The FDA has granted a priority review for MM-398 as a second-line treatment for metastatic pancreatic cancer after the drug demonstrated improved survival.
The US Food and Drug Administration (FDA) has granted a priority review for MM-398 as a second-line treatment for metastatic pancreatic cancer after gemcitabine-based therapy. MM-398 is comprised of irinotecan encapsulated in liposomal particles with a long half-life. An approval decision is expected by October 24.
The application is based on the 417-patient NAPOLI-1 trial, an open-label, phase III study that showed that the addition of MM-398 to 5-fluorouracil (5-FU) and leucovorin significantly improved overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) compared with the doublet therapy of 5-FU and leucovorin.
The median OS was 6.1 months in the triple-combination arm compared with 4.2 months with 5-FU and leucovorin alone (P = .012). The median PFS was 3.1 months for the triple combination vs 1.5 months with the control arm (P = .0001). The ORR was 16% in the triple-combination arm compared with 1% in the control arm (P < .001).
In the combination arm, MM-398 was administered intravenously at 80 mg/m2 before the administration of 5-FU at 2,400 mg/m2 and racemic leucovorin at 400 mg/m2 every 2 weeks.
The study also tested the efficacy of single-agent MM-398 but there was no statistically significant survival advantage compared with the control arm (median OS of 4.9 months vs 4.2 months, respectively; P = .5545).
The most common grade 3 or higher adverse events in the triple-combination arm were neutropenia (20%), fatigue (14%), diarrhea (13%), vomiting (11%), nausea (8%), asthenia (8%), and abdominal pain (7%). Thirty-nine percent of patients had dose reductions and 72% had dose delays due to adverse events. Thirteen percent of patients discontinued therapy compared with 10% in the control arm.
The European Medicines Agency (EMA) is also currently reviewing the MM-398 application based on these results.
The trial is the first to demonstrate a significant survival benefit in second-line pancreatic cancer treatment, according to the announcement by Merrimack Pharmaceuticals. There are currently no targeted agents or immunotherapies approved for the treatment of advanced pancreatic cancer.
Results from the NAPOLI-1 trial were originally presented at the European Society for Medical Oncology (ESMO) World Congress on Gastrointestinal Cancer in June 2014. There was also an updated analysis of the trial at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in January of this year.