We determined antitumor activity, safety, and pharmacokinetics of the small-molecule MET inhibitor AMG 337 in <i>MET</i>-amplified G/GEJ/E adenocarcinoma or other solid tumors.<b>Patients and Methods:</b> In this phase II, single-arm study, adults with <i>MET</i>-amplified G/GEJ/E adenocarcinoma (cohort 1) or other <i>MET</i>-amplified solid tumors (cohort 2) received AMG 337 300 mg/day orally in 28-day cycles.
When aberrantly activated, MET and its stroma-secreted ligand HGF (Hepatocyte Growth Factor) concur to tumor onset, progression, and metastasis in solid tumors, thus representing a relevant target for cancer precision medicine.
Cabozantinib is a tyrosine kinase inhibitor with activity against vascular endothelial growth factor receptor 2 (VEGFR2) and MET that has demonstrated clinical activity in advanced solid tumors.
To evaluate the safety (including adverse events and dose-limiting toxicities [DLTs]), tolerability, pharmacokinetics and antitumor activity of the investigational MET inhibitor rilotumumab alone in patients with advanced solid tumors (Part 1) or in combination with cisplatin plus capecitabine (CX) in patients with MET-positive advanced gastric or gastroesophageal junction cancer (Part 2).
Silk-elastinlike protein polymer (SELP) hydrogels were used for matrix-mediated delivery of oncolytic Ad, containing short hairpin RNA (shRNA) targeted to C-Met (sh-C-Met), to solid tumors in a nude mouse model of human head and neck cancer.
Recently, activation of the c-MET/hepatocyte growth factor signaling pathway was associated with poor prognosis in various solid tumors and was one of the mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor, gefitinib.
MET amplification was detected in 2.6% of patients with solid tumors and was associated with adenocarcinomas, high-grade histology, and higher metastatic burden.
Tyrosine kinase inhibitors (TKIs) targeted to MET are undergoing clinical trials in patients with solid tumors, but the precise mechanism of the antitumor activity of these drugs remains unclear.
Met protein is a tyrosine kinase receptor for hepatocyte growth factor (HGF). c-Met has morphogenic, mitogenic, and motogenic properties and is overexpressed in many solid tumors.
Summarizing these and previous results, mutations of the MET proto-oncogene were detected in 17/129 sporadic papillary renal carcinomas but not in other solid tumors.