Pegcetacoplan in Combination With Modified FOLFIRINOX for the Treatment of Metastatic Pancreatic Ductal Adenocarcinoma

PRIMARY OBJECTIVES: I. To determine the safety oxaliplatin, irinotecan, leucovorin calcium (leucovorin), and fluorouracil (mFOLFIRINOX) in combination with pegcetacoplan in patients with newly diagnosed metastatic pancreatic ductal adenocarcinoma (PDAC). (Phase I) II. To identify preliminary signals of clinical efficacy of the study treatment. (Phase II) SECONDARY OBJECTIVES: I. To evaluate the incidence of major thrombotic events and complications. II. To evaluate the efficacy (overall response rate, overall survival, disease control rate) of the combination treatment in the study population. EXPLORATORY OBJECTIVES: I. To evaluate the effect of therapy on circulating biomarkers of neutrophil extracellular traps (NETs), endothelial cell injury, and cytokine responses. II. For patients who agree to an optional on-treatment biopsy, the effects of therapy on innate and lymphocyte responses in the tumor microenvironment (TME) will be assessed. III. To assess the ability of the combination to control or prevent malignant effusions (pleural or ascites fluid). IV. To evaluate the pegcetacoplan levels in peripheral blood and other biological specimens. OUTLINE: Patients receive pegcetacoplan intravenously (IV) over 30 minutes on day 1 of cycle 1 and prior to mFOLFIRINOX and self-administered subcutaneously (SC) thrice weekly (every 2 days), when due on days in the office it will be given IV over 30 minutes prior to mFOLFIRINOX. Patients receive oxaliplatin IV over 2 hours, irinotecan and leucovorin IV concurrently over 90 minutes, and fluorouracil IV over 48 hours on day 1 of each cycle. Cycles repeat every 14 days for up to 8 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo ascites, pleural fluid (if present) and blood sample collection and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Additionally, patients may undergo tumor biopsy throughout the study. After completion of study treatment, patients are followed up at 30 days then every 3 months for up to 3 years.