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

NCT04981119 · A2 Biotherapeutics Inc.
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Official title
An Observational Study Obtaining Solid Tumor Tissue From Participants and Apheresis for CAR T-Cell Therapy Manufacturing
About this study
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
Eligibility criteria
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 1. 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. 2. Prior allogeneic stem cell transplant. 3. Prior solid organ transplant. Part 2 : Key Inclusion Criteria 1. 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. 2. Participants are germline HLA-A\*02 heterozygous confirmed by HLA typing. 3. Primary tumor tissue showing LOH of HLA-A\*02 by NGS testing. 4. Eastern Cooperative Oncology Group (ECOG) 0 or 1 performance status. Part 2: Key Exclusion Criteria 1. 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. 2. Prior allogeneic stem cell transplant. 3. Prior solid organ transplant. 4. 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. 5. 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). 6. Has known active central nervous system metastases. Subjects with previously treated brain metastases may participate upon medical monitor agreement. 7. 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.
Study design
Enrollment target: 200 participants
Age groups: adult, older_adult
Timeline
Starts: 2021-10-29
Estimated completion: 2029-04
Last updated: 2026-02-13
Interventions
Other: ApheresisDiagnostic Test: Next Generation Sequencing (NGS)Diagnostic Test: Long Range NGS HLA typing
Primary outcomes
  • Percentage of participants who can enroll in an A2 Biotherapeutics, Inc. CAR T-cell therapy study after undergoing apheresis (up to 2 years)
  • Percentage of screened participants experiencing loss of heterozygosity (LOH) of HLA-A*02 identified by next generation sequencing (Screening)
Sponsor
A2 Biotherapeutics Inc. · industry
With: Tempus AI
Contacts & investigators
ContactClinical Trials · contact · ClinicalTrials@a2bio.com · (310)431-9180
InvestigatorEric W Ng, MD, FAAP · study_director, A2 Biotherapeutics Inc.
All locations (16)
Banner HealthRecruiting
Gilbert, Arizona, United States
Mayo Clinic HospitalRecruiting
Phoenix, Arizona, United States
City of HopeCompleted
Duarte, California, United States
University of California San DiegoRecruiting
La Jolla, California, United States
Stanford UniversityRecruiting
Palo Alto, California, United States
UCLA Medical CenterRecruiting
Santa Monica, California, United States
Mayo Clinic JacksonvilleRecruiting
Jacksonville, Florida, United States
Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Massachusetts General Hospital/Dana Farber Cancer InstituteCompleted
Boston, Massachusetts, United States
Mayo Clinic RochesterRecruiting
Rochester, Minnesota, United States
Washington UniversityRecruiting
St Louis, Missouri, United States
NYU Langone Medical CenterRecruiting
New York, New York, United States
The Ohio State University Comprehensive Cancer CenterRecruiting
Columbus, Ohio, United States
Vanderbilt University Medical CenterRecruiting
Nashville, Tennessee, United States
MD Anderson Cancer CenterCompleted
Houston, Texas, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing · TrialPath