Efficacy and safety of sintilimab in combination with XELOX in first-line gastric or gastroesophageal junction carcinoma (GC/GEJC).

Abstract

4042 Background: Immune checkpoint inhibitors have shown clinical benefit in advanced GC/GEJC. This phase 1b study evaluates the efficacy and safety of sintilimab, an anti-programmed cell death-1 antibody (PD-1 Ab) in combination with XELOX for GC/GEJC in first-line setting. Methods: This phase 1b study enrolled treatment-naïve unresectable locally advanced or metastatic GC/GEJC patients without HER2 amplification in cohort F. Patients received sintilimab 200mg IV q3w until disease progression, unacceptable toxicity or death, in combination with XELOX regimen (oxaliplatin 130mg/m2 IV D1 and capecitabine 1000mg/m2 PO BID D1-14) for up to 6 cycles. The primary objective was to evaluate the efficacy of the combination per RECIST v1.1 and safety and tolerability. Results: Totally 20 patients were enrolled in cohort F. As data cutoff (15 Jan 2019), median follow up was 5.8 months (range, 2.4 to 12.5). The median dose of sintilimab was 6.5 (range, 4 to 12). The objective response rate (ORR) was 85.0% (95%CI, 62.1 to 96.8) and disease control rate (DCR) was 100.0% (95%CI, 83.2 to 100.0). Among 17 patient with BOR of PR, two patients achieved a complete response (CR) of the target lesion. The median duration of response (DOR) and median progression free survival (PFS) had not been met. Three patients underwent resection of primary tumor after achieving a BOR of partial response (N=2) and stable disease (N=1). The incidence of treatment emergent adverse events (TEAEs) was 85.0%. Treatment-related AEs (TRAEs) occurred in 14 (70.0%) patients. The incidence of TRAE ≥ Grade 3 was 15%. AEs of immune-related etiology, occurred in 6 patients (30.0%). There were no AEs that resulted in death. As data cutoff, 12 patients were still in treatment and 8 had discontinued treatment and were under survival follow up. The biomarker analysis including PD-L1 expression in tumor specimen was ongoing. Conclusions: Sintilimab in combination with XELOX in first-line GC/GEJC shows promising anti-tumor efficacy and a tolerable safety profile. The further randomized, phase 3 study of Sintilimab in combination with XELOX in this setting is ongoing (NCT03745170). Clinical trial information: NCT02937116.