We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT04981119
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04981119
Recruitment Status : Recruiting
First Posted : July 28, 2021
Last Update Posted : September 8, 2022
Sponsor:
Collaborator:
Tempus Labs
Information provided by (Responsible Party):
A2 Biotherapeutics Inc.

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 leukapheresis 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 subjects 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 Other: Leukapheresis 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, leukapheresis, 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 leukapheresed 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 leukapheresed (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 (Leukapheresis)
  • Post Leukapheresis safety follow-up (Day 7)
  • Two-year long term follow-up

Layout table for study information
Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: An Observational Study Obtaining Solid Tumor Tissue From Subjects With Primary Surgical Resection and Leukapheresis 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



Intervention Details:
  • Other: Leukapheresis
    Leukapheresis 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.


Primary Outcome Measures :
  1. Percentage of participants who can enroll in an A2 Biotherapeutics, Inc. CAR T-cell therapy study after undergoing leukapheresis. [ 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 leukapheresis. [ Time Frame: 7 days ]
    Adverse events will be collected and monitored for relatedness to leukapheresis during the course of the study.


Biospecimen Retention:   Samples With DNA

Blood and archived tumor tissue samples will be obtained for NGS to determine HLA type and 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
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), 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, 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), 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.
  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 leukapheresis 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.

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
Layout table for location contacts
Contact: Kirstin Liechty (310)431-9180 BASECAMP1@a2bio.com

Locations
Layout table for location information
United States, California
City of Hope Recruiting
Duarte, California, United States, 90101
Contact: Ripa Martirosyan       hmartirosyan@coh.org   
Principal Investigator: Marwan Fakih, MD         
University of California San Diego Recruiting
La Jolla, California, United States, 92093
Contact: Julia Applet       jappelt@health.ucsd.edu   
Principal Investigator: Sandip Patel, MD         
UCLA Medical Center Recruiting
Santa Monica, California, United States, 90404
Contact: Chris Hannigan       CHannigan@mednet.ucla.edu   
Principal Investigator: J. Randolph Hecht, MD         
Sub-Investigator: Edward Garon, MD         
United States, Florida
Moffitt Cancer Center Recruiting
Tampa, Florida, United States, 33136
Contact: Lauren Reagan       Lauren.Reagan@moffitt.org   
Principal Investigator: Kedar Kirtane, MD         
United States, Minnesota
Mayo Clinic Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Janet Lensing       lensing.janet@mayo.edu   
Principal Investigator: Julian Molina, MD, PhD         
Sub-Investigator: Yi Lin, 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: Diane Simeone, MD         
Sub-Investigator: Theodore Welling, MD         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Kimberly Ross    713-632-5909    kdross@mdanderson.org   
Sub-Investigator: Scott Kopetz, MD, PhD         
Principal Investigator: Maria Pia Morelli, MD, PhD         
Sponsors and Collaborators
A2 Biotherapeutics Inc.
Tempus Labs
Investigators
Layout table for investigator information
Study Director: William Go, MD, PhD A2 Biotherapeutics Inc.
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.

Layout table for additonal information
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: September 8, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
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:
Layout table for MeSH terms
Pancreatic Neoplasms
Neoplasms
Neoplasms by Site
Digestive System Neoplasms
Digestive System Diseases
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases