A Single-arm, Multicenter Exploratory Clinical Trial of Anlotinib Combined With TQB2450 and the SOX Regimen as First-line Treatment for Advanced Gastric Cancer With Low PD-L1 Expression

Launched by YONGXU JIA · Apr 15, 2025

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for patients with advanced gastric cancer, specifically for those whose tumors have low levels of a protein called PD-L1. The treatment being studied combines three medications: anlotinib, TQB2450, and the SOX regimen, which includes two chemotherapy drugs. The goal is to see how effective and safe this combination is for patients who have not yet received treatment for their advanced cancer.

To join the trial, participants need to be between 18 and 75 years old, have a confirmed diagnosis of gastric or gastroesophageal junction cancer that cannot be surgically removed, and must show that their cancer has returned at least six months after previous treatment. They should also have at least one measurable tumor and be willing to follow the study rules. If you or someone you know is considering this trial, you can expect regular check-ups and monitoring while receiving the study treatment, and the team will provide support throughout the process.

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Eligibility criteria

• 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 18-75 years.
• • 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.