SAN FRANCISCO—AMG-337, an oral investigational MET kinase inhibitor, caused responses in some patients with MET-amplified gastroesophageal junction (GEJ), gastric cancer, and esophageal cancer, a study (Abstract 1) presented this week at the 2015 Gastrointestinal Cancers Symposium has shown.
Disregulation of the MET pathway is known to promote cancer growth and metastasis, so researchers sought to investigate the clinical activity, safety, and tolerability of AMG-337 in patients with MET-amplified GEJ, gastric, and esophageal cancers.
As of April 2014, 80 patients with advanced solid tumors had received at least 1 dose of AMG-337. AMG-337 was administered at a starting dose of 25 mg either once daily or twice daily with planned dose escalation of 50 mg to 500 mg once daily and 100 mg to 200 mg twice daily.
Of the 51 evaluable patients, 10 patients had MET-amplified gastrointestinal cancers. Of those, one patient experienced a complete response with a duration of 100.4 weeks at the time of analysis and four patients had partial responses with durations up to 52 weeks at the time of analysis.
The once daily maximum tolerated dose was determined to be 300 mg, but the twice daily maximum tolerated dose has not yet been determined.
In regard to safety, the most common adverse events were constipation, fatigue, headache, nausea, and vomiting.
The researchers plan to enroll 50 patients with MET-amplified tumors at the maximum tolerated dose in a dose-expansion phase.
- Kwak EL, LoRusso P, Hamid O, et al. Clinical activity of AMG 337, an oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer. J Clin Oncol. 2015;33:(suppl 3; abstr 1).