EVEREST-1: A seamless phase 1/2 study of CEA logic-gated Tmod CAR T-cell therapy (A2B530) in patients with solid tumors associated with CEA expression also exhibiting HLA loss of heterozygosity (LOH)
Authors
Salman Punekar (New York University Langone Health), Theodore Welling (New York University Langone Health), J. Randolph Hecht (David Geffen School of Medicine at University of California at Los Angeles), Julian R. Molina (Mayo Clinic), Caleb Smith (Mayo Clinic), Edward Garon (David Geffen School of Medicine at University of California at Los Angeles), M. Pia Morelli (The University of Texas MD Anderson Cancer Center), Marwan Fakih (City of Hope), Kedar Kirtane (Moffitt Cancer Center), Patrick Grierson (Washington University in Saint Louis), Sandip P. Patel (University of California, San Diego), Yi Lin (Mayo Clinic), Scott Kopetz (The University of Texas MD Anderson Cancer Center), Frederick L. Locke (Moffitt Cancer Center), Jeffrey Ward (Washington University in Saint Louis), Ariane Lozac’hmeur (Tempus Labs, Inc.), Matthew Frigault (Massachusetts General Hospital), Sarah Nikiforow (Dana-Farber Cancer Institute), Wen-Kai Weng (Stanford University), Jennifer Specht (Fred Hutchinson Cancer Center), Tomislav Dragovich (Banner MD Anderson Cancer Center), Judy Vong (A2 Biotherapeutics, Inc.), Armen Mardiros (A2 Biotherapeutics, Inc.), Kirstin Liechty (A2 Biotherapeutics, Inc.), William Y. Go (A2 Biotherapeutics, Inc.), John Welch (A2 Biotherapeutics, Inc.), Eric W. Ng (A2 Biotherapeutics, Inc.), Marcela Maus (Massachusetts General Hospital), David Maloney (Fred Hutchinson Cancer Center), Diane M. Simeone (New York University Langone Health)
EVEREST-1 (NCT05736731) is a seamless, phase 1/2, open-label, nonrandomized study to evaluate the safety and efficacy of A2B530, a logic-gated CEA-targeting Tmod CAR T-cell therapy, in adult patients. Specificity for tumor cells is provided by a blocker that recognizes human leukocyte antigen (HLA) A*02, which is absent on tumor cells with HLA-A*02 LOH [6]. LOH for HLA-A*02 is observed in solid tumor malignancies. With this definitive discriminator target, A2B530 can potentially provide a therapeutic window to treat patients with CEA-expressing solid tumors exhibiting HLA LOH.