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

ABSTRACT: 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.

SUBMITTER: Yamamoto N

PROVIDER: S-EPMC5352798 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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

Yamamoto Noboru N Nokihara Hiroshi H Yamada Yasuhide Y Shibata Takashi T Tamura Yosuke Y Seki Yoshitaka Y Honda Kazunori K Tanabe Yuko Y Wakui Hiroshi H Tamura Tomohide T

Investigational new drugs 20161208 2

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 ...[more]

PMID: 27928714

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Project description:BackgroundSeveral programmed cell death ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti-PD-1 antibody, toripalimab, in Chinese patients.MethodsA single-center phase I study was conducted in Sun Yat-sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment-refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose-escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design.ResultsBetween 15th March 2016 and 27th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow-up time of 5.0 months (range: 1.5-19.8 months), we observed that the commonest treatment-related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose-limiting toxicity, treatment-related serious adverse events (SAEs), or treatment-related death occurred. Objective response rate was 12.5%. The half-life of toripalimab was 150-222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD-1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab.ConclusionsToripalimab is a promising anti-PD-1 antibody, which was well tolerated and demonstrated anti-tumor activity in treatment-refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted.

Dataset Information

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

Publications

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

Similar Datasets

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