ICI Rechallenge for Advanced NSCLC With Long-Term Response to First-Line ICI

Inclusion Criteria:

1. Participants must have a thorough understanding of this study and voluntarily signan informed consent form (ICF);

2. Age between 18 and 80 years, any gender;

3. Histologically or cytologically confirmed stage III-IV non-small cell lung cancer (NSCLC);

4. Previous treated with first-line immunotherapy (immunotherapeutic agents includecurrently marketed anti-PD-L1 or anti-PD-1 monoclonal antibodies: pembrolizumab,nivolumab, atezolizumab, durvalumab, tislelizumab, toripalimab, sintilimab,camrelizumab, etc.; investigational drugs not yet marketed need discussion with thestudy team prior to enrollment; with or without platinum-based doublet chemotherapy)for at least 35 cycles or disease stability confirmed by imaging assessment for atleast 2 years, and disease progression;

5. Measurable disease (at least 1 lesion) according to Response Evaluation Criteria inSolid Tumors version 1.1 (RECIST 1.1);

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2;

7. Adequate organ function: Hematology: Absolute neutrophil count (ANC) ≥1500/μL; Platelets ≥100000/μL;Hemoglobin ≥9.0g/dL; Renal: Serum creatinine ≤1.5×ULN or calculated creatinineclearance (CrCl) ≥60 mL/min (using Cock-Gault formula); Hepatic: Total bilirubin ≤1.5 ×ULN or, for subjects with total bilirubin levels >1.5×ULN, direct bilirubinwithin normal limits; AST (SGOT) and ALT (SGPT) ≤2.5×ULN; Coagulation: Internationalnormalized ratio (INR) or prothrombin time (PT), activated partial thromboplastintime (APTT) ≤1.5×ULN;

8. Subjects must be willing and able to comply with study visits, treatment plans,laboratory tests, and other study procedures;

9. Female subjects of childbearing potential and male subjects with female partners ofchildbearing potential must agree to use highly effective contraception during thestudy and for 180 days after the last dose of the study drug.

Exclusion Criteria:

1. Received two or more prior systemic therapies;

2. Known sensitive EGFR mutation (EGFR exon19 del or EGFR exon21 L858R) or ALKrearrangement;

3. Symptomatic or progressing CNS metastases, leptomeningeal metastases;

4. History of autoimmune disease, active autoimmune disease, immunodeficiency, orrequiring systemic corticosteroid/immunosuppressive therapy; (except: a history ofhypothyroidism; well-controlled stable type I diabetes mellitus);

5. Idiopathic pulmonary fibrosis (including interstitial pneumonia), drug-inducedpneumonitis, history of (non-infectious) pneumonia/interstitial lung diseaserequiring steroid therapy;

6. Known active tuberculosis, human immunodeficiency virus (HIV) infection; activehepatitis B (defined as positive HBsAg or positive hepatitis B virus DNA test resultabove the detection limit) or hepatitis C (defined as known positive HCV antibodyresult, known quantitative HCV-RNA analysis result above the detection limit)history; other known active infections requiring systemic therapy;

7. Received systemic immunostimulatory therapy within 4 weeks before initiation ofstudy treatment or within 5 half-lives of the drug (whichever is longer);

8. Pregnancy, lactation, planning to become pregnant, or fathering a child during theanticipated duration of the study (from screening visit to 180 days after the lastdose of investigational drug);

9. Prior allogeneic tissue/organ transplantation and other conditions unsuitable forimmunotherapy.