Journal Article

Phase I study of the antiprogrammed cell death‐1 Ab spartalizumab (PDR001) in Japanese patients with advanced malignancies

Toyoda, Masanori, Imamura, Yoshinori, Shimokata, Tomoya, Mitsuma, Ayako, Kiyota, Naomi, Doi, Toshihiko, Cameron, Scott, Ishihara, Kae, Naito, Yoichi, Minami, Hironobu, Tokushige, Kota, Matsubara, Nobuaki, Ando, Yuichi, Tajima, Takeshi

2021

Overview

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. This phase I study confirmed the safety of spartalizumab (PDR001), an anti‐programmed cell death‐1 (PD‐1) mAb, given at a dose of up to 10 mg/kg every 2 weeks in Japanese patients with advanced malignancies. No dose‐limiting toxicities were reported and the safety profile was consistent with other approved anti‐PD‐1 mAbs. The overall response rate was 11% in this heavily pretreated population.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Adult / Adverse events / Aged / Alkaline phosphatase / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Agents, Immunological - therapeutic use / Antitumor activity / Apoptosis / Cancer therapies / Cell death / clinical trial / Dose-Response Relationship, Drug / Drug dosages / Female / Hepatocellular carcinoma / humanized monoclonal antibody / Humans / Immune Checkpoint Inhibitors - therapeutic use / Immunoglobulin G / immunotherapy / Japan / Lung diseases / Lymphocytes / Male / Maximum Tolerated Dose / Metastasis / Middle Aged / Monoclonal antibodies / Neoplasms - drug therapy / Original / Patients / PD-1 protein / Pharmacokinetics / Programmed Cell Death 1 Receptor - antagonists & inhibitors / Safety / Statistical analysis / Toxicity / Transitional cell carcinoma / Tumors