Tislelizumab and hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine as conversion therapy for BRPC/LAPC: A Phase II trial with dynamic biomarker monitoring

Abstract Purpose: The optimal conversion treatment for patients with borderline resectable pancreatic cancer or locally advanced pancreatic cancer (BRPC/LAPC) remains unclear. Here we present the efficacy and safety results of a phase II trial evaluating tislelizumab combined with hypofractionated radiotherapy plus nab-paclitaxel/gemcitabine (THAG) in BRPC/LAPC patients (ChiCTR2000032955, NCT05634564). Patients and Methods: This phase II trial enrolled 56 BRPC/LAPC patients (BRPC: 17, 30.4%; LAPC: 39, 69.6%). Participants received tislelizumab plus AG (nab-paclitaxel/gemcitabine) in 21-day cycles. Non-progressing patients received concurrent radiotherapy during the third chemotherapy cycle. After four treatment cycles, a multidisciplinary team (MDT) assessed eligibility for radical surgery. Dynamic biomolecular profiling was performed. Results: Fifty-six eligible patients were enrolled. The objective response rate (ORR) was 51.8% (95% 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 reached criteria for surgical resectability, 22 patients (22/56, 39.3%) underwent radical resection, comprising 9 BRPC patients (9/17, 52.9%) and 13 LAPC patients (13/39, 33.3%). The R0 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 (AEs) occurred in 33/56 patients (58.9%). Dynamic biomarker exploration revealed that baseline IL-6 level (>5 pg/ml) predicted better PFS. Moreover, ctDNA status and clearance demonstrated superior survival. Conclusions: 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.