This is a Two-cohort, Exploratory Clinical Study Assessing the Activity of Benmelstobart Alone or Combined with Anlotinib Administered Prior to Surgery in Terms of Pathological Complete Response
The participants voluntarily joined this study and signed an informed consent form. They demonstrated good compliance and cooperated well during the follow-up
The participant must be aged between 18 and 75 years at the time of signing the informed consent form, regardless of gender
The Eastern Cancer Collaboration (ECOG) physical fitness score was 0 or 1
The histological confirmation of non-small cell lung cancer patients, with adequate sample size
Resectable stage II-IIIB (IIIB limited to T2-3N2b) (according to AJCC 9th edition TNM staging)
PD-L1 expression ≥50%
The anticipated survival period is no less than 12 weeks
Participants who have not undergone radiotherapy, chemotherapy, surgery, or targeted therapy prior to enrollment
Patients with measurable lesions (RECIST 1.1)
Both male and female patients of reproductive age agreed to the use of reliable contraceptive methods before entering the trial, during the study and up to 8 weeks after discontinuation of the drug
Agreed to the collection of tumor histological specimens required for the study and their use in related studies
Agreed to radical surgical treatment
Patients with no surgical contraindications judged by specialists
The subjects must possess adequate pulmonary function to undergo the anticipated lung resection surgery
The primary organ functions are normal and should meet the following criteria:
Pulmonary ventilation function tests must demonstrate that FEV1 is ≥ 1.5 L, or that the expected FEV1 after lobectomy or pneumonectomy is ≥ 800 mL.
The criteria for routine blood tests are as follows (no blood transfusions or blood products within the past 14 days, and no use of G-CSF or other hematopoietic growth factors for correction): Hemoglobin (HB) must be ≥ 90 g/L; Absolute Neutrophil Count (ANC) must be ≥ 1.5 × 10\^9/L; Platelet count (PLT) must be ≥ 80 × 10\^9/L.
Biochemical examinations should meet the following criteria: Total Bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) ≤ 2.5 × ULN; Serum Creatinine (Cr) ≤ 1.5 × ULN or Creatinine Clearance Rate (CCr) ≥ 60 mL/min.
For patients who have not previously received anticoagulant therapy, Prothrombin Time International Normalized Ratio (INR) should be ≤ 1.5, and Activated Partial Thromboplastin Time (APTT) should be ≤ 1.5 times the upper limit of normal values. Patients receiving full-dose anticoagulant therapy or parenteral anticoagulation may enter clinical trials if their dosage has been stable for at least two weeks prior to enrollment and coagulation test results fall within local treatment limits.
Women of childbearing age (ages 15-49 years) are required to undergo a urine pregnancy test within seven days prior to initiating treatment, with a negative result being mandatory.
You may not be if
Patients with large cell carcinoma, mixed cell lung cancer, and small cell lung cancer components
Imaging (CT or MRI) shows that the tumor lesion is less than 5 mm away from the large blood vessels, there is a central tumor that is less than or equal to 2cm away from the bronchial tree; Or significant pulmonary cavity or necrotic tumor
Any systemic anticancer treatment for NSCLC, These included cytotoxic drug therapy, immunodrug therapy, and investigational therapy
Patients who had local radiotherapy for NSCLC
Patients who had cancer other than NSCLC in the five years prior to the start of treatment in this study. Excluding cervical carcinoma in situ, cured basal cell carcinoma, and bladder epithelial tumors \[including Ta and Tis\]
Patients who have previously used anlotinib and other anti-angiogenic agents
Patients who have previously used benmelstobart, or other anti-PD-1, anti-PD-L1, anti-CTLA-1 antibodies, As well as any other antibody or drug therapy that targets T cell co-stimulation or checkpoint pathways, such as ICOS or agonists (e.g. CD40, CD137, GITR, OX40, etc.)
Allergy to any component of anlotinib or benmelstobart
Multiple factors that affect oral medications (e.g. Inability to swallow, chronic diarrhea, and intestinal obstruction)
Patients with any severe and/or uncontrolled disease, including: 1) patients with unsatisfactory blood pressure control (systolic ≥150 mmHg, diastolic ≥100 mmHg); 2) Have grade I or higher myocardial ischemia or myocardial infarction, arrhythmia (including QTc≥480ms), and ≥ grade 2 congestive heart failure (NYHA rating); 3) Abnormal coagulation function (INR\>1.5 or prothrombin time (PT) \>ULN+4 seconds or APTT \>1.5 ULN), have a tendency to bleed or are receiving thrombolytic or anticoagulant therapy; Note: Under the premise of INR ≤ 1.5, the use of low dose heparin (adult daily dose of 0.6 thousand to 12 thousand U) or low dose aspirin (daily dose of 100 mg or less) is permitted for preventive purposes; 4) Active or uncontrolled serious infection; 5) Cirrhosis, decompensated liver disease, active hepatitis or chronic hepatitis require antiviral therapy; 6) Renal failure requires hemodialysis or peritoneal dialysis; 7) Have a history of immunodeficiency, including HIV positive or suffering from other acquired or congenital immunodeficiency diseases, or have a history of organ transplantation; 8) Poor diabetes control (fasting blood glucose (FBG) \> 10 mmol/L); 9) Urine routine indicated urine protein ≥++, and confirmed 24-hour urine protein quantity \> 1.0g; 10) Patients who have seizures and require treatment; 11) Wounds or fractures that have not healed for a long time;
Clinically significant hemoptysis (\> 50ml daily hemoptysis) occurred within 2 weeks before enrollment; Or clinically significant bleeding symptoms or a definite tendency to bleed, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, stool occult blood ++ or above at baseline
Patients with imaging evidence that the tumor has invaded important blood vessels or who are determined by the investigators to be highly likely to invade important blood vessels and cause fatal major bleeding during follow-up studies
Patients with prior interstitial lung disease, drug-induced interstitial disease, radiation pneumonia requiring hormone therapy, or any clinically demonstrated active interstitial lung disease
Patients with acute arterial/venous thrombosis events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism within 6 months
Current peripheral neuropathy ≥CTCAE degree 2, except for trauma
Subjects who underwent major surgery or had severe trauma, prior to enrollment, The effects of surgery or trauma have been resolved less than 14 days
The patient is participating in another clinical study or has less than 4 weeks since the end of treatment in the previous clinical study
A live or attenuated vaccine was administered within 30 days prior to the first administration of benmelstobart, or a live or attenuated vaccine was planned for the study period
A known history of severe hypersensitivity to other monoclonal antibodies
Pregnant or nursing women
A clear history of neurological or psychiatric disorders, including epilepsy or dementia
In the investigator's judgment, the patient may have other factors that might have forced the study to be terminated. Such as other serious diseases or serious laboratory abnormalities or associated with other factors that may affect the safety of the subject, or the family or society of the test data and sample collection
Clareo Health | This is a Two-cohort, Exploratory Clinical Study Assessing the Activity of Benmelstobart Alone or Combined with Anlotinib Administered Prior to Surgery in Terms of Pathological Complete Response
