FDA Approves Irinotecan Liposome for First-line Treatment of Metastatic Pancreatic Adenocarcinoma

February 14, 2024

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On February 13, 2024, the Food and Drug Administration approved irinotecan liposome (Onivyde, Ipsen Biopharmaceuticals, Inc.) with oxaliplatin, fluorouracil, and leucovorin, for the first-line treatment of metastatic pancreatic adenocarcinoma.

Full prescribing information for Onivyde will be posted here

Efficacy was evaluated in NAPOLI 3 (NCT04083235), a randomized, multicenter, open-label, active-controlled trial in 770 patients with metastatic pancreatic adenocarcinoma who had not previously received chemotherapy in the metastatic setting. Randomization was stratified by region, liver metastases, and ECOG performance status. Patients were randomized (1:1) to receive one of the following treatments:

  • NALIRIFOX: irinotecan liposome 50 mg/m2 as an intravenous infusion over 90 minutes, followed by oxaliplatin 60 mg/m2 as an intravenous infusion over 120 minutes, followed by leucovorin 400 mg/m2 intravenously over 30 minutes, followed by fluorouracil 2400 mg/m2 intravenously over 46 hours, every 2 weeks.
  • Gem+NabP: Nab-paclitaxel 125 mg/m2 as an intravenous infusion over 35 minutes, followed by gemcitabine 1000 mg/m2 intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle. 

The main efficacy outcome measure was overall survival (OS). Additional efficacy measures were investigator-assessed progression-free survival (PFS) and objective response rate (ORR). NAPOLI 3 demonstrated a statistically significant improvement in OS and PFS for the NALIRIFOX arm over the Gem+NabP arm. Median OS was 11.1 months (95% CI: 10.0, 12.1) in the NALIRIFOX arm and 9.2 months (95% CI: 8.3, 10.6) in the Gem+NabP arm (Hazard Ratio [HR] 0.84 [95% CI: 0.71, 0.99]; p-value 0.0403). Median PFS was 7.4 months (95% CI: 6.0, 7.7) in the NALIRIFOX arm and 5.6 months (95% CI: 5.3, 5.8) in the Gem+NabP arm (HR 0.70 [95% CI: 0.59, 0.85]; p-value 0.0001). ORR was 41.8% (95% CI: 36.8, 46.9) in the NALIRIFOX arm and 36.2% (95% CI: 31.4, 41.2) in the Gem+NabP arm.

The most common adverse reactions of NALIRIFOX (≥20% with a difference between arms of ≥5% for all grades or ≥2% for Grades 3 or 4 compared to Gem+NabP) were diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight. The most common laboratory abnormalities (≥10% Grade 3 or 4) were decreased neutrophils, decreased potassium, decreased lymphocyte, and decreased hemoglobin.

The recommended irinotecan liposome dose is 50 mg/m2 administered by intravenous infusion over 90 minutes every 2 weeks. Administer irinotecan liposome before oxaliplatin, fluorouracil, and leucovorin. There is no recommended dosage of irinotecan liposome for patients with serum bilirubin above the upper limit of normal.

This application was granted orphan drug designation.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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