41P A window-of-opportunity study with atezolizumab and the oncolityc virus pelareorep in early breast cancer (REO-027, AWARE-1)

Background: A previous phase 2 study in metastatic breast cancer compared treatment with intravenously delivered oncolytic reovirus, pelareorep (pela), in combination with paclitaxel (PTX) versus PTX alone. This study demonstrated a statistically significant improvement in overall survival (OS), without differences in objective response or progression-free survival. We hypothesized that the OS benefit from pela + PTX may be attributed to an adaptive immune response triggered by pela. To test this hypothesis, and examine if pela can mediate the priming of an anti-tumor immune response, we designed a study called AWARE-1 (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 evaluating 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. The primary endpoint of the study is CelTIL score, 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 was examined for pela replication, and changes to the TME were assessed by immunohistochemistry and TCR-seq. Peripheral blood was also examined by TCR-seq. Results: Analysis of CelTIL show an increase in four of the six patients to date. Productive viral replication in day 3 and day ∼21 biopsies was very high, as measured by in situ detection of viral capsid protein in tumor cells. Immunohistochemistry analysis revealed an increase in CD8+ T cells and upregulation of PDL1 on day 3 and day 21 biopsies for all patients. TCR-seq from blood showed that levels of T cell clonality correlate with changes in the TME and CelTIL. Conclusions: Overall, the degree of viral replication was consistent with changes in CelTIL and changes within the TME. Preliminary data from the first six patients in AWARE-1 demonstrate pela-mediated priming of an adaptive immune response. Clinical trial identification: NCT04102618. Legal entity responsible for the study: Oncolytics Biotech Inc. Funding: Oncolytics Biotech Inc. Disclosure: L. Manso: Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche; Advisory/Consultancy, Speaker Bureau/Expert testimony: Astra; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Novartis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Tesaro; Advisory/Consultancy, Speaker Bureau/Expert testimony: Pfizer. P. Villagrasa: Speaker Bureau/Expert testimony: NanoString. Y. Izarzugaza: Honoraria (self), Research grant/Funding (institution), Non-remunerated activity/ies: Novartis; Research grant/Funding (institution): Breast Cancer Research Foundation-AACR Career Development Award; Research grant/Funding (institution): Breast Cancer Now Catalyst Grant; Honoraria (self), Non-remunerated activity/ies: Roche; Non-remunerated activity/ies: Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): Eisai. M. Juan: Advisory/Consultancy: Grifols. G. Wilkinson: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Oncolytics Biotech Inc. M. Coffey: Honoraria (self), Licensing/Royalties, Full/Part-time employment, Non-remunerated activity/ies: Oncolytics Biotech Inc. X. González-Farré: Honoraria (self): SOLTI; Honoraria (self), Non-remunerated activity/ies: Roche; Honoraria (self): Eisai. A. Prat: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: NanoString; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Roche; Honoraria (self), Advisory/Consultancy: Oncolytics Biotech; Honoraria (self), Speaker Bureau/Expert testimony: Daiichi Sankyo; Honoraria (self), Advisory/Consultancy: Puma; Honoraria (self), Advisory/Consultancy: BMS. J. Gavila Gregori: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self), Research grant/Funding (institution): Pfizer; Honoraria (self), Research grant/Funding (institution): Roche. All other authors have declared no conflicts of interest.