The Safety Committee evaluating Onclytics Biotech Inc’s pelareorep has found no safety concerns after evaluating the first 3 cohorts.1 Early findings from the AWARE-1 trial investigating pelareorep for early-stage breast cancer have found that T cell clonality may support the development of a biomarker for the disease, according to a press release.2

More than 2 million new breast cancer cases were diagnosed globally in 2018, representing about a quarter of all cancers in women.2

Pelareorep is an immune-oncolytic virus for intravenous (IV) delivery. The drug is a non-pathogenic, proprietary isolate of the unmodified reovirus for the treatment of solid tumors and hematological malignancies. It induces selective tumor lysis and promotes inflammation of the tumor phenotype through innate and adaptive immune responses.1

According to preliminary findings announced in 2019, the first 3 patients demonstrated immunohistochemically positive viral replication in the tumor mass following intravenous administration of pelareorep in combination with atezolizumab. Of the 3 patients, 2 showed greater than 50% of the tumor cells infected. The drug was found to generate inflammation and T cell recruitment at the tumor site.2

“These observations are supportive of our previous findings of improved survival in metastatic breast cancer patients, which will allow us to further refine our phase 3 registration study,” said Matt Coffey, PhD, MBA, president and CEO of Oncolytics Biotech, in a statement.2

Increases in programmed death-ligand 1 (PD-L1) expression on tumor cells were found in all 3 patients, and the data suggested a correlation between T cell clonality and viral replication with highly infected tumors. 2

Notably, no additional adverse effects (AEs) were seen in patients receiving the combination of pelareorep and atezolizumab beyond the AEs observed for each agent individually, according to the press release.2

The AWARE-1 trial has enrolled 38 patients who are divided into 5 cohorts: 10 will receive pelareorep and letrozole; 10 will receive pelareorep, letrozole, and atezolizumab; 6 will receive pelareorep and atezolizumab; 6 will receive pelareorep, trastuzumab, and atezolizumab; and the final 6 will receive pelareorep, trastuzumab, and atezolizumab. Cohort 1 has been fully enrolled and select patients from cohorts 2 and 3 were evaluated by the safety committee.1

Six of the patients have triple-negative breast cancer, whereas the rest are patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer.1

The patients are biopsied on day 1, followed immediately by treatment. They are then biopsied on day 3, and finally again after 3 weeks on the day of their mastectomy.1

The researchers hope to confirm that the virus is acting as a novel immunotherapy, as well as to provide comprehensive biomarker data by breast cancer subtype. The primary endpoint is overall pathologic response based on tumor cellularity and tumor-infiltrating lymphocytes.2

“While we have previously demonstrated tumor targeting following systemic delivery in the metastatic setting, these data provide the first evidence that pelareorep can be effectively delivered intravenously and target primary breast cancer,” Coffey said.2

Based on the positive safety update, recruitment for the study is continuing. The researchers plan to present updated data at the European Society for Medical Oncology Breast Cancer conference in May.1

REFERENCE
  1. Oncolytics Biotech Announces Favourable AWARE-1 Safety Update [news release]. Oncolytics Biotech; March 24, 2020. https://www.oncolyticsbiotech.com/press-releases/detail/497/oncolytics-biotech-announces-favourable-aware-1-safety. Accessed March 26, 2020.
  2. 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]. Oncolytics Biotech; July 23, 2019. https://www.oncolyticsbiotech.com/press-releases/detail/497/oncolytics-biotech-announces-favourable-aware-1-safety. Accessed March 26, 2020.