EGFR-TKIs Plus PD-1 in EGFR-Mutant Advanced NSCLC

This open-label, multicenter, single-arm exploratory clinical trial plans to enroll a total of 32 patients: 6 in a safety lead-in phase and the remaining 26 in an expansion phase. Eligible subjects are treatment-naïve patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR 19del or L858R mutations. All patients receive first-line oral therapy with standard-dose third-generation EGFR-TKIs (osimertinib, aumolertinib, or furmonertinib). Once stable disease is confirmed by two consecutive radiological assessments, sintilimab (200 mg intravenously every three weeks) is added as maintenance treatment until disease progression, unacceptable toxicity, or a maximum treatment duration of two years. The primary endpoint is progression-free survival (PFS). Secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events occurring throughout treatment. Exploratory analyses focus on the correlation of serum lipid profiles and the tumor immune microenvironment with the safe treatment window and mechanisms of drug resistance. The trial consists of screening, treatment, safety follow-up, and survival follow-up periods. Tumor imaging evaluations are performed every six weeks during the first 24 weeks of treatment and every nine weeks thereafter.