On May 4, 2022 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) and SOLTI-Innovative Cancer Research reported new clinical biomarker data demonstrating pelareorep’s immunotherapeutic effects, synergy with checkpoint inhibition, and potential to improve the outlook for patients with HR+/HER2- breast cancer (Press release, Oncolytics Biotech, MAY 4, 2022, View Source [SID1234613550]). The data, which are featured in a poster presentation at the 2022 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Breast Cancer Meeting, are from cohorts 1 and 2 of the AWARE-1 window-of-opportunity study in early-stage breast cancer patients.
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Patients in AWARE-1’s first two cohorts were treated with pelareorep and the aromatase inhibitor letrozole without (cohort 1), or with (cohort 2), the PD-L1 checkpoint inhibitor atezolizumab approximately 21 days prior to the surgical resection of their tumors. Cohorts 1 and 2 of AWARE-1 exclusively enrolled patients with HR+/HER2- disease, the breast cancer subtype that Oncolytics intends to examine in a future registrational study. Previously reported results showed AWARE-1 met its primary translational endpoint, with cohort 2 achieving the pre-specified success criteria for treatment-induced increases in CelTIL score (link to the PR). CelTIL score is a metric for tumor inflammation and cellularity and is associated with improved clinical outcomes in breast cancer patients.
"The latest data from AWARE-1 further demonstrate pelareorep’s potential to improve clinical outcomes in breast cancer patients through its ability to activate T cells and remodel the tumor microenvironment," said Thomas Heineman, M.D., Ph.D., Chief Medical Officer of Oncolytics. "Notably, pelareorep treatment increased markers of tumor cell death and, perhaps even more impressive, 100% of evaluable pelareorep-treated patients had a favorable Risk of Recurrence Score (ROR-S) compared to 55% at baseline. Together, these latest AWARE-1 results further establish pelareorep’s ability to attack tumors through multiple mechanisms."
Key data and conclusions from the ESMO (Free ESMO Whitepaper) Breast Cancer poster include:
Gene expression analyses showed 100% of evaluable patients had a Risk of Recurrence Score (ROR-S) classified as "low" at surgery vs. 55% with a "low" ROR-S at baseline (information pertaining to prognostic testing of gene signature assays in breast cancer can be found by clicking here)
Treatment with pelareorep with (cohort 2) or without (cohort1) atezolizumab led to the conversion of tumors from the more aggressive luminal B to the luminal A subtype, which is associated with improved clinical outcomes
100% of evaluable cohort 2 tumors were luminal A at surgery (21 days post-treatment) vs. 70% at baseline (pre-treatment)
70% of evaluable cohort 1 patients had luminal A tumors at surgery vs. 40% at baseline
Pooled analysis of tumors from cohorts 1 and 2 shows a statistically significant 4-fold post-treatment increase in the average expression of caspase 3, which is a marker of apoptotic cell death
Pooled analysis across cohorts 1 and 2 shows statistically significant increases in markers of T cell activation and no significant changes in markers of T cell exhaustion from baseline to surgery
Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics Biotech Inc., commented, "AWARE-1’s results continue to exceed our expectations. With each new dataset, we gain additional clarity on how pelareorep’s immunologic mechanism of action synergistically combines with checkpoint inhibition. The study has also identified changes in blood T cell populations as a potential biomarker to predict patient response. We are now working to confirm these promising findings with efficacy data and additional biomarker analyses from our ongoing BRACELET-1 trial. If positive, we expect BRACELET-1’s results to inform the design of a registrational study in HR+/HER2- breast cancer and validate our broader strategy of developing pelareorep in combination with leading anti-cancer agents."
BRACELET-1 is a randomized phase 2 trial in HR+/HER2- metastatic breast cancer. The trial includes cohorts evaluating paclitaxel monotherapy, paclitaxel plus pelareorep, and paclitaxel plus pelareorep in combination with a checkpoint inhibitor. Top-line data from the trial are expected in Q4 2022.
The poster, entitled, The oncolytic virus pelareorep primes the tumor microenvironment for checkpoint blockade therapy in early breast cancer patients – Results from AWARE-1 study, is being presented during the "Biomarkers and translational research and precision medicine" session of the ESMO (Free ESMO Whitepaper) Breast Cancer Meeting. Following the conclusion of the meeting, the poster will be available on the Posters & Publications page of Oncolytics’ website (LINK).
About AWARE-1
AWARE-1 was an open-label window-of-opportunity study in early-stage breast cancer. The study combined pelareorep, without or with atezolizumab, and the standard of care therapy according to breast cancer subtype. Tumor tissue was collected from patients as part of their initial breast cancer diagnosis, again on day three following initial treatment, and finally at three weeks following treatment, on the day their tumor is surgically resected. Key objectives of the study were to confirm that pelareorep is acting as a novel immunotherapy, to evaluate potential synergy between pelareorep and checkpoint blockade, and to collect biomarker data. The primary endpoint of the translational study was overall CelTIL score (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study included safety and tumor and blood-based biomarkers.