Camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma (ESPRIT): A phase II, single-arm, exploratory research.

e16139 Background: Camrelizumab has been verified as a standard therapy for advanced esophageal squamous cell carcinoma (ESCC). This study aimed to evaluate the efficacy and safety of neoadjuvant therapy with camrelizumab plus paclitaxel and nedaplatin in patients with locally advanced ESCC. Methods: In this single-arm, phase Ⅱ study, patients with stage IIa-IIIb ESCC were enrolled and received camrelizumab (200 mg), paclitaxel (155 mg/m 2 ), and nedaplatin (80 mg/m 2 ) intravenously on day one every 3 weeks. Patients underwent surgery after 2-4 cycles of treatment. The primary endpoint was pathological complete remission (pCR) rate, and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), disease-free survival (DFS), overall survival (OS) and safety. Results: In total, 75 patients were included with a median age of 62 years (range 48-74 years). Most patients presented with clinically staged T3 tumors (73.3%) and lymph node metastasis (61.3%). PD-L1 expression was assessed in tumor samples from 61 patients. Among the 62 patients who underwent surgery, the ORR was 48.4%, and the DCR was 98.4%. In terms of pathological remission, the pCR rate was 27.4%, and the MPR rate was 45.2%. Additionally, 39 patients (62.9%) achieved stage T downstaging, and 19 (30.6%) achieved nodal downstaging, with 21 (33.9%) showing pathological T0 and 34 (54.8%) reaching N0. Patients with a CPS ≥10 tended to exhibit higher ORR, pCR, and MPR rates compared to those with CPS < 10. With a median follow-up time of 35.0 months, the median OS for surgical patients was not reached, with 1-year, 2-year, 3-year, and 4-year OS rates of 98.4%, 91.6%, 89.8%, and 83.4%, respectively. And the 1-year, 2-year, 3-year, and 4-year DFS rates were 93.5%, 80.2%,70.8%, and 64.3%, respectively. Treatment related adverse events (TRAEs) were observed in 59 patients (78.7%), with grade 3 TRAEs in four patients (5.3%), and one patient (1.3%) experienced a grade 4 TRAE. Conclusions: The ESPRIT study indicates that camrelizumab combined with paclitaxel and nedaplatin as neoadjuvant therapy is well tolerated, effectively reducing tumor size and stage. This regimen also demonstrates favorable outcomes in overall survival and significantly extends disease-free survival. These promising results support the continued investigation of this treatment approach. Clinical trial information: ChiCTR2000033761 . Survival outcomes. pCR (n=17) Non-pCR (n=45) P value MPR (n=28) Non-MPR (n=34) P value mOS Not reached (NR) NR 0.399 NR NR 0.064 1-year OS rate 94.1% 97.8% / 96.4% 97.1% / 2-year OS rate 94.1% 90.6% / 96.4% 87.4% / 3-year OS rate 94.1% 88.1% / 96.4% 84.1% / mDFS NR NR 0.029 NR 41.0（26.9-55.2） 0.035 1-year DFS rate 94.1% 93.3% / 96.4% 91.2% / 2-year DFS rate 94.1% 74.9% / 89.3% 72.5% / 3-year DFS rate 94.1% 62.6% / 83.3% 61.0% /