TCR T-Cell Therapy to be Evaluated in Advanced Esophageal or EGJ Cancers


The SURPASS-2 trial will run parallel to the ongoing SURPASS trial.

The cell therapy ADP-A2M4CD8 (Adaptimmune) will be evaluated in the open-label, single-arm, phase 2 SURPASS-2 trial (NCT04752358) in patients with advanced esophageal or esophagogastric junction (EGJ) HLA-A*02- and MAGE-A4- positive cancers.1

ADP-A2M4CD8 consists of specific peptide enhanced affinity receptor (SPEAR) mixed CD4 and CD8 T-cells that express an engineered T-cell receptor (TCR). The SURPASS-2 trial was presented at the 2022 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers (GI) Symposium, January 20-22, 2022, by David S. Hong, MD, deputy chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center.

“These SPEAR T-cells also express wild-type CD8α co-receptors, designed to provide additional functionality to CD4 T-cells. MAGE-A4 expression has been described in several solid tumors, including esophageal and EGJ cancers,” Hong and colleagues wrote.1

The trial will enroll 45 patients between the ages of 18 and 75 years with at least 2 prior lines of therapy to be treated across North America and Europe. Participants will have measurable disease, Eastern Cooperative Oncology Group performance status of 0 or 1, no active autoimmune or leptomeningeal disease, carcinomatous meningitis, or symptomatic central nervous system metastases.

READ MORE: Improving Outcomes in Solid Tumors With Personalized Cell Therapies

Autologous T-cells will be transduced with a lentiviral vector targeted to MAGE-A4 and CD8α. Participants will be infused with ADP-A2M4CD8 approximately 1 week after lymphodepleting chemotherapy.Doses will range between 1 x 109 to 10 x 109 transduced cells.

The study’s primary endpoint is overall response rate as assessed by an independent assessment committee. It will also evaluate via adverse events (AEs), serious AEs, and AEs of special interest such as replication competent lentivirus, T-cell clonality and insertional oncogenesis. All treated participants will be followed-up for 15 years.

Also evaluating ADP-A2M4CD8 is the ongoing phase 1 SURPASS trial (NCT04044859), data on which were presented at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC), November 10-14, 2021.2

Investigators in the phase 1 study found that ADP-A2M4CD8 SPEAR T-cells manufactured with AKT inhibitors (AKTi) expanded more effectively during manufacturing compared to cells without AKTi, with increased stem cell memory content that may generate a more sustained immune response in patients.

Karen Miller, senior vice president, pipeline research, Adaptimmune, said in a previous statement that “The data we continue to generate in the Phase 1 SURPASS trial shows promising responses for patients across multiple solid tumor indications. We will continue to explore more next-gen enhancements and manufacturing improvements, informed by our ongoing translational research, to deliver the best cell therapies we can for people with cancer.”2

1. Hong DS, Jalal SI, Elimova E, et al. SURPASS-2 trial design: A phase 2, open-label study of ADP-A2M4CD8 SPEAR T cells in advanced esophageal or esophagogastric junction cancers. Presented at: 2022 ASCO GI Symposium. Abstract #TPS363
2. Translational Data at SITC 2021 from Adaptimmune’s Phase 1 SURPASS Trial Indicate Adding AKTi to Manufacturing May Contribute to Sustained Antitumor Activity of Next-gen SPEAR T-cells. News release. Adaptimmune. November 12, 2021.
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