120MO A phase II study of trifluridine/tipiracil and ramucirumab in patients with unresectable advanced or recurrent gastric cancer

Trifluridine/tipiracil improved overall survival in patients previously treated for advanced gastric cancer (AGC) in a phase III study. Survival benefit of ramucirumab, an anti-VEGFR2 antibody, was shown in patients pretreated for AGC. We conducted a phase II study to assess the efficacy and safety of trifluridine/tipiracil plus ramucirumab in patients pretreated for AGC. This study was an open-label, single-arm, two-cohort, phase II study. Patients with pathologically confirmed unresectable AGC or gastroesophageal junction adenocarcinoma were enrolled. Cohort A included patients previously treated with one line of chemotherapy without ramucirumab, and cohort B included patients previously treated with 2–4 lines of chemotherapy including ramucirumab. Patients received trifluridine/tipiracil 35 mg/m2 orally twice daily on days 1–5 and days 8–12 of each 28-day cycle, plus intravenous ramucirumab 8 mg/kg on days 1 and 15. The primary endpoint was disease control rate (DCR) assessed by each investigator. The secondary endpoints were overall response rate (ORR), progression-free survival (PFS), time to treatment failure, time to deterioration of ECOG PS, and safety. The sample size was 30 patients for each cohort assuming the point estimate of DCR to exceed the threshold (cohort A: 60%, B: 40%) by 15% with a probability of ≥90%. From April to October 2019, 64 patients were enrolled in Japan and included for efficacy and safety analyses (cohort A: 33 patients, B: 31 patients). In cohort A and cohort B, DCR was 84.8% (95% confidence interval [CI], 68.1–94.9) and 77.4% (95% CI, 58.9–90.4), ORR was 9.1% and 16.1%, and median PFS was 5.9 months and 5.3 months, respectively. Frequently reported adverse events of grade 3 or worse in cohorts A and B were neutropenia (81.8% and 74.2%), leukopenia (24.2% and 22.6%), thrombocytopenia (24.2% and 12.9%), anaemia (18.2% and 19.4%) and decreased appetite (12.1% and 3.2%), respectively. There was no treatment-related death. Trifluridine/tipiracil plus ramucirumab showed clinical activity and an acceptable safety profile in patients previously treated for AGC with or without previous ramucirumab exposure.