A diagnosis of metastatic pancreatic cancer is almost invariably a death sentence. “Even with the therapeutic advances of FOLFIRINOX (drug combination), and gemcitabine/nab-paclitaxel, responses are still limited to less than 30% of patients,” said Dr. O’Hara, who presented the data for APX005M, “And the median overall survival (OS) is still less than one year.” Further, despite the recent Nobel Prize accolades for the efficacy of so-called checkpoint inhibitors, nothing has changed. “No responses to single agent checkpoints have been noted,” said O’Hara, adding that a recent investigation of checkpoints combined with chemotherapy achieved only, “modest results.”
The target of APX005M is a molecule called CD40, which is not an immunologic brake pedal, as are the approved checkpoint agents to date, but rather, an immune system stimulant, which, among other activities, helps to prime and activate antigen presenting cells, the critical command posts for the mobilization of tumor-killing T cells.
In the present phase 1b study, Dr. O’Hara investigated the use of two different doses of the CD40 agonist, APX005M, combined with gemcitabine/nab-paclitaxel, +/- nivolumab (an anti-PD1 inhibitor) in four cohorts of treatment-naïve patients with metastatic pancreatic ductal adenocarcinoma. The primary and secondary endpoints were safety and efficacy, respectively (N=30).