Neoadjuvant camrelizumab combined with chemotherapy for resectable stage IIIA-IIIb non-small cell lung cancer: Single arm phase II study.

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 < 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 .