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Randomized Phase II Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront Treatment of Metastatic Pancreatic Adenocarcinoma.
Molecular Therapy (2016)
  • Miguel A. Villalona Calero, M.D.
Abstract
Pelareorep causes oncolysis in tumor cells with activated Ras. We hypothesized pelareorep would have efficacy and immunomodulatory activity in metastatic pancreatic adenocarcinoma (MPA) when combined with carboplatin and paclitaxel. A randomizedphaseII study (NCT01280058) was conducted in treatment-naïve patients with MPA randomized to two treatment arms: paclitaxel/carboplatin + pelareorep (Arm A, n=36 evaluable patients) versus paclitaxel/carboplatin (Arm B, n=37 evaluable patients). There was no difference in PFS between arms (Arm A PFS=4.9 months, Arm B PFS=5.2 months, p=0.6), and KRAS status did not impact outcome. Quality-adjusted Time without Symptoms or Toxicity (QTWiST) analysis revealed the majority of PFS time was without toxicity or progression (4.3 months). Patient immunophenotype appeared important, as soluble immune biomarkers were associated with treatment outcome (Fractalkine, IL-6, IL-8, RANTES, VEGF). Increased circulating T and NK-cell subsets were also significantly associated with treatment outcome. Addition of pelareorep was associated with higher levels of 14 pro-inflammatory plasma cytokines/chemokines and cells with an immunosuppressive phenotype (Tregs, CTLA4+ T cells). Overall, pelareorep was safe but does not improve PFS when administered with carboplatin/paclitaxel, regardless of KRAS mutational status. Immunologic studies suggest the chemotherapy backbone improves immune reconstitution and that targeting remaining immunosuppressive mediators may improve oncolytic virotherapy.Molecular Therapy (2016); doi:10.1038/mt.2016.66.
Publication Date
April, 2016
DOI
10.1038/mt.2016.66
Citation Information
Miguel A. Villalona Calero. "Randomized Phase II Trial of the Oncolytic Virus Pelareorep (Reolysin) in Upfront Treatment of Metastatic Pancreatic Adenocarcinoma." Molecular Therapy (2016)
Available at: http://works.bepress.com/miguel-villalonacalero/103/