by C.H. Weaver M.D. (08/2018)
AMG 337 is a novel small-molecule MET inhibitor that appears to show promise in the treatment of MET-amplified gastroesophageal junction, gastric, and esophageal cancers. MET inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase. These inhibitors may have therapeutic application in the treatment of various types of cancers.
The esophagus is a muscular tube that food and liquids pass through on their on their way to the stomach. Each year in the United States, more than 17,000 people are diagnosed with cancer of the esophagus and more than 15,000 die of the disease.
Gastric cancer refers to cancer of the stomach. Though gastric cancer has a relatively low incidence in the United States, it is the second leading cause of cancer death worldwide. The incidence of gastric cancer is quite high in Asian countries such as Korea, China, Taiwan, and Japan. Treatment of gastric cancer typically involves surgical removal of the cancer followed by the use of chemotherapy with or without radiation therapy. Current treatment of both Gastric and Esophageal cancer consists of mainly of surgery and systemic therapies are sorely needed to reduce the risk of recurrence.
The MET signaling pathway is abnormal in a wide variety of cancers and stimulates cell growth, invasion, and metastasis and promotes resistance to apoptosis. Because of its ubiquitous role in cancer cells, inhibition of the MET pathway could be beneficial in blocking the growth of a number of different cancers.
Understanding DNA Damage Response or DDR and Cancer Treatment
What is DNA Damage Response or DDR?
AMG 337 is a highly selective inhibitor of several forms of MET. Preclinical studies demonstrated an affinity for MET, and this observation led to this first study to evaluate AMG337 in humans.
A small subset of patients with MET-amplified gastrointestinal (GI) tumors, were treated with AMG 337. Of the 13 patients with MET-amplified gastric and esophageal cancers, eight experienced a response for an overall response rate of 62%. The study authors observed that the “response was rapid, with the time to response being only 4 weeks in most cases.”
A larger phase II clinical trial for patients with solid MET-amplified cancers is currently enrolling patients and should help to confirm the anti-cancer activity of AMG337 and further define its potential in the management of various cancers.
Reference: 2015 Gastrointestinal Cancers Symposium (GICS): Abstract 1. Presented January 15, 2015.