ASCO GI 2022 | SURPASS-2: investing ADP-A2M4CD8 SPEAR T-cell therapy to treat esophageal and GEJ cancers

David S. Hong, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, outlines the Phase II SURPASS-2 (NCT04752358) trial investigation of ADP-A2M4CD8 in patients with HLA-A2-positive esophageal or gastroesophageal junction (GEJ) cancers expressing the MAGE-A4 protein. A Phase I (NCT04044859) trial was conducted to explore SPEAR (Specific Peptide Enhanced Affinity Receptor) T-cells engineered with a CD8α co-receptor and TCR region that can recognise and bind to the MAGE-A4 HLA-restricted receptors. The CD8α co-receptor enables CD8-positive killer cell capability to the CD4-positive helper cells. The Phase I study results suggested additional engagement of tumor cell kill in epithelial tumors such as oesophageal and gastric cancer with the use of ADP-A2M4CD8. The Adaptimmune clinical-stage biopharmaceutical company have shown clinical efficacy when treating patients with sarcoma with ADP-A2M4CD8 and are now attempting to go beyond the rare tumor types to treat common tumor types expressing MAGE-A4, such as in GEJ cancers. The Phase I trial saw significant responses in a number of patients, with one patient lasting almost 9 months, prompting the development of the Phase II study with a primary endpoint of response. The Phase II SURPASS-2 trial will also be looking at progression-free survival (PFS), adverse events, replication competent lentiviruses and T-cell clonality. This interview took place at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium.