e-Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2020

NAPOLI-3: An open-label, randomized, phase III study of first-line liposomal irinotecan + 5‑fluorouracil/leucovorin + oxaliplatin versus nab-paclitaxel + gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma. (#407)

Andrew Dean 1 , Zev A Wainberg 2 , Tanios S Bekaii-Saab 3 , Richard Hubner 4 , Teresa Macarulla 5 , Andrew Scott Paulson 6 , Eric V Cutsem 7 , Fiona Maxwell 8 , Yan Moore 9 , Haofei Tiffany Wang 9 , Bin Zhang 9 , Eileen O'Reilly 10
  1. St John of God Subiaco, Subiaco, WA, Australia
  2. University of California, Los Angeles, Medical Center,, Los Angeles, CA, USA
  3. Mayo Clinic Cancer Center (MCCC), Scottsdale, Scottsdale, AZ, USA
  4. Christie Hospital NHS Foundation Trust, Manchester, UK
  5. Vall d'Hebron University Hospital, Barcelona, Spain
  6. Texas Oncology/The US Oncology Network, , Dallas, TX, USA
  7. University of Leuven, Leuven, Belgium
  8. Ipsen, Abingdon, UK
  9. Ipsen Bioscience, Inc., Cambridge, MA, USA
  10. Memorial Sloan Kettering Cancer Center, New York, NY, USA


Liposomal irinotecan administered with 5-fluorouracil/leucovorin (5-FU/LV) is FDA-approved in USA for metastatic pancreatic ductal adenocarcinoma (mPDAC) following progression with gemcitabine-based therapy. A phase 1/2 study in previously untreated locally advanced/metastatic PDAC showed promising anti-tumor activity with liposomal irinotecan 50mg/m free-base + 5-FU 2400mg/m + LV 400mg/m + oxaliplatin (OX) 60mg/m on days 1 and 15 of a 28-day cycle (Wainberg et al. Ann Oncol 2019;30 Suppl 4: SO-005). We present the phase-3 NAPOLI-3 study design, investigating the efficacy and safety of this regimen as first-line therapy in patients with mPDAC.


NAPOLI-3 (NCT04083235) is a phase-3, open-label, randomized, global study in adults with histologically/cytologically confirmed pancreatic adenocarcinoma, previously untreated in the metastatic setting. Patients must have ≥1 metastatic tumor measurable with computed tomography/magnetic resonance imaging and an Eastern Cooperative Oncology Group performance status score of 0–1. Site activation began in Dec-2019 and enrollment is ongoing. Random allocation (1:1) of 750 patients is planned to liposomal irinotecan + 5-FU/LV + OX (same regimen as phase 1/2 study) or nab-paclitaxel 125mg/m + gemcitabine 1000mg/m on days 1, 8 and 15 in a 28-day cycle. The primary endpoint is overall survival. Secondary endpoints (progression-free survival and overall response rate assessed with Response Evaluation Criteria in Solid Tumors v1.1) will be compared if primary endpoint shows superiority for liposomal irinotecan + 5-FU/LV + OX over nab-paclitaxel + gemcitabine. Safety assessments include adverse-event monitoring. Patients will continue treatment until disease progression, unacceptable toxicity or study withdrawal, and will then be followed for survival every 2-months until death or study-end (when all patients have died, withdrawn consent or lost to follow-up).


This study is funded by Ipsen.


© 2020 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2020 ASCO Annual Meeting. All rights reserved.