The following article features coverage from the 2020 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

The oncolytic virus pelareorep may mediate priming of an adaptive immune response in women with early breast cancer, according to a phase 1 study presented at the 2020 Virtual San Antonio Breast Cancer Symposium (SABCS).

“During the last few years, oncolytic viruses have emerged as a relevant tool for targeting different kinds of cancer, including breast cancer,” said Grey Wilkinson, PhD, of Oncolytics Biotech, Inc. “Pelareorep is an intravenously delivered and unmodified oncolytic virus that can replicate in tumor tissue and induce a T-cell inflamed phenotype by activating both innate and adaptive immune responses.”

Previous research had shown that intravenous pelareorep combined with paclitaxel significantly improved overall survival with equivalent objective response and progression-free survival in women with metastatic breast cancer.

Based on these results, the researchers hypothesized that the overall survival benefit from the combination may be because of an adaptive immune response triggered by the oncolytic virus.


Continue Reading

To test that, they designed the AWARE-1 study (within the “window program” of the SOLTI Breast Cancer Research Group; ClinicalTrials.gov Identifier: NCT04102618) evaluating the effects of pelareorep plus atezolizumab on the tumor microenvironment in 38 women with early breast cancer.

In the study, patients are treated with the oncolytic virus on days 1, 2, 8, and 9; and atezolizumab is administered on day 3. Tumor biopsies are collected on day 3 and around day 21. Outcomes were examined in different cohorts of disease subtypes.

Cohort 1 is hormone receptor (HR)-positive, HER2-negative disease cohort of patients treated with pelareorep plus letrozole. Cohort 2 is an HR-positive, HER2-negative disease cohort treated with pelareorep plus letrozole and atezolizumab. Cohort 3 is a group of patients with triple-negative breast cancer treated with pelareorep plus atezolizumab. Cohort 4 is made up of patients with HER2-positive, HR-positive treated with pelareorep plus trastuzumab plus atezolizumab. Cohort 5 is comprised of patients with HER2-positive, HR-negative disease treated with pelareorep plus trastuzumab plus atezolizumab.

The primary endpoint was CelTIL score, which represented changes in tumor cellularity and tumor-infiltrated lymphocytes. An increase in CelTIL is associated with a favorable response to treatment.

Data from the first 18 patients enrolled in the study showed a 72% CelTIL response rate irrespective of cohort. Programmed cell death ligand 1 (PD-L1) expression at surgery increased in all samples analyzed. On average, there was 105-fold increase in PD-L1 expression from baseline to surgery, Dr Wilkinson said.

Preliminary analysis in 1 patient from cohort 1 demonstrated promotion of recruitment of B cells and CD4/CD8-positive T cells to the tumor microenvironment, and treatment promoted T-cell activation and recruitment of memory T cells. According to the poster authors, preliminary results from this single patient “demonstrate that treatment with pelreorep can prime the tumor microenvironment for checkpoint blockade therapy and promote a T-cell based response in metastatic [breast cancer].”

Read more of Cancer Therapy Advisor‘s coverage of the 2020 SABCS meeting by visiting the conference page.

Reference

Manso L, Villagrasa P, Chic N, et al. A window-of-opportunity study with atezolizumab and the oncolytic virus pelareorep in early breast cancer (REO-027, AWARE-1). Presented at: 2020 Virtual San Antonio Breast Cancer Symposium (SABCS); December 8-11, 2020. Abstract PS12-08.