Perioperative Surufatinib Plus Sintilimab Combined With Chemotherapy in Gastric/Gastroesophageal Junction Adenocarcinoma

For locally advanced gastric and gastroesophageal junction adenocarcinoma (cT3-4bNanyM0), perioperative PD-1 antibody combined with chemotherapy can downstage tumor stage, increase the R0 resection rate, and may improve the long-term survival. Combination of perioperative surufatinib, sintilimab and chemotherapy for locally advanced gastric and gastroesophageal junction adenocarcinoma could be a novel therapeutic strategy to increase response rate and therapeutic efficacy. Surufatinib, as the oral drug in this study is a small molecule kinase inhibitor that mainly acts on vascular growth factor receptor (VEGFR1, 2,3), fibroblast growth factor receptor 1(FGFR1) and colony stimulating factor 1 receptor (CSF1R). It is a proprietary product developed by Hutchison Whampoa Pharmaceutical (Shanghai, China) Co., LTD. Surufatinib has been approved for neuroendocrine tumor. This study is a monocenter, single-arm phase 2 clinical trial to evaluate tolerability, safety and efficacy of perioperative surufatinib in combination with sintilimab and chemotherapy in locally advanced gastric and gastroesophageal junction adenocarcinoma.

Inclusion Criteria: * signed informed consent * patients age 18-75 years; * Histologically CT/MRI confirmed cT3-4bNanyM0 gastric or GEJ adenocarcinoma; * ECOG 0-1, no surgery contraindications; * Expected survival ≥3 months; Exclusion Criteria: * signs of distant metastases * Prior chemotherapy, radiotherapy, surgery for gastric cancer; * Significant cardiovascular disease * major surgical procedure within 4 weeks prior to initiation of study treatment * current treatment with anti-viral therapy or HBV * pregnancy or breastfeeding * history of malignancy within 5 years prior to screening * Present or history of any autoimmune disease or immune deficiency; * Prior therapy with a PD-1, anti-PD-Ligand 1 (PD-L1) or CTLA-4 agent; * There are active gastric and duodenal ulcers, ulcerative colitis and other gastrointestinal diseases, or active bleeding in unresectable tumors. * Poorly controlled hypertension or diabetes;