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806 Changes in T cell clonality in AWARE-1 study, a window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer
  1. Luis Manso1,
  2. Patricia Villagrasa2,
  3. Nuria Chic3,
  4. Begoña Bermejo4,
  5. Juan Cejalvo4,
  6. Yann Izarzugaza5,
  7. Blanca Cantos6,
  8. Salvador Blanch7,
  9. Mireia Margeli8,
  10. Jose Alonso9,
  11. Alejandro Martínez10,
  12. Rafael Villanueva11,
  13. Juan Guerra12,
  14. Raquel Andrés13,
  15. Pilar Zamora14,
  16. Esteban Nogales15,
  17. Manel Juan3,
  18. Blanca Gonzalez-Farre3,
  19. Thomas Heineman16,
  20. Gerard Nuovo17,
  21. Grey Wilkinson16,
  22. Matt Coffey16,
  23. Azucena Gonzalez3,
  24. Débora Martínez3,
  25. Laia Paré2,
  26. Fernando Salvador2,
  27. Xavier Gonzalez18,
  28. Aleix Prat3 and
  29. Joaquín Gavilá7
  1. 1Hospital Universitario 12 de Octubre, Madrid, Spain
  2. 2SOLTI Breast Cancer Research Group, Barcelona, Spain
  3. 3Hospital Clinic de Barcelona, Barcelona, Spain
  4. 4Hospital Clínico Universitario de Valenc, Valencia, Spain
  5. 5Hospital Universitario Fundación Jiménez, Madrid, Spain
  6. 6Hospital Universitario Puerta de Hierro-, Madrid, Spain
  7. 7Instituto Valenciano de Oncología (IVO), Valencia, Spain
  8. 8Institut Català d’Oncologia, Barcelona, Spain
  9. 9Hospital Clínico Universitario Virgen de, Murcia, Spain
  10. 10Hospital Universitari Quirón Dexeus, Barcelona, Spain
  11. 11Hospital Moisès Broggi, Sant Joan Despí, Barcelona, Spain
  12. 12Hospital Universitario de Fuenlabrada, Madrid, Spain
  13. 13Hospital Clínico Universitario Lozano Bl, Zaragoza, Spain
  14. 14Hospital Universitario La Paz, Madrid, Spain
  15. 15Hospital Universitario Virgen Macarena, Sevilla, Spain
  16. 16Oncolytics Biotech Inc., San Diego, CA, USA
  17. 17Ohio State University, Columbus, OH, USA
  18. 18Hospital Universitari General de Catalun, Sant Cugat del Vallés, Spain


Background A previous phase 2 study in metastatic breast cancer demonstrated a statistically significant improvement in overall survival (OS) in patients treated with pelareorep (pela) in combination with paclitaxel (PTX) versus PTX alone.1 Given that pela is an intravenously delivered immuno-oncolytic reovirus, we hypothesized that the OS benefit from pela + PTX may be attributed to an adaptive T cell response triggered by pela. To examine if pela can mediate the priming of an anti-tumor immune response, we are conducting together with the SOLTI group the AWARE-1 study (a window-of-opportunity study of pela in early breast cancer), which is currently enrolling and for which initial translational research results are presented.

Methods AWARE-1 is a window-of-opportunity study to evaluate the safety and effect of pela ± atezolizumab on the tumor microenvironment (TME) in 38 women with early breast cancer. Patients are treated with pela on days 1, 2, 8, and 9, while atezolizumab is administered on day 3. Tumor biopsies are collected at diagnosis, day 3, and day ~21. Five cohorts will be examined: Cohort 1: HR+/HER2-neg (10 patients) receiving pelareorep + letrozole; Cohort 2: HR+/HER2-neg (10 patients) receiving pelareorep + letrozole + atezolizumab; Cohort 3: TNBC (6 patients) receiving pelareorep + atezolizumab; Cohort 4: HER2+/HR+ (6 patients) receiving pelareorep + trastuzumab + atezolizumab; Cohort 5: HER2+/HR- (6 patients) receiving pelareorep + trastuzumab + atezolizumab. The primary endpoint of the study is CelTIL score [2], a metric for quantifying the changes in tumor cellularity and infiltration of TILs, where an increase in CelTIL is associated with a favorable response to treatment. Tumor tissue is being examined for pela replication, and changes to the TME are being assessed by immunohistochemistry and T cell receptor sequencing (TCR-seq). Peripheral blood is also being examined by TCR-seq.

Results Detailed TCR-seq results from peripheral blood and tumor tissue are presented for the ten-patients enrolled into Cohort 1 who received pela and letrozole. In tumor tissue, T cell clonality increased in day 21 biopsies relative to baseline biopsies, with similar increases in T cell fraction (the number of T cells) in the majority of patients. In general, most of the tissue-expanded T cell clones were also seen in the peripheral blood.

Conclusions Overall, these preliminary data from cohort 1 of AWARE-1 demonstrate that pela mediates priming of a T cell-based immune response that occurs both systemically and within breast cancer tissue.

Trial Registration NCT04102618

Ethics Approval This study was approved by the Spanish Health Authority, protocol number 2018-003345-42.


  1. Bernstein V, et al. A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213. Breast Cancer Res Treat 2018;167(2):485-493.

  2. Nuciforo P, et al. A predictive model of pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) in HER2-positive breast cancer treated with chemo-free dual HER2 blockade. Ann Oncol 2018;29(1):170-177.

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