Cixutumumab

Cixutumumab
Monoclonal antibody
TypeWhole antibody
SourceHuman
TargetIGF-1 receptor
Clinical data
Routes of
administration		IV
ATC code
  • none
Identifiers
CAS Number
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC6500H10052N1724O2036S44
Molar mass146336.59 g·mol−1
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Cixutumumab (IMC-A12) is a human monoclonal antibody for the treatment of solid tumors.[1][2]

This drug was developed by ImClone Systems, since acquired by Eli Lilly, using phage display technology from Dyax.

It is a fully human IgG1 monoclonal antibody directed against the human insulin-like growth factor-1 receptor (IGF-1R) with potential antineoplastic activity. Cixutumumab selectively binds to membrane-bound IGF-1R, thereby preventing the binding of the ligand IGF-1 and subsequent activation of PI3K/AKT signaling pathway. Downregulation of the PI3K/AKT survival pathway may result in the induction of cancer cell apoptosis and may decrease cancer cellular proliferation. IGF-1R, a receptor tyrosine kinase of the insulin receptor superfamily overexpressed by many cancer cell types, stimulates cell proliferation, enables oncogenic transformation, and suppresses apoptosis; IGF-1R signaling has been implicated in tumorigenesis and metastasis.[3]

Research

Phase II clinical trials have been completed in patients with non-small cell lung cancer,[4][5][6] metastatic rhabdomyosarcoma,[7] metastatic prostate cancer,[8] metastatic pancreatic cancer,[9] metastatic esophageal cancer,[10] bone cancer,[11] sarcoma,[12] solid tumors,[13] ocular melanoma,[14] hepatocellular carcinoma,[15][16] breast cancer[17] and other forms of cancer. Despite these extensive trials, more than 45 phase I and II clinical trials in total, phase III trials have never been undertaken and Eli Lilly has removed cixutumumab from their development pipeline.[18]

References

  1. ↑ "Statement On A Nonproprietary Name Adopted – Cixutumumab" (PDF). The USAN Council. American Medical Association.
  2. ↑ McKian KP, Haluska P (July 2009). "Cixutumumab". Expert Opinion on Investigational Drugs. 18 (7): 1025–33. doi:10.1517/13543780903055049. PMC 2939377. PMID 19548856.
  3. ↑ "Cixutumumab". National Cancer Institute. 2011-02-02.
  4. ↑ Clinical trial number NCT01263782 for "BATTLE-FL: Front-Line Biomarker-Integrated Treatment Study in Non Small Cell Lung Cancer" at ClinicalTrials.gov
  5. ↑ Clinical trial number NCT00955305 for "Paclitaxel, Carboplatin, and Bevacizumab With or Without Cixutumumab in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer" at ClinicalTrials.gov
  6. ↑ Clinical trial number NCT00986674 for "Carboplatin and Paclitaxel Combined With Cetuximab and/or IMC-A12 in Patients With Advanced Non-Small Cell Lung Cancer" at ClinicalTrials.gov
  7. ↑ Clinical trial number NCT01055314 for "Temozolomide, Cixutumumab, and Combination Chemotherapy in Treating Patients With Metastatic Rhabdomyosarcoma" at ClinicalTrials.gov
  8. ↑ Clinical trial number NCT01120236 for "Bicalutamide and Goserelin or Leuprolide Acetate With or Without Cixutumumab in Treating Patients With Newly Diagnosed Metastatic Prostate Cancer" at ClinicalTrials.gov
  9. ↑ Clinical trial number NCT00617708 for "S0727 Gemcitabine Hydrochloride and Erlotinib Hydrochloride With or Without Monoclonal Antibody Therapy in Treating Patients With Metastatic Pancreatic Cancer That Cannot Be Removed By Surgery" at ClinicalTrials.gov
  10. ↑ Clinical trial number NCT01142388 for "Paclitaxel With or Without Cixutumumab as Second-Line Therapy in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer" at ClinicalTrials.gov
  11. ↑ Clinical trial number NCT01016015 for "Temsirolimus and Cixutumumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Soft Tissue Sarcoma or Bone Sarcoma" at ClinicalTrials.gov
  12. ↑ Clinical trial number NCT01614795 for "Cixutumumab and Temsirolimus in Treating Younger Patients With Recurrent or Refractory Sarcoma" at ClinicalTrials.gov
  13. ↑ Clinical trial number NCT00831844 for "Cixutumumab in Treating Patients With Relapsed or Refractory Solid Tumors" at ClinicalTrials.gov
  14. ↑ Clinical trial number NCT01413191 for "Cixutumumab in Treating Patients With Metastatic Melanoma of the Eye" at ClinicalTrials.gov
  15. ↑ Clinical trial number NCT00906373 for "A Study of IMC-A12 in Combination With Sorafenib in Patients With Advanced Cancer of the Liver" at ClinicalTrials.gov
  16. ↑ Clinical trial number NCT00639509 for "IMC-A12 in Treating Patients With Advanced Liver Cancer" at ClinicalTrials.gov
  17. ↑ Clinical trial number NCT00728949 for "A Study for Safety and Effectiveness of IMC-A12 by Itself or Combined With Antiestrogens to Treat Breast Cancer" at ClinicalTrials.gov
  18. ↑ "Clinical Development Pipeline". Eli Lilly and Company. Archived from the original on 13 January 2017.
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