2019 - Neoadjuvant Camrelizumab Combined with Chemotherapy for Resectable Stage IIIA-IIIB Non-Small Cell Lung Cancer: Single Arm Phase II Study

G. Cai¹, K. Wang¹, X. Wang¹, J. Zhao¹, Z. Wang², X. Han³, H. Zhou³, C. Xie³, S. Fu⁴, J. Hui³, Y. Huang⁵, W. Li⁵, F. Teng⁶, S. Wang¹, J. Yu¹, P. Song⁷, and X. Meng¹; ¹Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ²Department of Pneumosurgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ³Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ⁴Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, ⁵Department of Imaging, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China, ⁶Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, China, ⁷Department of Pneumosurgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, China

Purpose/Objective(s): 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). Materials/

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/m² or pemetrexed (for adenocarcinoma), 500mg/m² plus platinum [cisplatin, 75 mg/m²; carboplatin, area under the curve, 5]). Radical surgery was performed within 4-6 weeks after neoadjuvant therapy. Patients undergo ¹⁸F-fluorodeoxyglucose (FDG) PET/CT scans in 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 surgery. 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 < 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 (11.1%), 1 neutropenia (3.7%), and 1 pneumonia (3.7%). 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.
Conclusion: Neoadjuvant camrelizumab combined with chemotherapy for NSCLC patients show promising pathological response rates and tolerable safety.