The data with AMG 337 are very compelling. Granted, it was only 13 patients, but in 13 patients, 8 [responders] is a big number.
—Jaffer A. Ajani, MD
Jaffer A. Ajani, MD, Professor of Gastrointestinal Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, discussed the two studies.
He emphasized the impressive cytoreductive activity of AMG 337. “Granted, it was only 13 patients, but in 13 patients, 8 [responders] is a big number,” he said. “The data with AMG 337 are very compelling,” he observed. “It’s really hard to argue against it…. We can say that the biomarker and the drug are good, and this should be pursued further.”
Dr. Ajani tempered his enthusiasm, however, by noting that the risk of resistance to small-molecule inhibitors is real and suggested “we start planning to combine molecules.”
However, this is little reason to anticipate benefits from onartuzumab or the other anti-MET monoclonal antibody, rilotumumab, he said. “The monoclonal antibodies meant to inhibit the MET receptor have not produced desirable results when MET immunohistochemistry positivity is the enrichment biomarker.”
“Here, you can say the antibody is good, but the biomarker is not useful, or the biomarker is good, and the antibody is not useful, or you can say both are not useful,” he said. “There is, perhaps, a solution, and that is to develop an antibody/drug conjugate,” a so-called MET bomb, Dr. Ajani suggested. “This could make the drug better and make the biomarker more relevant,” he predicted. ■
Disclosure: Dr. Ajani reported no potential conflicts of interest.
The MET pathway appears to be important in gastroesophageal cancers, but response to a targeted agent may depend on the class of drugs. A robust response to the novel small-molecule MET inhibitor AMG 337 was observed, but a monoclonal antibody targeting MET fell flat, in studies reported at the...