title: Phase I study of the second-generation, recombinant, human EGFR antibody necitumumab in Japanese patients with advanced solid tumors.
abstract: OBJECTIVE
  To establish the safety and pharmacokinetic profile of necitumumab in Japanese patients with advanced solid tumors not responsive to standard therapy or for which no standard therapy was available.
  
  
  METHODS
  In this phase I study, patients aged ≥20 years with advanced solid tumors, and an Eastern Cooperative Oncology Group performance statuses of 0-1 were enrolled in a 3 + 3 design, with dose-escalation based on dose-limiting toxicity (DLT). Planned dose levels were: cohort 1: 600 mg IV, days 1 and 8, every 3 weeks; cohort 2: 800 mg IV, day 1, every 2 weeks; and cohort 3: 800 mg IV, days 1 and 8, every 3 weeks. After the first 6-week cycle, patients with an objective response or stable disease could continue to receive necitumumab (same dose and schedule) until disease progression or other withdrawal criteria were met. Safety, antitumor activity, and pharmacokinetics were assessed.
  
  
  RESULTS
  Fourteen of 15 enrolled patients received all scheduled infusions in cycle 1 (median cycles: N = 2, range 1-4). No DLTs were observed. The most common treatment-emergent adverse events were headache (73 %), dry skin (67 %), pruritus (60 %), and rash (53 %), mostly grade 1/2. All patients achieved serum trough concentrations >40 µg/mL, a level associated with antitumor activity in preclinical models. No patients had an objective response; stable disease was seen in 67 % of patients.
  
  
  CONCLUSIONS
  Necitumumab can be safety administered to Japanese patients at dose levels established in Western patients: 800 mg every 2 weeks, or on days 1 and 8 of a 3-week cycle.
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Tamura
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nokihara
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Honda
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tanabe
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Asahina
authors.affiliation: Department of Medical Oncology, Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Eli Lilly Japan, Kobe, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Enatsu
authors.affiliation: Lilly Deutschland GmbH, Bad Homburg, Germany.
authors.forename: Raffael
authors.initials: R
authors.lastname: Kurek
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan. tamuratomohide@gmail.com.|St Luke's International Hospital, Tokyo, Japan. tamuratomohide@gmail.com.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Tamura
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D044466:Asian People; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C527969:necitumumab; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Dosing; EGFR antibody; Japan; Necitumumab; Solid tumors