ADP-A2M4CD8 as Monotherapy or in Combination With Either Nivolumab or Pembrolizumab in HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)

Study Overview
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Brief Summary
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This study will investigate the safety and tolerability of ADP-A2M4CD8 T-cell therapy in subjects who have the appropriate human leukocyte antigen (HLA) and MAGE-A4 tumor antigen. Tumor indications include endometrial, esophageal, esophagogastric junction (EGJ), gastric, head and neck, melanoma, non-small cell lung (NSCLC), ovarian or urothelial cancer.

Detailed Description
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Conditions: Endometrial Esophageal Cancer Esophagogastric Junction (EGJ) Gastric (stomach) Head and Neck Melanoma Non-small Cell Lung (NSCLC) Ovarian Cancer

Official Title
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A Phase 1 Dose Escalation Study To Assess Safety And Efficacy Of ADP-A2M4CD8 As Monotherapy Or In Combination With Either Nivolumab Or Pembrolizumab In HLA-A2+ Subjects With MAGE-A4 Positive Tumors (SURPASS)

Conditions
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Endometrial Cancer, Esophageal Cancer, Esophagogastric Junction (EGJ), Gastric (Stomach) Cancer, Head and Neck Cancer, Melanoma, Ovarian Cancer, Non-small Cell Lung (NSCLC), Urothelial Cancer

Intervention / Treatment
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* Genetic: Autologous genetically modified ADP-A2M4CD8 cells alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks


Participation Criteria
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Eligibility Criteria
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Key Inclusion criteria Age ≥18 and ≤ 75 years Subject is positive for at least 1 HLA-A*02 inclusion allele Histologically or cytogenetically confirmed diagnosis of urothelial cancer, esophageal, esophagogastric junction (EGJ) cancer, gastric cancer, non-small cell lung carcinoma (NSCLC), head and neck or ovarian cancer, endometrial cancer, melanoma Measurable disease according to RECIST v1.1 prior to leukapheresis and lymphodepletion. Tumor shows MAGE-A4 expression as confirmed by central laboratory ECOG Performance Status of 0 or 1. Left ventricular ejection fraction (LVEF) ≥50% or the institutional lower limit of normal range, whichever is lower Note: other protocol defined Inclusion/Exclusion criteria may apply Subjects must have ≥ 90% room air oxygen saturation at rest at Screening (within 7 days of leukapheresis) and at Baseline. 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 alone or in combination with nivolumab every four weeks or pembrolizumab every 6 weeks<br>* Infusion of autologous genetically modified ADP-A2M4CD8 on Day 1 alone or in combination with either nivolumab 480 mg IV every four weeks or pembrolizumab 400mg IV every 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab | Determination of incidence of dose-limiting toxicities, adverse events and tolerable dose | 2.5 years | 
| To evaluate safety of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab | Incidence of patients with Replication-competent Retrovirus, persistence of ADP-A2M4CD8 T-cells and incidence of insertional oncogenesis. | Up to 15 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-tumour activity: Overall Response Rate (ORR) | ORR is defined as incidence of complete responses or partial responses as assessed by RECIST v1.1 | 2.5 years | 
| Anti-tumor activity: 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-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab, the time taken 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 as monotherapy or in combination with either nivolumab or pembrolizumab, the DOR is the date of first response (including confirmation) up until disease progression per RECIST v 1.1 or death | 2.5 years | 
| Duration of stable disease (DoSD) | For patients who are observed to have stable disease by RECIST v 1.1, the duration of period of stable disease until disease progression or death | 2.5 years | 
| Progression Free Survival (PFS) | PFS is assessed from date of infusion of ADP-A2M4CD8 as monotherapy or in combination with either nivolumab or pembrolizumab 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 as monotherapy or in combination with either nivolumab or pembrolizumab up until the date of patient death. | 15 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, Urothelial, Head and Neck, Gastric (stomach), Esophagogastric Junction (EGJ), Non-small Cell Lung (NSCLC), Esophageal Cancer, Ovarian Cancer, Endometrial Cancer, Melanoma