2023 Targeted Therapies of Lung Cancer Meeting (Poster)-P1.34. BASECAMP-1: Leveraging Human Leukocyte Antigen A (HLA-A) Loss of Heterozygosity (LOH) in Solid Tumors by Next-Generation Sequencing (NGS) to Identify Patients With Relapsed Solid Tumors for Carcinoembryonic Antigen (CEA) and Mesothelin (MSLN) Logic-Gated

P1.34. BASECAMP-1: Leveraging Human Leukocyte Antigen A (HLA-A) Loss of Heterozygosity (LOH) in Solid Tumors by Next-Generation Sequencing (NGS) to Identify Patients With Relapsed Solid Tumors for Carcinoembryonic Antigen (CEA) and Mesothelin (MSLN) Logic-Gated

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The BASECAMP-1 study aims to identify patients with somatic loss of heterozygosity (LOH) of the HLA-A*02 gene in solid tumors for potential treatment with carcinoembryonic antigen (CEA) and mesothelin (MSLN) logic-gated Tmod chimeric antigen receptor (CAR) T-cell therapy. The study involves screening patients to determine germline HLA-A*02 heterozygosity and then analyzing tumor tissue for somatic LOH of HLA-A*02 using next-generation sequencing (NGS) testing.<br /><br />If HLA-A*02 LOH is detected in the tumor and the participant meets eligibility criteria, they will undergo leukapheresis. Safety evaluations will be conducted 7 days after leukapheresis, and participants will be followed for relapse. Banked T cells will be available for use in the EVEREST-1 A2B530 CEA Tmod and EVEREST-2 A2B694 MSLN Tmod interventional studies.<br /><br />The Tempus clinical workflow informs physicians of matched patients and provides a list of patient matches for the principal investigator and research team. The study has identified 5 patients with HLA LOH out of 37 resulted patients so far.<br /><br />The rationale for the study is to address the challenge of translating CAR T-cell therapy to solid tumors, where there is a need for tumor-specific targets. The Tmod CAR T-cell approach utilizes dual receptors, with an activator that recognizes an antigen present on tumor cells and a blocker that recognizes an HLA allele lost only in tumor cells. The LOH of HLA-A*02 is irreversible and clonal, making it a reliable marker for distinguishing tumor from normal tissue.<br /><br />In in vivo studies, Tmod CAR T cells have shown selectivity in targeting tumor cells while sparing normal cells. The CAR T HLA LOH approach has also been independently validated.<br /><br />The study is being conducted in multiple sites, including New York University Langone Medical Center, Mayo Clinic, Moffitt Cancer Center, University of California Los Angeles, and University of California San Diego.<br /><br />The BASECAMP-1 study aims to identify patients with somatic HLA LOH in solid tumors for potential treatment with CEA and MSLN logic-gated Tmod CAR T-cell therapy. The study utilizes screening, NGS testing, and leukapheresis to identify eligible patients and evaluate safety.

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Caleb Smith, Mayo Clinic, United States

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Speaker Caleb Smith, Mayo Clinic, United States

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Keywords

BASECAMP-1 study

somatic loss of heterozygosity

HLA-A*02 gene

solid tumors

carcinoembryonic antigen

mesothelin

logic-gated Tmod chimeric antigen receptor

CAR T-cell therapy

next-generation sequencing

leukapheresis