Testing Mosunetuzumab Alone, With Zanubrutinib, or With Polatuzumab Vedotin for Treating Marginal Zone Lymphoma That Came Back or Didn't Get Better With Treatment
MOZART MZL: A Randomized Phase II Study Evaluating Mosunetuzumab Alone and in Combination With Either Zanubrutinib or Polatuzumab Vedotin for the Treatment of Patients With Relapsed/Refractory Marginal Zone Lymphoma
3 other identifiers
interventional
138
0 countries
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Brief Summary
This phase II trial compares the effect of mosunetuzumab alone to mosunetuzumab with zanubrutinib or polatuzumab vedotin in patients with marginal zone lymphoma that has come back after a period of improvement (relapsed) or that does not respond to treatment (refractory). Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Zanubrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as marginal zone lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. Polatuzumab vedotin is a monoclonal antibody, called polatuzumab, linked to a drug, called monomethyl auristatin E. Polatuzumab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD79B receptors, and delivers monomethyl auristatin E to kill them. Giving mosunetuzumab alone or with zanubrutinib or polatuzumab vedotin may work well for treating relapsed or refractory marginal zone lymphoma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2026
Typical duration for phase_2
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 5, 2026
CompletedFirst Posted
Study publicly available on registry
June 10, 2026
CompletedStudy Start
First participant enrolled
October 3, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
July 31, 2028
Study Completion
Last participant's last visit for all outcomes
July 31, 2029
June 10, 2026
June 1, 2026
1.8 years
June 5, 2026
June 5, 2026
Conditions
Outcome Measures
Primary Outcomes (2)
Complete response rate (arm 1 versus arm 2)
Defined by the Lugano Classification.
Up to 5 years
Complete response rate (arm 1 versus arm 3)
Defined by the Lugano Classification.
Up to 5 years
Secondary Outcomes (5)
Progression free survival
From date of randomization to date of first observation of progressive disease, transformation to diffuse large B cell lymphoma, or death due to any cause, up to 5 years
Overall survival
From date of randomization to date of death due to any cause, up to 5 years
Overall response rate
Up to 5 years
Duration of response
From date of first documentation of response to treatment to date of first documentation of progression, transformation to diffuse large B cell lymphoma, or death due to any cause among participants who achieve a response, up to 5 years
Incidence of adverse events
Up to 5 years
Other Outcomes (1)
Incidence of symptomatic adverse events
Up to 5 years
Study Arms (3)
Arm 1 (mosunetuzumab)
EXPERIMENTALPatients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients who achieve CR or PD discontinue treatment. Patients with PR or SD continue treatment for an additional 9 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT, CT, clinically indicated bone marrow biopsy, and blood sample collection throughout the study.
Arm 2 (mosunetuzumab and zanubrutinib)
EXPERIMENTALPatients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients also receive zanubrutinib PO QD or BID on days 1-21 of each cycle. Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients who achieve CR or PD discontinue treatment. Patients with PR or SD continue treatment for an additional 9 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT, CT, clinically indicated bone marrow biopsy, and blood sample collection throughout the study.
Arm 3 (mosunetuzumab and polatuzumab vedotin)
EXPERIMENTALPatients receive mosunetuzumab SC on days 1, 8 and 15 of cycle 1 and day 1 of subsequent cycles. Patients also receive polatuzumab vedotin IV, over 30-90 minutes, on day 1 of each cycle (cycles 1-6 only). Cycles repeat every 21 days for 8 cycles in the absence of disease progression or unacceptable toxicity. After 8 cycles, patients who achieve CR or PD discontinue treatment. Patients with PR or SD continue treatment with mosunetuzumab alone for an additional 9 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET/CT, CT, clinically indicated bone marrow biopsy, and blood sample collection throughout the study.
Interventions
Undergo bone marrow biopsy
Undergo CT scan
Given SC
Given IV
Ancillary studies
Given PO
Undergo PET scan
Undergo blood sample collection
Eligibility Criteria
You may qualify if:
- Participants must have histologically diagnosed CD20+ marginal zone lymphoma (MZL) as per World Health Organization (WHO) criteria including splenic, nodal, and extranodal subtypes, but excluding gastrointestinal-only marginal zone lymphoma (MZL) with disease assessments that can only be evaluated through endoscopic methods and cutaneous-only MZL.
- NOTE: A repeat biopsy to confirm MZL diagnosis is NOT required at time of relapse unless:
- The participant has received prior CD3/CD20 bispecific antibody, then a repeat biopsy to document continued CD20+ MZL disease is required after the completion of the prior CD3/CD20 bispecific antibody therapy and prior to study registration.
- The participant has splenic MZL in which a bone marrow biopsy pre-registration is required within 42 days prior to registration
- Participants must have measurable disease by PET-CT (preferred), or CT as defined by extranodal lesion ≥ 1cm or nodal lesion ≥ 1.5cm.
- Participants with splenic MZL are included in the study if spleen standardized uptake value (SUV) (or any splenic masses) is \> liver (standardized uptake value) SUV background and/or spleen size is \> 13cm.
- Participants must have staging imaging performed within 42 days prior to registration, as follows. PET-CT baseline scans are preferred. If a baseline PET-CT scan cannot be obtained, CT scans of the neck, chest, abdomen, and pelvis, are acceptable. All disease must be assessed and documented on the Baseline Tumor Assessment Form
- Participants must have one or more of the following criteria for further systemic therapy as per the discretion of the treating physician:
- Symptoms due to progressive or bulky nodal disease.
- Progressive disease that is currently compromising or may compromise normal organ function if left untreated.
- Presence of systemic B symptoms (i.e. fevers, weight loss, night sweats).
- Presence of symptomatic extranodal disease.
- Cytopenias due to bone marrow infiltration or hypersplenism.
- An increase in the tempo of disease progression
- Participants must not have known or clinically suspected transformation to diffuse large B-cell lymphoma or high-grade B-cell lymphoma. Participants with prior transformed disease but now in relapse with MZL only are allowed on study
- +44 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- SWOG Cancer Research Networklead
- National Cancer Institute (NCI)collaborator
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Boyu Hu
SWOG Cancer Research Network
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NETWORK
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 5, 2026
First Posted
June 10, 2026
Study Start (Estimated)
October 3, 2026
Primary Completion (Estimated)
July 31, 2028
Study Completion (Estimated)
July 31, 2029
Last Updated
June 10, 2026
Record last verified: 2026-06