1. More than half of peritoneal metastases are from digestive tract. Peritoneal metastasis has poor prognosis, poor treatment response and limited means. 2. rmhTNF-NC or bevacizumab are effective in the treatment of malignant pleuroabdominal effusion.
3, There is increasing evidence that PD-1/PD-L1 inhibitors in combination with vascular endothelial growth factor receptor (VEGFR) inhibitors have a complementary mechanism of action: VEGF pathway inhibitors normalize blood vessels in tumors and promote immune cell maturation and infiltration, thus playing a synergistic role with ICIs. The strategy of systemic immunotherapy combined with antivascular therapy has been confirmed by several large phase III clinical trials such as IMbrave-150. Basic studies have confirmed that uncontrolled tumor vessels in peritoneal metastasis and malignant ascites microenvironment also play an important role in promoting disease progression. Therefore, this project intends to explore the treatment of malignant abdominal effusion by local intraperitoneal injection of bevacizumab and PD-1 on the basis of rmhTNF-NC
Age ≥18 years old, gender unlimited;
Malignant ascites confirmed by histology or cytology as originating from digestive system tumors (malignant confirmed by ascites cytology or clinically diagnosed as peritoneal metastases by imaging and symptoms);
B ultrasound examination of ascites ≥3cm in lying position;
Accompanied by clinical symptoms (chest tightness, shortness of breath, abdominal distension and discomfort, which were judged by researchers to be related to abdominal fluid accumulation);
History of allergy to tumor necrosis factor and its derivatives, bevacizumab analogues, and Serplulimab;
Malignant diseases other than digestive tract neoplasms were diagnosed within 5 years prior to initial administration (excluding radical basal cell carcinoma of the skin, squamous epithelial carcinoma of the skin, and/or carcinoma in situ after radical resection);
Received any other investigational drug therapy or participated in an interventional clinical investigator within 7 days prior to initial dosing; Or received anti-tumor drug treatment (including Chinese herbal medicine with anti-tumor indication) within 7 days prior to the first use of the study drug;
Pregnant or lactating women, women of childbearing age who did not want to use contraception during the study period; Or the man is unwilling to use effective contraception during treatment and during the following 1 year;
Parallel
serplulimab
DrugAdditional intraperitoneal injection of bevacizumab or rmhTNF-NC is added to the PD-1 inhibitor.
Bevacizumab
DrugIntraperitoneal injection of bevacizumab is added to PD-1 inhibitor or rmhTNF-NC.
rmhTNF-NC
DrugIntraperitoneal injection of rmhTNF-NC is added to PD-1 inhibitor or bevacizumab.
Objective response rate of ascites
Defined as the percentage of patients achieving CR or PR according to the WHO criteria detected by ultrasound.
Duration of ascites relief
Time since first CR or PR to PD
Ascites control rate
percentage of patients achieving CR, PR and SD.
Incidence of Treatment-Emergent Adverse Events
Adverse events according to the NCI CTCAE 5.0
The score of chronic abdominal effusion function scale changed
Measured by FACIT-AI,score range 1 to 5, higher scores mean a better
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