Clinical Research Papers:

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 and Setsuya Aiba

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Oncotarget. 2017; 8:71181-71187. https://doi.org/10.18632/oncotarget.17090

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Taku Fujimura1, Takanori Hidaka1, Yumi Kambayashi1, Sadanori Furudate1, Aya Kakizaki1, Hisayuki Tono1, Akira Tsukada1, Takahiro Haga1, Akira Hashimoto1, Ryo Morimoto2, Takuhiro Yamaguchi3, Tadao Takano4, Setsuya Aiba1

1Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, Japan

2Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University Hospital, Sendai, Japan

3Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Japan

4Clinical Research, Innovation and Education Center, Tohoku University Hospital, Sendai, Japan

Correspondence to:

Taku Fujimura, email: [email protected]

Keywords: IFN-β, PD-1, safe dose, traditional rule-based 3 + 3 design

Received: January 24, 2017    Accepted: March 21, 2017    Published: April 13, 2017


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 dose-limiting 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.

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PII: 17090