SPEARHEAD-1: A phase II trial of ADP-A2M4 SPEAR T cells in patients with advanced synovial sarcoma or myxoid/round cell liposarcoma.

TPS11569 Background: ADP-A2M4 specific peptide enhanced affinity receptor (SPEAR) T-cells are genetically engineered to target MAGE-A4 + tumors in the context of HLA-A*02. MAGE-A4 has been described as having high expression in synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCLS) [1, 2]. This Phase 2 trial was initiated based on the favorable benefit:risk profile of ADP-A2M4 observed in a Phase 1 trial (NCT03132922) of ADP-A2M4 which demonstrated compelling clinical responses in patients with SS. Methods: This Phase 2, open-label trial (SPEARHEAD-1; NCT04044768) is designed to evaluate the efficacy, safety and tolerability of ADP-A2M4 in patients with advanced/metastatic SS or MRCLS who are HLA-A*02 positive and whose tumors express the MAGE-A4 protein. Enrolled patients are to undergo apheresis, and their isolated T-cells are then transduced with the MAGE-A4 c1032 TCR, and expanded. Prior to ADP-A2M4 infusion, patients are to receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m 2 /day x 4 days) and cyclophosphamide (600 mg/m 2 /day x 3 days). Patients are to receive 1 – 10 × 10 9 transduced T-cells. An independent Data Safety Monitoring Board will review ongoing safety and benefit:risk during the interventional phase of the study. Disease will be assessed by independent review per RECIST v1.1 by CT/MRI at weeks 4, 8, 12, 16, 24, and every 2 months thereafter until confirmed disease progression. As of 24 Jan 2020, there were 17 clinical sites open in the US, one in Canada, and two in Spain. References: 1. Iura K, et al. Cancer-testis antigen expression in synovial sarcoma: NY-ESO-1, PRAME, MAGEA4, and MAGEA1. Human Pathology 2017; 61:130-139. 2. Iura K, et al. MAGEA4 expression in bone and soft tissue tumors: its utility as a target for immunotherapy and diagnostic marker combined with NY-ESO-1. Virchows Archiv 2017;471:383–392. Clinical trial information: NCT04044768 .