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

This is a single-arm, open, single-center, prospective and exploratory clinical study. We planned to enroll 29 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 tislelizumab in the treatment of NSCLC with NED, in order to provide a new treatment option for NSCLC patients with NED.

Inclusion Criteria:

• Histopathologically confirmed locally advanced or metastatic unresectable lung cancer (IIIB-IV) with an abnormal NED or NE phenotype (without neuroendocrine morphologic features and positive immunohistochemical expression of at least one neuroendocrine marker (CD56, CgA, Syn));
• Have at least one measurable lesion according to RECIST v1.1;
• ECOG performance status: 0-1;
• Patients who were deemed by the investigator to be eligible for first-line single-agent immunotherapy or who progressed on first-line standard therapy;
• Urine protein < ++ . If Urine protein ≥ ++ ,the amount of urine protein in 24 hours ≤1.0g;
• Expected survival time > 3 months;

Exclusion Criteria:

• Pulmonary neuroendocrine tumors (typical carcinoid, atypical carcinoid, small cell carcinoma, large cell neuroendocrine carcinoma);
• Prior anti-VEGF/VEGFR-targeted therapy or anti-PD (L)1 antibody;
• Have uncontrolled hypertension, defined as systolic blood pressure >150 mmHg or diastolic blood pressure >90 mm Hg, while under anti-hypertension treatment;
• Patients with active ulcer, intestinal perforation and intestinal obstruction;
• 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.