Testing Mosunetuzumab Alone, With Zanubrutinib, or With Polatuzumab Vedotin for Treating Marginal Zone Lymphoma That Came Back or Didn't Get Better With Treatment

Starting soon · Phase 2

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

In brief

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.

Key facts

Study ID: NCT07638722
Run by: SWOG Cancer Research Network
People needed: 138
Starts: 2026-10-03
Expected to finish: 2035-04-03
Last updated by the study team: 2026-07-13

Who can join

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

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
Participants with central nervous system (CNS) involvement are eligible if follow-up CNS evaluation shows no evidence of progression, or if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first eight cycles (6 months) of protocol therapy
Participants must have relapsed/refractory MZL after at least one line of prior CD20-directed systemic therapy (either as monotherapy or in combination with chemotherapy or lenalidomide).
Prior antibiotic and radiation treatments for localized MZL disease are allowed and do not count as one line of systemic therapy
Participants who have been treated with prior Bruton's tyrosine kinase inhibitor (BTKi) or CD3/CD20 targeting bispecific antibodies for their MZL must have completed treatment 180 days prior to registration and must have received a best response of either a partial or complete response
Participants being treated with strong and moderate CYP3A4 inducers must be off these therapies within 14 days or 5 half-lives of the drug prior to registration, whichever is shorter
Participants must have recovered (< grade 2) from any side effects of prior therapy, except for alopecia and lymphopenia
Participants must not have been treated with prior polatuzumab vedotin for any condition
Participants must not have received chimeric antigen receptor T-cells (CAR-T) within 28 days prior to registration
Participants must not have received autologous stem cell transplantation within 100 days prior to registration
Participants must not have received allogeneic stem cell transplantation within 180 days prior to registration nor have active graft versus host disease requiring the current use of systemic steroid treatment ≥ 10mg of prednisone (or equivalent)

Full record on ClinicalTrials.gov

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