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e21174 Background: Personalized medicine has become increasingly important in the management of oncology patients. Traditional approaches require a large numbers of unselected patients to enroll on...

237 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 2nd-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 August 2010, 37 pts were enrolled at 3 centers in the U.S. and Taiwan. Characteristics for the first 31 evaluable pts: 13 M/18 F; age 39-82 yrs; 19 Asian/12 Caucasian, KPS 100/90/80/70: 5/14/4/8. Mean number of treatment cycles is 5 (range, 1-22). Disease control rate (minor response + stable disease >2 cycles) is 52%. 8 of 24 pts (33%) with elevated baseline CA19-9 have had >50% biomarker decline. To date, 23/31 pts (74%) have survived > 3 months, with 4 pts still alive after 1 year. Reasons for study discontinuation: 74% progressive disease, 9% drug-related toxicity, 17% other. Preliminary safety data is available for the first stage. Most common G3/4 adverse events included: fatigue (31%), neutropenia (25%), nausea/vomiting (19%), and diarrhea (13%). 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 standard options. [Table: see text]

e13024 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan (CPT-11) that has improved PK and tumor biodistribution of CPT-11 and its active metabolite-SN38 with encouraging safety and tumor response in preclinical studies and a single-agent phase I study. The study is to define the DLT, MTD, and PK of PEP02 when in combination with high-dose fluorouracil/leucovorin (HDFL) in patients (pt) with advanced solid tumors. Methods: Pts who had failed to standard chemotherapy, ECOG PS 0-1 and adequate organ functions, no prior CPT-11, were eligible. PEP02 was given as 90 mins i.v. infusion on D1 in combination with 24-hr infusion of 5FU (2,000 mg/m2)/ LV (200 mg/m2) on D1 and D8, every 3 weeks. Cohorts of 3-6 pts were treated at 60, 80, 100, and 120 mg/m2. PK and PGx samples were collected. Results: A total of 16 pts were enrolled, with 3, 6, 5, and 2 at 60, 80, 100, and 120 mg/m2. DLTs were observed in 4 pts, including 2 each at 100 and 120 mg/m2 dose levels. DLTs were mainly G3 diarrhea...

2565 Background: PEP02 is a novel nanoparticle liposome formulation of irinotecan aiming to enhance tumor localization and improve pharmacokinetic properties of irinotecan and its active metabolite-SN38. The aims of the study are to define the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of PEP02 in patients with advanced refractory solid tumors. Methods: Pts with advanced refractory solid tumors, ECOG PS 0–1, and adequate hematological, hepatic and renal functions were eligible. PEP02 was given as 90mins i.v. infusion, repeated every 3 weeks. The doses would have been escalated from 60, 120, 180 to 240 mg/m2 in a single-patient cohort accelerated titration design. PK samples were collected on days 1, 2, 3, 8 and 21. Results: A total of 11 pts (M/F 1/10; median age 47, range 41–67) were enrolled onto three dose levels, with 1, 6 and 4 pts at dose level I (60 mg/m2), II (120 mg/m2) and III (180 mg/m2), respectively. DLT was observed in 3 pts, including 1 at dose leve...