RE:SABC Abstracts have been publishedPublication Number: OT-13-02 Bracelet-1 (pre0113): A study to assess overall response rate by inducing an inflammatory phenotype in metastatic breast cancer with the oncolytic reovirus pelareorep in combination with anti-PD-L1 avelumab and paclitaxel Kathy Miller1, Fengmin Zhao 2, Amy Clark 3, Grey Wilkinson 4, Rita Laeufle 5 and Antonio Wolff6. 1Indiana University, Indianapolis, IN;2Dana- Farber Cancer Institute, Boston, MA;3University of Pennsylvania, Philadelphia, PA;4Oncolytics Biotech Inc., Calgary, AB, Canada 5Oncolytics Biotech Inc., San Diego, CA;6Johns Hopkins University, Baltimore, MD Background: A randomized phase 2 study with the intravenously delivered oncolytic virus, pelareorep, in combination with paclitaxel (PTX) demonstrated a statistically significant improvement in overall survival (OS) from 10.4 months with PTX alone to 17.4 months with pelareorep + PTX (HR 0.65, 80% CI 0.46-0.91, P = 0.1) in metastatic breast cancer (mBC) patients. The greatest benefit in OS was seen in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) disease (Bernstein et al, 2018). However, pelareorep + PTX did not improve progression-free survival or objective response relative to PTX alone, suggesting a late-onset adaptive immune response. A subsequent window of opportunity study in early breast cancer has shown that pelareorep can indeed promote an adaptive immune response in breast cancer tissue, enhancing CD8+ T cell infiltration and upregulating PD-L1 expression, correlating with high levels of viral replication in HR+/HER2- tumor tissue (Manso et al, 2020). Moreover, high levels of peripheral T cell clonality (PTCC) have been identified as a candidate blood-based on-treatment biomarker for pelareorep therapy, further highlighting the role of an adaptive immune response in driving pelareorep mediated efficacy (Mahalingam et al, 2020; Manso et al, 2020). Thus, BRACELET- 1 will test the hypothesis that pelareorep mediated priming of an adaptive immune response will be synergistic with checkpoint blockade therapy in HR+/HER2- mBC. Moreover, BRACELET-1 will further assess PTCC as an on-treatment biomarker. The overall goal of this study is to expand the number of mBC patients who can benefit from better immunotherapy. Study Design: This is an open-label randomized phase 2, three-cohort study in HR+/HER2- mBC. Patients must be refractory to endocrine therapy and have received prior treatment with a CDK4/6 inhibitor. Study cohorts include: Cohort 1, a control group receiving PTX (n = 15); Cohort 2, treatment with pelareorep added to PTX (n = 15); Cohort 3, treatment with pelareorep, PTX, and avelumab (n = 18). The study includes a three patient safety run-in for Cohort 3. Specific aims: (1) Evaluation of efficacy in terms of overall response rate (ORR) at week 16, according to RECIST v1.1; (2) Examination of the safety of the study treatments; and (3) Assessment of key biomarkers, such as PTCC which will be correlated to treatment efficacy. Present accrual and target accrual: The study is currently enrolling and is registered on clinicaltrials.gov: NCT04215146. Current enrollment = 2; Target enrollment = 48. This study is conducted through PrECOG, LLC and Oncolytics Biotech, Inc. Study contact information: PrE0113@precogllc.org.