Phase 1 and dose-finding study of patritumab (U3-1287), a human monoclonal antibody targeting HER3, in Japanese patients with advanced solid tumors

Cancer Chemother Pharmacol. 2014 Mar;73(3):511-6. doi: 10.1007/s00280-014-2375-2. Epub 2014 Jan 18.


Purpose: Patritumab (U3-1287) is a human epidermal growth factor receptor-3 (HER3)-targeted antibody that blocks ligand-associated activation of HER3. This open-label, phase 1 and dose-finding study ( Identifier: JapicCTI-101262) aimed to assess the safety, pharmacokinetics, incidence of anti-patritumab antibody, recommended dose for subsequent clinical studies, preliminary efficacy, and patritumab-related biomarkers in Japanese patients with advanced solid tumors.

Methods: Patients received patritumab 9 or 18 mg/kg intravenously every 3 weeks until disease progression or intolerable toxicity occurred. Adverse events (AEs) were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0). Dose-limiting toxicities (DLTs) were evaluated from the initial dose to Cycle 1 Day 21. Tumor response was assessed with Response Evaluation Criteria in Solid Tumors (RECIST version 1.1).

Results: Nine patients received patritumab 9 mg/kg (n = 3) or 18 mg/kg (n = 6). Five patients were male, all patients had Eastern Cooperative Oncology Group performance status (PS) ≤ 1, and median (range) age of 67 (50-69) years. No DLTs were reported. Patritumab-related AEs reported in ≥2 patients were ALT increase (three patients), thrombocytopenia, diarrhea, stomatitis, cheilitis, rash maculo-papular and AST increase (two each). Pharmacokinetics profile was similar to the preceding US phase 1 study. Soluble HER3 concentration in serum unexpectedly increased in all patients. These changes did not correlate with clinical response. Four patients had a best response of stable disease. All patients tested had negative for anti-patritumab antibody formation.

Conclusions: Patritumab was well tolerated up to 18 mg/kg without DLTs in Japanese patients with advanced solid tumors. Soluble HER3 increased in all patients.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / pathology
  • Receptor, ErbB-3 / immunology
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antibodies, Neutralizing
  • Broadly Neutralizing Antibodies
  • patritumab
  • Receptor, ErbB-3