β-Glucan Combined With Camrelizumab And SOX Regimen As The First-Line Treatment For Advanced Gastric Or Gastroesophageal Junction Adenocarcinoma:A Single-Arm,Exploratory Clinical Study

Background:Immune checkpoint inhibitors combined with chemotherapy have been used as the first-line treatment for patients with HER2-negative advanced gastric and gastroesophageal junction adenocarcinoma.β-glucan is a polysaccharide component existing in nature.As a natural immune regulator,it has been widely used in tumor immunotherapy.Therefore,we try to explore whetherβ-glucan can have a synergistic effect with immunotherapy and chemotherapy in gastric cancer or adenocarcinoma of the esophagogastric junction.Methods:From April 1,2021,this study recruited patients with Her-2 negative advanced gastric or gastroesophageal junction adenocarcinoma with ECOG PS≤2.Eligible patients receivedβ-glucan(500mg,po,bid,d1-14)+carrelizumab(200mg,i.v.,d1)+oxaliplatin(130mg/m~2,d1,i.v.)+S-1(For body surface area<1.25m~2,40mg per dose;for body surface area 1.25-1.5m~2,50mg per dose;for body surface area>1.5m~2,60mg per dose).Every 3 weeks for a course of treatment.The first evaluation was performed at the time of enrollment,followed by a efficacy evaluation(RECIST v1.1)every two courses(6 weeks)until death or progression.The primary endpoints of this study were objective response rate and safety.The secondary endpoints were median progression-free survival and median overall survival.Blood samples were collected from patients to evaluate immune activation-related indicators at baseline and the first efficacy evaluation.Results:Until October 31,2022,a total of 30 patients were included in the study.Among these patients,26.7%had an ECOG score of 2,and no patient had a score of 0;male accounted for 66.7%;the median age was 67.5(53-81)years;the positive expression of PD-L1 accounted for 53.3%.The final objective remission rate was 60%,including 3.3%complete remission and 56.7%partial remission.The disease control rate was 93.3%.Among these patients,the median progression-free survival was 10.4months(95%confidence interval,9.52-11.27 months),and the median overall survival was 14.0 months(95%confidence interval,11.09-16.91 months).The most common treatment-related adverse reactions were nausea(53.3%,16 cases)and loss of appetite(50%,15 cases).The incidence of grade 3 and above adverse reactions was 30%(9cases).The special adverse reaction was hemangioma(33.3%,10 cases).No adverse events associated with oralβ-glucan were observed.The levels of IL-2 and IFN-γwere significantly increased after two cycles of treatment(P<0.05).In the analysis of T cell subsets,it was also found that the number of CD4~+T cells increased significantly after treatment(P<0.05).Conclusion:Our study shows that even in patients with poor ECOG PS,β-glucan combined with carrelizumab and SOX regimen has certain curative effect and good safety.It is worth further expanding the sample study.