Minami, Hironobu, Doi, Toshihiko, Toyoda, Masanori, Imamura, Yoshinori, Kiyota, Naomi, Mitsuma, Awake, Shimokata, Tomoya, Naito, Yoichi, Matsubara, Nobuaki, TAJIMA, TAKESHI, TOKUSHIGE, KOTA, ISHIHARA, KAE, Cameron, Scott and Ando, Yuichi (2020) Phase I study of the antiprogrammed cell death-1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies. Cancer Science, 00. pp. 1-9. ISSN 13497006

Abstract

Spartalizumab is a humanized IgG4/κ mAb directed against human programmed cell death-1 (PD-1). In this phase I study, we investigated safety, pharmacokinetics, preliminary antitumor activity, and toxicity of spartalizumab in patients with advanced malignancies. Patients (n = 18) with a range of tumor types received spartalizumab i.v. at doses of 1, 3, and 10 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or discontinuation at the discretion of the investigator or patient. Most patients (61%) had received five or more prior lines of therapy. No dose-limiting toxicities were reported and, hence, the maximum tolerated dose was 10 mg/kg or more. Pharmacokinetics in Japanese patients aligned with those reported in a global dose-escalation study. The safety profile was consistent with other approved anti-PD-1 mAbs; the most common drug-related adverse events were maculopapular rash (22%), followed by malaise and increased blood alkaline phosphatase (11% each). Partial responses were reported in two patients (11%), one with transitional cell carcinoma and the other with hepatocellular carcinoma. In conclusion, this study confirmed the safety of spartalizumab given at a dose of up to 10 mg/kg every 2 weeks in Japanese patients with cancers.

Item Type:	Article
Keywords:	clinical trial humanized monoclonal antibody immunotherapy Japan maximum tolerated dose
Date Deposited:	16 Jan 2021 00:45
Last Modified:	16 Jan 2021 00:45
URI:	https://oak.novartis.com/id/eprint/42118