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491 BASECAMP-1: an observational study to identify relapsed solid tumor patients with human leukocyte antigen (HLA) loss of heterozygosity (LOH) and leukapheresis for future CAR T-cell therapy
  1. Julian Molina1,
  2. William Go2,
  3. Scott Kopetz3,
  4. Diane Simeone4,
  5. Sandip Patel5,
  6. Yi Lin1,
  7. Kirstin Liechty2,
  8. Michelle Fan-Port2,
  9. Jason Perera6,
  10. Armen Mardiros2,
  11. Karl Beutner7,
  12. Ariane Lozac’hmeur7,
  13. Eric Ng2,
  14. David Maloney8 and
  15. J Randolph Hecht9
  1. 1Mayo Clinic, Rochestser, MN, USA
  2. 2A2 Biotherapeutics, Inc., Agoura Hills, CA, USA
  3. 3University of Texas MD Anderson Cancer, Houston, TX, USA
  4. 4New York University Langone Health, New York, NY, USA
  5. 5University of California San Diego, La Jolla, CA, USA
  6. 6former Tempus, Chicago, IL, USA
  7. 7Tempus, Chicago, IL, USA
  8. 8Fred Hutchinson Cancer Research Center, Seattle, WA, USA
  9. 9David Geffen School of Medicine at UCLA, Los Angeles, USA


Background Solid tumors comprise >90% of cancers. Metastatic colorectal cancer, non-small cell lung cancer, and pancreatic cancer are among the leading causes of cancer-related mortality (5-year overall survival: 14%, 6%, and 3%, respectively).1Chimeric antigen receptor (CAR) T-cell therapy demonstrated clinical outcomes in hematologic malignancies.2 3 However, translating engineered T-cell therapies to solid tumors proves difficult due to a lack of tumor-specific targets that discriminate cancer cells from normal cells. In previous studies, the use of a carcinoembryonic antigen T-cell receptors and mesothelin CARs both resulted in dose-limiting on-target, off-tumor toxicities.4 5 TmodTM CAR T-cell therapy addresses these challenges by leveraging dual receptors to create a robust AND NOT signal integrator capable of killing tumor cells, while leaving healthy cells intact (figure 1).6 Tmod platform technology is a versatile system that may be applied to T cells and natural killer cells in autologous and allogeneic settings.HLA LOH offers a definitive tumor versus normal discriminator target for CAR T-cell therapy.6 7 The 2 receptors comprise an activator that recognizes an antigen present on the surface of normal and tumor cells and a blocker that recognizes a second surface antigen from an allele lost only in tumor cells. HLA LOH has been observed in ~13% across all solid tumors and up to 33% of pancreatic cancers.8 New technologies have shown higher HLA LOH rates; however, it is unclear whether patients with HLA LOH in their primary tumor tissues are at higher risk for recurrence. BASECAMP-1 is an observational study with key objectives: 1) To determine and identify patients with somatic HLA LOH eligible for Tmod CAR T-cell therapy, and 2) Subsequent leukapheresis and manufacturing feasibility for future Tmod CAR T-cell trials.

Methods BASECAMP-1 (NCT04981119) patient eligibility has 2 parts (figure 2): 1) Patients will be initially screened to identify germline HLA-A*02 heterozygosity by central next-generation sequencing (NGS). If HLA-A*02 heterozygosity is confirmed, primary archival tumor tissue will be analyzed by xT-Onco NGS testing9 to determine if somatic tumor HLA-A*02 LOH is present; 2) If the tumor demonstrates HLA-A*02 LOH and the patient screens eligible, the patient will undergo leukapheresis. Patients enrolled in the study who undergo leukapheresis will be evaluated for safety 7 days post-leukapheresis and followed for relapsed status. Banked T cells will be available for subsequent autologous Tmod CAR T-cell therapy at the time of relapse.

Abstract 491 Figure 1

Illustration of the Tmod T cell engaging with tumor cells with somatic loss of HLA-A*02 and with normal cells

Abstract 491 Figure 2

Study schema. HLA, human leukocyte antigen; LOH, loss of heterozygosity; NGS, next generation sequencing

Trial Registration NCT04981119


  1. American Cancer Society. Cancer Facts & Figures 2021. Atlanta: American Cancer Society; 2021.

  2. Neelapu S, Locke F, Bartlett N, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med 2017;377(26):2531–2544.

  3. Maude S, Laetsch T, Buechner J, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med 2018;378(5):439–448.

  4. Parkhurst M, Yang J, Langan R, et al. T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis. Mol Ther 2011;19(3):620–626.

  5. Haas AR, Tanyi JL, O’Hara MH, et al. Phase I study of lentiviral-transduced chimeric antigen receptor-modified T cells recognizing mesothelin in advanced solid cancers. Mol Ther. 2019;27(11):1919–1929.

  6. Hamburger A, DiAndreth B, Cui J, et al. Engineered T cells directed at tumors with defined allelic loss. Mol Immunol 2020;128:298–310.

  7. Hwang M, Mog B, Douglass J, et al. Targeting loss of heterozygosity for cancer-specific immunotherapy. Proc Natl Acad Sci U S A 2021;118(12):e2022410118.

  8. The Cancer Genome Atlas (TCGA) Research Network. Accessed June 2021.

  9. 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):103.

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