Novel Immunotherapy Strategy Demonstrates Favorable Toxicity in Early-Stage Breast Cancer

In Clinical Studies News by Barbara Jacoby

By: Danielle Ternyila


Patients with early-stage breast cancer who received pelareorep demonstrated consistent data with safety run-in data and had a favorable toxicity profile, according to an cohort analysis from the window-of-opportunity study, AWARE-1 (NCT04102618).1

Safety parameters were evaluated by a committee of investigators from patients who participated in the safety run-in portion of the trial. The committee determined no safety concerns with this therapy.

“After reviewing the totality of safety data, including patients receiving pelareorep plus the standard of care and those also receiving Tecentriq, the Safety Committee for AWARE-1 confirmed no significant toxicity resulting from treatment,” said Rita Laeufle, MD, PhD, chief medical officer at Oncolytics Biotech. “The study is continuing as planned, recruiting additional patients and examining the combination of pelareorep, plus the standard of care plus Tecentriq.”

An amendment has been made to the study, reducing the dose of TECENTRIQ to be consistent with the currently approved dose of 840 mg for patients with breast cancer. Patients will continue to be enrolled on the study; cohorts 1 and 2 represent the target tumor type, hormone receptor (HR)-positive and HER2-negative. Data from these 2 cohorts will inform the design of the expected phase III study.

The trial is enrolling patients to 5 cohorts, including patients with HR-positive/HER2-negative early-stage disease receiving pelareorep plus letrozole (cohort 1), HR-positive/HER2-negative receiving pelareorep plus letrozole and atezolizumab (Tecentriq; cohort 2), triple-negative breast cancer receiving pelareorep plus atezolizumab (cohort 3), HR-positive/HER2-positive with pelareorep plus trastuzumab and atezolizumab (cohort 4), and HR-negative/HER2-positive receiving pelareorep plus trastuzumab plus atezolizumab.

Cohorts 1 and 2 are expected to enroll 10 patients each, while the remaining cohorts will enroll 6 total patients each. Patients are treated with the standard of care regimen for their type of breast cancer, plus pelareorep and atezolizumab.

Pelareorep is an unmodified oncolytic reovirus that is given intravenously. Prior studies have demonstrated that this therapy can replicate tumor tissue and promote inflamed tumor phonotype characterized recruitment of CD8-positive T cells and upregulation of PD-L1 expression.2

Investigators hypothesize that the therapy can be used to mediate anti-tumor immune responses and could act as a novel strategy for controlling or eliminating tumor cells in breast cancer. In the preoperative setting for early-stage breast cancer, investigators believe pelareorep could offer clinical benefit in combination with anti-PD-L1 therapy, such as atezolizumab.2

According to preliminary findings, 3 patients demonstrated immunohistochemically positive viral replication in the tumor mass, and 2 of these patients showed more than 50% of the tumor cells infected. All patients had increased in PD-L1 expression on tumor cells. These early data suggested a correlation between T cell clonality and viral replication with highly infected tumors.3

To be included in this study, patients must have biopsiable disease, and a histologically confirmed HER2 status, as well as HR. They should also have an ECOG performance status of 0 or 1 and adequate organ function within 14 days of randomization. Patients with inoperable locally advanced or inflammatory, metastatic, or bilateral invasive breast cancer are not eligible to enroll. Patients cannot be included if they have had prior therapy for breast cancer or prior therapy with a tumor vaccine.

Patients are biopsied on day 1 and immediately treated, then again on day 3, followed by a final biopsy after 3 weeks on the day of their mastectomy. The data from this trial is intended to confirm the virus is acting as a novel immunotherapy and provide a greater understanding of biomarker data by breast cancer subtype. The primary end point of the trial is an overall measurement of cellularity and tumor-infiltrating lymphocytes (CelTIL). Secondary end points also include CelTIL by breast cancer subtype, safety and tumor, and blood-based biomarkers.



  1. Oncolytics Biotech® Announces Favourable AWARE-1 Safety Update [News Release]. San Diego, CA: Oncolytics Biotech, Inc.; March 24, 2020. Accessed March 25, 2020.
  2. Manso L, Villagrasa P, Chic N, et al. A window-of-opportunity study of pelareorep in early breast cancer (AWARE-1). Presented at: 2019 Society of Immunotherapy of Cancer (SITC) Annual Meeting; November 6-10, 2019; National Harbor, MD.
  3. Oncolytics Biotech® Announces Preliminary AWARE-1 Trial Data Demonstrating Viral Replication and Promotion of Inflammation Following Systemic Administration of Pelareorep When Combined with Tecentriq [News Release]. San Diego, CA: Oncolytics Biotech, Inc.; July 23, 2019. Accessed March 25, 2020.