Safety, tolerability, and pharmacokinetics of single and multiple doses of intravenous cixutumumab (IMC-A12), an inhibitor of the insulin-like growth factor-I receptor, administered weekly or every 2 weeks in patients with advanced solid tumors

Investigational New Drugs
C S HiganoJ M Mehnert

Abstract

Type 1 insulin-like growth factor receptor (IGF-IR) signaling is often dysregulated in cancer. Cixutumumab, a fully human IgG1 monoclonal antibody, blocks IGF-IR and inhibits downstream signaling. The current study determined the recommended dose, safety, and pharmacokinetic (PK) profile of weekly or every-2-week dosing of cixutumumab. Two open-label, multicenter phase I studies evaluated weekly (3-15 mg/kg) or every-2-weeks (6-15 mg/kg) dosing of cixutumumab in patients with advanced solid tumors. Serial blood samples for PK were collected up to 168-336 h (day 8-15) following the first administration of cixutumumab. Efficacy was evaluated as best overall tumor response. A total of 24 and 16 patients were enrolled in the weekly and every-2-week dosing studies, respectively. Treatment-emergent adverse events (≥10%) included hyperglycemia, fatigue, anemia, nausea, and vomiting. Severe adverse events (AE) were infrequent; one serious AE (grade 3 electrocardiogram QT prolongation) was deemed possibly cixutumumab-related (10 mg/kg every-2-weeks). One death occurred due to disease progression (6 mg/kg weekly cohort). Maximum serum concentrations increased with dose. A maximum tolerated dose was not identified; pre-determined target s...Continue Reading

References

Jun 17, 2000·Endocrine Reviews·H M KhandwalaK E Friend
Jul 7, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·M Pollak
Sep 21, 2000·Journal of the National Cancer Institute·H Yu, T Rohan
Oct 9, 2001·Epidemiologic Reviews·M Pollak
Dec 26, 2001·Journal of the National Cancer Institute·Y LuM Pollak
Nov 6, 2002·Oncology·Stergios J Moschos, Christos S Mantzoros
Dec 21, 2002·The Journal of Biological Chemistry·Dong YuMasahiko Miura
Jul 2, 2004·Nature Reviews. Cancer·Michael N PollakSusan E Hankinson
Feb 7, 2007·Cancer Research·Gregory W AllenPaul M Harari
Dec 3, 2008·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Brian M WolpinCharles S Fuchs
May 1, 2010·Japanese Journal of Clinical Oncology·Yasuhito FujisakaTomohide Tamura
Jul 7, 2011·Journal of Hematology & Oncology·Jennifer Wu, Andrew X Zhu
Jul 19, 2011·Diseases of the Esophagus : Official Journal of the International Society for Diseases of the Esophagus·M OrdituraF De Vita
Oct 26, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heribert JuergensAntonio Gualberto
Apr 3, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aung NaingRazelle Kurzrock
May 4, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Kim N ChiMichael Pollak
Aug 9, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ezra E W CohenMark J Ratain
Oct 23, 2012·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·V Van DammeJ Vansteenkiste
Jul 10, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·P SchöffskiD O Grebennik
Sep 17, 2013·British Journal of Clinical Pharmacology·Honghai MaJiajun Du

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Citations

Jul 31, 2016·The Oncologist·Jonathan W GoldmanSarah R Rettinger
Oct 3, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Wade T Iams, Christine M Lovly

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