Inclusion Criteria:
* 1\. Willing and able to provide written informed consent and comply with study procedures.
* 2\. Histologically or cytologically confirmed HER2-negative (or HER2 status undetermined) unresectable locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma variants).
* 3\. Disease recurrence \>6 months after completion of (neo)adjuvant chemotherapy or radiotherapy.
* 4\. At least one measurable or evaluable lesion according to RECIST v1.1 criteria. Measurable lesions must not have received prior local therapy (e.g., radiotherapy); however, lesions within previously irradiated fields may be designated as target lesions if documented progression is demonstrated per RECIST v1.1.
* 5\. Age 18 and above.
* 6\. ECOG performance status 0-1.
* 7\. Life expectancy ≥3 months.
* 8\. Organ Function Requirements and Laboratory Test Criteria During Screening (1) Complete Blood Count (CBC) Criteria： Hemoglobin (Hb): ≥ 90 g/L (no blood transfusion within 14 days) Absolute Neutrophil Count (ANC): ≥ 1.5 × 10⁹/L Platelet Count (PLT): ≥ 100 × 10⁹/L (no use of interleukin-11 \[IL-11\] or thrombopoietin \[TPO\] within 14 days) White Blood Cell Count (WBC): ≥ 4.0 × 10⁹/L (no granulocyte colony-stimulating factor \[G-CSF\] administration within 14 days) (2) Biochemical Panel Requirements: Total Bilirubin (TBIL): ≤ 1.5 × ULN (upper limit of normal),Alanine Aminotransferase (ALT) \& Aspartate Aminotransferase (AST): ≤ 2.5 × ULN,Serum Creatinine (Cr): ≤ 1.5 × ULN or Creatinine Clearance (CrCl): ≥ 60 mL/min (calculated by Cockcroft-Gault formula),Serum Albumin: ≥ 25 g/L (2.5 g/dL) For Subjects with Hepatic Metastases:Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT): ≤ 5 × ULN，White Blood Cell Count (WBC): ≥ 4 × 10⁹/L，Platelet Count (PLT): ≥ 100 × 10⁹/L (without transfusion support)， Absolute Neutrophil Count (ANC): ≥ 1.5 × 10⁹/L (without granulocyte colony-stimulating factor \[G-CSF\] therapy) (3) Cardiac Function Assessment (Echocardiography)：Left Ventricular Ejection Fraction (LVEF): ≥ 50% (or above institutional lower limit of normal) (4) Coagulation Profile：International Normalized Ratio (INR) or Prothrombin Time (PT): ≤ 1.5 × ULN
* 9\. Women of reproductive age must use effective contraception during the study period, after the last dose, and for at least 6 months following chemotherapy. It is recommended to start using contraception at least 3 months before the administration of the investigational drug; unsterilized males must also be required to use effective contraception for at least 6 months during the study period, after the last dose, and following chemotherapy. It is recommended to start using contraception at least 3 months before the administration of the investigational drug.
* 10\. PD-L1 combined positive score ( CPS) \<5
Exclusion Criteria:
* 1\. Prior treatment with anlotinib hydrochloride or any immune checkpoint inhibitors (anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibodies);
* 2\. History of immunodeficiency disorders, including HIV infection, other acquired or congenital immunodeficiency diseases, or prior organ transplantation;
* 3\. Active hepatitis B or C infection, or active pulmonary tuberculosis;
* 4\. CT-confirmed ulcerative lesions or fecal occult blood positivity;
* 5\. History of clinically significant bleeding (excluding epistaxis) within 1 month prior to enrollment;
* 6\. Previous allogeneic bone marrow or solid organ transplantation;
* 7\. Interstitial lung disease including idiopathic pulmonary fibrosis, drug-induced pneumonitis, organizing pneumonia, or CT-confirmed active pneumonia;
* 8\. Administration of live attenuated vaccines within 4 weeks before study initiation or anticipated during the study through 5 months post-treatment;
* 9\. Systemic corticosteroids (\>10 mg/day prednisone equivalent) or immunosuppressive therapy within 2 weeks prior to study initiation (inhaled or topical corticosteroids are permitted);
* 10\. Known symptomatic CNS metastases or leptomeningeal carcinomatosis. Patients with previously treated CNS metastases may be eligible if neurologically stable for ≥4 weeks without steroids or anticonvulsants;
* 11\. Conditions impairing oral drug absorption (e.g., dysphagia, chronic diarrhea, or intestinal obstruction);
* 12\. Grade ≥2 peripheral neuropathy per NCI CTCAE v5.0;
* 13\. Active infections requiring systemic antibiotics within 14 days prior to study entry;
* 14\. Hepatic tumor burden exceeding 50% of total liver volume;
* 15\. Bone metastases with impending spinal cord compression risk;
* 16\. Uncontrolled comorbidities including:
* Poorly controlled hypertension (SBP ≥150 mmHg or DBP ≥100 mmHg despite antihypertensives)
* Grade ≥2 myocardial ischemia, myocardial infarction, or arrhythmias (QTc ≥480 ms)
* NYHA Class III-IV heart failure or LVEF \<50% by echocardiography
* Uncontrolled active infections
* Decompensated liver cirrhosis or active hepatitis
* Uncontrolled diabetes (FBG \>10 mmol/L)
* Proteinuria ≥++ on dipstick or confirmed 24-hour urinary protein \>1.0 g
* 17\. Non-healing wounds or fractures;
* 18\. Coagulopathy (INR \>1.5 or aPTT \>1.5×ULN), bleeding diathesis, or requiring therapeutic anticoagulation:
* Known bleeding disorders (hemophilia, coagulopathies) or thrombocytopenia
* Hemoptysis (\>2.5 mL/day) within 2 months
* Clinically significant bleeding within 3 months (GI bleeding, hemorrhagic ulcers, etc.)
* Chronic anticoagulation (warfarin/heparin) or antiplatelet therapy (aspirin ≥300 mg/day or clopidogrel ≥75 mg/day)
* 19\. Major surgical procedures within 4 weeks prior to study or anticipated during treatment;
* 20\. History within 6 months of:
* GI perforation/fistula
* Arterial/venous thromboembolism (excluding stable cerebral infarcts)
* 21\. Clinically significant pleural/peritoneal effusions requiring intervention (asymptomatic minimal effusions not requiring treatment may be permitted);
* 22\. Severe malnutrition;
* 23\. Active substance abuse or psychiatric disorders impairing compliance;
* 24\. Other active malignancies except:
* Curatively treated malignancies with \>2 year disease-free interval
* Adequately treated non-melanoma skin cancer or lentigo maligna
* Carcinoma in situ with complete resection
* 25\. Pregnancy or lactation;
* 26\. Any condition deemed by investigators to compromise patient safety or study integrity;
* 27\. Participation in other clinical trials within 30 days prior to enrollment or planned during study period.
