FDA Receives Type C Meeting Request for Pelareorep in HR+/HER2– Metastatic Breast Cancer


The FDA has received a type C meeting request from Oncolytics Biotech to discuss a registration-enabling trial for pelareorep in HR+/HER2– breast cancer.

Matt Coffey, PhD

Matt Coffey, PhD

The FDA has received a type C meeting request from Oncolytics Biotech to discuss a registration-enabling trial to evaluate pelareorep for the treatment of patients with hormone receptor (HR)–positive, HER2-negative metastatic breast cancer.1

“A key focus for Oncolytics in 2024 is defining the regulatory path for pelareorep in breast cancer treatment. We are optimistic that pelareorep, in combination with paclitaxel, could significantly enhance clinical outcomes for patients with HR-positive/HER2-negative metastatic breast cancer. Our position is strengthened by encouraging data from 2 [phase 2] randomized studies, [the BRACELET-1 (NCT04215146) and IND-213 (NCT01656538) trials], as well as the [early phase 1] AWARE-1 study [NCT04102618], paving the way for the next phase of pelareorep’s development and its registration. Ongoing discussions with our clinical collaborators and partners have helped us to prepare a robust, compelling briefing document,” Matt Coffey, PhD, president and chief executive officer of Oncolytics Biotech, stated in a news release.

Pelareorep is a type 3 reovirus designed to invade and lyse tumor cells, as well as promote an inflammatory tumor microenvironment.2

Findings from BRACELET-1 presented at the 2023 ASCO Annual Meeting showed that patients treated with the combination of pelareorep and paclitaxel (n = 16) experienced an overall response rate (ORR) of 31% (95% CI, 11%-59%) at week 16 compared with 20% (95% CI, 4%-48%) in patients given paclitaxel alone (n = 15) and 14% (95% CI, 2%-43%) in patients treated with pelareorep plus paclitaxel and avelumab (Bavencio; n = 14). All responders achieved partial responses, and the disease control rates were 62% (95% CI, 35%-85%), 47% (95% CI, 21%-73%), and 64% (95% CI, 35%-87%), respectively.

Additionally, pelareorep plus paclitaxel elicited a median progression-free survival (PFS) of 9.6 months (95% CI, 6.5–not reached [NR]) vs 6.4 months (95% CI, 2.0-NR) for paclitaxel alone and 5.8 months (95% CI, 3.5-NR) for pelareorep plus paclitaxel and avelumab. The 6-month PFS rates were 86% (95% CI, 54%-96%), 62% (95% CI, 28%-84%), and 50% (95% CI, 18%-74%), respectively.

The study enrolled patients with advanced or metastatic HR-positive/HER2-negative breast cancer, and after 3 patients were enrolled to receive pelareorep plus paclitaxel and avelumab as a safety run in, subsequent enrollees were randomly assigned 1:1:1 to receive paclitaxel alone (cohort 1); pelareorep plus paclitaxel (cohort 2); or pelareorep plus paclitaxel and avelumab (cohort 3). Pelareorep was administered on days 1, 2, 8, 9, 15, and 16 of each 28-day cycle; paclitaxel was given on days 1, 8, and 15 of each cycle; and avelumab was given on days 3 and 17 of each cycle.

ORR at week 16 served as the trial’s primary end point. Secondary end points included ORR at the end of the study, overall survival (OS), PFS, safety, and biomarker assessments.

OS data from the study are expected to be reported in the second half of 2024.1

Regarding safety, the most common any-grade adverse effects (AEs) attributed to study drugs included alopecia (paclitaxel, 50%; pelareorep/paclitaxel, 56%; triplet, 47%), anemia (58%; 31%; 59%), anorexia (33%; 31%; 29%), chills (0%; 44%; 29%), diarrhea (8%; 38%; 47%), fatigue (42%; 75%; 47%), infusion-related reaction (8%; 19%; 53%), leucopenia (17%; 19%; 65%), liver-function test abnormality (25%; 38%; 53%), lymphopenia (25%; 19%; 24%), nausea (33%; 44%; 47%), neuropathy (25%; 50%; 59%), neutropenia (25%; 31%; 59%), proteinuria (17%; 38%; 24%), and pyrexia (0%; 50%; 65%).2

Notably, viral-like symptoms were more common in patients who received a pelareorep-based regimen. These AEs of special interest included chills (paclitaxel, 0%; pelareorep/paclitaxel, 44%; triplet, 29%), pyrexia (0%; 50%; 65%), influenza-like symptoms (0%; 25%; 29%), and infusion-related reactions (8%; 19%; 53%).

“The data from the randomized BRACELET-1 trial showcased compelling results for the pelareorep/paclitaxel combination therapy in [patients with] HR-positive/HER2-negative metastatic breast cancer, with a nearly tripled confirmed ORR, a 50% improvement in median PFS, and a hazard ratio of 0.29 compared to the paclitaxel alone control,” Thomas Heineman, MD, PhD, chief medical officer at Oncolytics Biotech, added in the press release.1 “Importantly, these data support the statistically significant near doubling of median OS in another randomized phase 2 study, IND-213, which also evaluated pelareorep and paclitaxel in [patients with HR-positive/HER2-negative metastatic breast cancer.”

Findings from IND-213 showed that at a median follow-up of 29.5 months, patients treated with pelareorep/paclitaxel experienced a median OS of 17.4 months vs 10.4 months for those given paclitaxel alone (HR 0.65; 80% CI, 0.46-0.91; P = .1). Additionally, the median PFS was 3.78 months vs 3.38 months, respectively (HR 1.04; 80% CI, 0.76-1.43; P = .87).3


  1. Oncolytics Biotech advances toward registration-enabling trial for pelareorep in breast cancer with submission of type C meeting request to FDA. News release. Oncolytics Biotech. April 11, 2024. Accessed April 12, 2024. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-advances-toward-registration-enabling-trial-for-pelareorep-in-breast-cancer-with-submission-of-type-c-meeting-request-to-fda-2/
  2. Clark AS, Zhao F, Klein P, et al. BRACELET-1 (PrE0113): inducing an inflammatory phenotype in metastatic HR+/HER2- breast cancer with the oncolytic reovirus pelareorep in combination with paclitaxel and avelumab. J Clin Oncol. 2023;41(suppl 16):1012. doi:10.1200/JCO.2023.41.16_suppl.1012
  3. Bernstein V, Ellard SL, Dent SF, et al. A randomized phase II study of weekly paclitaxel with or without pelareorep in patients with metastatic breast cancer: final analysis of Canadian Cancer Trials Group IND.213. Breast Cancer Res Treat. 2018;167(2):485-493. doi:10.1007/s10549-017-4538-4
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