36 Two-year survival and tumor immune microenvironment dynamics in NACI study: an open-label, multi-centre, single-arm, phase 2 trial of neoadjuvant chemotherapy plus camrelizumab for locally advanced cervical cancer

Introduction/Background Locally advanced cervical cancer (LACC) is characterised by a poor prognosis, primarily due to limitations in the existing therapeutic repertoire. The use of immune checkpoint inhibitors in the neoadjuvant setting represents a potential solution to these challenges. Our aim was to evaluate the efficacy of neoadjuvant chemo-immunotherapy (NACIT) specifically tailored for the treatment of LACC. Methodology This multicentre phase 2 trial enrolled patients with previously untreated cervical cancer (IB3, IIA2, or IIB/IIIC1r with tumour diameter ≥ 4cm FIGO, 2018). Eligible patients received one cycle of priming chemotherapy (intravenous cisplatin: 75–80 mg/m2 and nab-paclitaxel: 260mg/m2) followed by two cycles of combination chemotherapy with Camrelizumab (200mg, intravenously) administered at three-week intervals per treatment cycle. The primary endpoint was objective response rate (ORR), while secondary endpoints included pathological complete response (pCR), event-free survival (EFS) and overall survival (OS). In addition, we conducted an exploratory analysis to track the changing dynamics of the tumour immune microenvironment before the start of priming chemotherapy, before the start of the chemo-immunotherapy cycle and during definitive surgery. Results 85 participants were included in the full analysis set with a median follow-up of 14.0 months (IQR 11.0–18.0) until the cut-off date of 7th November 2023. The findings indicate an objective response in 83 patients (97.6% 95% CI 91.8–99.7), with 32 (37.6% 95% CI 27.6–48.8) achieving pCR. The two-year EFS was 96.0% (95% CI 91.5–100) and no fatalities were observed. A progressive increase in plasma cells (pConclusion Neoadjuvant chemotherapy plus camrelizumab demonstrated significantly improved pathological regression and short-term survival. An exploratory analysis has indicated that patients who attained pCR showcased more pronounced immune activation associated with B cells throughout their treatment. NACIT may be a promising first-line option for patients with LACC. Disclosures This study received support from the National Key Technology Research and Development Program of China (2022YFC2704400 and 2022YFC2704403) and the National Clinical Research Center of Obstetrics and Gynaecology (2015BAI13B05). Jiangsu Hengrui Medicine provided Camrelizumab. The funder did not influence the study's design or decision to publish it. The authors confirm that the research was conducted without any commercial or financial ties that could be perceived as possible conflicts of interest.