Combination of Atezolizumab and Tazemetostat in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results From a Phase Ib Study.

Abstract

BACKGROUND:

The combination of atezolizumab, a monoclonal antibody that targets programmed death-ligand 1 (PD-L1) and inhibits the interaction between PD-L1 and its receptors, and tazemetostat, an EZH2 inhibitor, may lead to selective epigenetic reprogramming, alter the tumor microenvironment, and provide additive or synergistic response to patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

MATERIALS AND METHODS:

This was an open-label, phase Ib study assessing the safety, tolerability, and preliminary efficacy of atezolizumab plustazemetostat in patients with R/R DLBCL. Atezolizumab (1200 mg) was administered via intravenous (IV) infusion on day 1 of each cycle and tazemetostat (800 mg) was given orally twice daily (BID) on days 1 to 21. Primary endpoints were safety and tolerability, and to identify a recommended phase II dose (RP2D) for atezolizumab. Secondary efficacy endpoints included response rate and duration of response.

RESULTS:

A total of 43 patients were enrolled, receiving a median of 3 prior lines of treatment (range: 1-9). The RP2D for atezolizumab was 1200 mg IV infusion every 3 weeks in combination with tazemetostat 800 mg BID. At the RP2D, adverse events reported in ≥20% patients were anemia(11 patients [26%]), fatigue (10 patients [23%]), and nausea (10 patients [23%]). Overall response rate was 16% (complete response rate: 7%). Median progression-free survival was 2 months (range: 0-24) and median overall survival was 13 months (range: 1-29).

CONCLUSIONS:

The combination of atezolizumab and tazemetostat was determined to be safe and tolerable. However, anti-tumor activity of the combination was modest.

• Authors: Maria Lia Palomba, Guillaume Cartron, Leslie Popplewell, Vincent Ribrag, Jason Westin, Ling-Yuh Huw, Shefali Agarwal, Mahesh Shivhare, Wan-Jen Hong, Aparna Raval, Alice C Chang, Elicia Penuel, Franck Morschhauser
• Journal: Clinical lymphoma, myeloma & leukemia (Clin Lymphoma Myeloma Leuk) Vol. 22 Issue 7 Pg. 504-512 (07 2022) ISSN: 2152-2669 [Electronic] United States
• PMID: 35151584 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Benzamides
• Biphenyl Compounds
• Morpholines
• Pyridones
• atezolizumab
• tazemetostat

Topics

• Antibodies, Monoclonal, Humanized
• B7-H1 Antigen
• Benzamides
• Biphenyl Compounds
• Humans
• Lymphoma, Large B-Cell, Diffuse (drug therapy, pathology)
• Lymphoma, Non-Hodgkin (drug therapy)
• Morpholines
• Pyridones
• Tumor Microenvironment