A Phase I/IIa Randomized Trial Evaluating the Safety and Efficacy of SNK01 Plus Pembrolizumab in Patients with Stage IV Non-Small Cell Lung Cancer.

Purpose The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized Phase I/IIa clinical trial. Materials and Methods Overall, 18 patients with advanced NSCLC and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/- 6 weekly infusions of SNK01 at either 2 x 109 or 4 x 109 cells per infusion (pembrolizumab monotherapy vs SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life. Results Since no dose-limiting toxicity (DLT) was observed, the maximum tolerated dose (MTD) was determined as SNK01 4 x109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR: 41.7% vs. 0%; 1-year survival rate: 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 vs. 1.6 months; p=0.001). Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events (AEs).