The Abramson Cancer Center at the University of Pennsylvania will serve as a second trial site in the Phase 1 study of CPI-613 for T-cell lymphoma patients, according to Rafael Pharmaceuticals, the drug’s developer.
The trial is focused on the safety and finding the best dose of CPI-613, given together with bendamustine, in patients who are resistant to therapy or whose disease worsened following a successful initial therapy.
“I am excited to launch this study at Penn with CPI-613 in combination with bendamustine for patients with relapsed or refractory T-Cell Lymphoma who currently do not have adequate treatment options,” Sunita Nasta, MD, who will lead the trial at the Abramson Cancer Center, said in a news release.
Nasta is an associate professor of clinical medicine in the Division of Hematology Oncology at the Perelman School of Medicine at the University of Pennsylvania, as well as the study’s principal investigator.
“Our motto, ‘To Save A Life Is To Save A Universe,’ illustrates our desire to develop potential treatments for patients with severe unmet clinical need,” said Sanjeev Luther, Rafael Pharmaceutical’s president and CEO.
“We are fortunate to have the opportunity to activate the second site of this T-Cell Lymphoma trial with Dr. Nasta as its Principal Investigator at the University of Pennsylvania,” Luther added.
The trial in ongoing at the first site, at the Comprehensive Cancer Center at Wake Forest Baptist Medical Center in Winston-Salem, North Carolina.
Mitochondria, the energy-producing “powerhouses” of cells, act as a central hub for cell survival, cell metabolism, and pathways for cell death. But mitochondria also play a part in tumor cell growth and survival in otherwise harsh environments, such as during cancer treatments.
Considering the many roles of mitochondria in tumor formation, targeting mitochondria may present an effective approach to treating cancer.
The first-in-class investigational therapy CPI-613 specifically targets enzymes in the mitochondrial respiratory processes of cancer cells. Ultimately, CPI-613 shuts down the cancer cells’ powerhouses, depriving cells of the energy they need to survive.
One of the advantages of this experimental therapy is that by attacking the process of cellular respiration, CPI-613 increases the sensitivity of cancer cells to a variety of standard chemotherapeutic agents, allowing for a more effective chemotherapy approach than with other cancer drugs.
In the open-label, dose-escalation Phase 1 trial (NCT02168140), researchers will investigate CPI-613 in combination with the chemotherapy bendamustine as a treatment for adult patients with relapsed or refractory T-cell non-Hodgkin’s lymphoma or Hodgkin’s lymphoma. Researchers plan to enroll 14 subjects.
Patients will receive CPI-613 directly into the vein on days one to four of week 1, and on days one and four of weeks 2 and 3. Participants will also receive bendamustine on days four and five of week 1. The treatment is repeated every four weeks for up to six courses in the absence of disease worsening or unacceptable toxicity. After the therapy plan is completed, patients are followed up every two months.
This study’s primary endpoint is to determine CPI-613’s maximum tolerated dose. Secondary endpoints include response rate, disease control rate, overall survival, progression-free survival (time elapsed between treatment initiation and cancer progression or death from any cause), and combined-therapy safety.
So far, scientists have studied 10 patients at the Wake Forest Baptist Medical Center in North Carolina. Of these, seven were evaluated for treatment effectiveness.
Interim results showed an overall response rate of 86%, including 43% complete responses. The findings were first presented at the American Society of Hematology (ASH) Annual Meeting in 2016.
“Although the number of patients was small, these results warrant continued investigation with this novel combination in the poor-risk patient population,” said Zanetta Lamar, MD, the principal investigator of this trial at Wake Forest Baptist.
The Abramson Cancer Center now joins the Comprehensive Cancer Center of Wake Forest University in assessing CPI-613’s potential in T-cell lymphomas.
The U.S. Food and Drug Administration has granted CPI-613 orphan drug designation to advance it as a potential treatment for Burkitt’s lymphoma, pancreatic cancer, acute myeloid leukemia, myelodysplastic syndromes, and peripheral T-cell lymphoma.