FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma

PRIMARY OBJECTIVES: I. To establish the safety, schedule, and dosing of DDX5 degrader FL118 (FL118) in patients with advanced pancreatic ductal adenocarcinoma (PDAC). II. To determine the pharmacokinetics (PK) of FL118 in patients with advanced PDAC. SECONDARY OBJECTIVES: I. To determine the pharmacodynamics (PD) of FL118 in patients with advanced PDAC. II. To determine the preliminary antineoplastic efficacy of FL118 in patients with advanced PDAC. EXPLORATORY OBJECTIVES: I. To evaluate biomarkers predictive of response or resistance. II. Evaluate changes in the tumor microenvironment. III. To determine the significance of somatic and germline DNA damage repair mutations as predictive biomarkers of antineoplastic activity. OUTLINE: This is a dose-escalation study of FL118 followed by a dose-expansion study. Patients receive FL118 orally (PO) on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial. Patients may optionally undergo biopsy at screening and on study. After completion of study treatment, patients are followed up at 30 days and then every 3 months for up to 12 months.