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Background Q-1802 is the first recombinant humanized Claudin18.2/PD-L1-tagerting bispecific antibody consisting of a N-terminal Claudin 18.2 antibody and a C-terminal PD-L1 antibody simultaneously targeting Claudin18.2 on tumor cells and PD-L1 in the tumor microenvironment (TME). Meanwhile, it retains the full antibody Fc effector function comparable to IgG1, which can mediate antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) activity.Methods This study is a multi-center, open-label, non-randomized parallel controlled phase I/II clinical trial (Qure-1802-201). Patients with untreated advanced GC/GEJ are administered with Q-1802 (IV, Q2W) respectively at 10 mg/kg and 20 mg/kg dose level in combination with XELOX standard chemotherapy (Oxaliplatin IV, d1 and capecitabine PO, d1-14, Q3W). The primary endpoint of phase I refers to safety and tolerability, while that of phase II is objective response rate (ORR) per RECIST v1.1.Results As of March 31, 2025, a total of 51 subjects with untreated advanced GC/GEJ were enrolled, 45 of which were in 10mg/kg of Q-1802 cohort and 6 were in 20mg/kg cohort. No dose-limiting toxicity (DLT) was observed and maximum tolerated dose (MTD) was not reached. Chemotherapy related treatment emergent adverse events (TEAEs) were consistent with historical data. The most common Q-1802 related TEAEs included nausea (72.5%), elevated aspartate aminotransferase (60.8%), vomiting (58.8%), and fatigue (51.0%) etc. The most common≥3 grades Q-1802 related TEAEs included neutrophil count decreased (7.8%), platelet count decreased, fatigue, nausea, and vomiting (the last 4 terms are all 3.9%) etc.Among total 49 evaluable subjects including 43 of 10mg/kg and 6 of 20mg/kg, the overall objective response rate (ORR) and disease control rate (DCR) were respectively 63.3% (31/49) and 98.0% (48/49). Among total 43 evaluable subjects in 10mg/kg of Q-1802 cohort, the ORR were 65.1% (28/43). Subgroup analysis showed that the ORR in subjects with Claudin18.2 high expression (defined as moderate to strong membranous expression of CLDN18.2 in ≥70% of tumor cells) was 70.3% (26/37), and the ORR in subjects with Claudin18.2 high expression accompanied by PD-L1 expression CPS≥5 was 81.8% (9/11).Conclusions The preliminary results showed the combination of Q-1802 and XELOX was safe and controllable in patients with untreated advanced GC/GEJ. Promising clinical efficacy signals were observed at 10mg/kg dose level with an obvious correlation trend between CLDN18.2/PD-L1 expression and ORR. Survival indicators are under following-up and 20 mg/kg cohort is still enrolling.Trial Registration ClinicalTrials.gov ID: NCT05964543.Ethics Approval This study has been approved by Medical Ethics Committee of Peking University Cancer Hospital with approval number 2023YW14-ZY01; and written informed consent was obtained from the patients before taking part in the trial.Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.