A Random, Non-controlled, Open Clinical Study of Apatinib Mesylate Combined With Albumin-bound Paclitaxel ± Adebrelimab in Treating Advanced Second-line Gastric Cancer

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.

Inclusion Criteria:

• 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.

Exclusion Criteria:

• Those allergic to therapeutic drugs or those who have received first-line investigational drug treatment;
• Patients who have received first-line VEGFR inhibitor therapy, such as sorafenib, sunitinib, apatinib, etc.; Patients who have received first-line paclitaxel drugs.
• (1) Have received any investigational drug within 4 weeks prior to first use; (2) Subjects who require systemic corticosteroids (> 10 mg prednisone equivalent daily) or other immunosuppressants within 2 weeks prior to first use of the study drug, excluding cases of corticosteroid use targeting local esophageal inflammation and preventing allergies, nausea, and vomiting. (3) Other special circumstances require communication with the sponsor. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal corticosteroid replacement doses > 10 mg/day of prednisone are permitted; (4) Those who have received anti-tumor vaccines or received live vaccines within 4 weeks prior to the first administration of the study drug;
• Having any active autoimmune disease or a history of autoimmune diseases (such as interstitial lung).

inflammation, uveitis, enteritis, hepatitis, pituititis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism); Excluding vitiligo or patients with recovered childhood asthma/allergies who do not require any intervention in adulthood; Patients with autoimmune-mediated hypothyroidism treated with stable doses of thyroid replacement hormone and type I diabetes patients on stable doses of insulin may be included;

• History of immunodeficiency, including positive HIV testing, or other acquired or pre-acquired conditions Congenital immunodeficiency diseases, or history of organ transplantation and allogeneic bone marrow transplantation;
• Uncontrolled cardiac clinical symptoms or diseases, such as (1) NYHA II or above Heart failure (2) Unstable angina pectoris (3) Myocardial infarction within 1 year (4) Subjects with clinically significant supraventricular or ventricular arrhythmias requiring clinical intervention;
• Severe infection within 4 weeks prior to first use of the study drug (CTC AE> level 2), Such as severe pneumonia, bacteremia, or complications such as infections requiring hospitalization; Baseline chest imaging indicates active lung inflammation, symptoms and signs of infection within 2 weeks prior to first use of the study drug, requiring oral or intravenous antibiotic treatment, except for prophylactic antibiotic use; History of interstitial lung disease, non-infectious pneumonia, pulmonary fibrosis, or other uncontrolled acute lung diseases; Patients with active pulmonary tuberculosis infection found through medical history or CT scan, or those with a history of active pulmonary tuberculosis infection within the past year prior to enrollment, or those with a history of active tuberculosis infection more than 1 year ago without formal treatment; Subjects with active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL), hepatitis C (hepatitis C antibody positive, HCV-RNA above the detection lower limit of the assay);
• Before using the study drug for the first time, diagnosed with any other malignant tumor, except for those with low risk of metastasis and death (5-year survival rate >90%), such as fully treated basal cell or squamous cell skin cancer or cervical carcinoma in situ;
• Pregnant or breastfeeding women; subjects of reproductive potential who are unwilling or unable to use effective contraception;
• Patients deemed unsuitable for enrollment according to the investigator's judgment.