Dr. O'Hara on the Rationale for APX005M in Combination With Chemotherapy and Nivolumab in Pancreatic Cancer

Mark H. O’Hara, MD, assistant professor of medicine, Hospital of the University of Pennsylvania, discusses the rationale for evaluating APX005M in combination with chemotherapy and nivolumab (Opdivo) in pancreatic cancer.

APX005M is a CD40 agonist of the immune system, explains O’Hara. This agent was tested in combination with gemcitabine, nab-paclitaxel (Abraxane) and nivolumab in a phase Ib study in treatment-naïve patients with pancreatic cancer. Investigators believed that the use of chemotherapy would increase the production of tumor antigens, after which the use of APX005M would lead to priming of the immune system with a greater capacity for response.

A lot of the rationale for the trial stemmed from preclinical work that showed that the combination of both chemotherapy agents and the CD40 agonist led to increased tumor destruction reliant on T cells, explains O’Hara. The addition of the PD-1 inhibitor also led to increased survival in mice, he added.