Results of a phase II, open-label pilot study evaluating the safety and activity of liposomal irinotecan (Nal-IRI) in combination with 5-FU and oxaliplatin (NALIRIFOX) in preoperative treatment of pancreatic adenocarcinoma (NEO-Nal-IRI study).
Authors: Thomas J. George, Sherise C. Rogers, Ibrahim Nassour, Ilyas Sahin, Brian Hemendra Ramnaraign, Jesus Fabregas, Kathryn Hitchcock, Tuo Lin, Gonghao Liu, Robert Zlotecki, Omar Roger Kayaleh, Anita Ahmed Turk, Z. Hugh Fan, Karen Bullock Russell, David L. DeRemer, Ji-Hyun Lee, Steven J. Hughes
Journal: Journal of Clinical Oncology (2024)

655 Background: Neoadjuvant treatment for resectable pancreatic cancer (PDAC) is increasing in acceptability, but a standard regimen has yet to be established. The modified FOLFIRINOX (5-fluorouracil, leucovorin, oxaliplatin and irinotecan) regimen often requires dose modifications, delays and growth factor support due to toxicity. Liposomal irinotecan injection (Nal-IRI) is FDA-approved with a well-tolerated safety profile in relapsed, refractory mPDAC. This current study substitutes Nal-IRI for traditional irinotecan in the mFOLFIRINOX regimen (NALIRIFOX) and aims to demonstrate safe neoadjuvant delivery. NALIRIFOX is currently under review by the FDA for frontline mPDAC. Methods: This phase 2, open-label, multicenter single-arm study enrolled adult patients (pts) with operable PDAC, resectability (borderline vs. resectable) confirmed by multiD conference, adequate organ function, and ECOG performance status (0-1). Pts received NALIRIFOX (per NAPOLI-3) every 2 wks x 4 mo followed by repeat imaging and surgical resection 4-8 wks later. Primary endpoint is the composite 30 day post-op major complication rate (hospital re-admission, death, second surgery, procedure or major complication extending hospital stay). A sample size of 25 pts will detect a 20% reduction in 1° endpoint (from 30% to 10%; 1-sided exact test; α=0.05; β=.8). Toxicity, treatment completion, R0 resection, clinical, biochemical and radiographic response rates and QOL during treatment (FACT-G) are 2° endpoints. Serial microbiota specimens have been collected for exploratory analysis. Results: From May 2019 to Feb 2023, 45 pts were enrolled from 4 centers. Median age was 63 (41-76), majority women (53%), white (89%) with borderline (n=30) or resectable (n=15) disease. All 45 pts initiated treatment with 34 proceeding to surgery and 29 completing definitive resection. Most common grade &gt;3 AEs included non-febrile neutropenia (41%), diarrhea (30%), and anorexia (22%). Those not obtaining definitive resection had progressive disease (radiographic n=6; intra-op n=5), physician change of tx (n=2), toxicity (n=2; CMV colitis and TPN requirement/sepsis) or consent withdraw (n=1). Three (10%) pts had a post-op major complication (p=0.012). One pt died from post-op bleeding complications. Resections included both borderline (n=15) and resectable (n=14) initial disease with overall R0 resection rate of 89%. Conclusions: Neoadjuvant NALIRIFOX was safe, having met the primary study objective, with reasonable rates of treatment completion and surgical outcomes for this relatively high-risk group of pts. Additional analyses are ongoing and will be reported at the meeting. Clinical trial information: NCT03483038 .