FDA Grants Fast Track Designation to CPI-613 in Metastatic Pancreatic Cancer

The FDA has granted a Fast Track designation to CPI-613 for the treatment of metastatic pancreatic cancer.

The FDA has granted a Fast Track designation to devimistat (CPI-613) for the treatment of metastatic pancreatic cancer.1

“Pancreatic cancer is notoriously challenging to treat and long overdue for a new approach,” said Philip A. Philip, MD, PhD, FRCP, professor of Oncology at the Barbara Ann Karmanos Cancer Institute at Wayne State University, in a statement. “We have remained hopeful throughout our pancreatic cancer trials, and now with Fast Track designation, our optimism is further fueled. We believe with this designation, cancer metabolism is truly being propelled forward, with devimistat at the helm.”

The movement in the FDA for devimistat comes on the heels of milestones achieved over the course of 2020. One milestone was reaching the target enrollment in the phase 3 AVENGER clinical trials of devimistat in combination with a modified regimen of folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) as frontline treatment of patients with metastatic pancreatic cancer.

On August 6, 2020, the trial reached 500 patients, making it 1 of the largest phase 3 clinical trials currently available for patients with metastatic pancreatic cancer. The study is being conducted at 75 sites around the world, including in; the United States, South Korea, Israel, Belgium, France and Germany, and others.2

In the experimental arm of the study, patients received devimistat 500mg/m2 by intravenous (IV) infusion in combination with modified FOLFIRINOX. For the chemotherapy regimen, oxaliplatin is administered at 65 mg/m2 by IV infusion, Folinic acid is given at 400 mg/m2 immediately following oxaliplatin, Irinotecan 140mg/m2 is given via IV infusion, fluorouracil at 400 mg/m2 aw bolus then at 2400mg/m2 after treatment with irinotecan and folic acid are complete. Patients in the comparator are given equivalent dosing of FOLFIRINOX.

The primary end point of the AVENGER 500 trial is progression-free survival. The study is also assessing 3 secondary end points which included overall survival, duration of response, and overall response rate.

In order for patients to be granted enrollment into the study, they must be between the ages of 18 and 75 with histologically of cytologically confirmed metastatic stage IV adenocarcinoma of the pancreas. Patients are also required to have an ECOG performance status of 0 or 1, measurable disease per RECIST v1.1, and a life expectancy of at least 3 months.

At baseline screening, patients are required to show adequate hematologic values, hepatic function, renal function, and coagulation function. The criteria also mention that individuals with metastatic pancreatic cancer seeking to join the study should not previously treated for their disease, at least 2 weeks must have passed from any prior surgery with resolution of any sequela, and patients can not have active infection and/or serious infection within the past 30 days prior to randomization in AVENGER 500.

Devimistat could be an important drug for the treatment of pancreatic cancer. The agent targets the mitochondrial tricarboxylic acid (TCA) cycle, a cycle that contributed to multiplication of tumor cells. Currently, devimistat is being investigated in phase 1-3 clinical trials as a potential treatment option for acute myeloid leukemia, myelodysplastic syndrome, peripheral T-cell lymphoma, and Burkitt’s lymphoma, in addition to pancreatic cancer.2,3


1. Rafael Pharmaceuticals receives FDA Fast Track designation for cpi-613® (devimistat) for the treatment of pancreatic cancer. News release. Rafael Pharmaceuticals. November 10, 2020. Accessed November 10, 2020. https://bit.ly/3eIrG8H

2. Rafael Pharmaceuticals achieves target enrollment of 500 patients in pivotal phase 3 trial (AVENGER 500) of CPI-613 ®️ (devimistat) for patients with metastatic pancreatic cancer. News release. Rafael Pharmaceuticals. November 10, 2020. Accessed November 10, 2020.https://bit.ly/3kiLXTt

3. CPI-613® (devimistat). Rafael Pharmaceuticals website. https://bit.ly/32tateA Accessed November 10, 2020.