Final results from the phase 2 BRACELET-1 study reveal that combining pelareorep with paclitaxel significantly improves overall survival (OS) in patients with hormone receptor-positive (HR+), HER2-negative advanced or metastatic breast cancer. The study, a randomized, open-label trial, demonstrated a notable survival benefit and progression-free survival (PFS) advantage, suggesting a promising new treatment approach for this patient population.
Improved Survival Outcomes
The data indicated that the median OS was not reached in the pelareorep/paclitaxel arm, while patients receiving paclitaxel monotherapy had a median OS of 18.2 months (HR, 0.48; 95% CI, 0.17-1.35). Based on continued follow-up, the estimated median OS in the pelareorep arm was 32.1 months. The 2-year OS rates were 64% in the combination arm compared to 33% in the paclitaxel-only arm.
"The fact that the median overall survival was not reached because more than half the patients were still alive at the end of the study is a remarkable achievement for us," said Wayne Pisano, interim chief executive officer and chair of Oncolytics' board of directors. "It shows just how promising pelareorep treatment can be for extending the lives of breast cancer patients. This is further exemplified by the near doubling of the 2-year survival rate for patients who received pelareorep combination therapy."
Progression-Free Survival and Response Rates
The final median progression-free survival (PFS) in the pelareorep/paclitaxel arm was 12.1 months (95% CI, 6.6-15.9), compared to 6.4 months (95% CI, 3.7-NR) in the paclitaxel arm (HR, 0.39; 95% CI, 0.12-1.24). The confirmed overall response rate (ORR) was 37.5% with the combination, versus 13.3% with paclitaxel alone. At week 16, the respective response rates were 31% vs 20%.
BRACELET-1 Study Design
The BRACELET-1 trial enrolled 45 patients with HR-positive, HER2-negative, endocrine-refractory metastatic breast cancer, randomly assigning them to paclitaxel monotherapy (n = 15), pelareorep plus paclitaxel (n = 16), or triplet therapy with paclitaxel, pelareorep, and avelumab (n = 17). Paclitaxel was administered at 80 mg/m2 intravenously on days 1, 8, and 15 of a 28-day cycle. Pelareorep was given at 4.5 x 10^10 TCID50 intravenously on days 1, 2, 8, 9, 15, and 16, and avelumab at 10 mg/kg intravenously on days 3 and 17.
The primary endpoint was ORR at week 16, with exploratory endpoints including PFS, T cell clonality, inflammatory markers, and safety/tolerability. Patients had to have disease progression on at least one prior line of hormone-based therapy, including a CDK4/6 inhibitor.
Clinical Implications
"The overall survival and final progression-free survival results from the BRACELET-1 final analysis exceeded our expectations. In addition, our translational data strongly suggest that the OS benefit was linked to pelareorep's immunologic activity. Taken together, the BRACELET-1 results provide compelling support for the potential of pelareorep-based combination therapy to benefit patients with advanced or metastatic HR+/HER2– breast cancer," said Thomas Heineman, MD, PhD, chief medical officer at Oncolytics Biotech Inc.
Martine J. Piccart, MD, PhD, a professor of Oncology at the Université Libre de Bruxelles, emphasized the remaining unmet need in advanced breast cancer treatment, stating, "With the encouraging results of BRACELET-1 and the prior positive results of the IND-213 study, pelareorep should continue to be developed and evaluated in the clinical setting."
