preoperative neoadjuvant immunotherapy combined with chemotherapy for stage ⅲ unresectable non-small cell lung cancer

Conditions: Non-small-cell Lung Cancer (NSCLC)

Summary: explorative study, which evaluates the effect of tislelizumab combined with chemotherapy in neoadjuvant treatment of stage ⅲ unresectable non-small-cell lung carcinoma.

this is a open-label, single-arm prospective clinical trial to evaluate the efficacy and safety of tislelizumab combined with chemotherapy in neoadjuvant treatment of newly diagnosed stage ⅲ unresectable non-small cell lung cancer.

Eligibility criteria:
inclusion criteria: 1. age :18 years to 75 years; 2. ecog physical score status of 0 or 1 points; 3. expected survival time ≥ 6 months; 4. according to the eighth edition of the ajcc/uicc tnm staging system, patients were pathological diagnosed with stage iii nsclc and had one of the following conditions: 1) a complete resection (r0) would not be possible, based on evaluation within a multidisciplinary team, including an experienced thoracic surgeon; 2) multiple ipsilateral mediastinal lymph nodes metastasized into large masses or multistation metastases (iiia: t1-2n2 or iiib: t3-4n2); 3) contralateral hilar or mediastinal lymph nodes, or ipsilateral or contralateral scalene or supraclavicular lymph nodes metastasis (iiib: t1-2n3; iiic: t3-4n3); 4) the lesion invaded the heart, aorta, or esophagus (iiia: t4n0-1). 5. egfr mutation or alk mutation was negative; 6. patients with at least one evaluable or measurable lesions as per recist version 1.1; 7. patients were newly diagnosed with non-small cell lung cancer, without radiotherapy, chemotherapy, surgery or molecule-targeted treatment. 8. patients must have enough cardiopulmonary function for the expected pulmonary resections for lung cancer. 9. the main organ function meets the following criteria:1) blood routine:a. anc ≥ 1.5×109/l; b. plt ≥ 100×109/l; c. hb ≥ 90 g/l; 2) blood biochemistry:tbil ≤ 1.5×uln;alt、ast≤ 2.5×uln;scr≤1.5×uln; 3) blood coagulation: inr≤1.5×uln and aptt≤1.5×uln，endogenous creatinine clearance rate≥45ml/min(cockcroft-gault formula); 10. pregnancy test (serum or urine) has to be performed for woman of childbearing age within 7 days before enrolment and the test result must be negative. they shall take appropriate methods for contraception during the study until the 3 months post the last administration of study drug. for men, (previous surgical sterilization accepted), shall agree to take appropriate methods of contraception during the study until the 3 months post the last administration of study drug; 11. patient has to voluntarily join the study and sign the informed consent form for the study. exclusion criteria: 1. patients with autoimmune disease, or a history of autoimmune disease within 2 years prior to the first use of the study drug including but not limited to the following: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism which can be included after hormone replacement therapy; subjects with childhood asthma have been completely alleviated and without any intervention or vitiligo in adulthood can be included; 2. subjects with congenital or acquired immunodeficiency such as hiv infection, active hepatitis b (hbv dna ≥ 2000 iu/ml), hepatitis c (hepatitis c antibody is positive); 3. subjects with a condition requiring other immunosuppressive medications before 7 days of study drug administration firstly, not including inhaled corticosteroids or physiological doses of systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents); 4. has received a live vaccine within 4 weeks of planned start of study therapy; 5. other malignancies have been diagnosed within 5 years prior to the first use of the study drug (excluding skin basal cell carcinoma that has been cured, skin squamous cell carcinoma, and / or carcinoma in situ that has undergone radical resection); 6. patients with a current or history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiologic pneumonia, drug-induced pneumonia and severe impairment of lung function; 7. patients with serious or uncontrollable systemic diseases, such as: patients with hypertension that is difficult to control (systolic blood pressure ≥140 mmhg and diastolic blood pressure ≥90 mmhg); patients with myocardial ischemia and myocardial infarction above class ii (including qt interval prolongation, for man ≥ 450 ms, for woman ≥ 470 ms); 8. severe infection within 4 weeks before the first administration (such as intravenous drip of antibiotics, antifungal drugs or antiviral drugs), or fever of unknown origin (\> 38.5 ℃) within 4 weeks before the first administration; 9. allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 10. pregnant or nursing women; 11. patients with a history of hypersensitivity to any of the study drugs, similar drugs, or excipients; 12. participated in other clinical trials within 4 weeks; 13. patients has received the following therapies: anti-pd-1, anti-pd-l1, or anti-pd-l2 drugs or drugs that target another stimulator or synergistically inhibit t cell receptors (e.g., ctla-4, ox-40, cd137); 14. the investigator believes that there are any conditions that may damage the subject or result in the subject being unable to meet or perform the research request.

Keywords: non-small-cell lung cancer (nsclc) immunotherapy chemotherapy