NCT06206876

FL118 for Treating Patients With Advanced Pancreatic Ductal Adenocarcinoma

First-in-Human Phase I Trial of FL118 in Patients With Advanced Pancreatic Ductal Adenocarcinoma

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Roswell Park Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial tests the safety, side effects, and best dose of FL118 in treating patients with pancreatic ductal adenocarcinoma that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). FL118 is a small anti-tumor molecule that inhibits the expression of multiple cancer-associated anti-apoptotic proteins. An anti-apoptotic protein is a protein that interferes with or inhibits cell death. In adults, apoptosis is used to rid the body of cells that have been damaged beyond repair. Apoptosis also plays a role in preventing cancer. If apoptosis is for some reason prevented, it can lead to uncontrolled cell production that can subsequently develop into a tumor. FL118 has been shown to inhibit or block the proteins that prevent damaged/mutated (genetically changed) cells from dying, and, by doing so, prevent the growth of cancerous cells and tumor development.

Detailed description

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.

Conditions

• Advanced Pancreatic Ductal Adenocarcinoma
• Locally Advanced Pancreatic Ductal Adenocarcinoma
• Metastatic Pancreatic Ductal Adenocarcinoma
• Refractory Pancreatic Ductal Adenocarcinoma
• Stage II Pancreatic Cancer AJCC v8
• Stage III Pancreatic Cancer AJCC v8
• Stage IV Pancreatic Cancer AJCC v8
• Unresectable Pancreatic Ductal Adenocarcinoma

Interventions

Type	Name	Description
PROCEDURE	Biopsy	Undergo biopsy
PROCEDURE	Biospecimen Collection	Undergo collection of blood samples
PROCEDURE	Computed Tomography	Undergo CT
DRUG	DDX5 Degrader FL118	Given PO
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI

Timeline

• Start date: 2025-10-01
• Primary completion: 2027-10-01
• Completion: 2027-10-01
• First posted: 2024-01-16
• Last updated: 2025-01-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study