Matuzumab

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Matuzumab
Identifier
External IDs
Drug information
Drug class Cytostatic , monoclonal antibody

Matuzumab (also known as EMD72000) is a therapeutic, largely humanized, monoclonal antibody of the IgG1 type, against the EGF receptor (Epidermal Growth Factor Receptor), to fight cancerous tumors.

Matuzumab is a development by Merck KGaA . Merck discontinued further development of matuzumab in 2007.

In contrast to cetuximab , which is a chimeric antibody with protein components from mice and humans , which has already been approved for various types of cancer, matuzumab is almost entirely of human origin. Therefore, better tolerability for patients can be expected.

Mechanism of action

The antibody is directed against a protein that can be found in the cell membranes of human body cells. This enzyme , a receptor tyrosine kinase called EGFR, receives chemical signals called growth factors , which are found in tissue fluid, and then stimulates cell metabolism. Cancer cells often have a large number of EGFR molecules in their cell membranes. In colon cancer, EGFR is overexpressed in 80% of cells, that is, significantly more frequently than in normal tissue cells. Matuzumab binds to the EGFR. This binding inhibits the activation of the receptor and the downstream signal transmission system, which is intended to reduce both the invasion of the tumor cells into healthy tissue and the spread of the tumors into new areas of the body (metastasis).

Clinical testing

Matuzumab is still in clinical trials. After the pharmacokinetic properties have been presented in a phase I study, the substance is currently being investigated in advanced gastric cancer in several phase II studies.

At the conference of the American Society of Clinical Oncology (CASCO) in May 2005, the following results from clinical phase II studies with matuzumab were presented:

Advanced Non-Small Cell Lung Cancer (NSCLC)

The response to therapy with matuzumab and paclitaxel was independent of mutations in the kinase domain of the EGFR. Such mutations are seen in about 2 to 25 percent of NSCLC patients. Some research had shown a correlation between the effectiveness of EGFR tyrosine kinase inhibitors and the presence of mutations. According to the current data, the effect of matuzumab does not appear to be dependent on this mutation.

Advanced adenocarcinomas of the stomach and esophagus

Preliminary results of two studies show that matuzumab is well tolerated in combination with two standard chemotherapies - cisplatin , 5-fluorouracil and leukovorin (PFL) as well as epirubicin , cisplatin and capecitabine (ECX) - as part of a first-line therapy. Response rates of up to 53% with a combination of matuzumab and epirubicin / cisplatin / capecitabine.

In August 2007, Merck announced that matuzumab would not be used in colorectal cancer due to negative results in phase II studies.

Individual evidence

  1. ↑ Annual Report of Merck KGaA 2007
  2. ↑ Cancer drug flops ( Memento from October 16, 2008 in the Internet Archive ). n-tv , August 29, 2007.
  3. ↑ Merck KGaA: Matuzumab - Hope for fewer side effects and more convenient dosage ( Memento of October 21, 2007 in the Internet Archive )
  4. ↑ Österreichische Apotheker-Zeitung: Matuzumab - a further advance in targeted cancer therapy, EMD-72000 ( memento of February 26, 2008 in the Internet Archive ), accessed on August 29, 2007.
  5. ↑ Vanhoefer U. et al .: Phase I study of the humanized antiepidermal growth factor receptor monoclonal antibody EMD72000 in patients with advanced solid tumors that express the epidermal growth factor receptor , J. Clin. Oncol. , 2004, 22: pp. 175-184
  6. ↑ Valverde, CM et al. (2006): Novel targets in gastric and esophageal cancer. In: Crit. Rev. Oncol. Hematol. 59: pp. 128-138; PMID 16829119 ; doi: 10.1016 / j.critrevonc.2006.02.001 .
  7. ^ Wall Street turns the tide , boerse.ard.de

literature

  • C. Bokemeyer, K. Oechsle, MR Mueller, JT Hartmann, L. Kanz: Aprepitant as salvage therapy in patients (pts) with chemotherapy (ctx) - induced nausea and emesis (n / a) refractory to prophylaxis with 5-HT3- antagonists and dexamethasone (dexa) . In: Journal of Clinical Oncology . tape 23 , 16_suppl, 2005, p. 8166–8166 , doi : 10.1200 / jco.2005.23.16_suppl.8166 .
  • T. Trarbach, N. Schleucher, D. Weber, J. Tillner, I. Fassmann, S. Seeber, U. Vanhoefer: Phase I study of the humanized anti-epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with cisplatin, 5-fluorouracil and leucovorin (PFL) in patients (pts) with advanced esophago-gastric (EG) adenocarcinoma . In: Journal of Clinical Oncology . tape 23 , 16_suppl, June 2005, p. 3156-3156 , doi : 10.1200 / jco.2005.23.16_suppl.3156 .
  • D. Cunningham, WH Allum, SP Stenning, S. Weeden: Perioperative chemotherapy in operable gastric and lower oesophageal cancer: Final results of a randomized, controlled trial (the MAGIC trial, ISRCTN 93793971) . In: Journal of Clinical Oncology . tape 23 , 16_suppl, June 2005, p. 4001–4001 , doi : 10.1200 / jco.2005.23.16_suppl.4001 .
  • A. Thalheimer et al. : Antibody therapy in clinical and preclinical use in gastrointestinal carcinoma. In: The oncologist. Issue 13, number 3, year 2007, pp. 236–249. doi: 10.1007 / s00761-007-1190-3