NCT06015880

Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma

A Phase 1 Study of Mosunetuzumab With Polatuzumab Vedotin and Lenalidomide (M+Pola+Len) in Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

PRIMARY OBJECTIVE: I. To determine the safety and tolerability of mosunetuzumab + polatuzumab vedotin + lenalidomide in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). SECONDARY OBJECTIVE: I. To observe and record anti-tumor activity of the combination of mosunetuzumab, polatuzumab vedotin, and lenalidomide in R/R DLBCL. EXPLORATORY OBJECTIVES: I. To assess the efficacy in patients that have failed prior polatuzumab vedotin containing regimens (i.e., patients who progressed/relapsed after prior polatuzumab). II. To assess anti-tumor activity in patients that a) have ≥ Deauville score of 3 within the first 90 days after standard of care chimeric antigen receptor (CAR) T-cell therapy; b) other patients who have failed prior treatment (e.g. relapse after Day 90 from CAR-T, or relapsed after other therapies and were not considered candidates for CAR-T). III. To identify biomarkers that can predict the response to mosunetuzumab + polatuzumab vedotin + lenalidomide. IV. To describe anti-tumor activity in patients whose tumors have previously failed to respond to polatuzumab (i.e., patients who progressed/relapsed after prior polatuzumab). OUTLINE: This is a dose-escalation study of mosunetuzumab, followed by a dose-expansion study. Patients receive mosunetuzumab intravenously (IV) over 2-4 hours on days 1, 8, and 15 of cycle 1 and then day 1 of each subsequent cycle. Cycles repeat every 28 days for 8 cycles in patients who achieve a complete response (CR) or up to 17 cycles for patients with a partial response (PR) or stable disease (SD) in the absence of disease progression or unacceptable toxicity. Patients also receive polatuzumab vedotin IV over 30-90 minutes on day 1 of each cycle and lenalidomide orally (PO) on days 1-21 of each cycle. Cycles of polatuzumab vedotin repeat every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Cycles of lenalidomide repeat every 28 days for 8 cycles in patients who achieve CR, or up to 17 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/ computed tomography (CT) and blood sample collection throughout the study. After completion of study treatment, patients are followed up every 3-6 months for 2 years.

Conditions

• Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• High Grade B-Cell Lymphoma
• Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Computed Tomography	Undergo PET/CT
DRUG	Lenalidomide	Given PO
BIOLOGICAL	Mosunetuzumab	Given IV
DRUG	Polatuzumab Vedotin	Given IV
PROCEDURE	Positron Emission Tomography	Undergo PET/CT

Timeline

• Start date: 2024-05-20
• Primary completion: 2027-06-30
• Completion: 2027-06-30
• First posted: 2023-08-29
• Last updated: 2026-04-16

Locations

7 sites across 1 country: United States

Regulatory

• FDA-regulated drug study