A phase II trial of CapeOX plus nivolumab for early relapsed HER2-negative gastric cancer (JACCRO GC-11: FirSTAR trial).

Abstract

TPS423 Background: Fluoropyrimidine-based post-operative chemotherapy is one of the standard adjuvant therapies for curatively resected gastric cancer (GC).1,2 The current standard first-line chemotherapy consists of fluoropyrimidine and oxaliplatin combined with nivolumab in advanced HER2-negative GC patients including cases with a recurrence > 6 months after completion of post-operative chemotherapy, based on the CheckMate 649 and ATTRACTION-4 trials. However, in GC patients with early recurrence during or ≤ 6 months after completion of post-operative 5-FU based chemotherapy, optimal treatments remain to be established. A previous phase II study showed that capecitabine plus cisplatin is an active regimen for early relapsed GC after post-operative S-1 monotherapy.3 This trial aims to investigate the efficacy of capecitabine plus oxaliplatin (CapeOX) plus nivolumab for patients with early relapsed HER2-negative GC. Methods: This is a multicenter single-arm phase II trial. The main eligibility criteria include: histologically confirmed HER2-negative adenocarcinoma of stomach or esophagogastric junction; radiologically diagnosed recurrence during or ≤ 6 months after post-operative chemotherapy with S-1 or S-1 plus docetaxel conducted for stage II/III GC after curative resection; age ≥ 18 years; ECOG performance status 0-1; having measurable lesions according to RECIST ver. 1.1; and adequate oral intake and organ functions. Enrolled patients will receive 21-day cycles of nivolumab with CapeOX at the following dose until disease progression or unacceptable toxicities: capecitabine, 1000 mg/m2 twice per day on day 1-14; oxaliplatin, 130 mg/m2 on day 1; and nivolumab, 360 mg on day 1. The primary endpoint is objective response rate (ORR), and the secondary endpoints include overall survival, progression-free survival, disease control rate, duration of response, and safety. PD-L1 combined positive score will be tested for the association with efficacy. We assume null ORR of 20% and alternative ORR of 32%. With two-sided alpha level of 10% and 80% power, sample size would be calculated as 85. Thus, a total of 92 patients are planned for enrollment within a 2.5-year accrual period. Enrollment opened in March 2023. Clinical trial information: jRCTs031220572. 1. N Engl J Med. 2007;357:1810-20. 2. J Clin Oncol. 2019;37:1296-1304. 3. Gastric Cancer. 2018;21:811-8. Clinical trial information: jRCTs031220572 .