Background: TST001 (osemitamab) is a high affinity recombinant humanized ADCC enhanced antibody that can specifically bind to the extracellular structure of claudin 18.2 protein and eliminate cancer cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Pre-clinical studies have shown that TST001 has potent single agent anti-tumor activity and synergistic effect when used in combination with immune checkpoint inhibitors in claudin 18.2 positive tumors. In the ongoing phase I/IIa clinical trial (NCT04495296), TST001 alone or in combination with capecitabine and oxaliplatin (CAPOX) in the treatment of G/GEJ adenocarcinoma has revealed encouraging preliminary efficacy (IGCC 2022, ESMO 2022). The combination of TST001 with nivolumab (in 2^nd/3^rd line treatment) or nivolumab + standard of care chemotherapy (in 1^st line) are being explored in the same study. Methods: Each cohort includes a dose escalation phase in CLDN18.2 non-selected patients and a dose expansion phase in CLDN18.2 positive patients, aiming to identify the recommended Phase 2 dose and evaluate the safety, tolerability and preliminary efficacy of TST001 in combination with nivolumab plus CAPOX or nivolumab in patients with G/GEJ adenocarcinoma. First line, treatment naïve patients with HER2 negative or unknown, locally advanced or metastatic G/GEJ adenocarcinoma will receive 21 days cycles of TST001 combined with CAPOX plus nivolumab until disease progression or unacceptable toxicity, with oxaliplatin for a maximum of 8 cycles and capecitabine per investigator’s discretion after that; 2^nd or 3^rd line patients with locally advanced or metastatic G/GEJ adenocarcinoma will receive 21 days cycles of TST001 combined with nivolumab. AEs will be categorized by CTCAE v5.0. Efficacy will be evaluated every 6 weeks per RECIST1.1. These two cohorts will be initiated in September 2022 from about 40 sites in China. Combinations with nivolumab are being explored in the US study too (NCT04396821). Clinical trial information: NCT04495296.