Pelareorep Plus Paclitaxel Extends Survival in HR+/HER2– Breast Cancer

Breast cancer, female anatomy: © peterschreiber.media - stock.adobe.com

The median overall survival (OS) was not reached with the combination of the oncolytic viral therapy pelareorep (Reolysin) plus paclitaxel for the treatment of patients with hormone receptor (HR)-positive/HER2-negative breast cancer, according to positive results from the phase 2 BRACELET-1 study (NCT04215146).¹

Final efficacy data from the randomized BRACELET-1 trial were collected and analyzed 2 years following the enrollment of the last patient, as specified by the protocol. In the pelareorep/paclitaxel arm, more than half of the patients remained alive at the end of the study compared with a median OS of 18.2 months in the paclitaxel monotherapy arm (HR, 0.48).

If the study follow-up had continued beyond the 2-year mark, and patients had only lived until their next planned visit in 4 months, the projected median OS in the pelareorep plus paclitaxel arm would have been 32.1 months.

"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, in a press release. "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."

The 2-year survival rate in the pelareorep plus paclitaxel group was 64% vs 33% in the paclitaxel monotherapy group. For progression-free survival (PFS), the final median was 12.1 months for the pelareorep/paclitaxel arm compared with 6.4 months in the paclitaxel monotherapy arm, resulting in a 5.7-month PFS benefit (HR, 0.39).

In the pelareorep/paclitaxel arm, the confirmed overall response rate (ORR) was 37.5% compared with 13.3% for paclitaxel. As previously reported for the trial’s primary end point of ORR at week 16, rates were 31% and 20% in the pelareorep and paclitaxel and paclitaxel monotherapy groups, respectively.

"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,” explained Thomas Heineman, MD, PhD, chief medical officer at Oncolytics, in the press release. “Moreover, these results substantiate the statistically significant near doubling of median overall survival observed in the earlier randomized IND-213 study [NCT01656538] in a similar patient population treated with pelareorep plus chemotherapy compared to chemotherapy alone. Having recently discussed with the FDA key design elements for our next breast cancer study, in combination with the strong survival data from the BRACELET-1 and IND-213 studies, we are confident in our plan to conduct a registration-enabling study to assess pelareorep-based combination therapy in patients with advanced HR+/HER2- breast cancer."

Martine J. Piccart, MD, PhD, Université Libre de Bruxelles added, "While there has been progress in the treatment of advanced and metastatic breast cancer, an unmet medical need remains. 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."

Background on the BRACELET-1 Trial

The BRACELET-1 study is an open-label, randomized, phase 2 trial designed to evaluate treatment outcomes in patients with HR-positive/HER2-negative, endocrine-resistant metastatic breast cancer.² A total of 45 patients were randomly assigned in a 1:1:1 ratio across 3 treatment groups. Additionally, a safety run-in was conducted with 3 patients receiving pelareorep, paclitaxel, and avelumab (Bavencio) before the randomization phase.

Cohort 1 received paclitaxel alone, cohort 2 received paclitaxel combined with pelareorep, and cohort 3 received paclitaxel combined with pelareorep and avelumab. Patients in cohort 1 were administered paclitaxel on days 1, 8, and 15 within a 28-day treatment cycle. Cohort 2 followed the same paclitaxel schedule but also received pelareorep on days 1, 2, 8, 9, 15, and 16. Cohort 3 received both paclitaxel and pelareorep on the same schedule as cohort 2, with the addition of avelumab on days 3 and 17.

Enrollment in the study was open to female patients aged 18 years and older with a histological or cytological diagnosis of breast cancer, and ECOG performance status of 0 to 1, and measurable disease as defined by RECIST v1.1. Patients also must have received prior hormonal therapy, provide blood samples for research, and have adequate organ function.

The study’s primary end point is to assess the overall response rate at week 16. Secondary objectives include PFS, evaluation of T-cell clonality in blood and tumor samples, inflammatory markers, and safety/tolerability assessments.

REFERENCES:

1. Oncolytics Biotech® reports favorable results for BRACELET-1 breast cancer study reinforcing path to funding of a registration-enabling study. News release. Oncolytics Biotech, Inc. September 19, 2024. Accessed September 19, 2024. https://tinyurl.com/5n6rc3cs

2. A study to assess overall response rate by inducing an inflammatory phenotype in metastatic breast cancer with the oncolytic reovirus pelareorep in combination with anti-PD-L1 avelumab and paclitaxel - BRACELET-1 study. Clinicaltrials.gov. Updated November 30, 2024. Accessed September 19, 2024. https://www.clinicaltrials.gov/study/NCT04215146