Phase I study of nivolumab combined with IFN-β for patients with advanced melanoma

Taku Fujimura, Takanori Hidaka, Yumi Kambayashi, Sadanori Furudate, Aya Kakizaki, Hisayuki Tono, Akira Tsukada, Takahiro Haga, Akira Hashimoto, Ryo Morimoto, Takuhiro Yamaguchi, Tadao Takano, Setsuya Aiba

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19 Citations (Scopus)


The efficacy of nivolumab is greater than that of other anti-melanoma drugs, so nivolumab-based combined therapies that enhance anti-tumor immune responses in patients with metastatic melanoma are of great interest to dermato-oncologists. As we have previously reported, IFN-β enhances the anti-tumor immune response of anti-PD-1 antibodies against B16F10 melanoma in vivo. To explore the potential of this property of IFN-β as part of a combination therapy for the treatment of metastatic melanoma patients, we performed a phase 1 trial, using a traditional rule-based 3 + 3 design, on patients with advanced melanoma. The nivolumab dose was fixed at 2 mg/kg, every 3 weeks. IFN-β was administered to three groups at doses of 1 million, 2 million, and 3 million units, respectively. Dose-limiting toxicities were defined as any grade 3-5 adverse events occurring between day 0 and day 42 that might possibly be related to nivolumab and IFN-β. Of the nine patients who received this combined therapy, none experienced doselimiting toxicities, and all completed the treatment phase of the study. Patient follow-up continued for 6 months following the final treatment. There were two complete responses (22%) and one partial response (11%), all of which occurred in patients who had received monthly IFN-β immediately prior to the study. In this study, we determined the safe dose of IFN-β, when combined with nivolumab, to be 3 million units. To determine the efficacy of this combination therapy, further phase II trials are required.

Original languageEnglish
Pages (from-to)71181-71187
Number of pages7
Issue number41
Publication statusPublished - 2017


  • IFN-β
  • PD-1
  • Safe dose
  • Traditional rule-based 3 + 3 design


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