On December 9, 2020 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) and SOLTI-Innovative Breast Cancer Research reported an electronic poster at the 2020 San Antonio Breast Cancer Symposium (SABCS) with data from the AWARE-1 window-of-opportunity study in patients with early-stage breast cancer showing pelareorep delivers a significant boost known to increase the effectiveness of checkpoint inhibitors (Press release, Oncolytics Biotech, DEC 9, 2020, View Source [SID1234572519]).

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In the AWARE-1 study, a collaboration between Oncolytics Biotech and SOLTI, early-stage breast cancer patients are treated with pelareorep, with or without atezolizumab (Tecentriq), plus an appropriate therapy for each patient’s breast cancer subtype, followed by surgery. The SABCS poster includes 17 out of the 20 HR+/HER2- breast cancer patients comprising the study’s first two cohorts, the targeted patient population for our intended phase 3 study. Treatment with pelareorep increased the CelTIL score in tumor biopsies, which has been associated with improved clinical outcomes. In addition, pelareorep treatment dramatically upregulated PD-L1 expression in the tumor microenvironment (TME). These findings highlight the potential of pelareorep to act synergistically with checkpoint inhibitors and also provides a basis for the near doubling of overall survival observed in a prior phase 2 trial when pelareorep was added to chemotherapy in HR+/HER2- breast cancer patients (link to PR, link to poster).

"AWARE-1 data demonstrate pelareorep’s consistent remodeling of the tumor immune environment," said Dr. Aleix Prat, M.D., Ph.D., Translational Investigator of AWARE-1, SOLTI President and Head of the Medical Oncology Department at Hospital Clinic in Barcelona. "Pelareorep seems to train the immune system to target cancer cells while simultaneously promoting tumor inflammation and priming a response to immune checkpoint blockade. This demonstrates pelareorep’s potential to overcome the immunosuppressive nature of the tumor microenvironment which could limit checkpoint inhibitor efficacy."

Key data and conclusions from the SABCS poster include:

72% of evaluated patients (n=18) saw an increase in CelTIL, the study’s primary endpoint that is associated with favorable clinical outcomes.
The maximum percentage increase in CelTIL (~300%) was achieved in a cohort 2 patient receiving pelareorep in combination with checkpoint blockade therapy.
On average, there was a 105-fold increase in TME PD-L1 expression (n=13) from baseline (pre-pelareorep administration) to surgery (21-days post-administration).
Tumor microenvironment PD-L1 expression increased in all evaluated patients (n=13).
Preliminary imaging mass cytometry analysis showed pelareorep treatment promoted broad anti-tumor changes in the TME, including enhanced CD8+ T cell activation and the recruitment of memory T cells.
Thomas Heineman, M.D., Ph.D., Global Head of Clinical Development and Operations at Oncolytics, commented, "In the AWARE-1 study, pelareorep delivered consistent increases in tumor PD-L1 expression and recruitment of anti-cancer immune cells into tumors, as well as increases in CelTIL score for over 70% of the patients. This is highly encouraging given the association between CelTIL and clinical outcomes, and we hope to observe the same success from our phase 2 BRACELET-1 trial, which is exclusively enrolling HR+/HER2- breast cancer patients."

Andrew de Guttadauro, President of Oncolytics Biotech U.S. and Global Head of Business Development, added, "Immune deserts or immunosuppressive tumor microenvironments limit tumor PD-L1 expression levels and thereby limit regulatory approval and commercial success of checkpoint inhibitors in certain breast and other malignancies. AWARE-1 data show that pelareorep can alter the tumor microenvironment and induce robust PD-L1 expression, highlighting the potential of pelareorep to boost the efficacy of checkpoint inhibitors and increase the proportion of patients eligible for these therapies. We expect this synergistic potential to enable the continued execution of our strategy to develop pelareorep-based therapies in collaboration with industry leaders."

The electronic poster, titled "A window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer (REO-027, AWARE-1)" is available in the SABCS virtual poster hall and on the Posters & Publications page of Oncolytics’ website (LINK).

Ongoing ‘trial-in-progress’ posters giving an overview of Oncolytics’ IRENE and BRACELET-1 study designs were also presented at SABCS and are available at the same locations.

About AWARE-1

AWARE-1 is an open-label window-of-opportunity study in early-stage breast cancer enrolling 38 patients into five cohorts:

Cohort 1 (n=10), HR+ / HER2- (pelareorep + letrozole)
Cohort 2 (n=10), HR+ / HER2- (pelareorep + letrozole + atezolizumab)
Cohort 3 (n=6), TNBC (pelareorep + atezolizumab)
Cohort 4 (n=6), HR+ / HER2+ (pelareorep + trastuzumab + atezolizumab)
Cohort 5 (n=6), HR- / HER2+ (pelareorep + trastuzumab + atezolizumab)
The study combines pelareorep, with or without atezolizumab, and the standard of care therapy according to breast cancer subtype. Patients are biopsied as part of their initial breast cancer evaluation, then again on day three following initial treatment, and a final tissue sample after three weeks, on the day of their mastectomy. Data generated from this study are intended to confirm that the virus is acting as a novel immunotherapy and to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint of the study is overall CelTIL (a measurement of cellularity and tumor-infiltrating lymphocytes). Secondary endpoints for the study include CelTIL by breast cancer subtype, safety, and tumor and blood-based biomarkers.

For more information about the AWARE-1 study, refer to View Source

Tecentriq (atezolizumab) is a registered trademark of Genentech, a member of the Roche Group.

About Breast Cancer

Breast cancer is the most common cancer in women worldwide, with over two million new cases diagnosed in 2018, representing about 25 percent of all cancers in women. Incidence rates vary widely across the world, from 27 per 100,000 in Middle Africa and Eastern Asia to 85 per 100,000 in Northern America. It is the fifth most common cause of death from cancer in women globally, with an estimated 522,000 deaths.

Breast cancer starts when cells in the breast begin to grow out of control. These cells usually form a tumor that can often be seen on an x-ray or felt as a lump. The malignant tumor (cancer) is getting worse when the cells grow into (invade) surrounding tissues or spread (metastasize) to distant areas of the body.

About Pelareorep

Pelareorep is a non-pathogenic, proprietary isolate of the unmodified reovirus: a first-in-class intravenously delivered immuno-oncolytic virus for the treatment of solid tumors and hematological malignancies. The compound induces selective tumor lysis and promotes an inflamed tumor phenotype through innate and adaptive immune responses to treat a variety of cancers and has been demonstrated to be able to escape neutralizing antibodies found in patients.