Even after chemotherapy, radiation, and surgery, pancreatic cancer often returns. When it does, prognosis is poor. A University of Colorado Cancer Center clinical trial offered at UCHealth locations across Colorado is testing a promising new immunotherapy drug to prevent the recurrence of pancreatic cancer after surgery.

“Right now, after a patient has finished chemotherapy, radiation, and then had a successful surgery for pancreatic cancer, there’s not much to do other than surveillance with periodic blood tests and imaging. But many people want to be proactive in trying to keep it from coming back since it is such an aggressive cancer. This trial offers patients the possibility of doing immunotherapy in addition to observation,” says UCHealth Medical Oncology Chief Fellow, Gentry King, MD.

The trial (NCT03038477) tests the immunotherapy drug durvalumab as maintenance therapy in patients who have undergone successful surgery to remove pancreatic cancer. The trial is randomized such that some patients receive the drug once a month for a year following surgery, while others receive standard-of-care treatment, which, in this case, is carefully monitoring for tumor growth. For most patients, side effects are predicted to be minor. In an effort to make cutting-edge cancer care available beyond the Denver metro area, this is the first clinical trial offered at UCHealth locations across the state, including Poudre Valley Hospital in Fort Collins, Memorial Hospital in Colorado Springs, and Lone Tree Health Center, in addition to University of Colorado Hospital on the Anschutz Medical Campus in Aurora.

As an “investigator-initiated” clinical trial, the rationale for the trial comes from the basic research and clinical observations of researchers themselves, specifically from work by CU Cancer Center in collaboration with Johns Hopkins University. Basically, many cancers coat themselves in a protein called PD-L1 to deactivate the immune system. The body’s T cells that would otherwise recognize and attack cancer, see cancer cells’ “white flag” of PD-L1 and stop their attack. The drug durvalumab is one in a class of PD-L1 inhibitors, tearing down cancer cells’ PD-L1 white flags and thus clearing the way for the immune system to target cancer cells.

Research at CU and Hopkins shows that after being treated with chemotherapy and radiation, pancreatic cancer cells even more dramatically over-express PD-L1. This implies that using durvalumab to silence the action of PD-L1 could be effective against this cancer.

The drug earned FDA approval to treat some cases of bladder cancer and is in phase 3 clinical trials for use in some lung cancers.

“The concept is that chemotherapy and radiation may make pancreatic cancer especially susceptible to immunotherapy. In giving this therapy, when the cancer has already been minimized by chemo, radiation, and surgery, we hope it will continue to act against residual disease in a way that prevents recurrence,” says Wells Messersmith, MD, CU Cancer Center investigator, director of Gastrointestinal Medical Oncology at the CU School of Medicine, and the trial’s principal investigator.

King and Messersmith also point out that because the trial takes place after surgery, patients will not need to have any additional tissue removed to study the biological effects of the drug.

“We have the backing of our great immunology core here at the university to help us look in depth at tumors that respond and don’t respond to treatment. By discovering markers that predict response to immunotherapy, we can help deliver treatment to the right patients while also hinting at other drug combinations that would work well in this population,” King says.

If all goes well, the researchers hope to explore the use of durvalumab or other PD-L1 inhibitors in additional pancreatic cancer settings. One strategy is to determine if combining this immunotherapy with chemotherapy and radiation before surgery would increase the shrinkage rate of tumors, making them amenable to resection and ultimately increase cure rates.

“We hope this is a first step in bringing immunotherapy to a population that is very much in need of treatment advances,” Messersmith says.