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, HER2-negative metastatic breast cancer who had progressed on at least one line of endocrine therapy with a cyclin-dependent kinase 4/6 inhibitor and had not received chemotherapy for metastatic breast cancer 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 regimen. 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: Forty-eight patients were enrolled, with 45 randomized. The 16-week ORR was 20%, 31%, and 14% in the Pac, Pac/Pel, and Pac/Pel/Ave arms, respectively. The median progression-free survival was 6.4, 12.1, and 5.8 months 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 was observed by cycle 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 the ORR and progression-free survival compared with 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.