Overview

This is a Phase II Study of Candonilimab Combined with Fruquintinib and Paclitaxel Albumin-Bound as Second-Line Treatment for Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Eligibility

Inclusion Criteria:

1. Have a full understanding of the study and voluntarily sign the informed consent form;
2. Aged 18 to 75 years (inclusive);
3. Pathologically confirmed advanced gastric or gastroesophageal junction adenocarcinoma;
4. Prior failure of first-line standard chemotherapy;
5. HER2-negative status;
6. ECOG performance status of 0 to 2;
7. Expected survival of ≥3 months;
8. Presence of at least one measurable lesion, defined as:
   • Longest diameter ≥10 mm as assessed by spiral CT scan;
   • Diameter ≥20 mm as assessed by conventional CT scan(per Response Evaluation Criteria in Solid Tumors, RECIST version 1.1);
9. Major organ function meeting the following requirements (use of any blood products or hematopoietic growth factors within 14 days prior to enrollment is not permitted):
   • Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L;
   • Platelet (PLT) count ≥100 × 10⁹/L;
   • Hemoglobin (Hb) ≥90 g/L;
   • Total bilirubin (TBIL) \<1.5 × upper limit of normal (ULN);
   • Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \<1.5 × ULN (or \<3 × ULN for patients with liver metastases);
   • Serum creatinine \<1.5 × ULN;
   • Creatinine clearance rate (CCr) ≥50 ml/min;
10. Men and women of childbearing potential must agree to use effective contraceptive measures;
11. Willingness to provide sufficient tumor tissue samples for PD-L1 expression testing.

Exclusion Criteria:

Patients will be excluded from this study if they meet any of the following criteria:

1. Inability to comply with the study protocol or study procedures;
2. Prior treatment with vascular endothelial growth factor receptor (VEGFR) inhibitors or prior use of immune checkpoint inhibitors;
3. History of other malignant tumors within the past 5 years, except for basal cell carcinoma or squamous cell carcinoma of the skin, or carcinoma in situ of the cervix after curative resection;
4. Presence of central nervous system (CNS) metastases or history of brain metastases prior to enrollment;
5. Diagnosis of autoimmune disease or history of autoimmune disease within 4 weeks prior to enrollment;
6. Prior allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
7. Uncontrolled malignant ascites (defined as ascites that cannot be controlled by diuretics or paracentesis as judged by the investigator);
8. Severe cardiovascular diseases occurring within 6 months prior to the initiation of study treatment, including unstable angina pectoris or myocardial infarction; cardiovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris, or coronary artery bypass grafting (CABG) within 6 months prior to enrollment; congestive heart failure (CHF) with New York Heart Association (NYHA) classification \> Grade 2; ventricular arrhythmias requiring medication; left ventricular ejection fraction (LVEF) \< 50%;
9. Subjects with known hypersensitivity to the study drugs or any of their excipients;
10. Participation in other clinical trials of unapproved or unmarketed drugs in China and receipt of the corresponding investigational drug treatment within 4 weeks prior to enrollment;
11. International Normalized Ratio (INR) \> 1.5 or activated partial thromboplastin time (APTT) \> 1.5 × upper limit of normal (ULN);
12. Electrolyte abnormalities deemed clinically significant by the investigator;
13. Uncontrolled hypertension (defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg) that cannot be controlled with medications prior to enrollment;
14. Poorly controlled diabetes mellitus prior to enrollment (fasting blood glucose concentration ≥ Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 2 after standard treatment);
15. Any disease or condition that may affect drug absorption prior to enrollment, or inability to take fruquintinib orally;
16. Active peptic ulcers of the stomach and duodenum, ulcerative colitis, or other gastrointestinal diseases; active bleeding from unresected tumors; or other conditions judged by the investigator to potentially cause gastrointestinal bleeding or perforation prior to enrollment;
17. Active or uncontrolled severe infections (≥ CTCAE v5.0 Grade 2 infections);
18. Known human immunodeficiency virus (HIV) infection; known history of clinically significant liver disease, including viral hepatitis \[subjects known to be hepatitis B virus (HBV) carriers must be excluded if they have active HBV infection, i.e., HBV DNA positive (\> 1 × 10⁴ copies/mL or \> 2000 IU/mL); known hepatitis C virus (HCV) infection with positive HCV RNA (\> 1 × 10³ copies/mL)\];
19. Unresolved toxicities above CTCAE v5.0 Grade 1 resulting from any prior anticancer treatment, excluding alopecia, lymphopenia, and ≤ Grade 2 neurotoxicity caused by oxaliplatin;
20. Pregnant females (positive pregnancy test prior to drug administration) or females who are breastfeeding;
21. Receipt of blood transfusion, blood products, or hematopoietic factors (e.g., albumin, granulocyte colony-stimulating factor \[G-CSF\]) within 14 days prior to enrollment;
22. Any other diseases, clinically significant metabolic abnormalities, physical examination abnormalities, or laboratory test abnormalities; conditions judged by the investigator to make the subject unsuitable for study drug administration (e.g., epilepsy requiring treatment), potentially interfere with the interpretation of study results, or place the subject at high risk;
23. Urinalysis indicating urinary protein ≥ 2+ and 24-hour urinary protein excretion \> 1.0 g;
24. Complications requiring long-term immunosuppressive therapy, or systemic or local use of immunosuppressive corticosteroids (\> 10 mg/day prednisone or equivalent therapeutic hormones);
25. Subjects deemed unsuitable for enrollment in this study by the investigator.