Liposomal Irinotecan Combo Granted FDA Fast Track Designation for Advanced PDAC

A liposomal irinotecan combination was granted FDA Fast Track designation for the treatment of untreated and unresectable, locally advanced or metastatic pancreatic ductal adenocarcinoma.

The FDA has granted Fast Track Designation to liposomal irinotecan (Onivyde) in combination with 5-fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (NALIRIFOX) as treatment of patients with previously untreated and unresectable, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC).1

Liposomal irinotecan is already FDA approved in the United States in combination with 5-FU/LV alone as treatment of patients with PDAC after disease progression following gemcitabine-based therapy. However, it is not yet approved in the frontline setting for PDAC. 

“Since the initial approval of Onivyde in metastatic pancreatic cancer, we have continued to dedicate our research efforts to better understand the needs of pancreatic cancer patients. Through ongoing clinical investigations and exploratory real-world analyses, we have sought to determine whether patients who receive active treatment early have an improvement in survival,” Howard Mayer, MD, executive vice president, Head of Research and Development at Ipsen, said in a statement.

Liposomal irinotecan plus 5-FU/LV and oxaliplatin are being studied in a multicenter, open-label phase 1/2 clinical trial, from which final analysis results will be presented at the 2020 European Society of Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer in July 2020. 

The final overall survival (OS) results for long-term survivors from the phase 3 NAPOLI-1 trial were published in 2019 in the European Journal of Cancer, showing survival benefit with liposomal irinotecan plus 5-FU/LV over 5-FU/LV alone, which was maintained over an extended follow-up period.1,2

The median OS in the liposomal irinotecan combination arm was 6.2 months compared with 4.2 months in the 5-FU/LV only arm (unstratified HR, 0.75; 95% CI, 0.57-0.99; P = .039). Conversely, the median OS with liposomal irinotecan alone was 4.9 months and the was 4.2 months with 5-FU/LV alone (HR, 1.07; P = .568).

At 6 months, the OS rate observed with liposomal irinotecan plus 5-FU/LV was 53% (95% CI, 44%-62%). In the 5-FU/LV only arm, the 6-month OS rate was 38% (95% CI, 29%-47%). At 12 months, the OS rates in the liposomal irinotecan combination and 5-FU/LV arms were 26% (95% CI, 18%-35%) and 16% (95% CI, 10%-24%), respectively.

The median progression-free survival (PFS) observed with the combination of liposomal irinotecan and 5-FU/LV was 3.1 months (95% CI, 2.7-4.2). The median PFS in the 5-FU/LV alone arm was 1.5 months (95% CI, 1.4-1.8). The difference was considered significant (HR, 0.57; P = .0001).

An overall response rate of 17% (95% CI, 10%-24%) was achieved in the liposomal irinotecan plus 5-FU/LV group compared with only 1% (95% CI, 0%-2%) in the 5-FU/LV only group (P < .0001). The disease control rate (DCR) achieved was 52% (95% CI, 43%-61%), in the irinotecan plus 5-FU/LV, and 24% (95% CI, 17%-33%) in the control arms. Objective responses in the study included partial responses in 17% of patients in the experimental arm versus only 1% of the control arm. Additionally, 32% of patients who received liposomal irinotecan plus 5-FU/LV had stable disease (SD) compared with 22% of the 5-FU/LV-only arm. Progressive disease (PD) was observed in 29% of the liposomal irinotecan plus 5-FU/LV population versus 47% of the 5-FU/LV-only population.

The completed NAPOLI-1 trial investigated the efficacy and safety of liposomal irinotecan combined with 5-FU/LV with OS as the primary end point. The secondary end points were PFS, ORR, and serum CA19-9 levels.


Patients in the study were given liposomal irinotecan 120 mg/m2 every 3 weeks plus 5-FU 2000 mg/m2 plus LV 200 mg/m2 for the first 4 weeks of 6-week cycles.

The safety profiles of both liposomal irinotecan and 5-FU/LV were no differences in long-term OS this analysis than the main NAPOLI-1 study. The most frequently reported grade 3 or higher treatment-emergent adverse events (TEAEs) in the liposomal irinotecan-containing arms were neutropenia, diarrhea, vomiting, and fatigue. Seventy-three percent of patients in the study experienced dose delay, reduction, or discontinued treatment due to TEAEs.

The combination of liposomal irinotecan and 5-FU/LV is now under further investigation in the phase 3 NAPOLI-3 study (NCT04083235), which is evaluating the safety and efficacy of oxaliplatin compared with the chemotherapy combination of gemcitabine plus nab-paclitaxel in the first-line setting.1

“As we continue to enroll additional patients in the ongoing phase 3 NAPOLI-3 clinical study, we look forward to working closely with the FDA to potentially bring Onivyde to more pancreatic cancer patients earlier in the disease,” Mayer added.


1. Ipsen receives FDA Fast Track designation for liposomal irinotecan (ONIVYDE®) as a first-line combination treatment for metastatic pancreatic cancer. News release. Ipsen Pharmaceutical. June 17, 2020. Accessed June 17, 2020.

2. Wang-Gillam A, Hubner RA, Siveke JT, et al. NAPOLI-1 phase 3 study of liposomal irinotecan in metastatic pancreatic cancer: Final overall survival analysis and characteristics of long-term survivors. Eur J Cancer. 2019;108:78-87. doi:10.1016/j.ejca.2018.12.007

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