A Phase II Study of Anti-PD-1 Antibody, Sintilimab, as Second-line Therapy for Biomarker-selected Advanced or Metastatic NSCLC

Inclusion Criteria:

• ≥ 18 and ≤ 70 years of age , regardless of gender；
• Pathologically confirmed diagnosis of locally advanced or metastatic NSCLC (according to the eighth edition of AJCC staging, IIIB, IIIC, IV), with at least one measurable lesion (RECIST 1.1)
• treatment failure after first-line standard treatment (definition of treatment failure: intolerable side effects, disease progression during or after treatment);
• No known EGFR sensitive mutations and ALK gene rearrangements.
• Tumor tissue samples that meet the testing requirements for biomarker testing can be provided. Testing will be carried out in the central laboratory.
• NSCLC that is anti-programmed cell death ligand 1 (PD-L1) positive(TPS PD-L1 expression is ≥1% ), and CD8 expression is ≥20% (pre-treatment samples are sufficient).
• ECOG PS: 0-1

• Sufficient organ and bone marrow function as defined below:

  1. Routine blood examination:

     1. HB≥90g/L;
     2. ANC ≥1.5×109/L;
     3. PLT ≥90×109/L;

  2. Biochemical inspection shall:

     1. Total bilirubin ≤ 1.5 ULN;
     2. ALT and AST≤2.5ULN;
     3. Serum Cr≤1ULN, endogenous creatinine clearance rate>60ml/min (Cockcroft-Gault);
• The international normalized ratio (INR) ≤ 1.5 and partial prothrombin time (PPT or APTT) ≤ 1.5 ULN within the 7 days before enrollment.
• Life span expectation over 3 months;
• Provide written informed consent;

Exclusion Criteria:

• Allergic to any ingredients of Sintilimab preparations; or have had severe allergic reactions to other monoclonal antibodies in the past.
• Received more than one regimen for the treatment of locally advanced or metastatic NSCLC in the past (except for adjuvant/neoadjuvant chemotherapy that has exceeded the 24-week).
• Received any anti-PD-1/PD-L1 antibody, anti-CTLA4 antibody, or other immunotherapy in the past.
• Diagnosed other malignant tumors within 5 years before the first administration, excluding radically cured skin basal cell carcinoma, skin squamous cell carcinoma and/or radically excised carcinoma in situ.
• Be treated with anti-tumor vaccines or other immunostimulatory anti-tumor drugs (interferon, interleukin, thymosin, immune cell therapy, etc.) within 1 month before enrolled.
• Central nervous system metastasis with symptoms..
• Acute or chronic active hepatitis B (defined as positive for hepatitis B virus surface antigen HBsAg during the screening period) or hepatitis C infection.
• History of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severely impaired lung function and other lung diseases.
• Active tuberculosis (TB), who are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before the first administration.
• People infected with human immunodeficiency virus (HIV) (HIV antibody positive), people with known syphilis infection.
• Patients who are considered to be at greater medical risk due to severe, uncontrollable diseases, non-metastatic systemic diseases, or active, uncontrollable infections.
• An active autoimmune disease that requires systemic treatment (such as the use
• disease-relieving drugs, corticosteroids, or immunosuppressive agents) occurred within 2 years before the first administration.
• Have used immunosuppressive drugs within 4 weeks before the first administration, excluding nasal spray, inhaled or other local glucocorticoids or physiological doses of systemic glucocorticoids (ie not more than 10 mg/day prednisone Loose or equivalent doses of other glucocorticoids), allowing temporary use of glucocorticoids for the treatment of asthma, chronic obstructive pulmonary disease and other diseases such as dyspnea symptoms.
• Exclude subjects who are expected to require any other form of anti-tumor therapy (including maintenance therapy with other NSCLC drugs, radiotherapy, and/or surgical resection) in the study.
• Exclude those who underwent major surgery within 4 weeks before the first medication, those with non-thoracic radiation therapy >30 Gy within 4 weeks before the first medication, those with chest radiation >30 Gy within 24 weeks before the first medication, and 2 before the first medication Subjects who received palliative radiation <30 Gy within a week and who failed to recover from the toxicity and/or complications of these interventions to NCI-CTC AE ≤ 1 degree (except for hair loss and fatigue). Palliative radiotherapy for symptom control is permitted and must be completed at least 2 weeks before the start of treatment with the study drug, and there are no plans for additional radiotherapy to the same lesion. For patients who received radiotherapy 2 weeks before the first administration, all of the following conditions must be met before they can be enrolled: There is no radiotherapy-related toxic reaction, glucocorticoids are not required, and radiation pneumonitis, radiation hepatitis, radioactivity are excluded Enteritis and so on.
• Pregnancy or lactation.
• Participated in other drug clinical trials within four weeks.
• The investigator believes that there are any conditions that may damage the subject or result in the subject not being able to meet or perform the research request.