The oncolytic virus pelareorep primes the tumor microenvironment for checkpoint blockade therapy in early breast cancer patients -results from AWARE-1 study
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.
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.
https://oncologypro.esmo.org/meeting-resources/esmo-breast-cancer-congress/the-oncolytic-virus-pelareorep-primes-the-tumor-microenvironment-for-checkpoint-blockade-therapy-in-early-breast-cancer-patients-results-from-awar