of infection requiring treatment with IV antibiotics within 4 weeks of Day 1 of Cycle 1.
• Exposure to a live vaccine within 30 days of administration or anticipation that a live attenuated vaccine will be required during the study.
• Inactivated influenza vaccinations may be given during the influenza season.
• An approved coronavirus disease 2019 (COVID-19) vaccine (messenger ribonucleic acid (mRNA), inactivated virus, and replication deficient viral vector vaccines) is allowed.
• Known human immunodeficiency virus (HIV) infection or positivity on immunoassay. Note: HIV screening test is optional
• History of solid organ transplantation
• History of severe allergic or anaphylactic reaction to humanized, chimeric or murine monoclonal antibodies (Mabs)
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary (CHO) cells or any component of the epcoritamab, lenalidomide, or thalidomide formulation, including mannitol.
• Significant cardiovascular disease (eg, New York Heart Association Class III or IV cardiac disease, myocardial infarction within the previous 3 months, unstable arrhythmia, or unstable angina) or significant pulmonary disease (such as obstructive pulmonary disease or history of bronchospasm)
• Known or suspected chronic active Epstein-Barr virus (EBV) infection
• Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)

Where it is running

• University of Miami — Miami, Florida, United States (enrolling)

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.