A phase II trial of stereotactic body radiotherapy with concurrent anti-PD1 treatment in metastatic melanoma: evaluation of clinical and immunologic response

• DOI: 10.1186/s12967-017-1123-x
• Publication Date: 2017-01-31T02:47:34Z
• Authors: Katrien De Wolf; Vibeke Kruse; Nora Sundahl; Mireille van Gele; Ines Chevolet; Reinhart Speeckaert; Lieve Brochez; Piet Ost
• Keywords: Clinical endpoint

Antibodies blocking programmed cell death 1 (PD-1) have encouraging responses in patients with metastatic melanoma. Response to anti-PD-1 treatment requires pre-existing CD8+ T cells that are negatively regulated by PD-1-mediated adaptive immune resistance. Unfortunately, less than half of melanoma tumours these characteristics. Combining other immunomodulating treatments activate is therefore vital importance increase response rates and long-term survival benefit patients. Both preclinical retrospective clinical data support the hypothesis radiotherapy increases stimulating accumulation activation tumour microenvironment. a PD-1 antibody might even induce survival. The current phase II study will be testing hypotheses aims improve local distant exploiting pro-immunogenic effects addition treatment.The trial conducted Nivolumab or pembrolizumab, both antibodies target PD-1, administrated according recommended dosing schedule. Prior 2nd cycle, delivered three fractions 8 Gy largest FDG-avid lesion. primary endpoint proportion partial complete non-irradiated metastases RECIST v1.1. Secondary endpoints include rate related criteria, metabolic response, control To identify peripheral blood biomarkers, mononuclear serum samples collected prospectively before, during after subjected flow cytometry cytokine measurement.The at exploring suggested benefits combining radiotherapy. translational focus on immunologic markers suitable for predicting efficacy monitoring effect so patient selection future applications. ClinicalTrials.gov Identifier NCT02821182.