Pelareorep Plus Chemo Improves OS in Endocrine-Refractory HR+/HER2– Advanced Breast Cancer

Treatment with pelareorep plus paclitaxel led to improvements in overall survival (OS) and progression-free survival (PFS) vs paclitaxel alone in patients with endocrine-refractory hormone receptor–positive/HER2-negative advanced or metastatic breast cancer, according to final efficacy data from the phase 2 BRACELET-1 study (NCT04215146).

Findings reported 2 years after the last patient was enrolled showed that the median OS was not reached (NR) in the pelareorep plus paclitaxel cohort (n = 16) compared with 18.2 months for the paclitaxel monotherapy arm (HR, 0.48; 95% CI, 0.17-1.35). The median OS was 21.7 months for the combination of paclitaxel plus pelareorep and avelumab (Bavencio; n = 17; HR vs paclitaxel monotherapy, 1.08; 95% CI, 0.45-2.57). The 2-year OS rates were 64% for pelareorep plus paclitaxel, 33% for paclitaxel alone, and 39% for pelareorep plus paclitaxel and avelumab.

The median OS for patients in the pelareorep plus paclitaxel arm was estimated to be 32.1 months if all patients survived until the the next assessment, which would have been 4 months after the 2-year mark. If all patients survived only 1 day after their final follow-up visit, the median OS estimate would have been 28.7 months.

The final median PFS was 12.1 months (95% CI, 6.6-15.9) in the pelareorep/paclitaxel arm vs 6.4 months (95% CI, 3.7-NR) in the paclitaxel monotherapy arm (HR, 0.39; 95% CI, 0.12-1.24). Notably, the median PFS was 6.4 months (95% CI, 4.0-7.5) in the triplet group (HR vs paclitaxel monotherapy, 1.43; 95% CI, 0.49-4.12).

Moreover, the confirmed overall response rate (ORR) was 37.5% in the pelareorep/paclitaxel arm, 13.3% for the paclitaxel monotherapy arm, and 17.6% in the triplet treatment arm. ORRs at week 16 in the pelareorep plus paclitaxel and paclitaxel monotherapy cohorts were 31% and 20%, respectively.

“The fact that the median OS was NR because more than half the patients were still alive at the end of the study is a remarkable achievement for us,” Wayne Pisano, interim chief executive officer and chair of the board of directors at Oncolytics Biotech, stated in a press release. “It shows just how promising pelareorep treatment can be for extending the lives of [patients with] breast cancer. This is further exemplified by the near doubling of the 2-year OS rate for patients who received pelareorep [plus paclitaxel].”

The open-label, randomized study randomly assigned patients with hormone receptor–positive/HER2-negative, endocrine-refractory metastatic breast cancer in a 1:1:1 fashion to 3 cohorts. Cohort 1 evaluated paclitaxel alone, cohort 2 evaluated paclitaxel plus pelareorep, and cohort 3 evaluated paclitaxel plus pelareorep and avelumab. Notably, a 3-patient safety run-in was also conducted in those receiving pelareorep, paclitaxel, and avelumab prior to randomization.

Patients in cohort 1 were treated with paclitaxel on days 1, 8, and 15 of 28-day cycles; patients in cohort 2 were treated with the same paclitaxel regimen as cohort 1, plus pelareorep on days 1, 2, 8, 9, 15 and 16 of the 28-day cycle; and patients in cohort 3 were treated with the same combination and dosing regimen as cohort 2, plus avelumab on days 3 and 17 of the 28-day cycle.

The primary end point of the study is ORR at week 16; PFS, peripheral and tumor T cell clonality, inflammatory markers, and safety and tolerability assessments served as exploratory end points.

The 3 BRACELET-1 study groups were well balanced in key factors that could influence therapy response, such as performance status, visceral disease presence, and post-progression treatment.

“The OS and final PFS 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,” Thomas Heineman, MD, PhD, chief medical officer at Oncolytics Biotech, explained in the news release. “Taken together, the BRACELET-1 results provide compelling support for the potential of pelareorep-based combination therapy to benefit patients with advanced or metastatic hormone receptor–positive/HER2-negative breast cancer.”

In the news release, Oncolytics Biotech noted that the clinical benefits seen with the pelareorep plus paclitaxel combination were not observed in the avelumab group, likely due to the suppression of the activation of cytotoxic T cells due to the addition of avelumab, which is essential for pelareorep's antitumor activity. This suppression may have occurred due to avelumab binding to Fc receptors, resulting in the elimination of pelareorep-induced immune responses through antibody-dependent cellular cytotoxicity and other mechanisms.

Oncolytics Biotech is taking the next steps to secure funding for a registration-enabling study of pelareorep-based therapy in advanced or metastatic breast cancer.

Reference

Oncolytics Biotech reports favorable results for BRACELET-1 breast cancer study reinforcing path to funding of a registration-enabling study. News release. Oncolytics Biotech. September 19, 2024. Accessed September 19, 2024. https://oncolyticsbiotech.com/press_releases/oncolytics-biotech-reports-favorable-results-for-bracelet-1-breast-cancer-study-reinforcing-path-to-funding-of-a-registration-enabling-study/