The small-molecule MET inhibitor AMG 337 showed antitumor activity in MET-amplified gastric/gastroesophageal junction/esophageal (G/GEJ/E) adenocarcinoma, with an overall response rate of 18%, according to a recent study.1 However, this study was terminated after a review showed the overall response rate was lower than expected based on preliminary data from another separate study of AMG 337.2

“As of July 2014, the first-in-human study had shown responses in 8 of 13 (62%) patients with MET-amplified G/GEJ/E adenocarcinoma […] suggesting that the response rate in this study, which only enrolled patients with MET-amplified tumors, would be high,” the researchers wrote.

In this phase 2 study, 2 cohorts were examined. Cohort 1 was 45 patients with MET-amplified G/GEJ/E adenocarcinoma and cohort 2 was 15 patients with MET-amplified solid tumors. The majority of patients had metastatic disease (97%) and had either 1 (29%), or 2 or more (69%), prior lines of therapy.

Overall, 58 patients received at least 1 dose of the study drug. The overall response rate in cohort 1 was 18%, including 8 partial responses. None of the patients in cohort 2 responded to the investigational agent.

Looking at outcomes in 54 evaluable patients, the median progression-free survival was 3.4 months and the median overall survival was 7.9 months.

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Commonly occurring adverse events including headache, nausea, vomiting, abdominal pain, decreased appetite, and peripheral edema. The majority of patients (71%) had grade 3 or worse adverse events and 59% had serious adverse events.

“Although it is unlikely that monotherapy would be beneficial in a large group of patients, it is possible that a select group of patients could benefit from AMG 337 or that combination therapy strategies could be useful; however, such approaches would require further study,” the researchers wrote.

Disclosure: The original study was funded by Amgen Inc. For a full list of disclosures, please refer to the original study.

References

  1. Van Cutsem E, Karaszewska B, Kang Y, et al. A multicenter phase 2 study of AMG 337 in patients with MET-amplified gastric/gastroesophageal junction/esophageal adenocarcinoma and other solid tumors [published online October 26, 2018]. Clin Cancer Res. doi: 10.1158/1078-0432.CCR-18-1337
  2. Kwak EL, LoRusso P, Hamid O, et al. Clinical activity of AMG 337, on oral MET kinase inhibitor, in adult patients (pts) with MET-amplified gastroesophageal junction (GEJ), gastric (G), or esophageal (E) cancer [abstract]. J Clin Oncol. 2015;33(3_suppl);1-1. doi: 10.1200/jco.2015.33.3_suppl.1