A Study of Bemotuzumab Plus Chemotherapy and Anlotinib Induction Followed by Bemotuzumab, Anlotinib and Consolidative Thoracic Radiotherapy in Extensive-Stage Small Cell Lung Cancer

This is an exploratory Phase II clinical trial for previously untreated extensive-stage small cell lung cancer (ES-SCLC). The study evaluates a novel three-phase sequential treatment strategy: patients first receive induction therapy with Bemotuzumab combined with standard chemotherapy and Anlotinib; those achieving disease control then proceed to consolidation therapy with Bemotuzumab, Anlotinib, and concurrent thoracic radiotherapy; followed by a maintenance phase with Bemotuzumab plus Anlotinib. The primary objectives are to assess the regimen's efficacy in prolonging progression-free survival (PFS) and to observe its safety profile. The study plans to enroll approximately 25 patients.

**Inclusion Criteria:**

• Histologically or cytologically confirmed extensive-stage small cell lung cancer (ES-SCLC) per VALG staging.
• No prior systemic therapy for ES-SCLC.
• At least one measurable lesion as defined by RECIST 1.1 criteria.
• Age 18-75 years.
• ECOG performance status of 0-2.
• Life expectancy of ≥3 months.
• Adequate hematologic and organ function:

• Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L.
• Platelet count ≥ 100 × 10^9/L.
• Hemoglobin ≥ 80 g/L.
• Creatinine clearance ≥ 50 mL/min.
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
• AST and ALT ≤ 2.5 × ULN.
• Albumin ≥ 28 g/L.
• INR and APTT ≤ 1.5 × ULN.
• Left ventricular ejection fraction (LVEF) ≥ 50%.
• For females of childbearing potential: negative serum pregnancy test within 3 days prior to dosing and agreement to use highly effective contraception.
• For males: agreement to use barrier contraception.
• Willing and able to provide written informed consent and comply with study procedures.

**Exclusion Criteria:**

• Symptomatic brain metastases. (Asymptomatic, treated, and stable brain metastases for ≥1 month without steroids are allowed).
• Prior thoracic radiotherapy for SCLC.
• Prior treatment with anti-angiogenic agents (e.g., anlotinib, bevacizumab) or anti-PD-1/PD-L1 therapies.
• Factors affecting oral medication intake (e.g., inability to swallow, major gastrointestinal resection).
• Uncontrolled effusions requiring repeated drainage (pleural, pericardial, or ascites).
• Imaging evidence of tumor invasion of major blood vessels or high risk of fatal hemorrhage as judged by the investigator.
• History of significant bleeding tendency or coagulopathy, including clinically significant hemoptysis (>1 tablespoon daily within 3 months) or significant bleeding within 4 weeks prior to enrollment.
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to enrollment.
• Arterial/venous thrombotic events within 6 months prior to enrollment (e.g., cerebrovascular accident, deep vein thrombosis, pulmonary embolism).
• Active autoimmune disease requiring systemic treatment within 2 years prior to first dose.
• Any other condition that, in the investigator's judgment, increases risk or renders the patient unsuitable for the study.