Timely article :-)! I am back in MACK and AVEO, added ARIA significantly, also started SGYP due to major weakness from all four of them recently. MACK will have data points from several ph2 and ph3 trials in next 6-8 months.
Background: PEP02 (MM-398) 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 shown encouraging preclinical activity 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 (APC). This phase II study aims to evaluate PEP02 monotherapy as 2nd-line treatment in pts with metastatic, GEM-refractory APC.
Methods: Pts were eligible if they had metastatic pancreatic adenocarcinoma, KPS = 70, and progressed following one line of GEM-based therapy. Treatment consisted of intravenous injection of PEP02 120 mg/m2 over 90 minutes every 3 weeks. A Simon’s 2-stage design was used with 16 pts in the 1st 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: 7/17/6/10. Until end of May, 2 pts are still undergoing PEP02 treatment and 7 pts are still alive. Mean number of treatment cycles is 5.4 (range, 1-26). Objective response rate is 7.5% and disease control rate is 47.5%. Of the 25 pts who were evaluable for clinical benefit response (CBR), 5(20%) achieved CBR. Eleven (34.4%) of 32 pts with elevated baseline CA19-9 had > 50% biomarker decline. The OS3-month is 75%, with median progression free survival (PFS) and OS of 9.6 and 22.4 weeks, respectively. There was no correlation between duration of prior GEM-based therapy and survival after PEP02 treatment. The most common G3/4 toxicities are: neutropenia (30%), leucopenia (22.5%), anemia (15%), diarrhea (7.5%), and fatigue (7.5%).
Efficacy PEP02 achieved the primary endpoint of 3-month survival rate of 75% in metastatic pancreatic cancer patients who failed prior gemcitabine therapy. Median survival after PEP02 treatment was approximately 5.2 months, and more than 20% patients had significantly extended survival. Almost 30% of patients received PEP02 for 6 months or more. Significant tumor shrinkage and CA19-9 decline, as well as sustained clinical benefit, were noted in a number of patients.
Safety Grade 3/4 toxicities were primarily hematologic in nature, with non-hematologic toxicities (GI, fatigue) occurring in less than 10% of patients. Acute cholinergic symptoms were rarely reported.
Conclusion Based on these results, PEP02 deserves consideration for evaluation in phase III study designed for the treatment of refractory metastatic pancreatic cancer.
Brief Summary The study is an open label, randomized phase 3 study of MM-398 with or without 5-Fluorouracil (5-FU) and Leucovorin (also known as folinic acid), versus 5-FU and leucovorin in metastatic pancreatic cancer patients who have progressed on prior gemcitabine based therapy.
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