Clinical trial NCT05306847: Sintilimab Combined With Anlotinib Therapy for Initially Unresectable Non-small Cell Lung Cancer
Official title: Sintilimab Combined With Anlotinib Therapy for Patients With Initially Unresectable Stage II-III Non-small Cell Lung Cancer: A Prospective, Single-arm Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Non-small-cell lung cancer
Sintilimab
Anlotinib
Lead sponsor: Peking Union Medical College Hospital
Sponsor class: OTHER
Collaborators: name: Xinda Biopharmaceutical Group
name: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
First posted: 2022-04-01
Enrollment: 93
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Surgical conversion rate
timeFrame: 18 weeks from the initiation of the tested regime therapy
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: 18 weeks from the initiation of the tested regime therapy
measure: R0 resection rate
timeFrame: within 28 working days after operation
measure: Major pathological response rate
timeFrame: within 28 working days after operation
measure: Pathological complete response rate
timeFrame: within 28 working days after operation
measure: Overall survival (OS)
timeFrame: 2 years from the initiation of the tested regime therapy
measure: Progression-free survival (PFS)
timeFrame: 2 years from the initiation of the tested regime therapy
measure: Disease-free survival (DFS)
timeFrame: 2 years from the initiation of the tested regime therapy
measure: Treatment-related adverse events
timeFrame: 3 months from the end of the tested regime therapy
Other outcomes:
Locations:
Study officials:
affiliation: Peking union medical colloge hospital
name: Chunmei Bai, Professor
role: PRINCIPAL_INVESTIGATOR
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