First‐line envafolimab plus recombinant human‐endostatin in advanced non–small cell lung cancer with PD‐L1 tumor proportion score ≥1% (Endouble): A multicenter, prospective, single‐arm, phase 2 trial

BACKGROUND: This trial evaluates the efficacy and safety of combining envafolimab and recombinant human endostatin (Rh-endostatin) in advanced non-small cell lung cancer (NSCLC). METHODS: This trial included treatment-naive advanced patients with NSCLC with programmed death-ligand 1 (PD-L1)-positive and no driver gene mutations. All patients received treatment with envafolimab and Rh-endostatin every 21 days until disease progression or intolerable toxicity. The primary end points were objective response rate (ORR) and safety. Secondary end points included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and duration of response (DOR). An exploratory analysis was conducted to identify biomarkers associated with treatment efficacy. RESULTS: A total of 33 patients were included for efficacy and safety analysis. The ORR was 48.5% (95% CI, 30.8%-66.5%), and the DCR was 81.8% (95% CI, 64.5%-93.0%). The median PFS was 12.3 months (95% CI, 3.1 months-21.5 months). With a median follow-up of 13.9 months, the median OS was not reached, and the 1-year OS rate was 73.9%. Treatment-related adverse events (TRAEs) were observed in 25 (75.8%) patients. Grade ≥3 TRAEs were observed in six patients, and there were no grade 4 or 5 AEs. Based on plasma proteomic analysis, receiver operator characteristic analysis yielded area under the curve (AUC) values of 0.77 (95% CI, 0.61-0.93) for MMP1 and 0.68 (95% CI, 0.49-0.87) for TNFRSF6B. The combined model demonstrated an AUC of 0.81 (95% CI, 0.66-0.96). CONCLUSIONS: Envafolimab combined with Rh-endostatin demonstrated favorable efficacy and tolerable toxicity in patients with PD-L1-positive, advanced driver-gene negative NSCLC.