Abstract C52: The radioprotector GC4419 enhances the response of PDAC tumors to high dose per fraction radiation exposure

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States, with an estimated 5-year overall survival rate of ~6%. While surgery followed by adjuvant therapy is the standard of care, most patients present with advanced disease. Recent clinical trials have demonstrated that the traditional radiation dose limit of 50.4 Gy to tumors located at the head of the pancreas is not sufficient to generate tumor control at doses tolerable to the jejunum; however, doses exceeding 60 Gy, particularly when delivered as stereotactic body radiation therapy (SBRT), drastically enhance progression free-survival at 2 years. Here, we present evidence that the radioprotector GC4419 (Galera Therapeutics, St. Louis, MO) whose enantiomer, GC4403, has demonstrated radioprotective properties against GI toxicity, sensitizes PDAC cells and xenografts to radiation exposure. Furthermore, combination therapy with immune oncology agents targeting the PD-L1 pathway enhanced the response of Panc02 tumors (syngeneic to C57.BL/6 mice) to combined radiation and immune therapy. These results present the foundation for a newly initiated dose-escalation clinical trial for treating PDAC tumors with GC4419 and SBRT. Citation Format: Michael D. Story, Brock J. Sishc. The radioprotector GC4419 enhances the response of PDAC tumors to high dose per fraction radiation exposure [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 C52.