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

Razelle 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

Research output: Contribution to journalArticlepeer-review

141 Scopus citations

Abstract

Purpose: 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.

Original languageEnglish (US)
Pages (from-to)2458-2465
Number of pages8
JournalClinical Cancer Research
Volume16
Issue number8
DOIs
StatePublished - Apr 15 2010

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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