title: LJM716 in Japanese patients with head and neck squamous cell carcinoma or HER2-overexpressing breast or gastric cancer.
abstract: OBJECTIVE
  Human epidermal growth factor receptor 3 (HER3) has been identified as an important component of many receptor tyrosine kinase-driven cancers. LJM716 is a human IgG monoclonal antibody that binds HER3, trapping it in an inactive conformation. In this study, a phase I dose escalation was performed with a primary objective to establish the maximum tolerated dose and/or the recommended dose of LJM716 in Japanese patients with selected advanced solid tumors. Secondary objectives included the evaluation of the safety and tolerability, preliminary antitumor activity, and pharmacokinetics of LJM716 in Japanese patients.
  
  
  METHODS
  LJM716 was administered intravenously at doses of 10, 20, or 40 mg/kg once weekly, in 28-day cycles, to 12 patients with HER2-amplified breast cancer or gastric cancer, or with esophageal squamous cell carcinoma or squamous cell carcinoma of the head and neck, regardless of HER2 status.
  
  
  RESULTS
  The maximum tolerated dose was not reached, and the recommended dose was established at 40 mg/kg. No dose-limiting toxicities were observed in the first cycle. The most frequently reported adverse events were diarrhea, fatigue, stomatitis, pyrexia, and paronychia. One unconfirmed partial response was observed in a patient with breast cancer, and 50% of the patients achieved stable disease as the best overall response. Exposure increased with ascending dose, and half-life was estimated to be 11-14 days. No anti-LJM716 antibodies were detected.
  
  
  CONCLUSIONS
  LJM716 was well tolerated in Japanese patients, and a degree of tumor shrinkage was observed.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01911936.
authors.affiliation: Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan. s.takahashi-chemotherapy@jfcr.or.jp.
authors.forename: Shunji
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Department of Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Tomomatsu
authors.affiliation: Department of Breast Medical Oncology, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ito
authors.affiliation: Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.|Saiseikai Fukuoka General Hospital, Fukuoka, Japan.
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Oda
authors.affiliation: Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Kajitani
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakizume
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tajima
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Novartis Pharma K.K., Tokyo, Japan.
authors.forename: Heiko
authors.initials: H
authors.lastname: Maacke
authors.affiliation: Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Taito
authors.initials: T
authors.lastname: Esaki
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D000077195:Squamous Cell Carcinoma of Head and Neck; D013274:Stomach Neoplasms / Q000737:chemistry / Q000188:drug therapy*
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D018719:Erb-b2 Receptor Tyrosine Kinases; C000619694:elgemtumab; C508053:ERBB2 protein, human
keywords: HER2; HER3; LJM716; Monoclonal antibody; Phase I