Matuzumab

• CAS Number: 339186-68-4

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

Matuzumab is a development of Merck KGaA. The development of matuzumab presented Merck 2007.

Matuzumab is in contrast to the already approved for various types of cancer, cetuximab, which is a chimeric antibody with protein fractions from mouse and human, almost entirely of human origin. It is therefore to be expected for patients with better tolerability.

Mechanism of action

The antibody is directed against a protein which is found in the cell membrane of human cells. This enzyme, a receptor tyrosine kinase EGFR with the label receives chemical signals, known as growth factors, which are located in the tissue fluid, and then stimulates the cell metabolism. Cancer cells often have a lot of EGFR molecules in their cell membranes. In colorectal cancer EGFR is overexpressed in 80 % of the cells, that is much more often than in normal tissue cells. Matuzumab binds to the EGFR. This binding inhibits the activation of the receptor and the subsequent signal -transduction pathway, which both the invasion of normal tissues by tumor cells, as well as the spread of tumors to new sites (metastasis ) is to be reduced.

Clinical Trials

Matuzumab is still in clinical testing. According to the pharmacokinetic properties in a Phase I trial is currently done the investigation of the substance 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 were presented from phase II clinical trials with matuzumab:

The response to therapy with matuzumab and paclitaxel was independent of mutations in the kinase domain of the EGFR. Such mutations can be observed at about 2 to 25 percent of patients with NSCLC. Some research results have shown a correlation between the efficacy of EGFR - tyrosine kinase inhibitors and the presence of mutations. The effect of the current data according to matuzumab seems not to be dependent on this mutation.

Preliminary results of two studies show a good tolerability of matuzumab in combination with two standard chemotherapy regimens - cisplatin, 5-fluorouracil and leucovorin (PFL ) and 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 will not come due to negative results in phase II studies in colorectal cancer used.