Investigating PAS-004 for NF1-Related Plexiform Neurofibromas: A Phase 1/1b Study

This Phase 1/1b clinical trial evaluates the safety, tolerability, pharmacokinetics, and pharmacodynamics of PAS-004, a novel MEK 1/2 inhibitor, in adults with Neurofibromatosis Type 1 (NF1) and symptomatic plexiform neurofibromas. The study consists of two parts: Part A with sequential dose escalation (4mg to 18mg) and Part B with two parallel dosing cohorts based on Part A results.

The primary objectives focus on assessing safety through:

• Dose-limiting toxicities (DLTs)
• Adverse events (AEs)
• Clinical laboratory abnormalities
• Cardiac and visual function exams

Secondary outcomes include:

1. Pharmacokinetic parameters (Cmax, Tmax, AUC)
2. pERK inhibition in PBMCs
3. Tumor response via MRI volumetric analysis
4. Cutaneous neurofibroma changes
5. Quality of life assessments

Eligible participants must:

• Be ≥18 years with confirmed NF1 diagnosis
• Have symptomatic, inoperable plexiform neurofibromas ≥3cm
• Have Karnofsky performance status ≥70%
• Meet specific laboratory criteria

The study excludes patients with:

• Active malignancies (except certain skin/cervical cancers)
• Uncontrolled hypertension or cardiac disease
• Retinal disorders
• Recent chemotherapy/radiotherapy

Conducted by Pasithea Therapeutics with Novotech collaboration, this open-label trial aims to establish a safety profile for PAS-004 while evaluating preliminary efficacy signals in this underserved patient population.