Neoadjuvant camrelizumab plus chemotherapy in resectable stage IIIA–IIIB non-small cell lung cancer: integrated multidimensional biomarker analysis from a phase II study
Guoxin Cai, Pingping Song, Zhendan Wang, Jiarui Zhao, Kaiyue Wang, Min Li, Xingpeng Wang, Jingyu Zhu, Jing Xu, Baiyang Huang, Xiao Han, Haiyan Zhou, Chao Xie, Shuai Fu, Hui Jia, Feifei Teng, Suzhen Wang, Hongfu Sun, Wanhu Li, Jinming Yu, Xue MengBackground
This study evaluated biomarker profiles associated with therapeutic response and prognosis in resectable non-small cell lung cancer (NSCLC) receiving neoadjuvant camrelizumab plus chemotherapy.
Methods
In this single-arm phase II trial, patients with resectable stage IIIA–IIIB NSCLC received three cycles of camrelizumab plus chemotherapy, followed by surgery. Primary endpoints were pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), disease-free survival (DFS), and safety. Exploratory analyses assessed immune subsets in the tumor microenvironment (TME) and peripheral blood, cytokine profiles, circulating tumor DNA (ctDNA) dynamics, and spatial immune–tumor interactions.
Results
Thirty patients were enrolled (22 squamous, 8 adenocarcinoma); 27 underwent radical resection. The pCR and MPR rates were 33.3% and 50.0%, respectively. At a median follow-up of 27.2 months, the 2-year DFS rate was 77.4%. Grade≥3 treatment-related adverse events occurred in 13.3%. Achieving pCR was associated with higher baseline levels of CD8+ T cells and naïve-like T cells in both blood and TME. Elevated baseline CD8+ naïve-like T cells in both peripheral blood and tumor nests and their closer proximity to tumor cells correlated with improved DFS. Higher circulating baseline chemokine (C-C motif) ligand 3 (CCL3) levels were associated with both pCR and prolonged DFS. Postneoadjuvant treatment ctDNA positivity predicted shorter DFS, while longitudinal ctDNA monitoring identified relapse as early as 17.6 months before radiographic progression.
Conclusions
Baseline CD8+ naïve-like T-cell abundance and spatial proximity to tumor cells, circulating CCL3 levels, and ctDNA dynamics may serve as potential prognostic biomarkers in resectable NSCLC receiving neoadjuvant camrelizumab plus chemotherapy.
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