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

Purpose: Pelareorep (Pel) is a type 3 oncolytic reovirus that upregulates PD-L1 expression. We determined the objective response rate (ORR) with paclitaxel (Pac), Pac + Pel, or Pac + Pel + avelumab (Ave). Patients and Methods: Patients with hormone receptor positive (HR+) HER2 negative metastatic breast cancer (MBC) who had progressed on at least one line of endocrine therapy with a CDK 4/6 inhibitor and had not received chemotherapy for MBC were eligible. Patients were randomized 1:1:1 to Pac, Pac/Pel or Pac/Pel/Ave after a three-patient run-in confirmed safety of the triplet. Response was assessed every 8 weeks until week 16 and then every 12 weeks using RECIST v1.1. The primary endpoint was 16-week ORR. Statistical comparison across arms was not planned. Results: 48 patients enrolled with 45 randomized, 16-week ORR was 20%, 31% and 14% in the Pac, Pac/Pel and Pac/Pel/Ave arms, respectively. Median progression-free survival (PFS) was 6.4 months (m), 12.1m and 5.8m in the Pac, Pac/Pel and Pac/Pel/Ave arms respectively. There were more adverse events, particularly infusion reactions, in the combination arms than the Pac arm. Expansion of peripheral T cell clones were observed by cycle (C)4 in Pac/Pel but not the Pac or Pac/Pel/Ave arms. Conclusions: The addition of Pel to Pac was associated with increased toxicity, expanded peripheral T-cell clones, and numerically increased ORR and PFS compared to Pac; Pac/Pel/Ave further increased toxicity and blunted T cell responses without obvious increase in efficacy. Investigation of the Pac/Pel combination warrants consideration with careful attention to acute toxicity.