Faculty Collaboration Database

Atezolizumab Treatment of Tumors with High Tumor Mutational Burden from MyPathway, a Multicenter, Open-Label, Phase IIa Multiple Basket Study. Cancer Discov 2022 Mar 01;12(3):654-669

Date

12/09/2021

Pubmed ID

34876409

Pubmed Central ID

PMC9394388

DOI

10.1158/2159-8290.CD-21-0450

Scopus ID

2-s2.0-85125964453 (requires institutional sign-in at Scopus site)   36 Citations

Abstract

UNLABELLED: High tumor mutational burden (TMB-H) correlates with improved immunotherapy response. We assessed atezolizumab 1,200 mg every 3 weeks for TMB-H tumors from MyPathway (NCT02091141), a phase IIa multibasket study. One hundred twenty-one patients had advanced solid tumors with TMB ≥10 mut/Mb by any Clinical Laboratory Improvement Amendments (CLIA)-certified assay. The preplanned primary endpoint was objective response rate (ORR) in patients with TMB ≥16 mut/Mb tumors by FoundationOne TMB testing [F1(CDx)]. Patients with F1(CDx) TMB ≥10 and <16 mut/Mb were also evaluated. Ninety patients with 19 tumor types and F1(CDx) TMB ≥10 mut/Mb were efficacy evaluable. In 42 patients with F1(CDx) TMB ≥16 mut/Mb, confirmed ORR was 38.1% [16/42; 95% confidence interval (CI), 23.6-54.4], and disease control rate was 61.9% (26/42; 95% CI, 45.6-76.4) versus 2.1% (1/48; 95% CI, 0.1-11.1) and 22.9% (11/48; 95% CI, 12.0-37.3) for 48 patients with TMB ≥10 and <16 mut/Mb. Responses were observed in nine different tumor types (47%; 9/19).

SIGNIFICANCE: Atezolizumab monotherapy had promising, durable clinical activity across a variety of advanced solid tumor types in patients with TMB ≥16 mut/Mb tumors lacking other suitable treatment options and who were immunotherapy-naïve at enrollment, regardless of microsatellite instability status. Limited activity was observed in tumors with TMB ≥10 and <16 mut/Mb. See related commentary by Maron and Klempner, p. 602. This article is highlighted in the In This Issue feature, p. 587.

Author List

Friedman CF, Hainsworth JD, Kurzrock R, Spigel DR, Burris HA, Sweeney CJ, Meric-Bernstam F, Wang Y, Levy J, Grindheim J, Shames DS, Schulze K, Patel A, Swanton C

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal, Humanized
Biomarkers, Tumor
Humans
Microsatellite Instability
Mutation
Neoplasms