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

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.

NCT Number	NCT07638722
Lead Sponsor	SWOG Cancer Research Network Collaborators: National Cancer Institute (NCI)
Conditions	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
Enrollment	138 participants
Start Date	2026-10-03
Primary Completion	2034-04-03 (estimated)
Study Completion	2035-04-03 (estimated)
Updated on ClinicalTrials.gov	2026-07-13