ENTRÉE Lung: An Open-label Platform Study Investigating the Safety and Pharmacokinetics of Belrestotug Combinations in Advanced Non-Small Cell Lung Cancer

Purpose ENTRÉE Lung (NCT03739710) was a global, open-label, platform study investigating novel immunotherapy combinations in advanced non-small cell lung cancer (NSCLC) following progression on anti-PD-(L)1 and platinum-based treatment. We report findings with dostarlimab (anti-PD-1) plus belrestotug (anti-TIGIT) with or without nelistotug (anti-CD96). Patients and Methods The study included safety cohorts with dose escalation and expansion: Arm 4 safety cohort (Arm4-safety), dostarlimab 500 mg plus belrestotug 200-1000 mg (initial dose level: 400 mg); Arm5-safety, dostarlimab 500 mg plus belrestotug 400 mg and nelistotug 210-1400 mg (initial dose level: 700 mg); study treatments were administered intravenously every 3 weeks. A randomized cohort was added to Arm 5 (Arm5-randomized), assigning patients to nelistotug 210 or 1400 mg in the triplet combination. Primary endpoints were safety and tolerability. Results Sixty-two patients were enrolled (n=24 Arm4-safety; n=17 Arm5-safety; n=21 Arm5-randomized [n=11, 200 mg; n=10, 1400 mg]). Grade ≥3 treatment-related adverse events occurred in 4 (17%), 1 (6%) and 3 (14%) patients in Arm4-safety, Arm5-safety and Arm5-randomized, respectively. There were few treatment discontinuations due to adverse events. Most patients exhibited progressive disease as best response. There was one partial response (Arm5-randomized, 210 mg); stable disease ≥12 weeks was experienced by 4 (17%), 5 (29%) and 2 (10%) patients in Arm4-safety, Arm5-safety and Arm5-randomized, respectively. Conclusions Dostarlimab plus belrestotug, with or without nelistotug, was well tolerated but demonstrated no clinically meaningful activity in previously treated advanced NSCLC. Further research is required to identify patients who may benefit from other immunotherapy combinations.