A Random, Non-controlled, Open Clinical Study of Apatinib Mesylate Combined With Albumin-bound Paclitaxel ± Adebrelimab in Treating Advanced Second-line Gastric Cancer
This study is a prospective, randomized, non-controlled, open-label clinical trial aimed at evaluating the efficacy and safety of adebrelimab combined with apatinib mesylate and albumin-bound paclitaxel, as well as apatinib mesylate combined with albumin-bound paclitaxel, in treating advanced second-line gastric adenocarcinoma or gastroesophageal junction adenocarcinoma. The study's primary endpoint is median progression-free survival (mPFS), and it plans to enroll 50 patients with gastric adenocarcinoma or gastroesophageal junction adenocarcinoma who failed first-line systemic therapy. This is a randomized, non-controlled, open-label trial. Eligible participants will be randomly assigned in a 1:1 ratio to receive either adebrelimab combined with apatinib mesylate and albumin-bound paclitaxel (Cohort 1) or apatinib mesylate combined with albumin-bound paclitaxel (Cohort 2). The screening phase is 28 days. After completing screening tests and assessments, eligible participants will be randomly assigned to the following treatments: Cohort 1: * Adebrelimab: 1200 mg, IV infusion, once every 21 days, until PD or intolerance, maximum use 2 years; * Apatinib mesylate: 250 mg, orally, once daily, days 1-21; until PD or intolerance, maximum use 2 years; * Albumin-bound paclitaxel: 200-260 mg/m², IV infusion, day 1, once every 21 days, for 4-6 cycles. Cohort 2: * Apatinib mesylate: 250 mg, orally, once daily, days 1-21; until PD or intolerance, maximum use 2 years; * Albumin-bound paclitaxel: 200-260 mg/m², IV infusion, day 1, once every 21 days, for 4-6 cycles.
• Fully understand this study and voluntarily sign the informed consent form, with good compliance and cooperation during follow-up;
• Age ≥18 years and ≤80 years;
• ECOG score 0-1;
• Histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma, locally advanced and unresectable, with local recurrence or distant metastasis;
• Her2 negative;
• Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma that has failed first-line systemic therapy: (1) Patients with postoperative recurrence or metastasis who progress during concurrent chemoradiotherapy also qualify; (2) For neoadjuvant/adjuvant therapy, if the patient progresses during treatment or within 6 months after treatment, it is also considered first-line systemic therapy failure; (3) If first-line therapy included immunotherapy, the PFS of a regimen containing immune checkpoint inhibitors must be at least 5 months;
• Patient has at least one measurable lesion (according to RECIST 1.1 criteria);
• Major organ function is normal, i.e., meeting the following criteria:(1) Blood routine test standards must meet the following (no blood transfusion or blood products within 14 days, no use of G-CSF or other hematopoietic stimulating factors for correction):
⁃ A. Hemoglobin (Hb) ≥ 90 g/L; B. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; C. Platelet count (PLT) ≥ 80 × 10\^9/L;
⁃ (2) Biochemical test standards must meet the following: A. Total bilirubin (TBIL) \< 1.5 times the upper limit of normal (ULN); B. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 ULN, and \< 5 ULN for liver metastasis patients; C. Serum creatinine (Cr) ≤ 1.5 ULN or estimated creatinine clearance \> 60 ml/min (Cockcroft-Gault formula); D. Urinalysis shows protein (UPRO) \< 2 or 24-hour urine protein \< 1 g;
⁃ (3) Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ lower limit of normal (50%);
⁃ (4) Coagulation function: international normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time ≤1.5 × ULN;
⁃ (5) Lung function: forced expiratory volume in 1 second (FEV1) ≥1.2 L, FEV1% ≥50%, carbon monoxide diffusing capacity (DLCO) ≥50%;
⁃ (6) Echocardiography: left ventricular ejection fraction (LVEF) ≥50%;
⁃ (7) Electrocardiogram: QT interval corrected by Fridericia method (QTcF) \<470 ms for females, \<450 ms for males;
⁃ (8) Others: lipase ≤1.5 × ULN (patients with lipase \>1.5 × ULN can be included if there is no clinical or imaging evidence of pancreatitis); amylase ≤1.5 × ULN (patients with amylase \>1.5 × ULN can be included if there is no clinical or imaging evidence of pancreatitis); alkaline phosphatase (ALP) ≤2.5 ULN.
• Women of childbearing potential must agree to use effective contraception during the study and for 6 months after the study; must have a negative serum or urine pregnancy test within 7 days before enrollment, and must not be breastfeeding; men must agree to use contraception during the study and for 6 months after the study.