FDA approves irinotecan liposome for first-line treatment of metastatic pancreatic adenocarcinoma

Regulatory approval: On Feb 13, 2024, the FDA approved irinotecan liposome (Onivyde) in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) for first-line treatment of metastatic pancreatic adenocarcinoma. Approval was supported by the randomized phase 3 NAPOLI 3 trial (N=770), which showed statistically significant improvements in overall survival (median 11.1 vs 9.2 months; HR 0.84) and progression-free survival (median 7.4 vs 5.6 months; HR 0.70) versus gemcitabine plus nab-paclitaxel.

FDA approval: irinotecan liposome for first-line metastatic pancreatic adenocarcinoma (Feb 13, 2024)

Event type: Regulatory approval

On February 13, 2024, the FDA approved irinotecan liposome (Onivyde; Ipsen Biopharmaceuticals, Inc.) in combination with oxaliplatin, fluorouracil, and leucovorin (NALIRIFOX) for the first-line treatment of metastatic pancreatic adenocarcinoma.

Supporting evidence (NAPOLI 3; NCT04083235)

Approval was based on NAPOLI 3, 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. Patients were randomized 1:1 to NALIRIFOX vs gemcitabine plus nab-paclitaxel (Gem+NabP).

Primary endpoint: overall survival (OS). Additional endpoints included investigator-assessed progression-free survival (PFS) and objective response rate (ORR).

  • Median OS: 11.1 vs 9.2 months (HR 0.84, 95% CI 0.71–0.99; p=0.0403)
  • Median PFS: 7.4 vs 5.6 months (HR 0.70, 95% CI 0.59–0.85; p=0.0001)
  • ORR: 41.8% vs 36.2%

Safety and dosing highlights

Common adverse reactions reported for NALIRIFOX included diarrhea, fatigue, nausea, vomiting, decreased appetite, abdominal pain, mucosal inflammation, constipation, and decreased weight; common grade 3/4 lab abnormalities included decreased neutrophils, potassium, lymphocytes, and hemoglobin.

Recommended irinotecan liposome dose: 50 mg/m² IV over 90 minutes every 2 weeks, administered before oxaliplatin, fluorouracil, and leucovorin. No recommended dose is provided for patients with serum bilirubin above ULN. The application received orphan drug designation.

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