Onivyde Regimen Approved as First-Line Tx for Metastatic Pancreatic Adenocarcinoma

The Food and Drug Administration (FDA) has approved Onivyde^® (irinotecan liposome injection) in combination with oxaliplatin, fluorouracil, and leucovorin for the first-line treatment of metastatic pancreatic adenocarcinoma.

The approval was based on data from the open-label, randomized phase 3 NAPOLI 3 trial (ClinicalTrials.gov Identifier: NCT04083235), which included 770 patients with metastatic pancreatic adenocarcinoma who have not previously received chemotherapy in the metastatic setting. Patients were randomly assigned 1:1 to receive either Onivyde plus oxaliplatin, leucovorin, and fluorouracil (NALIRIFOX regimen) every 2 weeks or nab-paclitaxel and gemcitabine administered 3 times a month (days 1, 8, 15 of a 28-day cycle).

Results showed that patients in the NALIRIFOX arm demonstrated a statistically significant improvement in median overall survival (primary endpoint) of 11.1 months (95% CI, 10-12.1) compared with 9.2 months (95% CI, 8.3-10.6) for the nab-paclitaxel and gemcitabine arm (hazard ratio [HR], 0.84 [95% CI, 0.71-0.99]; P =.0403). 

Median progression free survival (secondary endpoint) was 7.4 months (95% CI, 6-7.7) in the NALIRIFOX arm vs 5.6 months (95% CI, 5.3-5.8) for the nab-paclitaxel and gemcitabine arm (HR, 0.70 [95% CI, 0.59-0.85]; P =.0001). The objective response rate was 41.8% (95% CI, 36.8-46.9) in the NALIRIFOX group and 36.2% (95% CI, 31.4-41.2) in the nab-paclitaxel and gemcitabine group.

The most common adverse events reported were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. Decreased neutrophils, potassium, lymphocytes, and hemoglobin were the most common laboratory abnormalities.

“The results from the phase 3 NAPOLI 3 trial represent the first positive data for an investigational regimen in first-line metastatic pancreatic adenocarcinoma vs the currently approved nab-paclitaxel and gemcitabine regimen,” said Christelle Huguet, EVP and Head of Research and Development, Ipsen. “With today’s approval, this Onivyde (NALIRIFOX) regimen can now offer a potential new standard-of-care treatment option with proven survival benefits for people living with metastatic pancreatic adenocarcinoma in the US.”

Onivyde, a topoisomerase inhibitor, is also indicated in combination with fluorouracil and leucovorin, for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.