Chemotherapy Combined With Apatinib and PD-1 Antibody

This study is a prospective, single-center, single-arm phase II clinical study, which aims to explore the efficacy of PD-1 antibody combined with apatinib combined with chemotherapy as a second-line and above regimen in the treatment of advanced gastric cancer.The enrolled patients were patients with advanced inoperable gastric cancer or gastroesophageal junction adenocarcinoma who had advanced first-line fluorouracil combined with platinum or advanced second-line paclitaxel and irinotecan, with an ECOG PS of 0-1. Treatment plan: PD-1 antibody: 200mg intravenous drip every 3 weeks; Apatinib 250mg/day; Chemotherapy: Irinotecan 150mg/m2, intravenous drip every 2 weeks, or Paclitaxel 150mg/m2, intravenous drip, once every 3 weeks. An imaging evaluation is performed every 6-8 weeks. Monitor blood routine, blood biochemistry, electrocardiogram, urine routine, thyroid function, heart function according to clinical routine, and record adverse events. Primary observational endpoints: objective effective rate (ORR), progression-free survival time (PFS), secondary observational endpoints: overall survival time (OS), disease control rate (DCR) and safety, and dynamic monitoring of serum biomolecular markers for exploration study .

Inclusion criteria

Patient age ≥18 years old;

• The ECOG score is 0-1 points;
• Patients with locally advanced gastric cancer or GEJ adenocarcinoma who have been histologically confirmed, metastatic or unresectable;
• Have received at least one systemic chemotherapy regimen in the past and have progressed; or have received adjuvant chemotherapy, but the disease has progressed or relapsed within 6 months after the end of the treatment; have not used any of the drug treatments in this study;
• There are measurable lesions that meet the RECIST 1.1 standard;
• It has sufficient organ and bone marrow function, and the laboratory examination meets the following requirements: a.HGB≥90g/L;b.NEUT≥1.5×109/L;c.PLT ≥100×109/L;d. BIL≤1.5 times the upper limit of normal (ULN);e. ALT and AST≤2.5×ULN; liver metastasis, then ALT and AST≤5×ULN;f. Endogenous creatinine clearance rate ≥50ml/min (Cockcroft-Gault formula);g. Urine routine is normal, or urine protein <(++), or 24-hour urine protein <1.0 g;
• Normal blood coagulation, no active bleeding and thrombosis: a. International normalized ratio INR≤1.5;b. Partial thromboplastin time APTT≤1.5 ULN;
• Women of childbearing age must undergo a negative pregnancy test (serum or urine) within 14 days before enrollment, and voluntarily use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug; for men, it should be surgery Sterilize or agree to use appropriate methods of contraception during the observation period and within 8 weeks after the last administration of the study drug;
• Estimated survival period ≥ 3 months;
• The patient voluntarily joined the study and signed an informed consent form (ICF);Those who are expected to have good compliance can follow up the efficacy and adverse reactions as required by the protocol.

Exclusion criteria

• Have received anti-angiogenesis drug therapy in the past;
• Have received anti-PD-1 and anti-PD-L1 antibody drug therapy in the past;
• Patients with high blood pressure who cannot be reduced to the normal range by antihypertensive drugs (systolic blood pressure>140 mmHg, diastolic blood pressure>90 mmHg), coronary heart disease above grade I, grade I arrhythmia (including QTc interval prolongation) Male>450 ms, female>470 ms) and grade I cardiac insufficiency;
• There are many factors that affect oral drugs (such as inability to swallow and intestinal obstruction, etc.);
• Allergic to the drugs in this program;
• Patients with a clear gastrointestinal bleeding tendency, including the following conditions: local active ulcer lesions, and fecal occult blood (+ +) cannot be included in the group; patients with a history of melena and hematemesis within 1 month;
• Patients with contraindications to apatinib: For patients with active bleeding, intestinal perforation, intestinal obstruction, within 30 days after major surgery, drug-uncontrollable hypertension, grade Ⅲ-Ⅳ cardiac insufficiency (NYHA standard), severe liver and kidney Patients with dysfunction (Grade 4); If you have immune system diseases, you need to use a daily dose of dexamethasone above 10mg;
• According to the judgment of the investigator, patients with concomitant diseases that seriously endanger the safety of the patient or affect the completion of the study;
• The researcher believes that it is not suitable for inclusion.