Overview

This is an open-label, single-arm, single-center clinical study to investigate the safety and efficacy of fuquinitinib combined with PD-1 inhibitors and first-line chemotherapy in the treatment of inoperable HER2-negative advanced GC/GEJC.

Eligible enrolled patients received 6 cycles of combined treatment with fuquinitinib combined with PD-1 inhibitor and chemotherapy (XELOX/SOX) regimen. Maintenance treatment was fuquinitinib combined with PD-1 inhibitor and Teghio/capecitabine until disease progression or toxicity became intolerable. The longest duration of PD-1 inhibitor treatment is 24 months.

Eligibility

Inclusion Criteria:

1. Have fully understood the study and voluntarily signed the informed consent;

2.18-80 years old (including 18 and 80 years old), male or female;

        3. Patients with unresectable advanced or metastatic gastric/esophagogastric junction
        adenocarcinoma confirmed by pathology or histology;
        4.ECOG physical status 0-1
        5. Expected survival ≥3 months;
        6. Have not received any anti-tumor therapy (including chemotherapy, targeted therapy,
        immunotherapy, etc.) for unresectable advanced or metastatic gastric cancer; If you have
        received adjuvant therapy after radical gastrectomy of gastric cancer, it is required that
        the time between the discovery of metastatic disease and the end of the last adjuvant
        chemotherapy is greater than 6 months);
        7. Must have at least one measurable lesion (meet the RECIST v1.1 standard);
        8. The functions of vital organs meet the following requirements (the use of any blood
        components and cell growth factors is not allowed within the first 14 days of enrollment) :
          -  Absolute neutrophil count ≥1.5×109/L, white blood cell ≥3.0×109/L;
               -  Platelet ≥90×109/L;
                    -  Hemoglobin ≥8g/dL;
                         -  Total bilirubin TBIL≤1.5 times ULN;
                            ⑤ALT and AST≤2.5 times ULN;
                            ⑥ Urea/urea nitrogen (BUN) and creatinine (Cr) ≤1.5×ULN (and creatinine
                            clearance (CCr) ≥ 50mL/min);
                            ⑦Left ventricular ejection fraction (LVEF) ≥50%;
                            ⑧Fridericia Corrected QT Interval (QTcF) <470 milliseconds;
                            ⑨INR≤1.5 x ULN, APTT≤1.5 x ULN;
                            ⑩Thyroid function, thyroid stimulating hormone (TSH) ≤ upper limit of
                            normal (ULN), if abnormal FT3 and FT4 levels should be examined, FT3
                            and FT4 levels can be included if normal;
                            9. Premenopausal and postmenopausal women &lt; Women of 1 year must
                            have a negative serum or urine pregnancy test before treatment.
        Exclusion Criteria:
          -  1. Patients with known HER-2 status (immunohistochemical 3+, or immunohistochemical
             2+&FISH positive);
             2. Had other malignancies within 5 years prior to admission, except basal cell or
             squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the
             cervix;
             3. Previously received allogeneic bone marrow transplantation or organ
             transplantation;
             4. Severe cardiovascular disease, including unstable angina pectoris or myocardial
             infarction, in the 6 months prior to enrollment;
             5. Subjects who are allergic to the investigational drug or any of its adjuncts;
             6. Hypertension that could not be controlled by drugs before enrollment was defined
             as: systolic blood pressure ≥150 mmHg and/or diastolic blood pressure ≥90 mmHg;
             7. Had any disease or condition affecting drug absorption before enrollment, or the
             patient could not take drugs orally;
             8. Gastrointestinal diseases such as active ulcer of stomach and duodenum, ulcerative
             colitis, or active bleeding of unexcised tumors, or other conditions that may cause
             gastrointestinal bleeding or perforation as determined by researchers before
             enrollment;
             9. Patients with evidence or history of significant bleeding tendency within 3 months
             prior to enrollment (bleeding within 3 months >30 mL, hematemesis, stool, stool
             blood), hemoptysis (within 4 weeks >5 mL of fresh blood) or had a thromboembolic event
             (including stroke events and/or transient ischemic attacks) within 12 months;
             10. Clinically significant cardiovascular disease, including but not limited to acute
             myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass
             grafting within 6 months prior to enrollment; New York Heart Association (NYHA) Grades
             for Congestive Heart Failure >Level 2; Ventricular arrhythmias requiring medical
             treatment; LVEF (Left ventricular Ejection Fraction) <50%;
             11. Active or uncontrolled severe infection (≥CTCAE v5.0 grade 2 infection);
             12. Known human immunodeficiency virus (HIV) infection. Known history of clinically
             significant liver disease, including viral hepatitis [Known hepatitis B virus (HBV)
             carriers must rule out active HBV infection, i.e., positive HBV DNA (≥1×104 copies /mL
             or >2000 IU/ mL); known hepatitis C virus infection (HCV) and HCV RNA positive (>1×103
             copies /mL);
             13. The patient has any active autoimmune disease or a history of autoimmune disease
             (e.g., but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis,
             enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism; The
             patient had vitiligo; Those with complete remission of asthma in childhood can be
             included without any intervention in adulthood; Patients with asthma requiring medical
             intervention with bronchodilators are not included); Replacement therapy is not
             considered systemic, and the following patients may be included: have a history of
             autoimmune related hypothyroidism and are receiving thyroid hormone replacement
             therapy; Type 1 diabetes can be controlled by insulin therapy.
             14. Immunosuppressive use of immunosuppressants or systemic hormone therapy within 7
             days prior to enrollment for immunosuppressive purposes (dose >10mg/ day prednisone or
             other therapeutic hormone).
             15. Currently suffering from interstitial lung disease or pneumonia, pulmonary
             fibrosis, acute lung disease, radiation pneumonia;
             16. Women who are pregnant (positive pregnancy test before medication) or
             breastfeeding;
             17. Any other medical condition, clinically significant metabolic abnormality,
             physical abnormality or laboratory abnormality, which, in the investigator's judgment,
             reasonably suspects that the patient has a medical condition or condition that is not
             suitable for the use of the investigational drug (such as having seizures and
             requiring treatment), or which would affect the interpretation of the study results or
             place the patient at high risk;
             18. Urine routine indicated urinary protein ≥2+, and 24-hour urinary protein volume
             ≥1.0g;
        Patients considered inappropriate for inclusion in this study.