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

Diffuse Large B-Cell Lymphoma, Not Otherwise Specified Clinical Trial

Official title: 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

Clinical Trial 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.

Clinical Trial 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 < complete response (CR) or Deauville score of 3 or worse at day 90 (D90) (or before) 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. Treatment repeats 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 for 6 cycles and lenalidomide orally (PO) on days 1-21 for 8 cycles in patients who achieve CR or up to 17 cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/ computed tomography (CT) and blood sample collection throughout the study.

After completion of study treatment, patients are followed up for 2 years. ;

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
• High Grade B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

• NCT number: NCT06015880
• Study type: Interventional
• Source: National Cancer Institute (NCI)
• Status: Recruiting
• Phase: Phase 1
• Start date: May 20, 2024
• Completion date: June 29, 2026