This prospective, single-arm trial explores the efficacy of Adibelimab monoclonal antibody combined with Famitinib and chemotherapy in treating locally advanced or metastatic NSCLC patients with negative driver genes who have progressed after PD-1 monoclonal antibody and chemotherapy treatment. The study focuses on assessing progression-free survival (PFS) in 40 participants. Key objectives include evaluating PFS and understanding the progression patterns post-first-line immunotherapy, with an interest in whether switching from PD-1 to PD-L1 inhibitors can overcome immune resistance.

This study is a prospective, single-arm clinical investigation. It aims to assess the effectiveness of the Adibelimab monoclonal antibody in combination with Famitinib and chemotherapy for treating patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) without driver mutations, who have progressed following initial treatment with PD-1 monoclonal antibodies and chemotherapy. The study's primary focus is on evaluating progression-free survival (PFS) among the 40 participants, spanning from December 2023 to December 2026. It intends to explore the therapeutic potential of switching from PD-1 to PD-L1 inhibitors in overcoming immune resistance and identify subgroups that may particularly benefit from this treatment strategy, thereby providing insights into personalized therapy for advanced NSCLC.

Inclusion Criteria:

• Participants must be adults (≥18 years) who have signed an informed consent form.
• They should have an ECOG performance status of 0-1. Diagnosed with stage IIIB-IV NSCLC and have progressed after PD-1 inhibitor treatment.
• Expected to live at least 3 months and have at least one measurable lesion per RECIST v1.1.
• Laboratory test results must meet specific criteria for blood counts, liver and kidney function, and coagulation parameters.
• Patients with stable, treated brain metastases are eligible.
• Women of childbearing potential and men with partners of childbearing potential must agree to use contraception.

Exclusion Criteria:

• Prior therapy with anti-PD-L1, anti-PD-L2, other immune checkpoint inhibitors, or specific cancer treatments.
• Certain cancer types, known mutations, or recent use of systemic corticosteroids or immunosuppressive medications.
• Active brain or leptomeningeal metastases without stability post-treatment, recent severe infections, or major surgery.
• Other conditions that might interfere with the study, such as uncontrollable third-space fluid accumulations, active autoimmune diseases or infections, significant bleeding or thromboembolic events, serious heart conditions, severe allergies to study drugs, other active malignancies, HIV/AIDS, hepatitis B or C infection, or participation in another interventional clinical study within a specified period.