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

Study Overview
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Brief Summary
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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) .

Official Title
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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

Conditions
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Synovial Sarcoma, Myxoid Liposarcoma

Intervention / Treatment
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* Genetic: afamitresgene autoleucel (previously ADP-A2M4)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 10 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) SPEAR™ T cells<br> | Genetic: afamitresgene autoleucel (previously ADP-A2M4)<br>* Single infusion of autologous genetically modified afamitresgene autoleucel (previously ADP-A2M4) Dose: 1.0 x109 to 10x109 transduced by a single intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Overall Response Rate (ORR) | ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2.5 years | 
| Evaluate safety of ADP-A2M4 through measurement of Replication -competent Retrovirus in genetically engineered T-cells | Evaluation of RCL using PCR -based assay in peripheral blood. | 2.5 years | 
| 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 ) | 2.5 years | 
| Efficacy: Best overall response (BOR) | BOR is per RECIST V1.1. | 2.5 years | 
| Time to response (TTR) | 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. | 2.5 years | 
| Duration of Response (DoR) | 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. | 2.5 years | 
| Progression Free Survival (PFS) | PFS is assessed from date of infusion of ADP-A2M4 up until the date of disease progression per RECIST v1.1 or death. | 2.5 years | 
| Overall Survival (OS) | OS is assessed from date of infusion of ADP-A2M4 up until the date of patient death | 15 years | 
| Quantitation of genetically engineered T-cells in PBMCs | Quantitation of genetically engineered T-cells in PBMCs by qPCR | 2.5 years | 
| Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by flow cytometry | 2.5 years | 
| Quantitation of genetically engineered T-cells in PBMCs | Quantitation of genetically engineered T-cells in PBMCs by flow cytometry | 2.5 years | 
| Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs | Time taken to achieve peak expansion of genetically engineered T-cells in PBMCs by qPCR | 2.5 years | 
| Invitro diagnostic (IVD) assay for screening | Development and validation of the MAGE-A4 antigen expression companion diagnostic assay | 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sarcoma, MRCLS, Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE A-4, Immuno-oncology