title: Phase 1 study of pembrolizumab (MK-3475; anti-PD-1 monoclonal antibody) in Japanese patients with advanced solid tumors.
abstract: Background This phase I study evaluated the safety and tolerability, pharmacokinetics and pharmacodynamics, immunogenicity, and antitumor activity of pembrolizumab in Japanese patients with advanced solid tumors. Methods Following an initial dose and a 28-day rest (cycle 1), pembrolizumab was administered as an intravenous infusion at escalating doses (2 or 10 mg/kg) every 2 weeks (Q2W) until disease progression or unacceptable toxicity. Adverse events (AEs) were assessed using CTCAE v4.0, and tumor response was assessed using both RECIST v1.1 and immune-related response criteria (irRC). Full pharmacokinetic sampling was performed during cycle 1. Results Three patients received pembrolizumab at 2.0 mg/kg and seven at 10 mg/kg. No dose-limiting toxicities were observed during cycle 1. Eighty percent of patients experienced drug-related AEs (mostly grade 1 or 2); the most common drug-related AEs were nausea, malaise, pyrexia, and aspartate aminotransferase/alanine transaminase (AST/ALT) elevations (n = 2 each). No drug-related grade 4 or 5 AEs occurred. Immune-related AEs comprised grade 3 ALT elevation (n = 1), grade 3 AST elevation (n = 1), grade 1 pneumonitis (n = 1), and grade 1 thyroid-stimulating hormone elevation (n = 1). The safety and pharmacokinetic profiles of Japanese patients were similar to those previously reported for Caucasian patients. A partial tumor response was observed in one patient with non-small-cell lung cancer (NSCLC) and in one patient with melanoma. Conclusions Pembrolizumab at both 2 and 10 mg/kg Q2W was well tolerated in Japanese patients with advanced solid tumors and showed encouraging anti-tumor activity against melanoma and NSCLC.
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan. jcog9511@hotmail.co.jp.
authors.forename: Toshio
authors.initials: T
authors.lastname: Shimizu
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Seto
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hirai
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Takenoyama
authors.affiliation: Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka, 811-1395, Japan.
authors.forename: Kaname
authors.initials: K
authors.lastname: Nosaki
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Junji
authors.initials: J
authors.lastname: Tsurutani
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kaneda
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Iwasa
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Hisato
authors.initials: H
authors.lastname: Kawakami
authors.affiliation: MSD K.K., Kitanomaru square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Noguchi
authors.affiliation: MSD K.K., Kitanomaru square, 1-13-12 Kudan-kita, Chiyoda-ku, Tokyo, 102-8667, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shimamoto
authors.affiliation: Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-sayama, Osaka, 589-8511, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D044466:Asian People; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000074322:Antineoplastic Agents, Immunological; C582435:pembrolizumab
keywords: Anti-PD-1 therapy; PD-L1; Pembrolizumab; Pharmacokinetics; Phase I study