Irinotecan Liposome Injection Plus NALIRIFOX Meets Primary End Point for Most Common Type of Pancreatic Cancer

Patients with metastatic pancreatic ductal adenocarcinoma—the most common type of pancreatic cancer—may benefit from treatment with irinotecan liposome injection in combination with fluorouracil/leucovorin and oxaliplatin, according to findings from the phase 3 NAPOLI3 trial.

Investigators reported that the primary end point of clinically meaningfully and statistically significantly improved overall survival (OS) among patients with metastatic pancreatic ductal adenocarcinoma was met in the phase 3 NAPOLI3 trial (NCT04083235), assessing irinotecan liposome injection (Onivyde) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX), according to a press release from Ipsen.

In addition to improving OS in a population of 770 patients with previously untreated disease, a key secondary end point of improved progression-free survival (PFS) vs nab-paclitaxel plus gemcitabine (the control arm) was also met. Safety was consistent with findings reported in a prior phase 1/2 study.

A new drug application will be submitted to the FDA for the regimen and results from the study will be presented at an upcoming medical conference.

“The positive results from the NAPOLI 3 trial demonstrate that compared with the standard-of-care, the investigational [irinotecan liposome injection] treatment regimen extended the lives of people living with metastatic pancreatic ductal adenocarcinoma who were previously untreated,” Howard Mayer, executive vice president and head of research and development at Ipsen, said in the press release. “The prognosis for people diagnosed with pancreatic cancer is extremely poor and we plan to submit these new findings to the regulatory authority as, if approved, we believe this regimen could offer up an important new treatment option for people living with an aggressive and hard-to-treat cancer.”

The randomized, open-label study treated patients with the irinotecan liposome/NALIRIFOX combination twice a month on days 1 and 15 of every 28-day cycle and compared it with injected nab-paclitaxel and gemcitabine 3 times a month on days 1, 8, and 15 of every 28-day cycle.

Other secondary outcomes for the study included objective response rate, quality of life, treatment-emergent adverse effects (AEs), serious AEs, and laboratory abnormalities.

To be included in the study, patients were required to have histologically or cytologically confirmed adenocarcinoma of the pancreas and were not given prior treatment for metastatic disease. Diagnosis of metastatic disease needed to take place 6 weeks or less before screening. Moreover, an ECOG performance status of 0 or 1, as well as adequate biological parameters, hepatic function, renal function, and coagulation studies were required for enrollment.

Patients with locally advanced disease, document serum albumin below 3 g/dL, known history of central nervous system metastases, or significant gastrointestinal disorder were not eligible for enrollment. Other exclusion criteria included having a history of a secondary malignancy within the last 2 years, concurrent illness counterindicated for trial participation, and treatment with CYP3A, CYP2C8 and UGT1A1 inducers or inhibitors.


Onivyde® regimen demonstrated statistically significant improvement in overall survival in previously untreated metastatic pancreatic ductal adenocarcinoma. News release. Ipsen. November 9, 2022. Accessed November 9, 2022.