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

• Published in: Cancer science Vol. 112; no. 2; pp. 725 - 733
• Main Authors: Minami, Hironobu, Doi, Toshihiko, Toyoda, Masanori, Imamura, Yoshinori, Kiyota, Naomi, Mitsuma, Ayako, Shimokata, Tomoya, Naito, Yoichi, Matsubara, Nobuaki, Tajima, Takeshi, Tokushige, Kota, Ishihara, Kae, Cameron, Scott, Ando, Yuichi
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.02.2021; John Wiley and Sons Inc
• Subjects: 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; Japan; clinical trial; maximum tolerated dose; humanized monoclonal antibody; Japan; immunotherapy
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.14678

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.