While novel treatments have been rapidly emerging onto the drug scene, new treatment options for pancreatic cancer have fallen behind.
But now, according to OncLive’s interview with Dr. P.A. Philip, Wayne State University, patients have a new outlook. The FDA has given Rafael Pharmaceutical the green light to initiate phase 3 clinical trials of devimistat to treat pancreatic cancer, giving patients reason for hope.
Dr. Philip told OncLive that devimistat (CPI-613) causes cancer cells to become sensitive to a range of chemotherapeutic agents. According to Dr. Philip, AVENGER 500 is the only phase 3 trial of its kind in the world.
The doctor went on to say that the tumors’ shrinkage was what they had expected from chemotherapy and pointed out that the shrinkage occurred with lower doses of the drugs. He said that a response such as this in pancreatic cancer had only been rarely accomplished in the past with chemotherapy as a single agent.
The treatment was reported as being well-tolerated with no deaths attributed to adverse events. There were no patients’ deaths related to treatment.
About AVENGER 500® Phase 3 Trial To Treat Pancreatic Cancer
The international AVENGER 500® phase 3 trial (NCT03504423) has reached full enrollment with the participation of five hundred patients between the ages of eighteen and seventy-five. The study is an open-label trial with doctors and patients aware of the dose, name of the drug, and who will receive the drug.
Subjects will receive 500 mg/m2 of devimistat on the first and third day of a fourteen-day cycle.
The trial’s primary endpoints are the overall response rate (ORR) as well as progression-free survival (PFS). A central review will determine ORR within the first twelve cycles. The secondary endpoints are overall survival (OS), safety, and durability of patients’ response.
CPI-613 added to modified FOLFIRINOX is being investigated and compared to standard FOLFIRINOX as a single agent. The drugs will be administered to patients who have been diagnosed with metastatic adenocarcinoma of the pancreas. The team is looking for a complete response to the drug and/or the disappearance of cancer.
Interim results of the trial are slated to be released after 167 participants become evaluable for a response.
About Devimistat (CPI-613)
CPI-613 was developed by Rafael Pharmaceuticals and was specifically designed as an orphan drug to treat acute myeloid leukemia, pancreatic cancer, myelodysplastic syndrome, peripheral T-cell lymphoma, soft tissue sarcoma, and Burkitt’s lymphoma.
CPI-613 plays a role in cancer cell energy metabolism. The agent has been developed to target the mitochondrial tricarboxylic acid (TCA) cycle of cancer cells. One of the key characteristics of cancer cells is mutations in the metabolic enzymes of the TCA cycle.
Tumor cells have many genetic and metabolic changes that contribute to their malignancy and growth. There is a strong connection between cancer and metabolism.
CPI-613 blocks enzymes associated with cancer cell metabolism. The enzymes can be found in the mitochondria where nutrients are converted into energy. This occurs when cells are functioning normally.
However, the mitochondria may shift their function due to changes in the regulation of the proteins in cancer cells. When this occurs nutrients will be converted to form new cancer cells.
Researchers are investigating CPI-613’s ability to inhibit mitochondria in cancer cells. This would preclude the cancer cells’ ability to survive chemotherapy.
About Pancreatic Cancer
Pancreatic adenocarcinoma diagnoses are on the rise. This fatal disease is slated to be the second cause of cancer death in some areas. To learn more about this cancer, click here.
Fast track designation covers a broad range of serious conditions. The designation has been designed to expedite the review of critical new drugs.
About the ARMADA 2000 TRIAL, An AML Regimen
The ARMADA 2000 clinical trial (NCT 03504410) involves the investigation of CPI-613 plus high-dose mitoxantrone and cytarabine as a treatment for AML. This combination is compared with high-dose mitoxantrone and cytarabine.
Patients must be fifty years of age or older with relapsed and refractory (resistant to treatment) AML and not eligible for aggressive chemotherapy.
The trial is specifically focused on whether the CPI-613 combination causes cancer cells to be more sensitive to chemotherapy. The increase in sensitivity would translate into lower doses of chemotherapy for patients and therefore fewer side effects.
As noted, the main goal of the trial is to compare chemotherapy regimens with the CPI-613 combination. The team will determine whether the new drug is responsible for an increase in a complete response or the elimination of all signs of cancer.
A second measure includes complete response rates and overall survival. These data may or may not include full recovery of blood cell counts.
A total of five hundred subjects are set to be recruited with interim findings slated to be released in October 2022.
The EMA, which is the FDA’s European counterpart, has also granted Rafael orphan drug status for CPI-613 for both pancreatic cancer and AML.
The orphan drug status follows an FDA fast track designation for CPI-613 to treat metastatic pancreatic cancer.