Expanded analyses of napoli-1: Phase 3 study of MM-398 (nal-IRI), with or without 5-fluorouracil and leucovorin, versus 5-fluorouracil and leucovorin, in metastatic pancreatic cancer (mPAC) previously treated with gemcitabine-based therapy.

Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Session Type and Session Title: 
Oral Abstract Session: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
General Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract
Abstract Number: 


Poster Board Number: 
General Poster Session B (Board #A5)
J Clin Oncol 33, 2015 (suppl 3; abstr 234)
Li-Tzong Chen, Daniel D. Von Hoff, Chung-Pin Li, Andrea Wang-Gillam, Gyorgy Bodoky, Andrew Peter Dean, Yan-Shen Shan, Gayle S. Jameson, Teresa Macarulla, Kyung-Hun Lee, David Cunningham, Jean-Frédéric Blanc, Richard Hubner, Chang-Fang Chiu, Gilberto Schwartsmann, Jens T Siveke, Fadi S. Braiteh, Victor M. Moyo, Bruce Belanger, Eliel Bayever; National Institute of Cancer Research, National Health Research Institutes, Tainan City, Taiwan; Clinical Trials, Virginia G. Piper Cancer Center at Scottsdale Healthcare/TGen, Scottsdale, AZ; Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Oncology, Washington University in St. Louis, St. Louis, MO; Szent László Hospital, Budapest, Hungary; St. John of God Hospital Subiaco, Subiaco, Australia; National Cheng Kung University Hospital, Tainan City, Taiwan; Vall d'Hebron University Hospital, Barcelona, Spain; Department of Internal Medicine and Cancer Research Institute, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea; Royal Marsden NHS Foundation Trust, London and Surrey, United Kingdom; Hôpital Saint-André, Bordeaux, France; Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, United Kingdom; China Medical University Hospital, Taichung, Taiwan; Federal University of Rio Grande do Sul, Porto Alegre, Brazil; Klinikum rechts der Isar der TU Muenchen, Munich, Germany; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Merrimack Pharmaceuticals Inc., Cambridge, MA

Abstract Disclosures


Background: MM-398 is a nanoliposomal encapsulation of irinotecan. OS in the ITT population was significantly longer with MM-398+5FU/LV over 5FU/LV alone, and the most frequent grade 3+ AEs included neutropenia, fatigue, and GI effects (diarrhea and vomiting). Expanded, pre-specified analyses of the Phase 3 study are presented. Methods: Patients (n=417) with mPAC previously treated with 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. The Intent To Treat (ITT) population included all randomized patients; the Per Protocol (PP) population included patients who received at least 80% of the target dose in the first 6 weeks and did not violate any inclusion/exclusion criteria. Results: Analysis of the PP populations confirmed the favorable OS, which was also reflected by the PFS, ORR and CA19-9 levels, of the combination MM-398+5FU/LV arm over the control 5FU/LV arm. The MM-398 monotherapy arm did not show a statistically significant improvement in OS compared with the control arm. Analysis of subgroups, based on pretreatment characteristics including stage at diagnosis, time since initial histological diagnosis, prior lines of therapy, time since last prior therapy, and CA19-9 levels, consistently favored OS for the MM-398+5FU/LV arm over the 5FU/LV arm. Conclusions: Expanded analysis of the PP population and sensitivity analyses support the favorability of MM-398+5FU/LV over 5FU/LV, with a manageable safety profile. Clinical trial information: NCT01494506

Median overall survival.

Months (95% CI)
6.1 (4.8 – 8.9)
8.9 (6.4 – 10.5)
Months (95% CI)
4.2 (3.3 – 5.3)
5.1 (4.0 – 7.2)
HR for survival0.67 (0.49 – 0.92)0.57 (0.37 – 0.88)
p-value (log-rank test)0.0120.011