Clinical study of adebrelimab in combination with apatinib and irinotecan for PD-1 inhibitor-ineffective advanced-stage gastric cancer: study protocol for a single-arm, single-centre, exploratory trial.

Introduction: Immunotherapy has revolutionised cancer treatment. Immune checkpoint inhibitors have demonstrated significant efficacy across multiple tumour types, including gastric cancer, where several approved programmed cell death 1/programmed cell death-ligand 1 (PD-1/PD-L1) inhibitors show promising antitumour activity. While PD-L1 expression serves as a predictive biomarker for PD-1 inhibitor response, and PD-L1-positive patients generally show better outcomes, therapeutic resistance remains a challenge. Many initial responders eventually develop resistance, and surprisingly, some PD-L1-positive patients fail to achieve expected response rates, indicating emerging resistance mechanisms in potentially responsive populations. Adebrelimab, a PD-L1 inhibitor, demonstrates mechanistic advantages over PD-1 inhibitors, with clinical studies suggesting promising therapeutic potential. When combined with irinotecan, apatinib has shown efficacy in second-line gastric cancer treatment. This study aims to evaluate the efficacy and safety of combining adebrelimab with apatinib and irinotecan for advanced gastric cancer refractory to PD-1 inhibitors.

Method And Analysis: This single-arm, single-centre exploratory trial will be conducted at Renji Hospital, enrolling 32 patients aged 18-75 years. Eligible patients must have initially achieved partial response, complete response or stable disease with progression-free survival (PFS)≥3 months during prior immunotherapy but subsequently progressive disease on imaging. Treatment will continue until meeting discontinuation criteria. The primary endpoint is objective response rate with Clopper-Pearson 95% CI. Secondary endpoints include disease control rate (95% CI), PFS and overall survival (estimated by Kaplan-Meier method), along with safety assessments.

Ethics And Dissemination: All participants will provide informed consent. The protocol has been approved by the Shanghai Jiaotong University School of Medicine, Renji Hospital Ethics Committee (LY2023-201-C). The results will be disseminated through peer-reviewed manuscripts, reports and presentations.

Trial Registration Number: ChiCTR2300077329.