SOX (tegafur plus oxaliplatin) plus anti-PD-1 antibody with or without CAR-like T cell immunotherapy in the treatment of patients with previously untreated metastatic gastric cancer/gastroesophageal junction adenocarcinoma: A multicenter, open-label, randomized, controlled, phase II trial.

Abstract

291 Background: Although PD-1 blockade plus chemotherapy has achieved response rate for advanced gastric/ gastroesophageal junction adenocarcinoma (GC/GEJC), patient survival remains unsatisfactory. In this phase 2 trial, we evaluated the efficacy and safety of a combination treatment of SmarT with PD-1 blockade and SOX in patients with advanced GC/GEJC. Methods: In this study, we enrolled adults (≥18 years) with previously untreated, unresectable, HER2-negative GC/GEJC, regardless of PD-ligand 1 (PD-L1) expression. Patients were assigned to PD-1 mAb plus chemotherapy (Tegafur and oxaliplatin every 3 weeks), or PD-1 mAb plus chemotherapy. The patients were enrolled and randomly assigned in a 1:1 ratio to receive either first-line SOX plus PD-1 mAb (the control group, n = 50) or the same regimen plus CAR-like T cell immunotherapy (the immunotherapy group, n = 50) every 21 days for up to 6 cycles, followed by maintenance treatment with Tegafur and PD-1 mAb. Results: The Overall response rates were 66% (33/50) and 52% (26/50) for CAR-like T cell plus PD-1 mAb as well as chemotherapy and PD-1 mAb plus chemotherapy. The disease controlled rates for both groups were 94% and 80.0%, respectively. The median follow-up for PFS was 207 days for PD-1 mAb plus chemotherapy. While the median PFS for SmarT group has not been reached. The most common any-grade treatment-related adverse events were nausea, elevated liver enzymes, and peripheral leukemia reduction across both groups. No new safety signals were identified. Conclusions: The addition of CAR-like T cells to first-line SOX plus PD-1 mAb demonstrates significant clinical improvement of ORR and PFS with well tolerability in patients with previously untreated gastric or gastroesophageal junction adenocarcinoma. Clinical trial information: ChiCTR2200061306 .