NALIRIFOX versus gemcitabine plus nab-paclitaxel in Chinese patients with advanced pancreatic adenocarcinoma: a randomized, open-label phase II trial.

In this phase 2 study (NCT05047991), patients with unresectable metastatic pancreatic adenocarcinoma were randomized to receive NALIRIFOX (liposomal irinotecan, 5-FU, leucovorin, and oxaliplatin) or gemcitabine plus nab-paclitaxel. The primary endpoint was progression free survival (PFS). Secondary endpoints included other efficacy outcomes (overall survival, objective response rate, disease control rate, and duration of response), as well as safety, pharmacokinetic parameters, and evaluation of the relationship between UGT1A1*6 and UGT1A1*28 polymorphisms and safety. A total of 117 patients were enrolled and randomly assigned to NALIRIFOX (n = 78) or gemcitabine plus nab-paclitaxel (n = 39). At a median follow-up of 18.7 months (interquartile range [IQR], 7.5-22.1) for NALIRIFOX and 12.1 months (IQR: 6.4-14.8) for the gemcitabine plus nab-paclitaxel, median PFS was 7.6 months (95% CI 5.52-9.23) with NALIRIFOX versus 3.7 months (95% CI 3.38-5.32) with gemcitabine plus nab-paclitaxel (hazard ratio, 0.56; 95% CI, 0.35-0.88; P = 0.0115). ≥ Grade 3 treatment-emergent adverse events (TEAEs) occurred in 73.1% of patients receiving NALIRIFOX and 84.6% of patients receiving gemcitabine plus nab-paclitaxel, respectively. Despite the premature termination (predetermined sample size of n = 153 not reached) of the study, NALIRIFOX demonstrated improvement in PFS compared with gemcitabine plus nab-paclitaxel, with a manageable safety profile in Chinese patients with advanced pancreatic adenocarcinoma.