Spearhead 1 Study in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

A Phase 2 Single Arm Open-Label Clinical Trial of ADP-A2M4 SPEAR™ T Cells in Subjects With Advanced Synovial Sarcoma or Myxoid/Round Cell Liposarcoma

This is a study to investigate the efficacy and safety of ADP-A2M4 in HLA-A*02 eligible and MAGE-A4 positive subjects with metastatic or inoperable (advanced) Synovial Sarcoma (Cohort 1, 2 and 3 ) or MRCLS (Cohort 1) .

Single infusion of autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) Dose: 1.0 x109 to 10x109 transduced by a single intravenous infusion

Number of subjects with treatment -related adverse events (AEs), including serious adverse events (SAEs) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Determine if treatment with ADP-A2M4 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs

Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells

Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs).

Measurement of T-cell clonality and insertional oncogenesis in peripheral blood mononuclear cells (PBMCs )

For patients who are observed to respond to ADP-A2M4, the time taken from date of infusion to achieve a partial response or complete response (TTR) is assessed.

For patients who are observed to respond to ADP-A2M4, the DoR is the date of initial response (including confirmation) from date of infusion up until disease progression per RECIST v 1.1 or death.

PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death.

Key Inclusion Criteria Age ≥16 (10 years at selected sites) and <=75 years Diagnosis of advanced synovial sarcoma (Cohort 1, Cohort 2 and Cohort 3) or myxoid liposarcoma / myxoid round cell liposarcoma (Cohort 1 only) confirmed by cytogenetics. Previously received either an anthracycline or ifosfamide containing regimen. Measurable disease according to RECIST v1.1 prior to lymphodepletion HLA-A*02:01, HLA-A*02:02, HLA-A*02:03 or HLA-A*02:06 positive Tumor shows MAGE-A4 expression confirmed by central laboratory. North America Only (United States and Canada): Tumor (either an archival specimen or a fresh biopsy) shows MAGE-A4 expression of ≥1+ staining in ≥10% of the cells by immunohistochemistry. ECOG Performance Status of 0 or1. For subjects aged ≥10 to ≥16 years old: Lansky Score ≥60%. • Left ventricular ejection fraction (LVEF) ≥50%. Note: other protocol defined Inclusion criteria may apply Key Exclusion Criteria: HLA-A*02:05 in either allele Received or plans to receive the following therapy/treatment prior to leukapheresis or lymphodepleting chemotherapy: Cytotoxic chemotherapy, Tyrosine kinase inhibitor (TKI) (e.g. pazopanib), Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors,), Anti-cancer Vaccine, Gene therapy using an integrating vector (subjects who have received a gene therapy using a lentiviral vector may be eligible for the study), Corticosteroids or any other immunosuppressive therapy, Investigational treatment or interventional clinical trial, Allogeneic hematopoietic stem cell transplant, Radiotherapy to the target lesions, Major surgery History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study. History of autoimmune or immune mediated disease Symptomatic CNS metastases including leptomeningeal disease. Other prior malignancy that is not considered by the Investigator to be in complete remission Clinically significant cardiovascular disease Uncontrolled intercurrent illness Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C virus, or human T cell leukemia virus Pregnant or breastfeeding Note: other protocol defined Exclusion criteria may apply.

Sanderson JP, Crowley DJ, Wiedermann GE, Quinn LL, Crossland KL, Tunbridge HM, Cornforth TV, Barnes CS, Ahmed T, Howe K, Saini M, Abbott RJ, Anderson VE, Tavano B, Maroto M, Gerry AB. Preclinical evaluation of an affinity-enhanced MAGE-A4-specific T-cell receptor for adoptive T-cell therapy. Oncoimmunology. 2019 Nov 24;9(1):1682381. doi: 10.1080/2162402X.2019.1682381. eCollection 2020.