A New Look at Pancreatic Cancer with Metabolism-based Treatment

Rafael Pharmaceuticals, Inc., a clinical stage company and leader in the field of cancer metabolism-based therapeutics, announced today, the initiation of a Phase I clinical trial of CPI-613 in combination with chemotherapeutic agents, gemcitabine and nab-paclitaxel, for patients with locally advanced or metastatic pancreatic cancer. The study will be conducted in collaboration with Atlantic Health System. CPI-613 is a first-in-class drug with a unique mode of action and is Rafael’s lead altered energy metabolism directed (AEMD) drug candidate. The drug is designed to disrupt the altered energy-production pathways in cancer cells by targeting their mitochondrial metabolism.

The primary aim of the study is to establish the maximum tolerated dose of CPI-613 when given in combination with gemcitabine/nab-paclitaxel for patients with locally advanced or metastatic pancreatic cancer.

Secondary aims include:

(1) To describe the safety profile for the gemcitabine/nab-paclitaxel/CPI-613 combination.
(2) To determine the clinical activity of gemcitabine/nab-paclitaxel/CPI-613 in metastatic pancreatic cancer as measured by tumor response rate (RR) by RECIST criteria, progression-free survival (PFS), and overall survival (OS).

Encouraging results observed in earlier trials, including Phase I data from a trial led by Angela Alistar, MD that was recently published in The Lancet Oncology, demonstrated the preliminary efficacy of CPI-613 in combination with modified FOLFIRINOX (a multidrug treatment for advanced pancreatic cancer) in patients with metastatic pancreatic cancer. These results support further evaluation of CPI-613 in this indication.[1] The safety profile of CPI-613 in earlier trials, which shows the drug to be well tolerated, provides further support for evaluation of CPI-613 in combination with other drugs to maximize benefit.

In 2013, the MPACT study, a multinational, phase III clinical trial comparing gemcitabine/nab-paclitaxel to gemcitabine alone, demonstrated an improved median survival of 8.5 months as compared with 6.7 months for gemcitabine monotherapy (p=0.000015). While some clinical benefit was shown, these outcomes also highlight the need for new combination strategies to improve upon the outcomes seen with gemcitabine/nab-paclitaxel in the treatment of metastatic pancreatic cancer.

Dr. Alistar, medical director of GI Medical Oncology at the Carol G. Simon Cancer Center of Morristown Medical Center, Atlantic Health System, and the Principal Investigator for this trial, remarked, “Strategies to enhance our current standard of care options are sorely needed in pancreatic cancer. Due to the low toxicity profile of CPI -613 as a single agent, I anticipate good tolerance in combination with the gemcitabine/nab-paclitaxel regimen. I am excited to be able to offer this novel option to our patients with pancreatic cancer. Targeting metabolism in pancreatic cancer has a strong scientific rationale.”

Sanjeev Luther, Rafael Pharmaceuticals’ Chief Executive Officer, commented, “Our company’s motto of “One Patient at a Time” is especially relevant in this situation. Patients with a low tolerance for toxicity may not be eligible for the FOLFIRINOX combo. We believe that the gemcitabine/nab-paclitaxel regimen has the potential to be a potent treatment with less toxicity.”