A multicenter phase II trial of ramucirumab plus irinotecan in patients with early relapsed gastric cancer during or after adjuvant docetaxel plus S-1 therapy: RAMIEL trial (OGSG1901).

358 Background: There is no established chemotherapy for patients with early recurrence during or within 6 months after completing adjuvant chemotherapy with docetaxel plus S-1 (DS) following D2 gastrectomy which is a standard of care for stage III gastric cancer (GC). Methods: This was a prospective, open-label, multicenter, phase II trial evaluating the efficacy and safety of ramucirumab plus irinotecan in GC patients with early recurrence during or within 6 months after completing adjuvant chemotherapy with DS. Ramucirumab (8 mg/kg, days 1) and irinotecan (150mg/m 2 , day 1) were administered every 2 weeks until disease progression or unacceptable adverse events (AE). The primary endpoint was overall survival (OS) and the main secondary endpoints included progression free survival (PFS), an objective response rate (ORR), disease control rate (DCR) and safety. The sample size was set at 40 to preserve power of 0.8 with a one-sided alpha error of 0.05 for rejecting median OS of 7 months with expectation of 11 months. Results: Between November 2019 and July 2023, 43 patients were enrolled from 14 institutions, and 39 patients were included in the primary analysis, excluding 3 ineligible patients and one who did not receive the protocol treatment. Patient characteristics were: median age of 68 years (range, 40–81), male in 82.1%. ECOG performance status 0 in 61.5%. The median OS was 15.9 months (95% CI, 8.8–42.0; 90% CI, 11.1–24.6, one-sided P=0.003). The median PFS was 5.5 months (95% CI, 3.9–8.1), the ORR was 38.5% (95% CI, 20.2–59.4) and DCR was 76.9% (95% CI, 56.4–91.0), respectively. Grade >3 AEs observed in more than 10% of patients were neutropenia (25.6%), leucopenia (10.3%) and hypertension (25.6%). No treatment-related deaths or new safety signals were observed. In the subgroup analysis, tumor response (Progressive disease vs complete response, partial response and stable disease; HR 9.17, p