The official results of the BRACELET-01 (PrECOG 0113) trial have been published in Clinical Cancer Research, detailing the safety and efficacy of pelareorep, an investigational oncolytic virus immunotherapy, when added to paclitaxel chemotherapy, both with and without the checkpoint inhibitor avelumab. The trial included 48 patients with unresectable metastatic hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) tumors. All had experienced disease progression after receiving at least one line of endocrine therapy with a cyclin-dependent kinase 4/6 inhibitor.
"Our study results support further investigation of the paclitaxel-pelareorep combination while monitoring acute toxicity. Until now, immunotherapy in patients with HR+ HER2- metastatic breast cancer has been largely unsuccessful, prompting the trial to test if paclitaxel and pelareorep could enhance sensitivity to checkpoint inhibition with avelumab," said Amy S. Clark, MD, a medical oncologist at Penn Medicine in Philadelphia and first author of the report.1
Pelareorep is a naturally occurring, non-pathogenic oncolytic virus with two key complementary actions when administered intravenously. First, it stimulates anti-tumor immune responses; second, it enhances the immune system's ability to recognize and respond to tumors.
BRACELET-1 tested the hypothesis that exposure to paclitaxel (Pac) and pelareorep (Pel) can upregulate PD-L1 expression, thereby sensitizing HR+ HER2- tumors to checkpoint inhibition with avelumab (Ave). Furthermore, the study aimed to investigate an intriguing finding by the Canadian Cancer Trials Group. Pooled data from four separate trials across various solid tumors suggested that Pac/Pel improved overall survival compared to Pac alone in the HR+ HER2- metastatic breast cancer cohort.2
Forty-eight patients with HR+ HER2- metastatic breast cancer enrolled in BRACELET-1 between June 2020 and June 2022. The median age was 55 (range 37-74). Most participants were White, non-Hispanic, and postmenopausal. Following a safety run-in of the Pac/Pel/Ave combination, 45 patients were randomized 1:1:1 into three treatment groups: Pac, Pac/Pel, or Pac/Pel/Ave. Patients remained on study until progression or unacceptable toxicity. Safety was assessed continuously.
The primary endpoint was the objective response rate (ORR) at 16 weeks, which was 20% for Pac, 31% for Pac/Pel, and 14% for Pac/Pel/Ave. Progression-free survival (PFS) was also assessed, showing a median PFS of 6.4 months for Pac, 12.1 months for Pac/Pel, and 5.8 months for Pac/Pel/Ave.
"There were numerically higher ORR and PFS in the Pac/Pel group, compared to Pac alone, but more adverse events were reported in the combination arms. Notably, a boost in T-cell clones was seen by cycle 4 in the Pac/Pel arm but not in the Pac arm, suggesting enhanced immune potential with the combination," said Dr. Clark.
T-cell proliferation is crucial in immunotherapy as it enhances the immune system's ability to target and eliminate cancer cells. Pac/Pel/Ave further increased toxicity and blunted T-cell responses without an obvious increase in efficacy.
"These intriguing results from PrECOG 0113 merit additional study of this novel treatment," said Peter J. O'Dwyer, MD, chief executive officer of PrECOG.
More About the Trial
The BRACELET-1 / PrECOG 0113 study ( NCT04215146 ) was coordinated by PrECOG, LLC and funded by Oncolytics Biotech, Pfizer, and Merck KGaA, Darmstadt, Germany.
The full report, A Phase II Randomized Study of Paclitaxel Alone or Combined with Pelareorep with or without Avelumab in Metastatic Hormone Receptor–Positive Breast Cancer: The BRACELET-01/PrE0113 Study, is publicly available here .
About PrECOG
PrECOG, LLC is a cancer research organization that designs and conducts innovative oncology studies through industry partnerships and research networks. The central focus of PrECOG is to conduct trials that align with the overall scientific mission and research goals of the ECOG-ACRIN Cancer Research Group. Visit www.precogllc.org and follow us on Twitter @PrECOGonc , Facebook , and LinkedIn .
References
1 Clark AS, Zhao F, Klein P, Montero AJ, Falkson C, Krill-Jackson E et al. A Phase II Randomized Study of Paclitaxel Alone or Combined with Pelareorep with or without Avelumab in Metastatic Hormone Receptor–Positive Breast Cancer: The BRACELET-01/PrE0113 Study. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-2701
2 Gutierrez AA, Reid C, Dzugalo A, Crawford M, Cheetham K, Parsi M, et al. Pooled Data Analysis of the Safety and Tolerability of Intravenous Pelareorep in Combination with Chemotherapy in 500+ Cancer Patients. Ann Oncol 2017; 28: v403–27; https://doi.org/10.1093/annonc/mdx376.056
