Toripalimab as Maintenance Therapy in Patients With Driver-gene Negative Advanced NSCLC After First-line Chemotherapy

Toripalimab as Maintenance Therapy in Patients With Driver-gene Negative Advanced NSCLC After First-line Chemotherapy ：a Single-arm Phase II Trial

Lung cancer is the malignant tumor with the highest incidence and mortality in China. Non-small cell lung cancer (NSCLC) ,which includes non-squamous cell carcinoma (including adenocarcinoma, large cell carcinoma, and other cell types) and squamous cell carcinoma, accounts for about 80% of lung cancer. Platinum-based two-drug chemotherapy is the first-line standard treatment for driver-gene negative advanced NSCLC, but most patients experience disease progression after 4 to 6 months. To extend the efficacy of first-line treatment, maintenance therapy is a logical clinical option for patients who are effective after 4 to 6 cycles of standard treatment. There is currently no standard regimen for maintenance treatment of NSCLC. We evaluated the effectiveness and safety of maintenance therapy with the anti-PD-1 monoclonal antibody (Toripalimab injection) followed by the first-line standard regimen in advanced NSCLC patients who are effective after standard treatment. With a view to exploring treatment methods that are effective for the maintenance treatment of driver-gene negative advanced NSCLC and have little toxic and side effects,thereby improving the survival prognosis of these patients.

Platinum-based two-drug chemotherapy is the first-line standard treatment for driver-negative advanced NSCLC, but most patients experience disease progression after 4 to 6 months. To extend the efficacy of first-line treatment, maintenance therapy is a logical clinical option for patients who are effective after 4 to 6 cycles of standard treatment. There is currently no standard regimen for maintenance treatment of NSCLC. We evaluated the effectiveness and safety of the anti-PD-1 monoclonal antibody (Toripalimab injection) followed by maintenance therapy in advanced NSCLC that was effective in the first-line standard regimen.Thereby improving the survival prognosis of advanced NSCLC.

Criteria:

Inclusion Criteria:

• Fully understand the research and voluntarily sign the informed consent form (ICF)

• Age 18 to 75 years

• Histological or cytological documentation of non-small cell lung cance.

• Diagnosed as stage IV by imaging (staging according to AJCC eighth edition).

• Gene test is negative for EGFR, ALK, ROS1 confirmed by molecular pathology (tissue, ARMS method or NGS).

• Previously received first-line standard chemotherapy for non-small cell lung cancer (platinum combined with third-generation chemotherapy drugs in a two-drug combination regimen: pemetrexed or paclitaxel or docetaxel or gemcitabine or vinorelbine combined with cisplatin or carboplatin), and which were assessed the effectiveness by imaging(SD, PR or CR).

• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.

• ECOG performance status 0-1

• Expected overall survival time≥3 months

• Adequate bone marrow, Coagulation function，hepatic and renal function should be assessed by the following laboratory requirements conducted within 7 days before starting study treatment:

  • Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥9g/ dL.
  • Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN.
  • Serum creatinine ≤ 1.5 x the ULN.
  • Calculated creatinine clearance or 24 hour creatinine clearance ≥ 40 mL/ min.
  • INR≤1.5, Activated partial thromboplastin time(APTT)≤1.5×ULN.

• Patients with hepatitis B virus (HBV) infection and inactive/asymptomatic HBV carriers, or patients with chronic or active HBV, if the HBV DNA is <500IU/ml, or 2500copies/ml at the time of screening,can enter the group.

• Male subjects and women of childbearing age must have contraception within 24 weeks from the start of the study to the last time of using the drug.

Exclusion Criteria:

• Tumor histology or cytology pathology confirmed with small cell lung cancer components or sarcomatoid lesions.
• Previously received any T-cell co-stimulation or immune checkpoint therapy, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 / 2 inhibitors or other drugs that target T cells.
• Major autoimmune diseases.
• Subjects who were vaccinated or planned to be vaccinated within 4 weeks before the first time using the study drug.
• LD, drug-induced pneumonia, radiation pneumonitis requiring steroid therapy, or clinically active pneumonia or severe pulmonary dysfunction.
• TB or subjects with a history of active tuberculosis infection ≤ 48 weeks before screening, whether or not treated.
• Symptomatic cardiac disease, such as: heart failure above NYHA level 2, unstable angina pectoris, myocardial infarction occurred within 24 weeks, clinically significant supraventricular or ventricular arrhythmias require treatment or intervention.
• Acquired immunosuppression (AIDS or major immunosuppressive agents)
• Suffering from active viral hepatitis. Defined as: Hepatitis B virus (HBV) infection and HBV DNA ≥ 2500 copies / ml; or Hepatitis C virus (HCV) infection (quantitative test results of anti-HCV positive and HCV RNA are greater than the lower limit of detection) .
• Mental illness, alcohol, drug or substance abuse
• Pregnant or lactating women.