Background: First-line chemotherapy for advanced human epidermal growth factor receptor 2 (HER2)-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma results in median overall survival (mOS) < 1 year. The programmed death (PD)-1 inhibitor provided superior OS in advanced G/GEJ adenocarcinoma combind with chemotherapy. However, the continuous explore about PD-1 inhibitors of first-line treatment with G/GEJ adenocarcinoma patients is promising. Camrelizumab, an anti-PD-1 monoclonal antibody, has been shown to have synergistic antitumor effects in the treatment of G/GEJ adenocarcinoma patients. We aimed to evaluate the safety and efficacy of camrelizumab combined with SOX in the first-line treatment of advanced G/GEJ adenocarcinoma. Methods: In this study (ChiCTR2000029691), eligible patients were diagnosed as unresectable advanced, postoperative recurrent ormetastatic, HER2-negative G/GEJ adenocarcinoma, and treatment-naive with chemotherapy, VEGFR2 inhibitors or PD-1/PD-L1 inhibitors. Patients received camrelizumab (200 mg, I.V., d1) and SOX regimen (oxaliplatin, 130 mg/m², d1; S-1, 20mg/m², bid, d1-14) every 3 weeks, until disease progression, intolerable toxicities, or physician/patient withdrawal. The safety and efficacy were assessed by investigators per CTCAE v5.0 and RECIST v1.1, respectively. The primary endpoint was progress free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Results: From March 30, 2020 to March 18, 2021, 27 patients had been enrolled to receive therpy with camrelizumab and SOX regimen. The patients were characterized with a median age of 60 years (range 26-79), 88.9% males and 11.1% females, 40.7% GEJ adenocarcinoma, 88.9% lymph node metastasis, 25.9% liver metastases, and 18.5% of patients had a history of tumor-related surgery. As of Nov 2, 2021, with a median follow-up of 8.8 months (range, 0.9-16.8), safety and efficacy were assessed in 20 evaluable patients, with overall response of 8 partial response (PR) and 9 stable disease (SD). Confirmed ORR and DCR were 40.0% (95% CI, 20.0%-63.6%) and 85.0% (95% CI, 61.1%-96.0%), respectively. The median PFS and OS were 12.7 months (95% CI, 4.9-20.5) and 16.8 months (95% CI, 3.5-30.0), respectively. Grade 3-4 treatment-related adverse events occurred in 18.5% of patients, with anemia and neutropenia ranking the most frequent. No new safety signals was identified. Conclusions: Camrelizumab combined with SOX was well tolerated and demonstrated encouraging efficacy for previously untreated with chemotherapy, VEGFR2 inhibitors or PD-1/PD-L1 inhibitors, unresectable advanced or metastatic, HER2-negative G/GEJ adenocarcinoma. Clinical trial information: ChiCTR2000029691.