Ipsen plans to seek FDA approval for the NALIRIFOX regimen based on positive results from the phase 3 NAPOLI 3 clinical trial.
Treatment with irinotecan liposome injection (Onivyde) plus 5 fluorouracil/leucovorin and oxaliplatin (NALIRIFOX) demonstrated a statistically significant improvement in overall survival (OS) vs nab-paclitaxel and gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC).1
With a significant OS improvement, the primary end point of the phase 3 NAPOLI 3 clinical trial (NCT04083235) has been met, according to an announcement by Ipsen. It was also reported that the trial met its key secondary end point of progression-free survival (PFS), and the safety of the irinotecan liposome injection in NAPOLI 3 was consistent with what was shown in the phase 1/2 study.
Specifically, the box label for irinotecan liposome injection notes that the most common adverse events (AEs) observed with the drug are diarrhea (59%), fatigue/asthenia (56%), vomiting (52%), nausea (51%), decreased appetite (44%), stomatitis (32%), and pyrexia (23%). The most common high-grade AEs include diarrhea (13%), fatigue/asthenia (21%), and vomiting (11%). The irinotecan liposome injection can lead to fatal neutropenic sepsis (0.8%) and severe diarrhea (13%).
The label also warns that the therapy can lead to interstitial lung disease, severe hypersensitivity reactions, and embryo-fetal toxicity.
Based on the phase 3 findings, Ipsen plans to submit a supplement new drug application to the FDA seeking approval of the NALIRIFOX regimen for the treatment of patients with treatment-naive mPDAC. Further, full 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,” said Howard Mayer, executive vice president and head of Research and Development at Ipsen, 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. We thank the patients who participated in the study, their families, and their healthcare teams.”
NAPOLI 3 is a randomized, open-label study. Roughly 770 patients with mPDAC were enrolled and assigned to receive NALIRIFOX regimen twice in a month on days 1 and 15 of a 28-day cycle in the experimental arm or nab-paclitaxel and gemcitabine 3 times a month on days 1, 8, 15 of a 28-day cycle.2
The trial is investigating the primary end point of OS and the secondary end points of progression-free survival, objective response rate, quality of life, incidence of treatment-emergent adverse events, and laboratory abnormalities.
To be eligible for enrollment in the study, patients were required to have histologically or cytologically confirmed mPDAC, an ECOG performance status of 0 or 1, and adequate biological parameters, hepatic function, renal function, and coagulation studies.
The study did not permit inclusion of patients who have received prior treatment surgery, radiotherapy, chemotherapy or, investigational therapy for metastatic pancreatic cancer, prior treatment with adjuvant chemotherapy, or those with certain comorbidities that may impact the effectiveness of treatment.
1. 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. https://bit.ly/3TsnOuZ
2. A study to assess the effectiveness and safety of irinotecan liposome injection, 5-fluorouracil/leucovorin plus oxaliplatin in patients not previously treated for metastatic pancreatic cancer, compared to nab-paclitaxel+gemcitabine treatment (NAPOLI 3). ClinicalTrials.gov. Updated October 27, 2022. Accessed November 9, 2022. https://clinicaltrials.gov/ct2/show/NCT04083235