Tislelizumab and Hypofractionated Radiotherapy plus Nab-Paclitaxel/Gemcitabine as Conversion Therapy for BRPC/LAPC: A Phase II Trial with Dynamic Biomarker Monitoring.

Abstract

The optimal conversion treatment for patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer (BRPC/LAPC) remains unclear. In this study, we present the efficacy and safety results of a phase II trial evaluating tislelizumab combined with hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine (THAG) in patients with BRPC/LAPC (ChiCTR2000032955, NCT05634564). This phase II trial enrolled 56 patients with BRPC/LAPC (BRPC: 17, 30.4%; LAPC: 39, 69.6%). Participants received tislelizumab plus nab-paclitaxel/gemcitabine (AG) in 21-day cycles. Nonprogressing patients received concurrent radiotherapy during the third chemotherapy cycle. After four treatment cycles, a multidisciplinary team assessed eligibility for radical surgery. Dynamic biomolecular profiling was performed. Fifty-six eligible patients were enrolled. The objective response rate was 51.8% [95% confidence interval (CI), 38.0%-65.3%]. Median progression-free survival (mPFS) was 13.2 months (95% CI, 11.6-19.4 months), and median overall survival (mOS) was 21.3 months [95% CI, 18.8-not reached (NR)]. Among 30 patients who met criteria for surgical resectability, 22 patients (22/56, 39.3%) underwent radical resection, comprising nine patients with BRPC (9/17, 52.9%) and 13 patients with LAPC (13/39, 33.3%). The margin-negative resection rate reached 90.9% (95% CI, 70.8%-98.9%), and the mOS of patients who underwent surgery was 34.0 months (95% CI, 20.1-NR). Grade ≥3 adverse events (AE) occurred in 33/56 patients (58.9%). Dynamic biomarker exploration revealed that baseline IL6 level (>5 pg/mL) predicted better PFS. Moreover, circulating tumor DNA (ctDNA) status and clearance demonstrated superior survival. The THAG regimen as preoperative therapy showed encouraging clinical activity with a manageable safety profile. Dynamic biomarker findings reveal potential for guiding precision treatment strategies with THAG.