e16097 Background: Whether combined immunotherapy on the basis of neoadjuvant chemotherapy is beneficial for locally advanced esophageal squamous cell carcinoma (ESCC) remain to be inconclusive. This phase 2 study (ChineseClinical Trial Registry: ChiCTR2000041081) evaluate the efficacy and safety of neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin in locally advanced ESCC. Methods: Patients with locally advanced ESCC (T2N+M0, T3N0-2M0, T4aN0-2M0, or no distant metastases, or viable or potentially viable) were enrolled and received 3 cycles of neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin. Surgery was scheduled within four to six weeks of completing the neoadjuvant treatment. Three additional cycles of adjuvant sintilimab monotherapy or sintilimab plus chemotherapy were scheduled after a multidisciplinary discussion. The primary endpoint was the MPR rate. Results: From November 2020 to November 2021, twenty-four patients (median age: 64.5 years, men: 21/24,lower segment tumor location12/24,stage IV disease 15/24) were included in this study. All patients completed three cycles of neoadjuvant treatment and surgery. The median dose intensities for sintilimab, carboplatin and albumin-bound paclitaxel were 100% (range, 66.7–105.0%), 98.4% (range, 64.1–104.0%), and 100% (range, 38.1–105.8%), respectively. The R0 resection rate was 100%. The pCR rate and MPR rate was 33.3% and 41.7%. Among the 10 patients with PD-L1 CPS of ≥1, the pCR and MPR rates were 40% and 50%. 20 (83.1%) had TNM downstaging. The median DFS and median OS had not been reached yet, 500 days DFS and OS rate was 85.3% (95%CI 85.4%-97.2%) and 94.1% (95%CI 94.8%-100.0%). PD-L1 protein expression showed a higher life expectancy trend in the post-neoadjuvant therapy esophageal tissue samples than in the pre-therapy samples. The most common grade 3-4 treatment-related adverse events were anemia (29.2%), increased gamma-glutamyl transferase level (4.2%) and hyponatremia (4.2%). Emergency reoperation and intensive care were not required, and there were no postoperative mortalities. Conclusions: Neoadjuvant sintilimab, albumin-bound paclitaxel, and carboplatin preliminarily demonstrate encouraging clinical benefits and acceptable safety. Preoperative immunotherapy combined with chemotherapy alters the immune microenvironment of locally advanced resectable ESCC. Clinical trial information: ChiCTR2000041081.