UC Davis Comprehensive Cancer Center is partnering with TargaGenix and Northeastern University to study pancreatic ductal adenocarcinoma (PDAC). The often-lethal cancer has an average five-year survival rate of less than 11%. The academic-industry partnership will receive nearly $3 million over five years thanks to National Institutes of Health (NIH) funding through its R01 grant program. The NIH gives R01 grants only to mature research projects driven by strong preliminary data.

The team will develop a treatment based on the novel chemotherapy TGX-1214, in combination with cancer immunotherapy. The researchers expect that by the end of the study, this will become part of a new treatment option for PDAC patients.

PDAC accounts for more than 90% of pancreatic cancer cases. It is usually diagnosed at a late stage by which point the disease has spread to other organs. Symptoms often are common and non-specific, such as weight loss and lack of appetite. By the time symptoms appear, the disease is at a late stage, making it inoperable and incurable.

Current challenges in treating pancreatic cancer

gerardo mackenzie
Gerardo Mackenzie
Edward Kim

“Surgery, which offers the only realistic hope for a cure, is a viable option in only a limited number of patients, and current chemotherapy and radiation therapy offer limited or no benefit at all,” UC Davis pancreatic cancer researcher Gerardo Mackenzie said.

Mackenzie is an associate professor in the Department of Nutrition. He and Edward J. Kim, oncologist and medical director of the cancer center’s Office of Clinical Research, are the UC Davis principal investigators for the study.

“The current chemotherapy combinations used to treat PDAC have marginally improved survival outcomes. The average survival in advanced disease is still less than a year. The limited benefit of these therapies, unfortunately, comes at the cost of significant toxicities, including suppressed immune system, fatigue, nausea, diarrhea and nerve damage, limiting their use to patients with relatively preserved function,” Kim said, “And most patients still ultimately relapse and progress.”

In addition, studies show that new immuno-oncology agents, such as anti-PD-1 or anti-CTLA-4 are not effective in PDAC. This is partly because the drugs create a microenvironment that weakens the immune system and prevents cancer-fighting T-cells from entering the tumor mass.

“That’s why there is a critical unmet need to develop better therapeutic options for aggressive and refractory PDAC,” said Mansoor Amiji, distinguished professor of pharmaceutical sciences and chemical engineering at Northeastern University. Amiji is Northeastern’s principal investigator for the study and the scientific advisor for TargaGenix.

“We are pleased to collaborate with colleagues at UC Davis and TargaGenix on this research,” Amiji said. “Based on the high mortality associated with pancreatic cancer, the opportunity for us to develop TGX-1214 for this dreadful disease is especially exciting.”

Promising TGX-1214 combination strategy for the treatment of advanced pancreatic cancer

The team will leverage the multidisciplinary expertise of scientists and clinicians to develop an effective treatment based on the combination of TGX-1214 and immune checkpoint inhibition, which block proteins called checkpoints. Immune checkpoint inhibitors are effective in helping T cells kill cancer cells.

Multiple animal studies have previously indicated that TGX-1214 is safe and effective. In preliminary studies, TGX-1214 strongly inhibited pancreatic cancer growth, with complete tumor regression in two pre-clinical models of pancreatic cancer.

The long-term goal of the research is to develop safe and effective treatment strategies for PDAC to test in clinical trials that will become available for patients.