Mapatumumab (HGS-ETR1) is an experimental

human Humans (''Homo sapiens'') or modern humans are the most common and widespread species of primate, and the last surviving species of the genus ''Homo''. They are Hominidae, great apes characterized by their Prehistory of nakedness and clothing ...

monoclonal antibody A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodie ...

undergoing clinical trials for the treatment of cancer. It targets TRAIL-R1, also known as DR4, which is expressed on the surface of many tumor cell types.

Development history

This drug was discovered by

Cambridge Antibody Technology Cambridge Antibody Technology Group Plc, (commonly referred to as CAT) was a biotechnology company headquartered in Cambridge, England. Its core focus was on antibody therapeutics, primarily using phage display, Phage Display and ribosome displ ...

, now

AstraZeneca AstraZeneca plc () (AZ) is a British-Swedish multinational pharmaceutical and biotechnology company with its headquarters at the Cambridge Biomedical Campus in Cambridge, UK. It has a portfolio of products for major diseases in areas includi ...

, and

Human Genome Sciences Human Genome Sciences (HGS) was a biopharmaceutical corporation founded in 1992 by Craig Venter, Alan Walton and Wally Steinberg. It uses the human DNA sequence to develop protein and antibody drugs. It had drugs under development to treat s ...

, now

GlaxoSmithKline GSK plc (an acronym from its former name GlaxoSmithKline plc) is a British Multinational corporation, multinational Pharmaceutics, pharmaceutical and biotechnology company with headquarters in London. It was established in 2000 by a Mergers an ...

, as a result of the collaboration between the two companies in 1999 in exploitation of CAT's

phage display Phage display is a laboratory technique for the study of protein–protein, protein–peptide, and protein–DNA interactions that uses bacteriophages (viruses that infect bacteria) to connect proteins with the genetic information that encodes ...

technology. Early work by the two companies indicated that mapatumumab induced cell death in multiple tumor types both in vitro and in vivo.

Clinical trials

A phase 1

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

in 2004 demonstrated the safety and tolerability of mapatumumab in cancer patients with advanced solid tumors or

non-Hodgkin’s lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tire ...

, and supported further evaluation in phase 2 clinical trials, both as a single agent and in combination with chemotherapy. In a phase 2 clinical trial, mapatumumab was well tolerated and could be administered safely in patients with advanced

non-small-cell lung cancer Non-small-cell lung cancer (NSCLC), or non-small-cell lung carcinoma, is any type of epithelial lung cancer other than small-cell lung cancer (SCLC). NSCLC accounts for about 85% of all lung cancers. As a class, NSCLCs are relatively insensitiv ...

(NSCLC) and advanced

colorectal cancer Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the Colon (anatomy), colon or rectum (parts of the large intestine). Signs and symptoms may include Lower gastrointestinal ...

. Stable disease was observed in a number of NSCLC patients. In two phase 1b clinical trials mapatumumab in combination with chemotherapy was well tolerated by patients with advanced

solid tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

s. Partial response was observed in a number of patients in each of the studies. The results of a phase 2 clinical trial demonstrated that mapatumumab was well tolerated and capable of producing clinical responses when administered as monotherapy in patients with advanced

, according to HGS.

Multiple myeloma

In 2008 HGS reported initial results of a randomised phase 2 trial of mapatumumab in combination with

bortezomib Bortezomib, sold under the brand name Velcade among others, is an anti-cancer medication used to treat multiple myeloma and mantle cell lymphoma. This includes multiple myeloma in those who have and have not previously received treatment. It is ...

in advanced

multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

. However, in 2010, mapatumumab failed in a midstage study. There was no difference in disease response or progression-free survival rates between patients receiving the drug for multiple myeloma and the control group.

Non-small-cell lung cancer

"In August 2008, ... initial dosing of patients in a randomized Phase 2 trial of HGS-ETR1 (10 mg/kg or 30 mg/kg) in combination with

paclitaxel Paclitaxel, sold under the brand name Taxol among others, is a chemotherapy medication used to treat ovarian cancer, esophageal cancer, breast cancer, lung cancer, Kaposi's sarcoma, cervical cancer, and pancreatic cancer. It is administered b ...

and

carboplatin Carboplatin, sold under the brand name Paraplatin among others, is a chemotherapy medication used to treat a number of forms of cancer. This includes ovarian cancer, lung cancer, head and neck cancer, brain cancer, and neuroblastoma. It is a ...

as first-line therapy in patients with advanced

(NSCLC); initial data from the study are anticipated in 2009."

Liver cancer

"In July 2008, HGS initiated dosing in ... a randomized Phase 2 trial of HGS-ETR1 in combination with Nexavar (

sorafenib Sorafenib, sold under the brand name Nexavar, is a kinase inhibitor drug approved for the treatment of primary kidney cancer (advanced renal cell carcinoma), advanced primary liver cancer (hepatocellular carcinoma), FLT3-ITD positive AML and ra ...

) in patients with advanced hepatocellular cancer, which accounts for 80-90% of all

liver cancer Liver cancer, also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy, is cancer that starts in the liver. Liver cancer can be primary in which the cancer starts in the liver, or it can be liver metastasis, or secondar ...

s."

References