Phase 1 Trial Of Gemcitabine/Nab-Paclitaxel In Combination With The Autophagy Inhibitor Hydroxychloroquine In Previously Untreated Patients With Metastatic Pancreatic Adenocarcinoma.

e15213 Background: Autophagy is important for sustained growth of pancreatic cancer (PDAC) human cell lines and xenograft models. Inhibition of autophagy with drugs such as chloroquine results in tumor growth retardation and increased survival in preclinical models. Hydroxychloroquine (HCQ), an antimalarial drug that inhibits autophagy, has acceptable toxicity at maximal doses in cancer patients (pts). We performed a phase 1/2 study of HCQ in combination with gemcitabine/nab-paclitaxel in patients with metastatic PDAC and here we report the initial phase 1 results. Methods: We enrolled 24 pts with untreated stage IV PDAC - 17M/7F, median age 65 – at three sites (Penn, JHU, TGEN). Two dose levels of HCQ were investigated: 400mg (7 pts) and 600mg (17 pts) BID. Results: The most common adverse events (AEs) were fatigue, nausea, anorexia, and neuropathy. Grade 4 toxicities, including elevated glucose, AST/ALT, and Tbili (1 each), sepsis (2), nausea (1), neutropenia (1), pneumothorax (1), bowel obstruction (1)...