# Liposomal irinotecan

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

## TL;DR

Irinotecan wrapped in a fat bubble so it circulates longer. It is approved for pancreatic cancer, and in bile duct and gallbladder cancer one Korean trial found it helped as second-line treatment while a German trial did not.

## Summary

Liposomal irinotecan is a nanoliposomal formulation of irinotecan that prolongs circulation of the active metabolite SN-38 and increases tumour exposure. It is approved for metastatic pancreatic adenocarcinoma after gemcitabine-based therapy (NAPOLI-1; United States 2015, European Union 2016) and, with oxaliplatin, fluorouracil and leucovorin (NALIRIFOX), as first-line treatment of metastatic pancreatic adenocarcinoma (NAPOLI 3; United States 2024). In biliary tract cancer it has no licence. The Korean NIFTY phase 2b trial randomised 174 patients who had progressed on gemcitabine and cisplatin to fluorouracil and leucovorin with or without liposomal irinotecan: blinded central review progression-free survival was 7.1 versus 1.4 months (hazard ratio 0.56) at the first analysis and 4.2 versus 1.7 months (hazard ratio 0.61) when the scans were re-read with extended follow-up, with grade 3 to 4 neutropenia in 24 percent versus 1 percent. The German NALIRICC trial (100 patients) found no benefit, and the earlier German NIFE trial compared it non-comparatively with gemcitabine and cisplatin in first line. NCCN lists it as an option after gemcitabine and cisplatin; in the UK it is not commissioned for biliary cancer, where FOLFOX (ABC-06) is the second-line standard. UGT1A1 poor metabolisers need dose reduction.

## Fields

- Kind: Treatment
- Status: approved
- Last checked: 2026-09-24
- Brand: Onivyde
- Code: nal-IRI, MM-398, PEP02
- Modality: Liposome-encapsulated topoisomerase I inhibitor (cytotoxic)
- Mechanism: Liposomal delivery of irinotecan; SN-38 traps topoisomerase I and DNA in cleavage complexes.
- Approvals: US 2015: Metastatic pancreatic adenocarcinoma after gemcitabine-based therapy, with fluorouracil and leucovorin (NAPOLI-1); EU 2016: Metastatic pancreatic adenocarcinoma after gemcitabine, with fluorouracil and leucovorin; US 2024: First-line metastatic pancreatic adenocarcinoma in NALIRIFOX (NAPOLI 3); UK 2017: Metastatic adenocarcinoma of the pancreas after gemcitabine-based therapy, with fluorouracil and leucovorin: NICE TA440 (26 April 2017) does not recommend it within its marketing authorisation; NICE NG85 1.9.9 restates the position; EU 2016: Metastatic adenocarcinoma of the pancreas after gemcitabine-based therapy, with fluorouracil and leucovorin (marketing authorisation 14 October 2016, orphan designation 2011); the EMA product information now also lists first-line use with oxaliplatin, fluorouracil and leucovorin (NALIRIFOX)
- Dosing: Intravenous; 70 mg/m² over 90 minutes every 2 weeks with leucovorin 400 mg/m² and fluorouracil 2,400 mg/m² over 46 hours (NIFTY schedule)
- Toxicity (grade 3+): Neutropenia (grade 3-4) 24%; Fatigue or asthenia (grade 3-4) 13%

## Notes

- Pancreatic cancer, regulators: the Onivyde label (effective 3 March 2025) carries two indications, NALIRIFOX first line (NAPOLI 3: overall survival 11.1 against 9.2 months, hazard ratio 0.84; progression-free survival 7.4 against 5.6 months, hazard ratio 0.70; FDA notice 13 February 2024) and with fluorouracil and leucovorin after gemcitabine (NAPOLI-1; FDA 2015), and states it is not indicated as a single agent. In England neither use is commissioned: TA440 does not recommend the second-line combination and the NALIRIFOX appraisal (TA1052) was terminated on 2 April 2025 because the company made no submission. Label safety for NALIRIFOX (383 patients): serious adverse reactions 54 percent, fatal 6 percent, discontinuation of Onivyde 17 percent.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Irinotecan
- FDA label (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=c8b58efa-1820-48a4-b70d-62918fc4abfc
- NIFTY, Lancet Oncology 2021: https://doi.org/10.1016/S1470-2045(21)00486-1
- NIFTY updated analysis, JAMA Oncology 2023: https://doi.org/10.1001/jamaoncol.2023.0016
- NICE TA440: pegylated liposomal irinotecan after gemcitabine, not recommended (26 April 2017): https://www.nice.org.uk/guidance/ta440
- Onivyde label (openFDA): NAPOLI 3 and NAPOLI-1 study sections: https://api.fda.gov/drug/label.json?search=openfda.brand_name:%22ONIVYDE%22
- EMA Onivyde pegylated liposomal product page: https://www.ema.europa.eu/en/medicines/human/EPAR/onivyde-pegylated-liposomal
- FDA notice: irinotecan liposome for first-line metastatic pancreatic adenocarcinoma (13 February 2024): https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancer-hematologic-malignancies-approval-notifications

