Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing

Study Overview
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Brief Summary
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Objective: To collect information on how often a solid tumor cancer might lose the Human Leukocyte Antigen (HLA) by next generation sequencing and perform apheresis to collect and store an eligible participant's own T cells for future use to make CAR T-Cell therapy for their disease treatment. Design: This is a non-interventional, observational study to evaluate participants with solid tumors with a high risk of relapse for incurable disease. No interventional therapy will be administered on this study. Some of the information regarding the participant's tumor analysis may be beneficial to management of their disease. Participants that meet all criteria may be enrolled and leukapheresed (blood cells collected). The participant's cells will be processed and stored for potential manufacture of CAR T-cell therapy upon relapse of their cancer.

Detailed Description
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Background: Human Leukocyte Antigen (HLA) is a protein on the outside of cells that allows the immune system to recognize it's own cells as normal and leave them alone or respond if infected with a virus or bacteria, or a tumor cell. HLA might not be expressed normally on cancer cells. This may be why cancer can grow undetected by the immune system and is referred to as a tumor escape mechanism. Tumor escape can occur for many reasons, but one reason is Loss of Heterozygosity (LOH). LOH is the loss of one of the genes that encodes HLA protein. A2 Biotherapeutics, Inc. (A2 Bio) is developing therapies to recognize, target, and kill cancer cells that do not express HLA normally, and minimize any damage to normal cells that express normal HLA. Once participants are identified as having LOH on their tumors, apheresis, a procedure to separate and collect white blood cells will be performed. It is the first required step in manufacturing CAR T-cell therapy. The collected T cells will be stored for patients that are likely to benefit from CAR T-cell therapy during their disease care. Study Design: Approximately 1000 participants will be screened for part 1 of the study, including HLA typing, approximately 500 participants will have NGS testing on their tumor samples and be followed for up to 2 years on the study, and up to 200 participants will be screened for part 2 of the study and enrolled if eligible and apheresed and be followed for up to 2 years on the study. Participants will be screened (Part 1) for HLA type, and based on results, participants will have archived tumor tissue tested by next generation sequencing (NGS) and be followed for up to 2 years. Based on the tumor NGS results, participants will be apheresed (Part 2) for Peripheral Blood Mononuclear Cell (PBMC) collection to store their T cells for a future interventional study upon relapse. Each participant will proceed through the following study periods: Screening (Part 1 and 2) Enrollment (Apheresis) Post Apheresis safety follow-up (Day 7) Two-year long term follow-up

Official Title
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An Observational Study Obtaining Solid Tumor Tissue From Participants and Apheresis for CAR T-Cell Therapy Manufacturing

Conditions
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Solid Tumor, Adult, Colorectal Cancer, Non Small Cell Lung Cancer, Pancreatic Cancer, CRC, NSCLC, Pancreas Cancer, Mesothelioma, Ovarian Cancer, Ovarian Neoplasms, Ovarian Carcinoma, Mesothelioma, Malignant, Mesothelioma; Lung, Cancer

Intervention / Treatment
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* Other: Apheresis
* Diagnostic Test: Next Generation Sequencing (NGS)
* Diagnostic Test: Long Range NGS HLA typing


Participation Criteria
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Eligibility Criteria
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Key Eligibility Criteria (additional criteria may apply) Part 1 Key Inclusion Criteria 1. Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), or Pancreatic Cancer (PANC), that is metastatic, unresectable locally advanced, or in the Investigator's opinion the subject is high risk for incurable relapse within two years. Part 1: Key Exclusion Criteria History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer. Prior allogeneic stem cell transplant. Prior solid organ transplant. Part 2 : Key Inclusion Criteria Pathologically confirmed solid tumors, e.g., Colorectal Cancer (CRC), Non-Small Cell Lung Cancer (NSCLC), Pancreatic Cancer (PANC), Mesothelioma, or Ovarian Cancer (OVAC) that is metastatic, unresectable locally advanced, or in the Investigator's opinion the subject is high risk for incurable relapse within two years. Participants are germline HLA-A*02 heterozygous confirmed by HLA typing. Primary tumor tissue showing LOH of HLA-A*02 by NGS testing. Eastern Cooperative Oncology Group (ECOG) 0 or 1 performance status. Part 2: Key Exclusion Criteria History of any of other malignancy in the past 5 years other than non-melanoma skin carcinoma, low grade localized prostate cancer, superficial bladder cancer, ductal carcinoma in situ (CIS) of the breast, CIS of the Cervix, or Stage I uterine cancer. Prior allogeneic stem cell transplant. Prior solid organ transplant. Participants who have received any cancer therapy on any investigational therapy for any indication, including but not limited to chemotherapy, small molecules, monoclonal antibodies, or radiotherapy (with bone marrow impact) within 2 weeks of planned apheresis or 3 half-lives, whichever is shorter. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment necessitating specific treatment, or any major episode of infection requiring treatment with Intravenous (IV) antimicrobials (e.g., IV antibiotics) or hospitalization (relating to completion of antibiotic course). Has known active central nervous system metastases. Subjects with previously treated brain metastases may participate upon medical monitor agreement. In the Investigator's judgement, any other condition or reason the subject would not complete the required study visits and procedures, and follow up visits, or comply with the study requirements for participation.

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Apheresis|Apheresis procedure performed for collection of PBMCs.|
|Diagnostic Test: Next Generation Sequencing (NGS)|NGS on tumor tissue and a matched normal sample for loss of heterozygosity in tumor tissue and tumor tissue markers.|
|Diagnostic Test: Long Range NGS HLA typing|Long range NGS on whole blood to determine germline HLA type.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who can enroll in an A2 Biotherapeutics, Inc. CAR T-cell therapy study after undergoing apheresis | Participants will be followed for their status of enrollment on an A2 Biotherapeutics, Inc. interventional study | up to 2 years | 
| Percentage of screened participants experiencing loss of heterozygosity (LOH) of HLA-A*02 identified by next generation sequencing | Percentage of participants experiencing LOH will be calculated based on NGS results | Screening | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of enrolled participants who experience an adverse event (AE) related to apheresis | Adverse events will be collected and monitored for relatedness to apheresis during the course of the study | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T Cell Therapy, Next Generation Sequencing, Leukapheresis, Apheresis, Immunotherapy