Currently, there are no standard treatment and relevant exploration for solid tumors patients with NED. The study aims to explore the efficacy and safety of surufatinib combined with serplulimab and standard chemotherapy in the treatment ofadvanced solid tumors with NED, in order to provide a new treatment option for advanced solid tumors patients with NED.

This is a single-arm, multi-cohort, open-label, single-center, prospective, exploratory clinical study. We planned to enroll 80 patients who would receive surufatinib plus tislelizumab until disease progression, intolerance, or withdrawal of consent. The study aims to explore the efficacy and safety of surufatinib combined with serplulimab and standard chemotherapy in the treatment of advanced solid tumors with NED, in order to provide a new treatment option for advanced solid tumors patients with NED.

Inclusion Criteria:

• Histopathologically confirmed locally advanced or metastatic unresectable ESCC, BTC, PC or GC with an abnormal NED or NE phenotype (without neuroendocrine morphologic features and positive immunohistochemical expression of at least one neuroendocrine marker (CgA, Syn));
• Have at least one measurable lesion according to RECIST v1.1;
• ECOG performance status: 0-1;
• No previous systemic therapy;
• Urine protein< ++ . If Urine protein ≥ ++ ,the amount of urine protein in 24 hours ≤1.0g;
• Expected survival time &gt; 3 months;

Exclusion Criteria:

• Have uncontrolled hypertension, defined as systolic blood pressure &gt;150 mmHg or diastolic blood pressure &gt;90 mm Hg, while under anti-hypertension treatment;
• With active bleeding or bleeding tendency;
• Severe history of cardiovascular and cerebrovascular diseases;
• Other malignancies diagnosed within the previous 5 years, except basal cell carcinoma or cervical carcinoma in situ after radical resection.