A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer

A H Ko, M A Tempero, Y-S Shan, W-C Su, Y-L Lin, E Dito, A Ong, Y-W Wang, C G Yeh, L-T Chen, A H Ko, M A Tempero, Y-S Shan, W-C Su, Y-L Lin, E Dito, A Ong, Y-W Wang, C G Yeh, L-T Chen

Abstract

Background: PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer.

Methods: Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ≥70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m(-2) was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS(3-month)).

Results: A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS(3-month) of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively.

Conclusion: PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.

Trial registration: ClinicalTrials.gov NCT00813163.

Figures

Figure 1
Figure 1
Maximum % change from baseline in sum of target lesion diameters (evaluable patients only, n=30). Abbreviations: PD=disease progression; PR=partial response; SD=stable disease.
Figure 2
Figure 2
Kaplan–Meier curves of overall and progression-free survival. Abbreviations: m=months; OS=overall survival; PFS=progression-free survival.
Figure 3
Figure 3
Overall survival (OS) and progression-free survival (PFS) relative to the duration of prior gemcitabine-based therapy. Abbreviations: Gem=gemcitabine; Tx=treatment.

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