Clinical efficacy of tislelizumab in combination with gemcitabine and nab-paclitaxel and chemoresistance analysis in borderline resectable pancreatic cancer: A prospective pilot study.

2630 Background: Neoadjuvant therapy has been demonstrated to improve the survival outcomes of patients with borderline resectable pancreatic cancer (BRPC). While neoadjuvant therapy is increasingly utilized, exploring novel combination strategies, such as immunotherapy plus chemotherapy, is essential to further enhance surgical resectability and survival outcomes. This study investigated the clinical feasibility of tislelizumab in combination with gemcitabine and nab-paclitaxel for BRPC in a neoadjuvant setting. Methods: In this prospective study, patients diagnosed with BRPC were enrolled. Preoperatively, intravenous injection of tislelizumab (200 mg per time, Q3W) was used for 3 cycles, in combination with gemcitabine (1 000 mg/m 2 , d1, d8) and nab-paclitaxel (125 mg/m 2 , d1, d8). Postoperatively, this regimen continued to be used. The primary endpoints were the margin-negative (R0) resection rate and treatment-related adverse events (TRAEs). Exploratory objectives were resistance to this neoadjuvant regimen. Results: Totally 30 patients were enrolled in this study, among whom 80.0% (24/30) completed neoadjuvant therapy and underwent surgical resection. R0 resection was achieved in 80.0% of the patients (24/30) and in 100.00% of the patients with surgical resection (24/24). Most patients experienced grade I-II TRAEs, and no serious TRAEs occurred. Through the quantitative proteomics and machine learning algorithms for differentially expressed proteins, NT5DC2, FAM3D, CXCL5 and TMT1B were identified to play crucial roles in resistance to the neoadjuvant regimen in pancreatic cancer. Conclusions: Neoadjuvant therapy with tislelizumab plus gemcitabine and nab-paclitaxel demonstrated clinical feasibility and encouraging antitumor activity in BRPC patients, with a favorable safety profile. NT5DC2, FAM3D, CXCL5 and TMT1B may be the biomarkers for preoperative drug resistance in pancreatic cancer. Clinical trial information: ChiCTR2200063680 . Clinical trial information: ChiCTR2200063680 .