SURPASS-2 trial design: A phase 2, open-label study of ADP-A2M4CD8 SPEAR T cells in advanced esophageal or esophagogastric junction cancers.

Abstract

TPS363 Background: ADP-A2M4CD8 is an autologous specific peptide enhanced affinity receptor (SPEAR) mixed CD4 and CD8 T-cell product that expresses an engineered T-cell receptor (TCR) designed to target the MAGE-A4 antigen in HLA-A*02-positive patients. 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 esophagogastric junction (EGJ) cancers[1]. In an ongoing phase 1 study (NCT04044859) of ADP-A2M4CD8 in patients with different tumor types, most adverse events have been consistent with those typically experienced by patients undergoing chemotherapy and/or adoptive T-cell therapies, and as of 2 August 2021, among evaluable patients with esophageal and EGJ cancers, best overall responses were 1 partial response (EGJ), 4 stable disease (2 EGJ, 2 esophageal), and 1 progressive disease (EGJ)[2]. Methods: SURPASS-2 (NCT04752358) is a phase 2, open-label, single-arm trial to assess safety and efficacy of ADP-A2M4CD8 SPEAR T-cells in HLA-A*02–positive patients with advanced esophageal or EGJ cancers that express MAGE-A4 antigen. A total of 45 patients between the ages of 18 and 75 years old will be treated across sites in North America and Europe. Key eligibility criteria include measurable disease per RECIST v1.1; ECOG performance status of 0 or 1; no active autoimmune or immune-mediated disease; no leptomeningeal disease, carcinomatous meningitis, or symptomatic CNS metastases; and ≤2 prior lines of combination or single agent systemic treatment for advanced or metastatic disease before treatment with ADP-A2M4CD8 as the next therapy. Leukapheresis can be performed before initiating or at the end of second-line treatment. Collected T-cells will be transduced with a self-inactivating lentiviral vector expressing the high affinity MAGE-A4-specific TCR and the CD8α co-receptor. Lymphodepleting chemotherapy, consisting of intravenous (IV) cyclophosphamide 600 mg/m2/day for 3 days and IV fludarabine 30 mg/m2/day for 4 days, will be given approximately 1 week prior to treatment with ADP-A2M4CD8. ADP-A2M4CD8 dose will range between 1 x 109 to 10 x 109 transduced cells administered by a single IV infusion. The primary endpoint is overall response rate per RECIST v1.1 by an independent radiological assessment committee. Safety evaluations will include adverse events (AEs); serious AEs; incidence, severity, and duration of the AEs of special interest; replication competent lentivirus; and T-cell clonality and insertional oncogenesis. All patients receiving ADP-A2M4CD8 cellular therapy will be followed for 15 years from time of last T-cell infusion for observation of delayed AEs. To date, one site is activated. [1] Ishihara et al. BMC Cancer 20, 606 (2020). [2] Hong et al. E-poster 540P: ESMO (2021). Clinical trial information: NCT04752358.