Endoscopic Photodynamic and Combination Therapy for Local and Metastatic Pancreatic Tumors

Project Leader: Vinay Chandrasekhara

The goal of Project 2 is to transform the management of pancreatic ductal adenocarcinoma (PDAC), a devastating disease that is most often diagnosed late when curative therapies are no longer possible. Treatment is required for patients with PDAC that are unresponsive or intolerant to chemotherapy which represents a sizeable number of patients. Our strategy is to target the disease using a combination of PDP and immune checkpoint inhibitor therapy. Here, we will utilize our experience in radiological and endoscopic (EUS) guided PDT treatment of PDAC. When a tumor is not accessible endoscopically, a radiologically guided fiberoptic illumination device will be used.

Verteporferin will be utilized as the photosensitizer and an endoscopic optical diffusing fiber will illuminate the tumor with the help of ultrasound or CT for guidance. Pembrolizumab, an anti-PD1 monoclonal antibody, will be administered within 2 weeks post-PDP and will continue to be administered until there is evidence of disease progression. Progression-free survival (PFS), overall survival (OS), and tumor response of both primary and metastatic sites will be measured via CT scan. Core C will be responsible for analyzing these images using novel techniques such as radiomics and will determine tumor necrosis, shrinkage and changes in the tumor and stromal properties.

Systemic immune activation after PDP will be analyzed with peripheral blood samples using immunoscore analysis with FACS at Mayo Clinic. Regional lymph nodes will be biopsied and studied for anti-tumor immune stimulation post-PDP with the use of EUS. Myeloid phenotype changes will be studied, notably including T-lymphocytes.

If successful, this study will be the first to demonstrate the effect of PDP in combination with immune checkpoint inhibitors in human PDAC. This project would also increase the number of patients indicated for ICI by extending patient eligibility to PDAC tumors without microsatellite instability which represents the majority of pancreatic cancer patients.