Phase Ib study of irinotecan and ramucirumab for advanced gastric cancer previously treated with fluoropyrimidine with/without platinum and taxane

PURPOSE: Optimal salvage chemotherapy for patients with treated advanced/metastatic gastric cancer (AGC) is unknown. Irinotecan is commonly used in Japan. Ramucirumab, a human IgG-1 monoclonal antibody targeting the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. We sought to determine the maximum tolerated dose (MTD) and recommended dose (RD) of ramucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platinum and taxane. METHODS: Patients received systemic chemotherapy with ramucirumab (8 mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150 mg/m(2)). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606). RESULTS: Six patients were enrolled from August 2015 to September 2017. No dose-limiting toxicity (DLT) was observed, and the maximum tolerated dose (MTD) was not reached at level 1. Irinotecan 150 mg/m(2) in combination with ramucirumab 8 mg/kg was administered with acceptable toxicity, and all patients were treated at these doses. No treatment-related deaths were observed. Adverse events of Grade 3/4 were neutropenia (17%), anemia (17%) and hypertension (17%). Patients were evaluated using the RECIST criteria, and response rate and disease control rate were 17% and 83%, respectively. CONCLUSIONS: Salvage chemotherapy with irinotecan plus ramucirumab was well-tolerated by patients previously treated for AGC. RD was defined as irinotecan 150 mg/m(2) in combination with ramucirumab 8 mg/kg.