Teniposide, Cisplatin and Serplulimab for Treatment of ES-SCLC, a Randomized Controlled Study

Two arms trial, PFS for outcome, for patients in extensive stage of SCLC

Inclusion criteria

• Has not received systematic treatment for extensive stage small cell lung cancer in the past
• Extensive stage small cell lung cancer patients who have been pathologically proven to be intolerant to synchronous radiotherapy and chemotherapy
• Patients who have previously received radiotherapy and chemotherapy for limited stage SCLC and have had an untreatable interval of at least 6 months from the end of systemic treatment to SCLC recurrence
• Lesions can only be considered measurable if there is clear progression of a previously irradiated lesion after radiotherapy, and the previously irradiated lesion is not the only one
• Age≥18 years
• ECOG: 0-1
• Expected survival time exceeds 3 months
• Hb≥100g/L; ANC≥1.5×109/L; PLT≥100×109/L; WBC≥3.0×109/L; ALT and AST≤2.5×ULN(with tumor liver metastases, ≤5×ULN); TBIL≤1.5×ULN(with tumor liver metastases,≤3×ULN); Cr≤1.5×ULN or EGFR≥50ml/min; APTT, INR, PT≤1.5×ULN; LVEF≥50%
• Women of childbearing age should agree to use contraceptive measures during the study period and within 6 months after the end of the study. Serum pregnancy test negative within 28 days prior to enrollment in the study, and must be a non lactating subject. Men should be subjects who agree to use contraception during the study period and within 6 months after the end of the study period
• The subjects should sign an informed consent form and had good compliance

Exclusion criteria

• Patients with unstable or clinically symptomatic brain metastases, including those with central symptoms, brain edema, and those requiring radiation therapy
• Active autoimmune diseases that require systemic treatment (such as the use of disease relieving drugs, corticosteroids, or immunosuppressants) within the two years prior to enrollment
• Diagnosed with immunodeficiency or receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (dose>10mg/day prednisone or other effective hormones), and continuing to use within 2 weeks prior to enrollment
• Within 5 years, the subject has previously or simultaneously suffered from other malignant tumors that have not been cured
• With multiple factors that affect oral medication, such as inability to swallow, postoperative gastrointestinal resection, chronic diarrhea, and intestinal obstruction
• Uncontrollable pleural effusion, pericardial effusion, or ascites that require repeated drainage
• Spinal cord compression that cannot be cured or relieved by surgery and/or radiotherapy, or previously diagnosed spinal cord compression with no clinical evidence of disease stabilization for ≥ 1 week before enrollment after treatment
• Within 2 weeks prior to enrollment, there was significant hemoptysis
• Subjects who did not recover to ≤ CTCAE v5.0 level 1 due to adverse events caused by previous treatment (excluding hair loss)
• Received significant surgical treatment or significant traumatic injury within 28 days prior to enrollment
• Serious arterial/venous thrombotic events, such as cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism, occurred within the 6 months prior to enrollment
• Individuals with a history of psychiatric drug abuse who are unable to quit or have mental disorders
• Subjects with poor blood pressure control (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg) (excluding patients who were able to control blood pressure with dual drugs before enrollment); 2) Suffering from grade I or above myocardial ischemia or infarction, arrhythmia (including male QTc ≥ 450ms (male), QTc ≥ 470ms (female)), and ≥ grade 2 congestive heart failure (New York Heart Association (NYHA) classification); 3) Active or uncontrolled severe infection (≥ CTCAE v5.0 level 2 infection); 4) Cirrhosis, active hepatitis [known carriers of hepatitis B virus (HBV) must exclude active HBV infection, i.e. HBV DNA positive (>1 × 104 copies/mL or>2000 IU/ml); Known hepatitis C virus infection (HCV) and HCV RNA positivity (>1 × 103 copies/mL, or other types of hepatitis or cirrhosis; 5) HIV test positive; 6) Urine routine indicates that urine protein is ≥ 3+, and it is confirmed that 24-hour urine protein quantification is greater than 3.0g;
• No blood transfusion, albumin therapy, recombinant human thrombopoietin or colony stimulating factor (CSF) treatment was performed within 14 days prior to the first dose in this study
• According to the researcher's judgment, there are accompanying diseases that seriously endanger the safety of the subjects or affect the completion of the study by the patients