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

NCT06796998 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20240621NCI-2025-06276
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Marginal Zone Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Nodal Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR)

  The proportion of participants achieving a best overall response of complete response (CR) after Cycle 12 of study therapy will be reported. Response will be assessed using modified Cheson criteria, if disease is not fluorodeoxyglucose (FDG)-avid in initial Screening; or by revised Lugano criteria if Screening FDG-positron emission tomography (PET)/ computed tomography (CT) demonstrated FDG avid disease. For Lugano criteria, CR will be defined by a Deauville score of ≤3.

  12 months

Secondary Outcomes (13)

• Complete Response (CR)

  Up to 7 months

• Partial Response (PR)

  Up to 12 months

• Complete Response

  24 months

• Overall Response Rate (ORR)

  Up to 12 months

• Time to Response (TTR)

  Up to 12 months

Study Arms (1)

Epcoritamab Group

EXPERIMENTAL

Participants will receive up to 12 cycles of Epcoritamab therapy, each cycle lasting 28 days. Total participation is up to 3 years.

Biological: Epcoritamab

Interventions

Epcoritamab BIOLOGICAL

Epcoritamab will be administered via subcutaneous (SC) injection using a step-up dosing schedule as follows: * Cycle 1, Day 1: 0.16 mg * Cycle 1, Day 8: 0.8 mg * Cycle 1, Day 15: 3 mg * Cycle 1, Day 22: 48 mg * Cycles 2 to 3, Days 1, 8, 15 and 22: 48 mg * Cycles 4 to 9, Days 1 and 15: 48 mg * Cycles 10 to 12; Day 1: 48 mg

Epcoritamab Group

Eligibility Criteria

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

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.

You may not qualify if:

• 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
• Involvement of 2 or more extranodal sites, with tumor/lesion in each extranodal site ≥1 cm
• Life expectancy \>3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2.

Sponsors & Collaborators

• Izidore Lossos, MD: lead
• Genmab: collaborator
• AbbVie: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell, Marginal Zone

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Izidore Lossos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Izidore Lossos, MD

CONTACT

+1 (305) 2434787; ilossos@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: January 28, 2025
• Study Start: October 13, 2025
• Primary Completion (Estimated): October 15, 2028
• Study Completion (Estimated): April 15, 2031
• Last Updated: October 28, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)