Abstract 6P
Background
Pelareorep (pela) is an intravenously delivered non-engineered oncolytic reovirus demonstrating anti-tumor activity through innate and adaptive immune responses. Previous data from the AWARE-1 study demonstrated that addition of atezolizumab (atezo) to pela increased the CelTIL score (study’s primary endpoint) by more than 30% in 60% of HR+/HER2- early breast cancer (BC) patients. CelTIL is a composite measure of tumor cellularity and tumor-infiltrating lymphocytes (TILs) and has been associated with a better prognosis in BC. The increase in CelTIL score observed in AWARE-1 was accompanied by PD-L1 upregulation. Here we report additional translational research results from AWARE-1.
Methods
HR+/HER2- early BC patients were enrolled in two cohorts: Cohort 1 (C1)– pela + letrozole (n=10); and Cohort 2 (C2)– pela + letrozole + atezo (n=10). Pela was administered on days 1, 2 and 8, 9, and atezo was given on day 3. Tumor biopsies collected pre-treatment and on days 3 and 21 were examined by immunohistochemistry (IHC), T cell receptor sequencing (TCR-seq), digital spatial profiling (DSP), and the PAM50 assay. Blood samples collected at these timepoints were evaluated by TCR-seq and flow cytometry.
Results
IHC showed a significant increase (p-value=0.04) in caspase 3 staining in all patients from day3 to day 21 that reached significance in C2. PAM50 analysis indicated a conversion of baseline disease from luminal B to luminal A in both cohorts, with 100% of patients converting to luminal A in C2. TCR-seq showed a decrease in pre- vs. post-treatment blood T cell diversity in both cohorts, which was significant (p-value=0.01) in C2. An association between decreased post-treatment T cell diversity and pre- vs. post-treatment increases in TILs was observed in both cohorts, reaching significance in C2 (p-value=0.01). DSP showed an increase in activated T cells but not exhausted T cells in both cohorts.
Conclusions
These data show that pela induces an inflamed tumor phenotype and demonstrate its synergy with atezo. Moreover, these data support pela’s immune-based mechanism of action and suggest that combining pela with atezo may improve outcomes in BC.
Clinical trial identification
EudraCT number: 2018-003345-42.
Legal entity responsible for the study
Oncolytics Biotech Inc.
Funding
Oncolytics Biotech Inc.
Disclosure
J. Gavila Gregori: Financial Interests, Personal, Other: AstraZeneca; Financial Interests, Personal, Other: Pfizer; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Other: Roche. H. Loghmani: Financial Interests, Personal, Full or part-time Employment: Oncolytics Bioteh Inc. L.M. Manso Sanchez: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Tesaro; Financial Interests, Personal, Advisory Board: Pfizer. T. Pascual: Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker: Lilly. M. Juan: Financial Interests, Personal, Advisory Role: Grifols. A. Prat: Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Institutional, Other, Contracted research:: Roche; Financial Interests, Personal, Invited Speaker, Lecture fees: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Novartis; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Amgen; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Amgen; Financial Interests, Personal, Invited Speaker, Lecture fees: BMS; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: BMS; Financial Interests, Personal, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: NanoString; Financial Interests, Institutional, Invited Speaker, Lecture fees: NanoString; Financial Interests, Institutional, Other, Contracted research: Novartis; Financial Interests, Institutional, Other, Contracted research: Roche; Financial Interests, Institutional, Other, Contracted research: Pfizer; Financial Interests, Personal, Invited Speaker, Lecture fees: Contracted research; Financial Interests, Personal, Invited Speaker, Lecture fees: Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker, Clinical trials: Daiichi Sankyo; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Puma; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Oncolytics; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: MSD; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Guardan Health; Financial Interests, Personal, Expert Testimony, Advisory role/consultancy: Peptomyc; Financial Interests, Personal, Advisory Board, Advisory role/consultancy: Lilly; Financial Interests, Institutional, Other, Clinical trials: Lilly; Financial Interests, Institutional, Other, Contracted research: Boehringer; Financial Interests, Institutional, Other, Contracted research: Sysmex Europa GmbH; Financial Interests, Institutional, Other, Contracted research: Medica Scientia inno. Research; Financial Interests, Institutional, Other, Contracted research: Celgene; Financial Interests, Institutional, Other, Contracted research: Astellas; Financial Interests, Institutional, Other, Clinical trials: Roche; Financial Interests, Institutional, Other, Clinical trials: AMgen; Financial Interests, Personal, Invited Speaker, Leadership role: Reveal Genomics, SL.; Financial Interests, Institutional, Other, Clinical trials: Boehringer; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: SOLTI Foundation; Non-Financial Interests, Institutional, Other, Leadership roles: Patronage committee: Actitud Frente al Cáncer Foundation. T.C. Heineman: Financial Interests, Personal, Officer, Chief Medical Officer: Oncolytics Biotech; Financial Interests, Personal, Stocks/Shares: Oncolytics Biotech. All other authors have declared no conflicts of interest.