Phase 1 Study of PAS-004, a MEK 12 Inhibitor, in Adults with Neurofibromatosis Type 1 and Symptomatic Plexiform Neurofibromas

What this Trial Is About

This research aims to evaluate PAS-004 in adults with Neurofibromatosis Type 1 NF1 who have symptomatic plexiform neurofibromas that are inoperable, incompletely resected, or recurrent. The study focuses on how well participants tolerate different doses of PAS-004 and to identify any side effects. It is a Phase 11b trial designed to assess safety, tolerability, pharmacokinetics, and pharmacodynamics of this MEK 12 inhibitor in this population. The study is divided into two parts. Part A involves sequential dose escalation of PAS-004 tablets given orally once daily in 28-day cycles, with doses of 4 mg, 8 mg, 12 mg, and 18 mg tested to determine tolerability and safety. In Part B, two dose levels selected based on Part A results will be tested in parallel cohorts. Participants may continue on their assigned dose in Part B for up to six months if eligible. Throughout the study, participants will take PAS-004 daily and keep a diary to record their dosing. Participants will have regular visits for health and safety monitoring including blood tests and MRI scans to measure tumor response. Additional assessments include photography and caliper measurements of cutaneous neurofibromas, quality of life surveys, and physical function assessments. The primary outcome is safety and tolerability over one 28-day cycle in Part A and six 28-day cycles in Part B. Secondary outcomes include drug concentration levels, tumor response by MRI, appearance of neurofibromas, and patient-reported outcomes. The study continues until six months or earlier if side effects, disease progression, or other criteria occur.

PAS-004 in Adults Who Have Neurofibromatosis Type 1 With Plexiform Neurofibromas