Adjuvant Immune Checkpoint Inhibitor Versus Observation in Patients With Completely Resected Non-Small Cell Lung Cancer at High Risk of Recurrence After Neoadjuvant Immunochemotherapy: A Multicenter, Randomized, Open-Label, Phase II Trial
This multicenter, randomized, open-label, phase II trial is designed to evaluate the efficacy and safety of adjuvant sintilimab in patients with completely resected non-small cell lung cancer who remain at high risk of recurrence after neoadjuvant immunochemotherapy. Approximately 100 eligible participants will be randomly assigned in a 1:1 ratio to receive either adjuvant sintilimab or observation. Participants assigned to the experimental arm will receive sintilimab at a dose of 200 mg intravenously every 4 weeks for up to 1 year, unless disease recurrence or progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion occurs. The primary outcome is the 18-month disease-free survival rate. Secondary outcomes include disease-free survival, overall survival, and safety. Peripheral blood and tumor tissue samples will also be collected for exploratory analyses of ctDNA, antitumor immune responses, and tumor immune microenvironment biomarkers.
• Male or female participants aged 18 to 75 years.
• Histologically or cytologically confirmed non-small cell lung cancer.
• Completion of 2 to 4 cycles of neoadjuvant immune checkpoint inhibitor therapy combined with chemotherapy, followed by complete (R0) surgical resection.
• At least one of the following protocol-defined high-risk features for postoperative recurrence:
‣ Pathologic lymph-node involvement;
⁃ Postoperative pathologic T2 or higher disease;
⁃ Failure to achieve a major pathologic response, defined as more than 10% residual viable tumor cells in the primary tumor;
⁃ Pleural invasion;
⁃ Intravascular tumor emboli;
⁃ High-risk histologic components, including solid, micropapillary, or adenosquamous components;
⁃ Detectable molecular residual disease.
• For participants with lung adenocarcinoma, absence of sensitizing EGFR mutations and ALK rearrangements. Molecular testing is not mandatory for participants with squamous cell carcinoma according to the current protocol.
• Eastern Cooperative Oncology Group performance status of 0 or 1.
• Adequate organ function within 7 days before randomization, as demonstrated by all of the following:
‣ Hemoglobin of at least 90 g/L;
⁃ Absolute neutrophil count of at least 1.5 × 10\^9/L;
⁃ Platelet count of at least 75 × 10\^9/L;
⁃ Total bilirubin no greater than 1.5 times the upper limit of normal;
⁃ Alanine aminotransferase and aspartate aminotransferase no greater than 2.5 times the upper limit of normal;
⁃ Serum creatinine no greater than 1.5 times the upper limit of normal or creatinine clearance of at least 60 mL/min;
⁃ Left ventricular ejection fraction of at least 50%;
⁃ International normalized ratio or prothrombin time no greater than 1.5 times the upper limit of normal.
• Women of childbearing potential must have a negative pregnancy test within 7 days before the first dose and must agree to use effective contraception during the study and for 3 months after the last dose of study treatment. Male participants with partners of childbearing potential must agree to use effective contraception during the study and for 8 weeks after the last dose.
• Ability to understand the study requirements, willingness to provide written informed consent, and ability to comply with study treatment and follow-up procedures.