This phase I trial studies the side effects and best dose of mosunetuzumab when given together with polatuzumab vedotin and lenalidomide in treating patients with diffuse large B-cell lymphoma (DLBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Mosunetuzumab and polatuzumab vedotin are monoclonal antibodies that may interfere with the ability of cancer cells to grow and spread. Polatuzumab, linked to a toxic agent called vedotin, attaches to CD79B positive cancer cells in a targeted way and delivers vedotin to kill them. Lenalidomide may stimulate or suppress the immune system in different ways and stop cancer cells from growing and by preventing the growth of new blood vessels that cancer cells need to grow. Giving mosunetuzumab with polatuzumab vedotin and lenalidomide may work better in treating patients with relapsed/refractory DLBCL.
Patients must have histologically confirmed DLBCL NOS, high-grade B-cell lymphoma, or transformed indolent lymphoma as per the World Health Organization 2022 criteria
All patients will have relapsed/refractory DLBCL after 1 or more prior lines of therapy with the exception of patients receiving CAR T in second line that have a D score of 3 at day (D)+ 30 through D+ 90
Patients who progressed/relapsed after prior polatuzumab vedotin are allowed
For the expansion cohorts only: cohort A must have Deauville score of ≥ 3 with the first 90 days) after standard of care chimeric antigen receptor (CAR) T-cell therapy; cohort B- other patients with relapsed/refractory after 1 or more prior lines of therapy (e.g. relapse after Day 90 from CAR-T, or relapsed after other therapies and were not considered candidates for CAR-T)
Plasmablastic lymphoma, primary mediastinal B-cell lymphoma, gray zone lymphoma
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
Patients who are receiving any other investigational agents or treatments
Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
Single group
Biospecimen Collection
Procedure/SurgeryUndergo blood sample collection
Computed Tomography
Procedure/SurgeryUndergo PET/CT
Lenalidomide
DrugGiven PO
Mosunetuzumab
Biological/VaccineGiven IV
Polatuzumab Vedotin
DrugGiven IV
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT
Safety and tolerability of monsunetuzumab+polatuzumab vedotin+lenalidomide for determination of recommended phase 2 dose
Dose limiting toxicity will be assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Objective response rate
Will be assessed per the Lugano 2014 criteria.
Complete response rate
Will be assessed per the Lugano 2014 criteria.
Progression free survival
Will be assessed per the Lugano 2014 criteria.
Duration of response
Will be assessed per the Lugano 2014 criteria.
CD79b expression levels
Will be assessed via ribonucleic acid and immunohistochemistry assessment and correlation with response.
Frequency of CD4 T-cells and IFN-gamma+ producing CD4 T-cells
Will be assessed via intracellular flow cytometry.
Ultrasensitive determination of cytokine profile
Will be assessed with Luminex assay to identify biomarkers that might predict a response.
Efficacy in relapsed/refractory double-expresser lymphoma and double-hit lymphoma
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