Updated Overall Survival Data and Predictive Biomarkers of autologous NK Cells plus Sintilimab as Second-Line Treatment for Advanced Non-Small Cell Lung Cancer

Lin Jia¹Naifei Chen¹XIAO CHEN¹Chao Niu¹Zi-Ling Liu¹Kewei Ma¹Lei Yang¹Yuguang Zhao¹Wei Song¹Jin Lu¹Chen Chen¹Xiaofeng Cong¹Xu Wang¹Yinghui Xu¹Guozhen Cui¹Zengguang Liu¹Rongrong Chen²Huan Yin²Na Zhang³Jiuwei Cui^1*

• ¹First Affiliated Hospital of Jilin University, Changchun, China
• ²Geneplus Beijing Institute, Huilongguan Town, Beijing, China
• ³GeneCast Biotechnology Co., Ltd., Beijing, China

Purpose: Combination strategies involving immune checkpoint inhibitors (ICIs) have been a prominent focus of research in the treatment of non-small cell lung cancer (NSCLC). Our prior findings demonstrated that the combination of autologous NK cells with the PD-1 antibody (Sintilimab), offered promising efficacy in NSCLC patients who failed the first-line platinum-based chemotherapy. Here, we present updated overall survival (OS) data from the final analysis, aiming to identify patient subgroups that derive maximal benefit from this therapeutic approach. Methods: Twenty NSCLC patients without driver gene mutations were enrolled and treated with a combination of autologous NK cells and Sintilimab every three weeks. Multicolor immunofluorescence staining was applied to evaluate static markers within the tumor microenvironment. Concurrently, dynamic assessments were conducted using next-generation sequencing and monitoring of PD-1/PD-L1 expression on NK cells to identify patient populations with favorable prognoses. Results: The median OS was 27.3 months (95% CI, 0.76 to 53.8), with six patients still alive at the follow-up cutoff. A significant correlation was observed between the CD56+PD-L1+ cellular phenotype and extended survival. Clearance of circulating tumor DNA (ctDNA) and an increased percentage of PD-L1+ NK cells following treatment was associated with significantly better survival outcomes. Notably, prolonged treatment exposure did not lead to increased toxicity.The combination of autologous NK cells with Sintilimab significantly enhances longterm survival in NSCLC patients without exacerbating adverse effects, presenting a promising strategy for future combination immunotherapy approaches in NSCLC treatment. ClinicalTrial.gov Identifier: NCT03958097.