BASECAMP-1: Solid Tumor Analysis for HLA Loss of Heterozygosity (LOH) and Leukapheresis for CAR T- Cell Manufacturing
Study Details
Study Description
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 | Phase |
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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:
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Screening (Part 1 and 2)
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Enrollment (Leukapheresis)
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Post Leukapheresis safety follow-up (Day 7)
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Two-year long term follow-up
Study Design
Outcome Measures
Primary Outcome Measures
- Percentage of participants who can enroll in an A2 Biotherapeutics, Inc. CAR T-cell therapy study after undergoing leukapheresis. [up to 2 years]
Participants will be followed for their status of enrollment on an A2 Biotherapeutics, Inc. interventional study.
- Percentage of screened participants experiencing loss of heterozygosity (LOH) of HLA-A*02 identified by next generation sequencing. [Screening]
Percentage of participants experiencing LOH will be calculated based on NGS results.
Secondary Outcome Measures
- Percentage of enrolled participants who experience an adverse event (AE) related to leukapheresis. [7 days]
Adverse events will be collected and monitored for relatedness to leukapheresis during the course of the study.
Eligibility Criteria
Criteria
Key Eligibility Criteria (additional criteria may apply) Part 1 Key Inclusion Criteria
- 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
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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.
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Prior allogeneic stem cell transplant.
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Prior solid organ transplant.
Part 2 : Key Inclusion Criteria
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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.
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Participants are germline HLA-A*02 heterozygous confirmed by HLA typing.
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Primary tumor tissue showing LOH of HLA-A*02 by NGS testing.
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Eastern Cooperative Oncology Group (ECOG) 0 or 1 performance status.
Part 2: Key Exclusion Criteria
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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.
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Prior allogeneic stem cell transplant.
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Prior solid organ transplant.
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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.
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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).
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Has known active central nervous system metastases. Subjects with previously treated brain metastases may participate upon medical monitor agreement.
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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
Locations
Site | City | State | Country | Postal Code | |
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1 | City of Hope | Duarte | California | United States | 90101 |
2 | University of California San Diego | La Jolla | California | United States | 92093 |
3 | UCLA Medical Center | Santa Monica | California | United States | 90404 |
4 | Moffitt Cancer Center | Tampa | Florida | United States | 33136 |
5 | Mayo Clinic Rochester | Rochester | Minnesota | United States | 55905 |
6 | NYU Langone Medical Center | New York | New York | United States | 10016 |
7 | MD Anderson Cancer Center | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- A2 Biotherapeutics Inc.
- Tempus Labs
Investigators
- Study Director: William Go, MD, PhD, A2 Biotherapeutics Inc.
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- American Cancer Society. Cancer Facts & Figures 2021. Atlanta: American Cancer Society; 2021
- 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.
- Hamburger AE, DiAndreth B, Cui J, Daris ME, Munguia ML, Deshmukh K, Mock JY, Asuelime GE, Lim ED, Kreke MR, Tokatlian T, Kamb A. Engineered T cells directed at tumors with defined allelic loss. Mol Immunol. 2020 Dec;128:298-310. doi: 10.1016/j.molimm.2020.09.012. Epub 2020 Oct 1.
- Hwang MS, Mog BJ, Douglass J, Pearlman AH, Hsiue EH, Paul S, DiNapoli SR, Konig MF, Pardoll DM, Gabelli SB, Bettegowda C, Papadopoulos N, Vogelstein B, Zhou S, Kinzler KW. Targeting loss of heterozygosity for cancer-specific immunotherapy. Proc Natl Acad Sci U S A. 2021 Mar 23;118(12). pii: e2022410118. doi: 10.1073/pnas.2022410118.
- McGranahan N, Rosenthal R, Hiley CT, Rowan AJ, Watkins TBK, Wilson GA, Birkbak NJ, Veeriah S, Van Loo P, Herrero J, Swanton C; TRACERx Consortium. Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. Cell. 2017 Nov 30;171(6):1259-1271.e11. doi: 10.1016/j.cell.2017.10.001. Epub 2017 Oct 26.
- 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
- Priestley P, Baber J, Lolkema MP, Steeghs N, de Bruijn E, Shale C, Duyvesteyn K, Haidari S, van Hoeck A, Onstenk W, Roepman P, Voda M, Bloemendal HJ, Tjan-Heijnen VCG, van Herpen CML, Labots M, Witteveen PO, Smit EF, Sleijfer S, Voest EE, Cuppen E. Pan-cancer whole-genome analyses of metastatic solid tumours. Nature. 2019 Nov;575(7781):210-216. doi: 10.1038/s41586-019-1689-y. Epub 2019 Oct 23.
- A2B101-101