Mosunetuzumab in Patients With Newly Diagnosed Extranodal Marginal Zone Lymphoma

NCT06569680 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 20240178
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test a new medication called Mosunetuzumab to see if it can help people with Extranodal Marginal Zone Lymphoma (EMZL). This study will include people who have not yet received any treatment for cancer and whose cancer is in stage I-IV. This study will help doctors understand if Mosunetuzumab improves outcomes in people with EMZL and if it is safe to use.

Conditions

Extranodal Marginal Zone Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete Response (CR) Rate

  The number of participants with best overall response of complete response (CR) to protocol therapy will be reported. Response will be assessed using Cheson 2014 criteria if disease is not FDG-avid in initial screening, and by revised Lugano 2014 criteria if screening Fluorodeoxyglucose (FDG) positron emission tomography (PET) computed tomography (CT) (FDG PET/CT) demonstrated FDG-avid disease.

  Up to 12 months

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  Up to 12 months

• Partial Response (PR) Rate

  Up to 12 months

• Number of Participants Experiencing treatment-related adverse events

  Up to 13 months

• Number of Participants Experiencing Cytokine Release Syndrome Adverse Events

  Up to 13 months

• Progression-Free Survival (PFS)

  Up to 2 years

Study Arms (1)

Mosunetuzumab Treatment Group

EXPERIMENTAL

Participants in this group will receive Mosunetuzumab for eight (8) 21-day cycles. Total participation is about 3.5 years.

Drug: Mosunetuzumab

Interventions

Mosunetuzumab DRUG

Mosunetuzumab will be administered via subcutaneous (SC) injection using a step-up dosing model. Participants will receive Mosunetuzumab on days 1, 8, and 15 of Cycle 1, and on day 1 of Cycles 2 through 8 as follows: * Cycle 1 Day 1: 5mg * Cycle 1 Day 8: 45mg * Cycle 1 Day 15: 45mg * Cycles 2 through 8, Day 1: 45mg

Also known as: ML44933, Lunsumio, Mosunetuzumab-axgb

Mosunetuzumab Treatment 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 EMZL 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 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 multiple skin lesions measuring \>1 cm in diameter on the body and at least one of them is histologically confirmed as EMZL.
• 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. At least one of the lesions needs be histologically confirmed as EMZL.
• Participants must be willing to provide tissue biopsy from the most recent available archival tissue or undergo an incisional or excisional lymph node or tissue biopsy. If biopsy can be reviewed to confirm the diagnosis but there is no extra tissue for exploratory studies, such participants can still be enrolled in this trial.
• Participant should have at least one of the following criteria for treatment initiation:
• Threatened extranodal organ function
• Involvement of ≥3 nodal sites, each with diameter of ≥3 cm

You may not qualify if:

• Evidence of diffuse large B cell lymphoma (DLBCL) transformation. Participants with presumptive evidence of transformation based on clinical assessment of factors such as, but not limited to, increasing lactate dehydrogenase, 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.
• Patients that need immediate cytoreduction.
• 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 permittable, 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 is permitted
• Allogeneic stem cell transplant, or autologous stem cell transplant or Chimeric antigen receptor 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.

Sponsors & Collaborators

• Izidore Lossos, MD: lead
• Genentech, Inc.: collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

Study Officials

• Izidore Lossos, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Izidore Lossos, MD

CONTACT

305-243-4785; 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

Study Record Dates

• First Submitted: August 22, 2024
• First Posted: August 26, 2024
• Study Start: November 19, 2024
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: November 3, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)