O-0003 - NAPOLI-1: randomized phase 3 study of MM-398 (nal-iri), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in meta...

Date 25 June 2014
Event World GI 2014
Session Cancer of the pancreas and bile ducts
Topics Anti-Cancer Agents & Biologic Therapy
Pancreatic Cancer
Presenter Daniel Von Hoff
Citation Annals of Oncology (2014) 25 (suppl_2): ii105-ii117. 10.1093/annonc/mdu193
Authors C.P. Li1, L.T. Chen2, A. Wang-Gillam3, G. Bodoky4, A. Dean5, G. Jameson6, K.H. Lee7, J.F. Blanc8, R. Hubner9, C.F. Chiu10, G. Schwartsmann11, J. Siveke12, F. Braiteh13, V. Moyo14, B. Belanger14, N. Dhindsa14, E. Bayever14
  • 1Taipei Veterans General Hospital and National Yang-Ming University, Taipei/TW
  • 2National Cheng Kung University Hospital, Tainan/TW
  • 3Washington University in St.Louis, St Louis/US
  • 4St László Teaching Hospital, Budapest/HU
  • 5St John of God Hospital SUBIACO, Subiaco/AU
  • 6Scottsdale Health Care, Scottsdale/US
  • 7Seoul National University Hospital, Seoul/KR
  • 8Hopital Saint Andre, Bordeaux/FR
  • 9The Christie NHS Foundation Trust, Manchester/UK
  • 10China Medical University Hospital, Taichung/TW
  • 11Hospital de Clinicas de Porto Alegre, Porto Alegre/BR
  • 12Klinikum rechts der Isar der TU Muenchen, Munich/DE
  • 13Comprehensive Cancer Centers of Nevada, Las Vegas/US
  • 14Merrimack, Cambridge/US



MM-398 (nal-IRI) is a novel encapsulation of irinotecan in a long-circulating nanoliposome. MM-398 had clinical activity in a Phase 2 study of pts with metastatic pancreatic adenocarcinoma (mPAC) after prior gemcitabine–based therapy.


Pts with mPAC after prior gemcitabine-based therapy, were randomized 1:1:1 in an open-label study to receive: (A) MM-398 (120 mg/m2 IV over 90 min) q3w; (B) 5FU (2,000 mg/m2 over 24 h) plus racemic leucovorin (LV) (200 mg/m2 over 30 min) x 4w followed by 2w rest; or (C) combination of MM-398 (80 mg/m2 IV over 90 min) prior to 5FU (2,400 mg/m2 over 46 h) and racemic LV (400 mg/m2 over 30 min) q2w. The primary endpoint was OS in arms A and C, each vs. the control arm B.


A total of 417 patients were randomized, of which 398 received treatment. Baseline characteristics were balanced, 61% head of pancreas, and 68% liver metastases. OS, PFS, TTF, and ORR were significantly improved by MM-398 + 5FU/LV vs. 5FU/LV. Median OS was 6.1m (95% CI: 4.8–8.9) and 4.2m (3.3–5.3), respectively, HR = 0.67, p = 0.012; and median PFS 3.1m (2.7–4.2) and 1.5m (1.4–1.8), respectively, HR = 0.56, p < 0.001. MM-398 alone did not demonstrate a statistical improvement in efficacy. Major grade ≥3 AEs in the MM-398 + 5-FU/LV, MM-398 and 5-FU/LV arms were neutrophil count decreased (23.1%, 15.3%, 3%), fatigue (13.7%, 6.1%, 3.7%), diarrhea (12.8%, 21.1%, 4.5%), and vomiting (11.1%, 13.6%, 3.0%), respectively; neutrophil count decreased was based on lab. values [by investigator report, “neutropenia”, (14.5%, 5.4%, 0.7%) and “neutrophil count decreased” (10.3%, 8.2%, 0.7%) respectively]. Additional AEs of interest were febrile neutropenia (1.7%, 4.1%, 0%) and sepsis (3.4%, 2.0%, 0.7%) in MM-398 + 5FU/LV, MM-398 and 5FU/LV respectively.