Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer

Sintilimab Combined With Anlotinib Therapy for Patients With Initially Unresectable Stage II-III Non-small Cell Lung Cancer: A Prospective, Single-arm Study

Concurrent or sequential chemoradiotherapy has been recommended as the standard treatment for locally advanced and unresectable non-small cell lung cancer (NSCLC). However, its efficacy remains to be improved. PD-1/PD-L1 inhibitors have been proven to be effective for late-stage NSCLC, and anti-angiogenesis agents have also been used for the first-line treatment of advanced or metastatic NSCLC. Therefore, we designed this single-arm clinical trial, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC.

Concurrent or sequential chemoradiotherapy is the standard treatment for patients with locally advanced NSCLC, but patients receiving chemoradiotherapy have limited improvement in prognosis and are almost impossible to achieve a radical cure. Considering the excellent effect of immunotherapy and anti-angiogenesis therapy in NSCLC, we designed this single-arm clinical study, which aims to investigate the safety and feasibility of sintilimab combined with anlotinib therapy for patients with initially unresectable stage II-III NSCLC, in order to enable patients to achieve further surgical treatment and prolonged survival.

Inclusion Criteria:

1. According to the 8th edition of the AJCC/UICC TNM staging system for NSCLC, patients with locally advanced (stage II-III C) NSCLC confirmed by histology who are initially unable to undergo surgery and concomitant radiochemotherapy and are confirmed to have at least one measurable lesion according to RECIST 1.1.

2. Age ≥18 years and ≤75 years.

3. ECOG PS score: 0 to 1.

4. The main organs function is normal, that is, the following criteria met:

   1. Good hematopoietic function, defined as absolute neutrophil count ≥1.5×109 /L, platelet count≥100 ×109 /L, hemoglobin ≥90g/L [no blood transfusion or no erythropoietin (EPO) dependence within 7 days before enrollment];
   2. Biochemical test results should meet the following criteria: BIL < 1.25 times the upper limit of normal value (ULN); ALT and AST < 2.5 × ULN; in case of liver metastases, ALT and AST < 5 × ULN; Cr ≤1.5×ULN or creatinine clearance (CCr) ≥60ml/min; Coagulation function is good, INR and PT ≤1.5 × ULN;
   3. The oxygen saturation of the finger tip ≥ 92% both at rest and during walking (without oxygen inhalation).

5. The life expectancy ≥12 weeks.

6. Signed and dated informed consent.

Exclusion Criteria:

1. Subjects at risk of massive hemoptysis or with blood in sputum, including but not limited to tumor lesions no more than 5 mm away from large vessels, tumors invading large vessels, and obvious lung cavity/necrotizing tumors.
2. Small cell lung cancer (including mixed small cell and non-small cell lung cancer) or central squamous cell carcinoma.
3. With driver mutation (EGFR/ALK/ROS1).
4. With uncontrollable hypertension (systolic pressure > 160 mmHg, diastolic pressure > 100 mmHg) even receiving antihypertensive drug therapy.
5. Has an active autoimmune disease, history of allogeneic stem cell transplantation or organ transplantation that has required systemic treatment. Replacement therapy is not considered a form of systemic treatment and is allowed.
6. Has an active infection requiring systemic therapy.
7. Has other malignant tumors (except radical cervical carcinoma in situ, non-melanoma skin cancer, etc.) or concomitant diseases that seriously endanger the patients or affect the patients completing the study at the same time.
8. With immunodeficiency status, including but not limited to HIV infection and primary immunodeficiency diseases.
9. Previously treated with ICIs.
10. Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.