A phase II study of NALIRIFOX (liposomal irinotecan, 5-fluorouracil, leucovorin and oxaliplatin) in patients with locally advanced pancreatic cancer (LAPC).

Abstract

e16447 Background: Surgical resection is the only curative option for pancreatic cancer, but nearly 30% of patients (pts) present with locally advanced pancreatic cancer (LAPC), rendering them unresectable. Systemic chemotherapy remains the standard treatment, yet LAPC-specific therapeutic strategies are limited. This study evaluates the efficacy and safety of NALIRIFOX regimen in LAPC pts, aiming to facilitate conversion to surgical resection and improve survival outcomes. Methods: This ongoing phase II trial is enrolling pts with histologically or cytologically confirmed LAPC, an ECOG PS of 0–1, and no prior resection, chemotherapy, targeted therapy or immunotherapy. Eligible pts receive NALIRIFOX (liposomal irinotecan 50 mg/m², oxaliplatin 60 mg/m², leucovorin 400 mg/m², 5-fluorouracil 2400 mg/m²) every 2 weeks. Tumor imaging is performed after 2 treatment cycles; if no progression is observed per RECIST 1.1, pts continue therapy until surgical resection, disease progression, intolerable toxicity, initiation of a new anticancer therapy, withdrawal, death, or loss to follow-up. The primary endpoint is surgical conversion rate. Secondary endpoints include overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and safety. Peripheral blood next-generation sequencing (NGS) is conducted before and after treatment to evaluate circulating tumor DNA (ctDNA) changes and their correlation with surgical outcomes and prognosis. Results: Herein, we reported preliminary result of the study, between Dec 2023 and Jan 2025, 20 pts were enrolled. Median age was 61 years (range: 42–70), with 40% females (n = 8) and 60% males (n = 12). Pts received a median of 4 treatment cycles (range: 2–6). Among 20 evaluable pts, 1 achieved pathological complete response (pCR), 6 had partial response (PR), 8 had stable disease (SD), and 5 had progressive disease (PD), resulting in an ORR of 35.0% (7/20) and a DCR of 75.0% (15/20). Surgical exploration was performed in 9 pts and all of them completed surgical resection (45.0%), including 5 pts with pancreaticoduodenectomy and 4 pts with distal pancreatectomy, all pts achieving R0 resection (100%). PFS and OS have not yet been reached. All pts (20/20, 100%) experienced treatment-emergent adverse events (TEAEs). Grade ≥3 TEAEs occurred in 12 pts (60%), and 3 pts (15%) required dose reductions. No TEAEs led to death. Grade 3–4 TEAEs occurring in > 5% of pts included decreased lymphocyte count (15%), abdominal pain (10%), decreased neutrophil count (10%), and arthralgia (10%). Conclusions: NALIRIFOX regimen demonstrated promising conversion efficacy with a manageable safety profile in LAPC pts. Further evaluation of final surgical conversion rate and key efficacy outcomes, including OS, PFS, ORR and DCR, are ongoing. Clinical trial information: NCT06467565 .