NALPAC: safety of NALIRIFOX in second-line mPDAC

In this video, Prof Dr Ivan Borbath discusses the NALPAC trial, presented at ESMO GI 2026.¹ NALPAC is a Belgian multicentre, non-comparative randomised phase II study evaluating NALIRI versus NALIRIFOX in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) progressing after gemcitabine-based first-line therapy. The study is recruiting in 13 Belgian centres, with a target accrual of 134 patients. At the time of presentation, 93 patients had been included. 

The rationale for the trial is based on the limited treatment options available after progression on gemcitabine-based therapy. NALIRI, consisting of nanoliposomal irinotecan with 5-FU/leucovorin, represents a standard second-line option in this setting. NALPAC evaluates whether adding oxaliplatin to this regimen, resulting in NALIRIFOX, can improve outcomes while maintaining acceptable tolerability. Because NALIRIFOX is a more intensive triplet regimen, safety in the second-line setting is a key concern.

The data presented focused on preliminary safety. Although adverse events were more frequent with NALIRIFOX than with NALIRI, toxicity appeared manageable. The main added toxicity was haematological, with some additional neurological toxicity, as expected with oxaliplatin. An independent safety monitoring committee reviewed the data in March 2026 and recommended that the study continue, as no safety concerns were identified.

Preliminary efficacy data were not yet mature, but there was a signal towards longer treatment duration with NALIRIFOX. Prof Dr Borbath emphasises that these findings remain early. If NALIRIFOX proves both safe and more effective than NALIRI, it could become a relevant second-line option for selected patients with mPDAC, although its future role will need to be considered in the context of emerging targeted therapies and KRAS inhibitors.