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

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 IV infusion over 90 minutes, followed by oxaliplatin 60 mg/m² as an IV infusion over 120 minutes, followed by leucovorin 400 mg/m² via IV over 30 minutes, followed by fluorouracil 2,400 mg/m² via IV over 46 hours, every two weeks.
• Gem+NabP: nab-paclitaxel 125 mg/m2 as an IV infusion over 35 minutes, followed by gemcitabine 1,000 mg/m² via IV 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 (HR = 0.84; 95% CI = 0.71, 0.99; p = 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 = 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 reported in at least 20% of patients (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, at least 10% of patients presenting with grade 3 or 4 toxicities, were decreased neutrophils, decreased potassium, decreased lymphocyte, and decreased hemoglobin.

The recommended irinotecan liposome dose is 50 mg/m² administered by IV infusion over 90 minutes every two 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.

View the full prescribing information for irinotecan liposome here (https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm).

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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact the Office of Oncology Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).