Neoadjuvant camrelizumab combined with chemotherapy for resectable stage IIIA-IIIb non-small cell lung cancer: Single arm phase II study.
Authors: Guoxin Cai, Kaiyue Wang, Xiaohan Wang, Jiarui Zhao, Xiao Han, Haiyan Zhou, Chao Xie, Hui Jia, Shuai Fu, Yong Huang, Wanhu Li, Feifei Teng, Suzhen Wang, Jinming Yu, Pingping Song, Xue Meng
Journal: Journal of Clinical Oncology (2024)

e20074 Background: This study aimed to evaluate the safety and efficacy of neoadjuvant camrelizumab combined with chemotherapy in patients with resectable non-small cell lung cancer (NSCLC). Methods: In this single-arm phase II clinical trial, patients aged 18-75 with pathologically confirmed resectable stage IIIA-IIIB (T3-4N2) NSCLC without EGFR, ALK, and ROS1 gene mutations were enrolled since December 2022. Patients were assigned to receive 3 cycles of camrelizumab (200 mg) plus chemotherapy (nab-paclitaxel, 130 mg/m 2 or pemetrexed (for adenocarcinoma), 500mg/m 2 plus platinum [cisplatin, 75 mg/m 2 ; carboplatin, area under the curve, 5]). Radical surgery was performed within 4-6 weeks after neoadjuvant therapy. Patients undergo 18 F-fluorodeoxyglucose (FDG) PET/CT scans within 1 week before treatment and surgery, respectively. The primary endpoints for follow-up are pathologic complete response (pCR) rate and major pathological response (MPR) rate, while secondary endpoints include safety and disease-free survival (DFS). Exploratory endpoints include molecular imaging research and biomarker analysis. Results: Up to December 2023, 30 patients (median age: 64 years) have been enrolled, including 22 cases of squamous carcinoma and 8 cases of adenocarcinoma. All patients received 3 cycles of neoadjuvant camrelizumab plus chemotherapy, and 27 patients underwent radical sugery. Three patients did not receive surgical treatment, 2 of whom refused surgery and 1 was unable to undergo surgery due to disease progression. Among patients received surgery, 27 (100%) achieved R0 resection, 10 (37.0%) achieved pCR, and 15 (55.6%) achieved MPR. For patients with squamous cell carcinoma, the MPR and pCR rates were 70% (14/20) and 45% (9/20), respectively, while for adenocarcinoma patients, the MPR and pCR rates were 14.3% (1/7) and 14.3% (1/7), respectively. There was no significant difference in pathological response rates between the PD-L1 tumor proportion score (TPS) ≥ 1% group and the PD-L1 TPS &lt; 1% group. Most of treatment-related adverse events (TRAEs) were grade 1-2, and the most common TRAEs was leukopenia (63.0%). Five patients (18.5%) developed grade ≥ 3 TRAEs, including 3 leukopenia, 1 neutropenia, and 1 pneumonia. Biomarker analysis showed that among patients with pCR, the proportion of increased circulating M1 macrophages and decreased mononuclear myeloid-derived suppressor cells (M-MDSCs) and M2 macrophages after treatment was higher than those in non-pCR patients. Circulating ctDNA analysis showed that the ctDNA concentration of patients with non-pCR after treatment was higher than that of patients with pCR. Patients with ctDNA remaining positive after treatment were all in the non-pCR group. Conclusions: Neoadjuvant camrelizumab combined with chemotherapy for NSCLC patients show promising pathological response rates and tolerable safety. Clinical trial information: NCT06241807 .