ADP-A2M4CD8 in HLA-A2+ Subjects With MAGE-A4 Positive Esophageal or Esophagogastric Junction Cancers (SURPASS-2)

Study Overview
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Brief Summary
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This study will investigate the efficacy of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and tumor antigen status and whose esophageal or esophagogastric junction (EGJ) cancer expresses the MAGE-A4 protein.

Official Title
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A Phase 2 Open-Label Clinical Trial of ADP-A2M4CD8 in Subjects With Advanced Esophageal or Esophagogastric Junction Cancers

Conditions
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Esophageal Cancer, Esophagogastric Junction Cancer

Intervention / Treatment
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* Genetic: Autologous genetically modified ADP-A2M4CD8 cells


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Age ≥18 and <75 years Diagnosis of Esophageal cancer or Esophagogastric junction cancer. Previously received treatment for advanced or metastatic disease. Measurable disease according to RECIST v1.1. HLA-A*02 positive Tumor shows MAGE-A4 expression confirmed by central laboratory. ECOG Performance Status of 0 or1. Left ventricular ejection fraction (LVEF) ≥50%. Note: other protocol defined Inclusion criteria may apply Key exclusion criteria Positive for any HLA-A*02 allele other than: one of the inclusion alleles History of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study Active autoimmune or immune mediated disease Leptomeningeal disease, carcinomatous meningitis or symptomatic CNS metastases 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 Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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 ADP-A2M4CD8 cells<br> | Genetic: Autologous genetically modified ADP-A2M4CD8 cells<br>* Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1<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-A2M4CD8 is safe and tolerable through assessment of adverse events (AEs) including Serious Adverse Events (SAEs) | 2.5 years | 
| Efficacy: Best overall response (BOR) | Best Overall Response (BOR) is per RECIST V1.1. | 2.5 Years | 
| Time to response (TTR) | For patients who are observed to respond to ADP-A2M4CD8, 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-A2M4CD8, 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-A2M4CD8 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-A2M4CD8 up until the date of patient death. | 15 years | 
| Invitro diagnostic (IVD) assay for screening | Development and validation of the MAGE-A4 antigen expression companion diagnostic assay | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cell Therapy, T Cell Therapy, SPEAR T Cell, MAGE-A4, Immuno-oncology, Metastatic, Esophagogastric Junction, Esophageal Cancer