Matuzumab
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Target | EGFR |
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Pharmacokinetic data | |
Bioavailability | N/A |
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Matuzumab (formerly EMD 72000) is a
Produced and developed by
Mechanism of action
Matuzumab binds to epidermal growth factor receptor (EGFR) on the outer membrane of normal and tumor cells. The matuzumab epitope has been mapped to domain III of the extracellular domain of the EGFR.[7][8] The EGFR is receptor tyrosine kinase which binds multiple growth factors including EGF (epidermal growth factor) and other members of the EGF family of growth factors, resulting in activation of its tyrosine kinase activity. Activation of the EGFR has diverse effects on target cells depending on cell type and tissue context. It directs cell fate decision relating to cell growth, survival and, differentiation. Development of matuzumab and other antibodies to the EGFR (for example cetuximab) as cancer therapeutics was motivated by observations that EGFR expression and/or signaling is frequently upregulated in cancer cells.
Preclinical and Clinical testing
After determining the pharmacokinetic characteristics in a phase I study,[9] several phase II studies investigating the treatment of advanced stomach carcinoma were conducted. At the conference of the American Society of Clinical Oncology (ASCO) in May 2005, the following results from clinical phase II studies with matuzumab were presented:
Advanced non-smallcellular lung carcinoma
Mutations in the kinase domain of the EGFR are observed with approximately 2 to 25% of
Advanced adenocarcinomas of stomach and esophagus
Results of two studies regarding
On August 27, 2007 Merck announced that matuzumab will not be used for
Discontinuation of development
No further clinical trials have been conducted since the phase I trial[10] in 2007. On February 18, 2008, Takeda and Merck announced that they would no longer pursue the development of the drug.[6][11]
References
- PMID 2434025.
- PMID 3297307.
- ^ Clinical trial number NCT00111839 for "Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer" at ClinicalTrials.gov
- ^ Clinical trial number NCT00215644 for "MATRIX EG (Matuzumab Treatment With ECX in Esophago-Gastric Cancer)" at ClinicalTrials.gov
- ^ a b "Krebsmedikament floppt" [Cancer drug flops] (in German). n-tv. August 29, 2007. Retrieved August 27, 2007.
- ^ a b "Merck KGaA stellt Entwicklung von Matuzumab ein" [Merck KGaA discontinues development of matuzumab] (in German). NewsVZ.de. February 18, 2008. Archived from the original on July 19, 2011. Retrieved January 5, 2010.
- PMID 18394550.
- PMID 18424917.
- PMID 14701780.
- ^ PMID 19238629.
- ^ "Takeda Discontinues Development of Matuzumab". Takeda Pharmaceutical Co., Ltd. February 18, 2008. Retrieved January 5, 2010.