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Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Apheresis for CAR T- Cell Manufacturing (BASECAMP-1)

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ClinicalTrials.gov Identifier: NCT04981119
Recruitment Status : Recruiting
First Posted : July 28, 2021
Last Update Posted : April 9, 2024
Sponsor:
Collaborator:
Tempus AI
Information provided by (Responsible Party):
A2 Biotherapeutics Inc.

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment
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 Other: Apheresis Diagnostic Test: Next Generation Sequencing (NGS) Diagnostic Test: Long Range NGS HLA typing

Detailed Description:

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
Study Design
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Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Observational Study Obtaining Solid Tumor Tissue From Participants and Apheresis for CAR T-Cell Therapy Manufacturing
Actual Study Start Date : October 29, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2026

Resource links provided by the National Library of Medicine


Groups and Cohorts
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Intervention Details:
  • 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.

Outcome Measures
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Primary Outcome Measures :
  1. Percentage of participants who can enroll in an A2 Biotherapeutics, Inc. CAR T-cell therapy study after undergoing apheresis [ Time Frame: up to 2 years ]
    Participants will be followed for their status of enrollment on an A2 Biotherapeutics, Inc. interventional study

  2. Percentage of screened participants experiencing loss of heterozygosity (LOH) of HLA-A*02 identified by next generation sequencing [ Time Frame: Screening ]
    Percentage of participants experiencing LOH will be calculated based on NGS results


Secondary Outcome Measures :
  1. Percentage of enrolled participants who experience an adverse event (AE) related to apheresis [ Time Frame: 7 days ]
    Adverse events will be collected and monitored for relatedness to apheresis during the course of the study


Biospecimen Retention:   Samples With DNA

Blood or saliva, or buccal swabs will be obtained to determine germline HLA type as wells a germline comparison for tumor comparison. Archived tumor tissue samples will be obtained for NGS to determine LOH status of tumor tissue. DNA and RNA will be retained for enrolled participants only, if repeat testing if required. No further genetic testing will be performed on these samples.

Peripheral Blood Mononuclear Cells (PBMCs) will be collected for enrolled subjects, enriched for T cells and cryopreserved for future manufacturing of an A2 Biotherapeutics, Inc. CAR T-cell therapy upon participant relapse. No further genetic testing will be performed on this sample.

Archival tumor slides will be obtained for immunohistochemistry (IHC)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Participants with 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, germline HLA-A*02 heterozygous, and have confirmed somatic LOH.
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04981119


Contacts
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Contact: Clinical Trials (310)431-9180 ClinicalTrials@a2bio.com

Locations
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United States, Arizona
Banner Health Recruiting
Gilbert, Arizona, United States, 85234
Contact: Natasha Tamula       natasha.tamula@bannerhealth.com   
Principal Investigator: Matthew Ulrickson, MD         
United States, California
City of Hope Recruiting
Duarte, California, United States, 90101
Contact: Janela Agonoy       jagonoy@coh.org   
Principal Investigator: Marwan Fakih, MD         
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Jona Plevin       jplevin@health.ucsd.edu   
Principal Investigator: Sandip Patel, MD         
Stanford University Recruiting
Palo Alto, California, United States, 94305
Contact: Shruti Murthy       shrutide@stanford.edu   
Principal Investigator: Saurabh Dahiya, MD         
UCLA Medical Center Recruiting
Santa Monica, California, United States, 90404
Contact: Alexa Berezowitz       aberezowitz@mednet.ucla.edu   
Principal Investigator: J. Randolph Hecht, MD         
Sub-Investigator: Edward Garon, MD         
United States, Florida
Mayo Clinic Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Jawad Khan       Khan.Jawad@mayo.edu   
Principal Investigator: Hermant Murthy, MD         
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33136
Contact: Gillian Zankel       Gillian.Zankel@moffitt.org   
Principal Investigator: Kedar Kirtane, MD         
Sub-Investigator: Frederick Locke, MD         
United States, Massachusetts
Massachusetts General Hospital/Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02114
Contact: Jong Chul Park, MD       JPARK73@mgh.harvard.edu   
Principal Investigator: Jong Chul Park, MD         
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Ethan Sunsvold       Sundsvold.Ethan@mayo.edu   
Principal Investigator: Julian Molina, MD, PhD         
Sub-Investigator: Yi Lin, MD, PhD         
United States, Missouri
Washington University Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Amberly Scott       amberly@wustl.edu   
Principal Investigator: Patrick Grierson, MD, PhD         
United States, New York
NYU Langone Medical Center Recruiting
New York, New York, United States, 10016
Contact: Tate Chan       Tate.Chan@nyulangone.org   
Principal Investigator: Kristen Spencer, DO         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: GI Clinical Trials       GIClinicalTrials@mdanderson.org   
Principal Investigator: Maria Pia Morelli, MD, PhD         
Sub-Investigator: Scott Kopetz, MD, PhD         
United States, Washington
Fred Hutchinson Cancer Center Recruiting
Seattle, Washington, United States, 98109
Contact: Shelby Colden         
Contact       scolden2@fredhutch.org   
Principal Investigator: Jennifer Specht, MD         
Sponsors and Collaborators
A2 Biotherapeutics Inc.
Tempus AI
Investigators
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Study Director: William Go, MD, PhD A2 Biotherapeutics Inc.
More Information
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Publications:
American Cancer Society. Cancer Facts & Figures 2021. Atlanta: American Cancer Society; 2021
Perera J, Mapes B, Lau D, et al. Detection of human leukocyte antigen class I loss of heterozygosity in solid tumor types by next-generation DNA sequencing. J Immunother Cancer. 2019, 7(Suppl 1):P103
Beroukhim R, Mermel CH, Porter D, Wei G, Raychaudhuri S, Donovan J, Barretina J, Boehm JS, Dobson J, Urashima M, Mc Henry KT, Pinchback RM, Ligon AH, Cho YJ, Haery L, Greulich H, Reich M, Winckler W, Lawrence MS, Weir BA, Tanaka KE, Chiang DY, Bass AJ, Loo A, Hoffman C, Prensner J, Liefeld T, Gao Q, Yecies D, Signoretti S, Maher E, Kaye FJ, Sasaki H, Tepper JE, Fletcher JA, Tabernero J, Baselga J, Tsao MS, Demichelis F, Rubin MA, Janne PA, Daly MJ, Nucera C, Levine RL, Ebert BL, Gabriel S, Rustgi AK, Antonescu CR, Ladanyi M, Letai A, Garraway LA, Loda M, Beer DG, True LD, Okamoto A, Pomeroy SL, Singer S, Golub TR, Lander ES, Getz G, Sellers WR, Meyerson M. The landscape of somatic copy-number alteration across human cancers. Nature. 2010 Feb 18;463(7283):899-905. doi: 10.1038/nature08822.

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Responsible Party: A2 Biotherapeutics Inc.
ClinicalTrials.gov Identifier: NCT04981119    
Other Study ID Numbers: A2B101-101
First Posted: July 28, 2021    Key Record Dates
Last Update Posted: April 9, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by A2 Biotherapeutics Inc.:
CAR T Cell Therapy
Next Generation Sequencing
Leukapheresis
Apheresis
Immunotherapy
Additional relevant MeSH terms:
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Pancreatic Neoplasms
Ovarian Neoplasms
Mesothelioma
Mesothelioma, Malignant
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Digestive System Neoplasms
Digestive System Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
 Endocrine System Diseases
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Genital Diseases
Gonadal Disorders
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial