Efficacy and Safety of Serplulimab Combined With Chemotherapy as Neoadjuvant Treatment for Locally Advanced Gastric Cancer or Adenocarcinoma of Esophagogastric Junction

This is a multicenter, double-blind, randomized, phase 2 trial to investigate the efficacy and safety of serlulimab combined with nab-paclitaxel plus SOX versus nab-paclitaxel plus SOX alone as neoadjuvant treatment for locally advanced GC or AEG. The goal of this clinical trial is to learn if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. It will also learn about the safety of serlulimab combined with nab-paclitaxel plus SOX. The main questions it aims to answer are: Does serlulimab increase the pCR of participants with locally advanced AEG/GC ? What medical problems do participants have when taking serlulimab? Researchers will compare to a placebo (a look-alike substance that contains no drug) to see if serlulimab combined with nab-paclitaxel plus SOX as neoadjuvant treatment for locally advanced AEG/GC. Participants will: Eligible patients were randomly assigned to receive serlulimab (4.5 mg intravenously on day 1) combined with chemotherapy (nap-paclitaxel 260 mg/m2 intravenously on days 1, OXA 130mg/ /m2, intravenously on days 1, and S-1 40 to 60 mg orally twice daily depending on BSA on days 1 to 14) or chemotherapy alone every 3 weeks for 3 preoperative cycles followed by 3 postoperative cycles. All patients will be followed for survival.

Gastric Cancer (GC) is the fifth most common malignancy globally and the third leading cause of cancer death. Half of the world's cases occur in eastern Asia \[1\], which has the highest mortality rate. According to the latest data released by the National Tumor Registration Center, it is estimated that in 2015, there were 679,000 new cases of gastric cancer in China, and 498,000 deaths, ranking second in both incidence and fatality rate among malignant tumors \[2\]. The overall prognosis is poor, posing a serious threat to human health. Environmental and genetic factors play an important role in the development of gastric cancer, with common risk factors including age, male gender, smoking, radiation and family history. Specific risk factors for gastric cancer include Helicobacter pylori infection and dietary factors \[3\]. Helicobacter pylori (H.pylori) infection often leads to chronic gastritis, gastric atrophy, and then intestinal metaplasia, abnormal hyperplasia and gastric cancer \[4-6\]. Dietary factors include low intake of fruits and vegetables, high salt, and intake of smoked foods. Radical surgical resection is still the main treatment for non-metastatic gastric cancer, but the postoperative recurrence and metastasis rate is as high as 40-80%, and the 5-year survival rate is 30-60%\[7-8\]. The treatment mode of neoadjuvant chemotherapy + surgery + adjuvant chemotherapy (perioperative treatment) is an important part of the comprehensive treatment of gastric cancer at present. A number of studies have proved that compared with surgery alone, this treatment mode can reduce the tumor stage, increase the R0 resection rate, and improve the overall survival, without increasing postoperative complications and mortality. The purpose of neoadjuvant chemotherapy is to reduce tumor load and increase the possibility of R0 resection \[9\], so as to improve the pathological complete response rate. Neoadjuvant chemotherapy can measure a patient's sensitivity to chemotherapy drugs and therefore predict a patient's response to subsequent chemotherapy. At present, it has been confirmed that pathological complete response rate is correlated with overall survival \[10\]. On September 28, 2019, at the ESMO Conference , Chinese scholars announced the results of the RESOLVE Phase III study on perioperative treatment of locally advanced gastric cancer \[11\], adding new evidence-based medical evidence for perioperative treatment of such patients. The RESOLVE study is A three-arm, randomized, multicenter, open-label Phase III trial comparing the efficacy and safety of using XELOX (Group A) or SOX (Group B) after radical D2 surgery versus perioperative use of SOX (group C). Finally, 1022 cases of ITT population were included in the analysis. In the perioperative group (group C), the R0 resection rate (92.88%) and the proportion of D2 lymph node dissection (95.59%) showed an increasing trend. The R0 removal rates of group A and group B were 86.47% and 87.83%, r Покажи пълното описание...

Inclusion Criteria: * Age older than 18 and younger than 75 years * Primary GC or AEG (Siewert II/III)confirmed pathologically by endoscopic biopsy * Clinical stage T3/T4N+M0 disease as assessed by CT/MRI, PET-CT, and laparoscopy, if feasible * At least one measurable lesion according to the RECIST, version 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 * Surgical treatment after neoadjuvant chemotherapy is planned according to clinical staging criteria. * Life expectancy of at least 3 months * Acceptable bone marrow, hepatic, and renal function, including: a)Blood routine examination(No blood transfusion within 14 days; No granulocyte colony-stimulating factor (G-CSF) or other hematopoietic stimulating factors were used): white blood cell count ≥3.5 ×109/L, neutrophils ≥1.5 × 109/L, platelet count \>100 × 109/L, and hemoglobin ≥90 g/L; b)Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ALT and AST≤2.5×ULN; total bilirubin (TBIL) ≤1.5×ULN (Gilbert syndrome patients, ≤3×ULN); c)Renal function: serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (Ccr) ≥60mL/ min; d)Coagulation function: activated partial thromboplastin time (APTT), international standardized ratio (INR), prothrombin time (PT) ≤1.5×ULN; * Written informed consent Exclusion Criteria: * Squamous cell carcinoma, adenosquamous cell carcinoma, small cell carcinoma, and undifferentiated gastric cancer were confirmed by pathology * Positive Her-2 detection (IHC3+ or IHC2+ amplified by FISH detection) * Prior chemotherapy, radiotherapy, hormone therapy, targeted therapy, or immunotherapy * Contraindications for surgical treatment or chemotherapy * Presence of distant metastasis * History of other malignant disease within the past 5 years, except: basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that have been treated radically and have shown no signs of disease for at least 5 years * Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo or resolved childhood asthma/atopy * History of immunodeficiency diseases, including human immunodeficiency virus (HIV), or other acquired or congenital immune-deficient disease, or transplantation * Severe mental disorder * Presence of digestive tract obstruction, jaundice, acute infectious diseases, inflammatory bowel disease, Crohn's disease, ulcerative colitis, chronic diarrhea, active tuberculosis * Immunosuppressive drugs are required for 2 weeks or within 2 weeks or during the study period, excluding the following: a) intranasal, inhaled, topical or topical steroid injections (e.g. intra-articular injections); b) Physiological dose of systemic corticosteroids (≤10mg/ day prednisone or equivalent dose); c) Short-term (≤7 days) use of steroids for the prevention or treatment of non-autoimmune allergic diseases; * Patients who have undergone major surgery or received live virus vaccine within 4 weeks * Pregnant or breast-feeding women, subjects who are unwilling to receive effective contraception during treatment and within 6 months after the end of treatment (including male subjects who have the ability to impregnate women and female subjects and their male partners) * Evidence of bleeding tendency or receiving thrombolytics or anticoagulants * According to the criteria of the term Common Adverse Events (NCI-CTCAE V5.0), the corresponding symptoms have been diagnosed; * Hepatitis B or hepatitis C virology tests at the time of screening meet any of the following: a) HBsAg positive and HBV-DNA titer ≥104 copy number /mL or ≥2000IU/mL (hepatitis B carriers should ask researchers for appropriate antiviral treatment); b) Active hepatitis C: HCV antibody positive and HCV-RNA higher than the lower detection limit of the assay; * Allergic to study drugs * The investigator believes that the subjects have other conditions that may affect their adherence to the protocol and evaluation of the study indicators, and the subjects are not suitable to participate in the study.