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A phase I study of weekly R1507, a human monoclonal antibody insulin-like growth factor-I receptor antagonist, in patients with advanced solid tumors.

AbstractPURPOSE:
A phase I study was conducted to evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of R1507-a fully human IgG1 type monoclonal antibody directed against the human insulin-like growth factor-I receptor.
EXPERIMENTAL DESIGN:
Patients with advanced solid tumors were assigned to receive i.v. R1507 weekly (qW), starting with 1 mg/kg. Subsequent cohorts were dosed at 3 and then 9 mg/kg. An additional 12 patients received 9 mg/kg R1507 qW. Patients remained on the study until the development of a dose-limiting toxicity or progressive disease.
RESULTS:
In total, 37 patients were treated with R1507 qW. No dose-limiting toxicities were identified and the maximum tolerated dose was not reached. The pharmacokinetics of R1507 were characterized by a slow clearance and limited volume of distribution, with an estimated elimination half-life justifying weekly administration. Serum IGF-I ligand levels increased proportionally to dose during the first 72 hours in all cohorts. R1507 was well tolerated. Two patients diagnosed with Ewing's sarcoma had partial responses of 11.5 and >26 months (ongoing at time of submission); 13 patients had stable disease; and 16 had progressive disease as best response by the Response Evaluation Criteria in Solid Tumors.
CONCLUSION:
R1507 is well tolerated and shows antitumor activity in patients with solid neoplasms, in particular Ewing's sarcoma. The recommended dose for the weekly schedule is 9 mg/kg qW.
AuthorsRazelle Kurzrock, Amita Patnaik, Joseph Aisner, Terri Warren, Stephen Leong, Robert Benjamin, S Gail Eckhardt, Joseph E Eid, Gerard Greig, Kai Habben, Cinara D McCarthy, Lia Gore
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 16 Issue 8 Pg. 2458-65 (Apr 15 2010) ISSN: 1557-3265 [Electronic] United States
PMID20371689 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Receptor, IGF Type 1
  • teprotumumab
Topics
  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Antibodies, Monoclonal (administration & dosage, pharmacokinetics)
  • Antibodies, Monoclonal, Humanized
  • Female
  • Humans
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms (drug therapy, pathology)
  • Receptor, IGF Type 1 (antagonists & inhibitors)
  • Survival Rate
  • Tissue Distribution
  • Treatment Outcome
  • Young Adult

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