Pancreatic cancer is the fourth most common cause of cancer death worldwide with nearly 300,000 deaths per year. Around 50,000 new cases are diagnoses yearly in the US alone. Patients’ life expectancy is dramatically low with only 20% of early spotted cases surviving for five years after initial diagnosis and these numbers drop drastically for cases diagnosed at more advanced stages. A new drug application has been recently submitted for MM-398 in combination with standard therapy for patients with metastatic pancreatic cancer potentially brightening their clinical prospects.
Pancreatic cancer is such a deadly disease because the signs and symptoms that accompany it may not appear until it has spread to other sites of the body, at which point an aggressive treatment is usually required. Where possible, surgical removal of the tumor is performed, followed up by administration of systemic chemotherapeutics such as gemcitabine. Unfortunately, many patients’ tumors progress following treatment, making it necessary to develop novel, safer and more effective options for therapy.
In 2011 the FDA and the European Medicines Agency granted to MM-398 orphan drug designation for metastatic pancreatic cancer following encouraging results from a single arm Phase II trial showing that 40 pancreatic cancer patients on the drug had a median overall survival of 22.4 weeks and one in 5 survived for more than a year.
MM-398 (also known as nal-IRI) is a nanoliposomal encapsulation of irinotecan, developed and marketed by Merrimack and Baxter. Once cancer cells take up the drug, they rapidly convert it into its active form (SN-38) which functions by inhibiting DNA replication and transcription. The liposomal encapsulation technology chosen for irinotecan delivery allows a higher drug uptake within tumor cells and keeps the compound stable in circulation for a longer time compared to standard irinotecan administration.
In November 2014, the FDA has granted fast track designation to MM-398 for patients with gemcitabine refractory metastatic pancreatic cancer. The application was based on promising results from the Phase III open label NAPOLI-1 study, which enrolled 417 patients who were randomly distributed into three arms of the trial: the MM-398 monotherapy arm, the control arm in which patients were given the standard of care therapy consisting of 5-FU with leucovorin, or the combination therapy arm where patients were given MM-398 plus 5-FU and leucovorin. Patients in the combination arm showed marked improvement in overall survival, progression free survival and overall response rate compared to 5-FU and leucovorin alone or MM-398 monotherapy.
MM-398 is currently being explored as a treatment for patients with other types of cancer. In a Phase I study MM-398 combination with cyclophosphamide is being tested for pediatric patients with solid tumors.
Crown Bioscience supports research on pancreatic cancer with a wide range of in vivo and in vitro platforms. Patients derived xenograft (PDX) models are a powerful personalised diagnostic tool and can improve the success of translating novel drug and therapies into the clinic. Our comprehensive and fully annotated collection of PDX models (HuPrime® and PDXact™), many of which are in constant passage, is the world’s largest commercially available. Our PDX collection is large enough to be truly reflective of the patient population and can be used to run HuTrials™, preclinical Phase II-like, human surrogate trials to evaluate your oncology agents. Crown Bioscience can also provides low cost, high throughput in vitro drug efficacy studies by offering a variety of in vitro/ex vivo platforms including our PrimePanel™ cancer cell lines collection, directly derived from our HuPrime PDX models. We have successfully established several pancreatic PrimePanel cell lines as 2D and 3D cultures that can be used for in vitro compound screening.
Contact us at busdev@crownbio.com to talk to our experts about how HuTrials can drive forward your pancreatic cancer research or for more information on our pancreatic PDX and PrimePanel resources.
