A multinational phase II study of PEP02 (liposome irinotecan) for patients with gemcitabine-refractory metastatic pancreatic cancer.

Abstract

4069 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved pharmacokinetics and tumor biodistribution of both CPT-11 and its active metabolite-SN38 compared to the free form drug. PEP02 has showed encouraging safety and efficacy in various tumor types, including significant antitumor activity in a human pancreatic cancer L3.6pl orthotopic nude mouse xenograft model. In previous phase I studies, PEP02 either alone or in combination with 5-FU/LV demonstrated prolonged disease control in 5 of 7 (71%) patients (pts) with gemcitabine (GEM)-refractory advanced pancreatic cancer (PC). This phase II study aims to evaluate PEP02 monotherapy as second-line treatment in pts with metastatic, GEM-refractory PC. Methods: Pts were eligible if they had metastatic pancreatic adenocarcinoma, KPS ≥ 70, and progressed following one line of GEM-based therapy. Treatment consisted of PEP02 120 mg/m2 administered as a 90-minute infusion every 3 weeks. A Simon’s 2-stage design was used with 16 pts in the first stage and 39 pts in total; primary objective was 3-month survival rate (OS3-month). Results: Between March 2009 and September 2010, 41 pts were enrolled at 3 centers in the U.S. and Taiwan. Characteristics for the 40 ITT pts: 19 M/21 F; age 39-82 yrs; 25 Asian/15 Caucasian, KPS 100/90/80/70: 7/16/7/10. Mean number of treatment cycles is 5.25 (range, 1-26). Objective response rate is 5% and disease control rate (minor response + stable disease > 2 cycles) is 50%. 10 (30.3%) of 33 pts with elevated baseline CA19-9 have had > 50% biomarker decline. The OS3-month is 75%, with median progression free survival (PFS) and OS of 9 and 21.6 weeks, respectively. There was no correlation between duration of prior GEM-based therapy and survival after PEP02 treatment. The most common G3/4 adverse events are: leucopenia/neutropenia, anemia, diarrhea, and fatigue. Conclusions: This study has already met its primary endpoint (predicted OS3-month ≥ 65%). PEP02 appears to have both activity and tolerable side effects for pts with metastatic, GEM-refractory PC, and represents a promising option for this pt population with few options.