ENTRÉE Lung Platform Trial Sub-study 1: Phase II Randomized Efficacy and Safety Analysis of Feladilimab Plus Docetaxel Versus Docetaxel Monotherapy in Advanced/Recurrent NSCLC

Background Combining treatments with different mechanisms may improve immunosurveillance and outcomes in advanced/recurrent non–small cell lung cancer (NSCLC) after immunotherapy. ENTRÉE Lung (NCT03739710) is a phase 2, open-label platform trial utilizing a master protocol to investigate novel regimens versus standard of care (SoC) in separate sub-studies. Sub-study 1 investigated the immunoglobulin G4 inducible T-cell costimulator agonist antibody, feladilimab, plus docetaxel versus SoC, docetaxel monotherapy. Patients and methods Patients with advanced/recurrent NSCLC who progressed on prior anti-programmed cell death (ligand)-1 and platinum-based combination chemotherapies were randomized to feladilimab (80 mg) plus docetaxel 75 mg/m² (both intravenous) or docetaxel 75 mg/m² every 3 weeks until progressive disease/unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), tumor response (including overall response rate [ORR]), and safety. Exploratory endpoints included biomarkers. Results A total of 105 patients were randomized to feladilimab plus docetaxel ( n = 70) or docetaxel ( n = 35). Median OS was 7.8 months with feladilimab plus docetaxel versus 8.2 months with docetaxel; hazard ratio (HR) 1.5 (95% confidence interval [CI], 0.92, 2.44). Median PFS for feladilimab plus docetaxel versus docetaxel was 3.4 months versus 3.3 months, and ORR was 19% versus 11%; HR 0.84 (95% CI, 0.54, 1.32). Most frequently reported treatment-related adverse events included anemia (34% vs. 24%), nausea (34% vs. 15%), alopecia (27% vs. 21%), and asthenia (27% vs. 18%). Conclusion Feladilimab plus docetaxel has an acceptable safety profile in the second-line treatment of advanced/recurrent NSCLC. No survival outcomes or tumor response advantages were observed with the addition of feladilimab to docetaxel in this setting.