Prediction of Response to PD-L1 Inhibitor After Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer Using Multi-omics-based Liquid Biopsy

Exclusion Criteria22

• \. Histological mixture of SCLC and NSCLC components;
• \. Extensive-stage SCLC;
• \. Patients with a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or those planned for transplantation;
• \. Treatment with immunosuppressive medications (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) within 14 days prior to the first dose of PD-L1 inhibitor, except for intranasal and inhaled corticosteroids or low-dose systemic steroids (i.e., ≤10 mg/day prednisolone or equivalent);
• \. History of hypersensitivity to etoposide, cisplatin, PD-L1 antibody, or excipients in the formulation; or history of severe allergic reactions to other monoclonal antibodies;
• \. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during study treatment;
• \. Active or history of autoimmune disease or immune deficiency (including but not limited to autoimmune hepatitis, interstitial pneumonitis, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism);
• Note:
• Patients with vitiligo or alopecia are eligible for this study;
• Patients with stable hypothyroidism undergoing hormone replacement therapy (e.g., Hashimoto's syndrome) are eligible for this study;
• \. Poorly controlled asthma despite systemic treatment, such as bronchodilators; Note: Patients with complete remission of asthma during childhood and no need for any intervention in adulthood can be allowed;
• \. Urinalysis shows proteinuria ≥ ++ or confirmed 24-hour urine protein ≥ 1.0g;
• \. Malignancies other than LS-SCLC, with the following exceptions:
• Adequately treated basal or squamous cell skin cancer or carcinoma in situ of the cervix;
• Malignancy that has been treated with curative intent, with no known active disease for ≥5 years prior to the first dose of the study treatment, and with a low potential risk of recurrence;
• \. Human immunodeficiency virus (HIV) infection or known to have acquired immunodeficiency syndrome (AIDS);
• \. Significant cardiovascular disease within 6 months prior to enrollment, such as myocardial infarction, severe/unstable angina, New York Heart Association cardiac disease (class II or greater), poorly controlled arrhythmias (including QTcF interval \>450 ms for males and \>470 ms for females, with QTcF interval calculated using the Fridericia formula), and symptomatic congestive heart failure;
• \. Severe infections within 4 weeks prior to first dose of study treatment, including but not limited to infections requiring intravenous antibiotics, antifungal, or antiviral agents , or unexplained fever ≥38.5°C occurring during the screening period or before the first dose of the study treatment;
• \. Active tuberculosis, hepatitis B (HBV-DNA ≥ 500 IU/ml), hepatitis C (positive hepatitis C antibody and HCV-RNA above the lower limit of detection of the assay), or co-infection with both hepatitis B and C;
• \. Treatment with any other investigational agent with therapeutic intent within 4 weeks prior to the first dose of the study treatment;
• \. History of abuse of psychotropic drugs or drug addiction;
• \. Patients with other severe physical or mental illnesses or abnormal laboratory test results that may increase the risk of participating in the study, or interfere with the study results, as well as those whom the investigator deems unsuitable for participation in the study for other reasons.