title: A phase I, first in human study of FP-1039 (GSK3052230), a novel FGF ligand trap, in patients with advanced solid tumors.
abstract: BACKGROUND
  Fibroblast growth factors (FGFs) play important roles in multiple cancers by supporting tumor growth and angiogenesis. FP-1039 (GSK3052230) is a FGF ligand trap consisting of the extracellular domain of FGF receptor 1 (FGFR1) fused with the Fc region of IgG1. FP-1039 binds and neutralizes multiple FGFs that normally bind FGFR1. The primary objective of this phase I study was to evaluate the safety and tolerability of FP-1039.
  
  
  METHODS
  Eligible patients with metastatic or locally advanced solid tumors for which standard treatments were ineffective were treated with weekly doses of FP-1039 for 4 weeks, followed by 2 weeks observation.
  
  
  RESULTS
  Thirty-nine subjects received a mean of 6 infusions of FP-1039 at doses ranging from 0.5 to 16 mg/kg weekly, with no maximally tolerated dose identified. Grade 3 or greater treatment emergent adverse events were uncommon. Four dose-limiting toxicities were reported at doses of 0.75 mg/kg (urticaria), 1 mg/kg (intestinal perforation and neutropenia), and 16 mg/kg (muscular weakness). Drug exposure was dose proportional, and the terminal elimination half-life was 2.6-3.9 days following a single dose. Target engagement as measured by low free plasma FGF2 levels was achieved. FGF pathway dysregulation was uncommon. No objective responses were observed.
  
  
  CONCLUSIONS
  In nonselected cancer patients with advanced disease, treatment with FP-1039 was well tolerated and toxicities associated with small molecule drugs that inhibit FGFR tyrosine kinases, including hyperphosphatemia, were not observed. Further studies of FP-1039 in patients selected for FGF pathway dysregulation, who are most likely to benefit, are now underway.
authors.affiliation: South Texas Accelerated Research Therapeutics (START), San Antonio atolcher@start.stoh.com.
authors.forename: A W
authors.initials: AW
authors.lastname: Tolcher
authors.affiliation: South Texas Accelerated Research Therapeutics (START), San Antonio.
authors.forename: K P
authors.initials: KP
authors.lastname: Papadopoulos
authors.affiliation: South Texas Accelerated Research Therapeutics (START), San Antonio.
authors.forename: A
authors.initials: A
authors.lastname: Patnaik
authors.affiliation: Wayne State University Hematology/Oncology, Karmanos Cancer Institute, Detroit.
authors.forename: K
authors.initials: K
authors.lastname: Wilson
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, USA.
authors.forename: S
authors.initials: S
authors.lastname: Thayer
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, USA.
authors.forename: J
authors.initials: J
authors.lastname: Zanghi
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, USA.
authors.forename: A T
authors.initials: AT
authors.lastname: Gemo
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, USA.
authors.forename: W M
authors.initials: WM
authors.lastname: Kavanaugh
authors.affiliation: Five Prime Therapeutics, Inc., South San Francisco, USA.
authors.forename: H N
authors.initials: HN
authors.lastname: Keer
authors.affiliation: Wayne State University Hematology/Oncology, Karmanos Cancer Institute, Detroit.
authors.forename: P M
authors.initials: PM
authors.lastname: LoRusso
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005346:Fibroblast Growth Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D015514:Oncogene Proteins, Fusion / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000378:metabolism / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins
chemical_list: D000970:Antineoplastic Agents; D007074:Immunoglobulin G; D015514:Oncogene Proteins, Fusion; D011993:Recombinant Fusion Proteins; D005346:Fibroblast Growth Factors; C559041:FP-1039; C496348:FGFR1 protein, human; D051496:Receptor, Fibroblast Growth Factor, Type 1
keywords: FGF; cancer; ligand trap; phase I