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

Autor: Scott Cameron, Ayako Mitsuma, Yoichi Naito, Tomoya Shimokata, Yuichi Ando, Takeshi Tajima, Kae Ishihara, Nobuaki Matsubara, Yoshinori Imamura, Hironobu Minami, Kota Tokushige, Toshihiko Doi, Naomi Kiyota, Masanori Toyoda
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Adult
Male
0301 basic medicine
Cancer Research
medicine.medical_specialty
Programmed Cell Death 1 Receptor
Antibodies
Monoclonal
Humanized
Gastroenterology
03 medical and health sciences
Antineoplastic Agents
Immunological
0302 clinical medicine
Pharmacokinetics
Japan
Clinical Research
Neoplasms
Internal medicine
medicine
Maculopapular rash
Humans
Adverse effect
Immune Checkpoint Inhibitors
Aged
maximum tolerated dose
Dose-Response Relationship
Drug
business.industry
clinical trial
Original Articles
General Medicine
Middle Aged
medicine.disease
Discontinuation
Clinical trial
030104 developmental biology
Transitional cell carcinoma
Oncology
030220 oncology & carcinogenesis
Hepatocellular carcinoma
Toxicity
humanized monoclonal antibody
Female
Original Article
immunotherapy
medicine.symptom
business
Zdroj: Cancer Science
ISSN: 1347-9032
Popis: 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.
Databáze: OpenAIRE
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