# NAPOLI-1

Source: https://onco.cc/trials/napoli-1/  
OnCo record `napoli-1` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

NAPOLI-1 gave pancreatic cancer its first licensed second-line treatment: liposomal irinotecan with fluorouracil extended median survival from 4.2 to 6.1 months after gemcitabine had failed, while the liposome alone did nothing. It is approved in the United States and Europe but NICE turned it down in 2017.

## Summary

NAPOLI-1 randomised 417 patients between January 2012 and September 2013: 117 to nanoliposomal irinotecan 80 mg/m2 with fluorouracil and folinic acid every two weeks (an arm added by amendment), 151 to nanoliposomal irinotecan 120 mg/m2 alone every three weeks and 149 to fluorouracil and folinic acid. Median overall survival was 6.1 months (95 percent confidence interval 4.8 to 8.9) with the combination against 4.2 months (3.3 to 5.3) with fluorouracil and folinic acid (hazard ratio 0.67, 0.49 to 0.92; p 0.012), while monotherapy gave 4.9 months (hazard ratio 0.99). Grade 3 or 4 neutropenia occurred in 27 percent, diarrhoea 13 percent, vomiting 11 percent and fatigue 14 percent of the combination arm. Four UK sites took part (Liverpool, London, Manchester, Sutton). The FDA approved Onivyde with fluorouracil and leucovorin in October 2015 and the European Commission on 14 October 2016 (orphan designation 2011); NICE TA440 (26 April 2017) does not recommend it within its marketing authorisation, a position NG85 restates (1.9.9). The same liposomal irinotecan later formed the NALIRIFOX first-line regimen tested in NAPOLI 3.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-24
- Also known as: NAPOLI 1; MM-398 phase 3
- Registry id: NCT01494506
- Phase: 3
- Setting: Metastatic pancreatic ductal adenocarcinoma after gemcitabine-based therapy at 76 sites in 14 countries: nanoliposomal irinotecan with fluorouracil and folinic acid, nanoliposomal irinotecan alone, or fluorouracil and folinic acid, with overall survival as the primary endpoint
- Sponsor: Merrimack Pharmaceuticals (now Ipsen)
- Enrolled: 417
- Result: Median overall survival 6.1 months with nanoliposomal irinotecan plus fluorouracil and folinic acid against 4.2 months with fluorouracil and folinic acid (hazard ratio 0.67, 95 percent confidence interval 0.49 to 0.92; p 0.012); monotherapy 4.9 months (hazard ratio 0.99).
- Outcomes: Overall survival: Nanoliposomal irinotecan + fluorouracil/folinic acid 6.1 months vs Nanoliposomal irinotecan alone 4.9 months vs Fluorouracil/folinic acid 4.2 months, HR 0.67

## Notes

- UK sites (registry, 4): Liverpool, London, Manchester and Sutton (facility names not given). England: NICE TA440 (26 April 2017) does not recommend pegylated liposomal irinotecan with fluorouracil and leucovorin after gemcitabine-based therapy.

## Sources

- ClinicalTrials.gov NCT01494506: https://clinicaltrials.gov/study/NCT01494506
- Wang-Gillam et al., NAPOLI-1 (Lancet 2016): https://doi.org/10.1016/S0140-6736(15)00986-1
- Onivyde label (openFDA): NAPOLI-1 study section: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ONIVYDE%22
- EMA Onivyde pegylated liposomal product page (marketing authorisation 14 October 2016): https://www.ema.europa.eu/en/medicines/human/EPAR/onivyde-pegylated-liposomal
- NICE TA440 (26 April 2017): not recommended: https://www.nice.org.uk/guidance/ta440

## Connected records

- cancers: [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/), [Topoisomerase-I inhibitors (and ADC payloads)](https://onco.cc/technologies/topoisomerase-inhibitors/)
- drugs: [Fluorouracil (5-FU)](https://onco.cc/drugs/fluorouracil/), [Leucovorin (folinic acid)](https://onco.cc/drugs/leucovorin/), [Liposomal irinotecan](https://onco.cc/drugs/liposomal-irinotecan/)
- companies: [Ipsen](https://onco.cc/companies/ipsen/), [Merrimack Pharmaceuticals](https://onco.cc/companies/merrimack-pharmaceuticals/)
- terms: [Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)](https://onco.cc/terms/pancreatic-cancer-uk-drug-access/)
- trials: [NAPOLI 3](https://onco.cc/trials/napoli-3/), [RASolute 302](https://onco.cc/trials/rasolute-302/)

---
JSON: https://onco.cc/api/v1/entities/napoli-1.json