## Connected records

- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [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/)
- companies: [Ipsen](https://onco.cc/companies/ipsen/), [Servier](https://onco.cc/companies/servier/)
- trials: [A Randomized, Two-cohort, Prospective Phase II Clinical Study of the Second-line Treatment of Advanced Biliary System Tumors With Liposomal Irinotecan (II) Combination Regimen](https://onco.cc/trials/nct07099794/), [A Study to Compare the Efficacy and Safety of YL201 With Standard Chemotherapy in Patients With Metastatic Pancreatic Cancer After Failure of Gemcitabine-Based](https://onco.cc/trials/nct07803783/), [Cadonilimab Combined With Liposomal Irinotecan Plus Leucovorin and Fluorouracil for Advanced Cholangiocarcinoma](https://onco.cc/trials/nct06438822/), [HR070803 in Combination With Oxaliplatin, 5-fluorouracil/LV Versus GX as Adjuvant Therapy for Pancreatic Cancer](https://onco.cc/trials/nct06217042/), [HR070803 in Combination With Oxaliplatin, S-1 Versus NALIRIFOX as Adjuvant Therapy for Pancreatic Cancer](https://onco.cc/trials/nct06383078/), [Ivonescimab in Combination With Liposomal Irinotecan and 5-FU/LV in Potentially Resectable Biliary Tract Malignancies](https://onco.cc/trials/nct06993025/), [Liposomal Irinotecan in Combination With Oxaliplatin and S-1 Versus Gemcitabine Combined With Capecitabine as Postoperative Adjuvant Therapy for Pancreatic Canc](https://onco.cc/trials/nct06571461/), [Liposomal Irinotecan Plus 5-FU/LV and Sintilimab With Sequential SBRT for Locally Advanced Biliary Tract Cancer](https://onco.cc/trials/nct07797816/), [NALIRICC (AIO)](https://onco.cc/trials/naliricc/), [NAPOLI 3](https://onco.cc/trials/napoli-3/), [NAPOLI-1](https://onco.cc/trials/napoli-1/), [NAPOLI-2: Fluorouracil, Leucovorin, and Nanoliposomal Irinotecan in Biliary Cancer](https://onco.cc/trials/nct04005339/), [Newly Emerging Immunotherapy for Pancreatic Cancer Treatment](https://onco.cc/trials/nct06370754/), [NIFE (AIO-YMO HEP-0315)](https://onco.cc/trials/nife/), [NIFTY](https://onco.cc/trials/nifty/), [PANORAMIX : Optimizing 1st-line NALIRIFOX and Exploring Microbiota's Role in 2nd Line Pancreatic Cancer Treatment](https://onco.cc/trials/nct07028424/), [Perioperative Treatment in High-risk Resectable Pancreatic Cancer With NALIRIFOX](https://onco.cc/trials/nct06210360/), [RASolute 302](https://onco.cc/trials/rasolute-302/), [Stereotactic Body Radiation Therapy Followed by NALIRIFOX vs NALIRIFOX for Borderline Resectable Pancreatic Cancer](https://onco.cc/trials/nct06259058/)
- key papers: [Metastatic Pancreatic Cancer: ASCO Guideline Update](https://onco.cc/key-papers/paper-asco-metastatic-pancreatic-cancer-guideline-update-jco-2020/), [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/)
- terms: [Pancreatic cancer drugs in England: NICE appraisals and the Cancer Drugs Fund (September 2026)](https://onco.cc/terms/pancreatic-cancer-uk-drug-access/)

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