Abstract I27: Pancreatic cancer immunotherapy: Moving forward

Abstract

Abstract As immunotherapy becomes a pillar of therapy for some of our patients with solid tumors, the role in pancreatic cancer remains limited despite a multitude of studies testing combinations of novel agents. The landscape of effective systemic therapies to date is limited to combination chemotherapy and PARP inhibitors in a small subset of patients with germline BRCA mutations. We also currently await the phase 3 data testing PEGPH20, a recombinant hyaluronidase, in combination with gemcitabine and nab-paclitaxel. These more recent studies were developed from studying and targeting the unique characteristics of pancreatic cancer based on the genomics, chemotherapy sensitivity, and tumor microenvironment characterization. Research in combination strategies that include immunotherapy agents is continuing to build on what we are actively learning about the genomics, epigenetics, RNA expression, and tumor microenvironment characterization specific to pancreatic cancer biology. Historically, studies involving single-agent immunotherapy approaches to pancreatic cancer have yielded responses in 0 or 1 patient. More recent studies with combination immunotherapy approaches with and without chemotherapy have increased the number of responders, but responses still occur in only a handful of patients except in studies where the agents are combined with chemotherapy, which may be the driver of the responses. Further characterization of the responders may help us to identify predictive biomarkers, and further understanding of the nonresponders can help drive future directions. This lecture will review the current strategies that have made it into clinical trials or strategies being proposed for further study and preliminary data that are available to support continued development. Advances in increasing T-cell delivery such as cell-based or neoantigen vaccines, modified T cells, viral and bacterial vectors, or bispecific antibodies may increase immune cell infiltration into tumors while new agonist agents promoting immune cell activation or antagonist targeting negative checkpoints or immune cell populations can increase the probability of success. The combination of increasing the number of responders and better understanding those subsets will eventually lead to additional treatment options for our patients. Citation Format: Dung T. Le. Pancreatic cancer immunotherapy: Moving forward [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I27.