Phase I study of Nivolumab, an anti-PD-1 antibody, in patients with malignant solid tumors

Summary Background This study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of single and multiple doses of nivolumab in Japanese patients with malignant solid tumors. Subjects and Methods This was an open-label, dose-escalation study in 17 patients with...

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Bibliographic Details
Published in:Investigational new drugs 2017-04, Vol.35 (2), p.207-216
Main Authors: Yamamoto, Noboru, Nokihara, Hiroshi, Yamada, Yasuhide, Shibata, Takashi, Tamura, Yosuke, Seki, Yoshitaka, Honda, Kazunori, Tanabe, Yuko, Wakui, Hiroshi, Tamura, Tomohide
Format: Article
Language:English
Subjects:
Adult
Aged
Antibodies
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - pharmacokinetics
Antibodies, Monoclonal - therapeutic use
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacokinetics
Antineoplastic Agents - therapeutic use
Arthritis
Cancer therapies
Chemotherapy
Clinical trials
Cytokines
Cytotoxicity
Diabetes
Disease
Drug dosages
Female
Humans
Immunology
Life expectancy
Ligands
Lymphocytes
Male
Medical research
Medicine
Medicine & Public Health
Melanoma
Metastasis
Middle Aged
Neoplasms - drug therapy
Neoplasms - metabolism
Oncology
Ovarian cancer
Pharmaceuticals
Pharmacokinetics
Pharmacology
Pharmacology/Toxicology
Phase I Studies
Programmed Cell Death 1 Receptor - immunology
Programmed Cell Death 1 Receptor - metabolism
Skin cancer
Studies
Treatment Outcome
Tumors
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Summary:Summary Background This study evaluated the safety, tolerability, pharmacokinetics, immunogenicity and antitumor activity of single and multiple doses of nivolumab in Japanese patients with malignant solid tumors. Subjects and Methods This was an open-label, dose-escalation study in 17 patients with advanced solid tumors with a life expectancy of ≥3 months. Patients were observed for 3 weeks after a single dose of nivolumab at 1, 3, 10 or 20 mg/kg, then received the same dose of nivolumab every 2 weeks until unacceptable toxicity or disease progression occurred. This study included a maximum dose of 20 mg/kg, which is the highest dose of nivolumab evaluated to date. The maximum dose was 10 mg/kg in previous studies. Results The commonest adverse drug reaction was lymphopenia, which occurred in 10 (58.8%) patients, including two (11.8%) with Grade ≥3 events. No dose-limiting toxicities (DLTs) were observed up to the maximum dose of 20 mg/kg. The area under the concentration–time curve from time 0 to the last measurable concentration was linear up to 20 mg/kg. The maximum concentration showed dose-dependency up to 10 mg/kg, but not between 10 and 20 mg/kg. One durable complete response and two partial responses were observed. Conclusions Nivolumab at doses of 1–20 mg/kg was not associated with DLTs, and it was generally well tolerated at doses of up to 20 mg/kg in Japanese patients with advanced solid tumors.
ISSN:0167-6997
1573-0646
DOI:10.1007/s10637-016-0411-2