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Clinical Trial
. 2025 Jul 1;31(13):2655-2662.
doi: 10.1158/1078-0432.CCR-24-2701.

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

Amy S Clark  1 , Fengmin Zhao  2 , Paula Klein  3 , Alberto J Montero  4 , Carla Falkson  5 , Elisa Krill-Jackson  6 , Kendrith Rowland  7 , Sagar Sardesai  8 , Jason Incorvati  9 , Patrick Dillon  10 , Antonio C Wolff  11 , Richard Trauger  12 , Thomas C Heineman  12 , Matthew C Coffey  13 , Kathy D Miller  14
Affiliations
Clinical Trial

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

Amy S Clark et al. Clin Cancer Res. .

Abstract

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.

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Conflict of interest statement

A.S. Clark reports grants from Eli Lilly and Novartis and personal fees from Seimans outside the submitted work. C. Falkson reports grants from PrECOG/Oncolytics Biotech during the conduct of the study and grants from Eli Lilly and Quantum Leap Healthcare Collaborative outside the submitted work. S. Sardesai reports personal fees from Stemline, AstraZeneca, and Gilead outside the submitted work. J. Incorvati reports personal fees from 2nd.MD outside the submitted work. P. Dillon reports grants from Merck, Gilead, AstraZeneca, Pfizer, Seattle Genetics, and Daiichi Sankyo outside the submitted work. T.C. Heineman reports personal fees from Oncolytics Biotech during the conduct of the study and outside the submitted work. M.C. Coffey reports personal fees and other support from Oncolytics Biotech during the conduct of the study and outside the submitted work; in addition, M.C. Coffey has a patent for 60+ pending and issued to Oncolytics Biotech. K.D. Miller reports other support from Oncolytics Biotech during the conduct of the study. No disclosures were reported by the other authors.

Figures

Figure 1.
Figure 1.
The swimmer plot summarizes the duration of treatment and discontinuation of each therapy during the time on the study. Arrows show patients still on treatment. Black * indicates Pac discontinuation. Blue # indicates Pel discontinuation. Yellow ^ indicates Ave discontinuation. Time on treatment was calculated using the date of C1 D1 through the last day the drug was administered on day +28 (as the C length of the treatment was 28 days).
Figure 2.
Figure 2.
Peripheral T-cell clones: expansion in Pac/Pel but not Pac/Pel/Ave. Unique T-cell receptor β CDR3 clones were identified and followed through treatment. The Y-axis depicts the number of unique clones, and the X-axis depicts the time the sample was collected.
See this image and copyright information in PMC

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