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Expanded Analyses of Phase III MM-398 NAPOLI-1 Study Substantiate Positive Results of MM-398 Combined With Fluorouracil/Leucovorin

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Key Points

  • MM-398 (aka PEP02) is a nanoliposomal encapsulation of irinotecan.
  • MM-398 in combination with 5-FU/leucovorin improved overall survival compared to a control arm of 5-FU/leucovorin alone, resulting in a hazard ratio of 0.57 (95% CI = 0.41–0.80, P = .0009).
  • The significant improvement was also observed in progression-free survival (overall and at 3 months), objective response rate, and CA19-9 tumor marker response for MM-398 in combination with 5-FU/leucovorin.

Additional analyses from the global phase III NAPOLI-1 study of MM-398 (aka PEP02), a nanoliposomal encapsulation of irinotecan, in metastatic pancreatic cancer were presented by Chen et al in an oral session at the 2015 Gastrointestinal Cancers Symposium  (Abstract 234).

The primary analysis of the NAPOLI-1 phase III trial, presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer 2014 in Barcelona, demonstrated a statistically significant increase in overall survival with an unstratified hazard ratio of 0.67 (95% CI = 0.49–0.92, P = .0122) and a median of 6.1 months for the combination of MM-398 plus fluorouracil (5-FU)/leucovorin compared to 4.2 months in the 5-FU/leucovorin control arm.

The expanded analyses presented at the 2015 Gastrointestinal Cancers Symposium further corroborate the top-line data presented at the ESMO meeting on achieving the primary endpoint of overall survival for treatment with MM-398, 80 mg/m2, in combination with 5-FU/leucovorin every 2 weeks in metastatic pancreatic cancer previously treated with gemcitabine-based therapy.

Key Findings

In the stratified analysis, which accounts for prespecified prognostic factors included in the study randomization stratification, the overall survival for 80 mg/m2 of MM-398 in combination with 5-FU/leucovorin compared to the control arm resulted in a hazard ratio (HR) of 0.57 (95% confidence interval [CI] = 0.41–0.80, P = .0009).

In the per-protocol population (patients who received 80% of the protocol-defined dose and were able to remain on treatment for at least 6 weeks), MM-398 in combination with 5-FU/leucovorin demonstrated superior overall survival and tumor control to the control arm of 5-FU/leucovorin alone. In the per-protocol analysis, median overall survival for the combination therapy arm was 8.9 months vs 5.1 months in the control arm (stratified HR = 0.47, 95% CI = 0.29–0.77, P = .0018).

The significant improvement was also observed in progression-free survival (overall and at 3 months), objective response rate, and CA19-9 tumor marker response for MM-398 in combination with 5-FU/leucovorin.

“On behalf of the global study team, I am privileged to present the expanded analyses of NAPOLI-1 study at the ASCO GI 2015. Such additional analyses further demonstrate the robust survival benefits of the MM-398/5-FU/[leucovorin] combination in metastatic pancreatic cancer patients in the postgemcitabine setting, and this regimen also showed a favorable safety profile,” said Li-Tzong Chen, MD, PhD, Director, Investigator and Attending Physician at the National Institute of Cancer Research, National Health Research Institutes in Taiwan.

NAPOLI-1 Trial Design

NAPOLI-1 (NAnoliPOsomaL Irinotecan) is a randomized, open-label phase III study in patients with metastatic pancreatic cancer who received prior gemcitabine-based therapy. The study evaluated two MM-398 regimens, 80 mg/m2, combined with 5-FU and leucovorin every 2 weeks, and 120 mg/m2 as a monotherapy every 3 weeks. Each arm was compared to a control arm of 5-FU and leucovorin.

A total of 417 patients were randomly assigned across the three arms. Each MM-398 regimen was compared against the control arm on the primary endpoint of overall survival. Patients were enrolled at 76 sites of the 105 sites initiated in North America, South America, Europe, Asia, and Australia.

About MM-398 (PEP02)

MM-398 is being developed by PharmaEngine and Merrimack Pharmaceuticals in Asia and Europe. In September 2014, Merrimack licensed the rights to MM-398 outside of the United States and Taiwan to Baxter. In 2011, MM-398 received Orphan Drug designation from the U.S. Food and Drug Administration (FDA) and European Medicines Agency for the treatment of pancreatic cancer. In addition, MM-398 received Fast Track designation for postgemcitabine metastatic pancreatic cancer from the US FDA in November 2014.

The NAPOLI-1 study was sponsored by Merrimack. 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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