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MM-398 PII results...

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.

http://merrimack.phpstage2.genuineinteractive.com/sites/merrimack.phpstage2.genuineinteractive.com/files/documents/ASCO%202011%20MM-398%20Panc%20AKo.pdf

MM-398 PIII ...

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.

http://clinicaltrials.gov/ct2/show/record/NCT01494506