(P 127) IDENTIFYING MAGE-A4-POSITIVE TUMORS FOR SPEAR T-CELL THERAPIES IN HLA-A*02-ELIGIBLE PATIENTS

Objective: Autologous T-cells engineered with T-cell receptors (TCRs) targeting tumor antigens are promising therapies for metastatic solid cancers.1 Specific peptide enhanced affinity receptor (SPEAR) T-cell therapies are T-cells with engineered HLA-restricted TCRs that precisely target tumor cells with specific antigens, such as MAGE-A4 (a cancer testis antigen), presented on the surface by HLA molecules. In SPEAR T-cell clinical trials targeting MAGE-A4, a 2-step prescreen is done before enrollment. 1) Patients undergo HLA typing via a high-resolution (allelic, 4-digit) sequence-based assay, and those who are positive for the inclusion alleles (HLA-A*02:01P, 02:02P, 02:03P, 02:06P) and not positive for the exclusion allele A*02:05P are eligible. 2) Tumor MAGE-A4 testing is done via an immunohistochemical clinical trial assay (MAGE-A4+ cutoff: ≥30% tumor cell staining at ≥2+ intensity) in HLA-eligible patients.

Methods: A screening protocol (NCT02636855) has been used in Phase 1 trials of first-and next-generation SPEAR T-cells targeting MAGE-A4 (NCT03132922, NCT04044859) with responses in multiple MAGE-A4+ tumors.

Results: As of November 19, 2021, 6,168 patients with 9 solid tumor types were screened at 32 sites across North America and Europe in this screening protocol; among which, 2,744 were HLA-eligible (eligibility rate: 45%, range per tumor type: 42%–55%). HLA-A*02:01 was the most frequent HLA-A*02 allele. Of these HLA-eligible patients, 1,549 had tumor tissues evaluable for MAGE-A4 expression; among which, 313 were MAGE-A4+ (MAGE-A4+ rate: 20%, range: 8%–54%) (Table). MAGE-A4 showed highest prevalence in synovial sarcoma and myxoid/round cell liposarcoma but was seen across all tumor types investigated. Our results will be discussed in the context of tumor histopathology, disease status, and demography.

Conclusion: HLA and MAGE-A4 biomarker data will inform the therapeutic opportunities for SPEAR T-cells targeting MAGE-A4 in metastatic solid cancers. 1. D’Angelo et al. Cancer Discov. 2018;8:944. Previously presented at American Association for Cancer Research (AACR; April 8–13, 2022) and published in Proceedings of the AACR. Reused with permission.

Table_Wang HLA and MAGE-A4 Screening Encore (AACR 2022) CTOS 2022.docx