# NALIRIFOX (liposomal irinotecan + oxaliplatin + 5-FU/LV)

Source: https://onco.cc/drugs/nalirifox/  
OnCo record `nalirifox` (Treatment). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

NALIRIFOX is a version of FOLFIRINOX using a liposome-wrapped irinotecan, approved in 2024 as a first-line option for metastatic pancreatic cancer.

## Summary

NALIRIFOX combines liposomal irinotecan, which gives prolonged exposure to the active metabolite SN-38, with oxaliplatin and 5-FU/leucovorin; it is a version of FOLFIRINOX built around the liposome-wrapped drug. It is a first-line option for metastatic pancreatic adenocarcinoma in patients fit enough for a multi-drug regimen. NAPOLI 3 (n=770) showed overall survival of 11.1 versus 9.2 months (HR 0.84) and PFS of 7.4 versus 5.6 months against gemcitabine plus nab-paclitaxel, and the FDA approved it in February 2024 (Ipsen). It was the first phase 3 head-to-head win between the two chemotherapy backbones, though the absolute gain is modest and critics note the absence of a modified FOLFIRINOX arm, so whether it beats conventional FOLFIRINOX is unknown. For a newcomer, it is four-drug pancreatic chemotherapy with a longer-acting irinotecan.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-06
- Brand: Onivyde regimen
- Modality: Cytotoxic regimen
- Mechanism: Liposomal irinotecan (prolonged SN-38 exposure) with oxaliplatin and 5-FU/leucovorin.
- Approvals: US 2024: First-line metastatic pancreatic adenocarcinoma; EU 2016: Onivyde 2L after gemcitabine (2016); NALIRIFOX label 2025; EU 2025: First-line treatment of metastatic adenocarcinoma of the pancreas (Onivyde pegylated liposomal with oxaliplatin, fluorouracil and leucovorin), listed in the EMA therapeutic indications read on 24 September 2026; the year is the corpus's regional row for the label extension

## Notes

- UK status: NICE's appraisal of NALIRIFOX (TA1052) was terminated on 2 April 2025 because the company made no evidence submission, and NG85 does not name it, so it is not routinely commissioned in England; NICE's other position on liposomal irinotecan is TA440 (second line, not recommended). NAPOLI 3 recruited at six UK sites (Guy's and St Thomas', the Royal Marsden, Imperial, the Christie, Nottingham City).

## Sources

- OncLive: FDA approves NALIRIFOX: https://www.onclive.com/view/fda-approves-frontline-nalirifox-for-metastatic-pancreatic-adenocarcinoma
- Onivyde label (openFDA): NALIRIFOX indication and NAPOLI 3 results table: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ONIVYDE%22
- NICE TA1052: pegylated liposomal irinotecan in combination for untreated metastatic pancreatic cancer, terminated appraisal (2 April 2025): https://www.nice.org.uk/guidance/terminated/ta1052

## Connected records

- cancers: [Adenosquamous carcinoma of the pancreas](https://onco.cc/cancers/pancreatic-adenosquamous-carcinoma/), [Borderline resectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/borderline-resectable-pdac/), [BRCA or PALB2-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/brca-palb2-pdac/), [Invasive carcinoma arising in an intraductal papillary mucinous neoplasm (IPMN-associated carcinoma)](https://onco.cc/cancers/ipmn-associated-carcinoma/), [KRAS G12C-mutant pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-g12c-pdac/), [KRAS wild-type pancreatic ductal adenocarcinoma](https://onco.cc/cancers/kras-wild-type-pdac/), [Locally advanced unresectable pancreatic ductal adenocarcinoma](https://onco.cc/cancers/locally-advanced-pdac/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [Platinum agents](https://onco.cc/technologies/platinum/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- companies: [Ipsen](https://onco.cc/companies/ipsen/)
- terms: [Living with FOLFIRINOX, NALIRIFOX and gemcitabine with nab-paclitaxel](https://onco.cc/terms/chemotherapy-side-effects-pancreatic/), [Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)](https://onco.cc/terms/pancreatic-cancer-uk-drug-access/), [Prodrug](https://onco.cc/terms/prodrug/)
- trials: [Basal-like PDAC Treated With Gemcitabine, Erlotinib, and Nab-paclitaxel](https://onco.cc/trials/nct06483555/), [Clinical Study of Radiotherapy Combined With Adebrelimab and NALIRIFOX for Conversion Therapy in Locally Advanced Pancreatic Cancer](https://onco.cc/trials/nct07827053/), [NAPOLI 3](https://onco.cc/trials/napoli-3/), [Onvansertib in Combination With NALIRIFOX for First Line Treatment of Advanced Pancreatic Cancer](https://onco.cc/trials/nct06736717/), [RASolute 302](https://onco.cc/trials/rasolute-302/)
- key papers: [Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy (NAPOLI-1): a global, randomised, open-label, phase 3 trial](https://onco.cc/key-papers/paper-napoli-1-nanoliposomal-irinotecan-lancet-2016/)
- roadmaps: [Pancreatic cancer roadmap: from Whipple's operation to gemcitabine, FOLFIRINOX, adjuvant chemotherapy, PARP inhibition, KRAS inhibition, vaccines and the surveillance question](https://onco.cc/roadmaps/pancreatic-roadmap/)

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