Identifying Mage-A4-Positive Tumors for TCR T Cell Therapies in Hla-A∗02-Eligible Patients

Authors

Tianjiao Wang
Jean-Marc Navenot
Stavros Rafail
Cynthia Kurtis
Mark Carroll
Marian Van Kerckhoven
Sofie Van Rossom
Kelly Schats
Konstantinos Avraam
Robyn Broad
Karen Howe
Ashley Liddle
Amber Clayton
Ruoxi Wang
Laura Quinn
Joseph P Sanderson
Cheryl McAlpine
Carly Carozza
Eric Pimpinella
Susan Hsu
Francine Brophy
Erica Elefant
Paige Bayer
Dennis Williams
Marcus O Butler
Jeffrey M Clarke
Justin F Gainor
Ramaswamy Govindan
Victor Moreno
Melissa Johnson
Janet Tu
David S Hong
George R Blumenschein

Publication Date

6-13-2024

Journal

Molecular Therapy: Methods & Clinical Development

Abstract

T cell receptor (TCR) T cell therapies target tumor antigens in a human leukocyte antigen (HLA)-restricted manner. Biomarker-defined therapies require validation of assays suitable for determination of patient eligibility. For clinical trials evaluating TCR T cell therapies targeting melanoma-associated antigen A4 (MAGE-A4), screening in studies NCT02636855 and NCT04044768 assesses patient eligibility based on: (1) high-resolution HLA typing and (2) tumor MAGE-A4 testing via an immunohistochemical assay in HLA-eligible patients. The HLA/MAGE-A4 assays validation, biomarker data, and their relationship to covariates (demographics, cancer type, histopathology, tissue location) are reported here. HLA-A∗02 eligibility was 44.8% (2,959/6,606) in patients from 43 sites across North America and Europe. While HLA-A∗02:01 was the most frequent HLA-A∗02 allele, others (A∗02:02, A∗02:03, A∗02:06) considerably increased HLA eligibility in Hispanic, Black, and Asian populations. Overall, MAGE-A4 prevalence based on clinical trial enrollment was 26% (447/1,750) across 10 solid tumor types, and was highest in synovial sarcoma (70%) and lowest in gastric cancer (9%). The covariates were generally not associated with MAGE-A4 expression, except for patient age in ovarian cancer and histology in non-small cell lung cancer. This report shows the eligibility rate from biomarker screening for TCR T cell therapies and provides epidemiological data for future clinical development of MAGE-A4-targeted therapies.

Keywords

HLA, immunotherapy, MAGE-A4, T cell receptor, T cell therapy, biomarker, assay validation, precision medicine, patient screening, clinical trial

Comments

Supplementary Material

PMID: 38872830

DOI

10.1016/j.omtm.2024.101265

PMID

38872830

PMCID

PMC11170170

PubMedCentral® Posted Date

May 2024

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes