PAS-004 for Neurofibromatosis

Recruiting at 6 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pasithea Therapeutics Corp.

Must not be taking: Chemotherapy, CYP3A4 inhibitors

Disqualifiers: Malignancy, Hypertension, Cardiac disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, PAS-004, for individuals with Neurofibromatosis Type 1 (NF1) who have painful or problematic plexiform neurofibromas (nerve tumors). The goal is to assess participants' tolerance to different doses and identify any side effects. In Part A, participants will try various doses to determine the safest options. In Part B, two doses from Part A will undergo further exploration for their potential impact on the tumors. Individuals with NF1 who have at least one problematic tumor that cannot be fully removed by surgery might be suitable for this trial. As a Phase 1 trial, this research aims to understand how PAS-004 works in people, offering participants the opportunity to be among the first to receive this new treatment.

Is there any evidence suggesting that PAS-004 is likely to be safe for humans?

Research has shown that PAS-004 is generally safe and well-tolerated by patients. In earlier studies, PAS-004 did not cause severe side effects that prevented patients from continuing treatment. Participants received different doses, and the treatment remained manageable at various levels.

Although the treatment is still in early testing for neurofibromatosis, the safety data from these studies are promising, suggesting that most people can tolerate PAS-004. Regular check-ups and tests are part of the trial to ensure ongoing safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for neurofibromatosis, which often include surgery, radiation therapy, or traditional chemotherapy, PAS-004 is unique because it involves a new sequential dose escalation approach. This approach allows researchers to carefully increase the dosage from 4 mg to 18 mg to find the most effective and safe dose for patients. Additionally, PAS-004 targets specific molecular pathways associated with the growth of neurofibromas, which could potentially offer a more precise treatment option compared to the broader effects of current therapies. Researchers are excited about PAS-004 because it promises to be more targeted, potentially leading to fewer side effects and better outcomes for patients.

What evidence suggests that PAS-004 might be an effective treatment for neurofibromatosis?

Research has shown that PAS-004 may help treat conditions related to certain genetic changes. In studies with patients who have advanced solid tumors with RAS, NF1, or RAF mutations, PAS-004 caused some tumors to shrink or stop growing temporarily. PAS-004, a MEK inhibitor, blocks specific pathways in cells that promote tumor growth. This trial will evaluate PAS-004 in two parts: Part A involves sequential dose escalation, and Part B involves two parallel cohorts dosing at levels selected based on Part A safety results. Although researchers are still studying this treatment, early results suggest it might help manage tumors in NF1, which is associated with neurofibromas. However, more research is needed to fully understand its effects. ^{1 2 6 7 8}

Who Is on the Research Team?

Tiago R Marques, MD

Principal Investigator

Pasithea Therapeutics Corp.

Are You a Good Fit for This Trial?

This trial is for adults with Neurofibromatosis Type 1 (NF1) who have at least one symptomatic plexiform neurofibroma that's at least 3 cm in size and not suitable for complete surgical removal. Participants must be able to swallow pills, have a performance level of ≥70%, and meet specific NF1 diagnostic criteria. They cannot join if they might have similar conditions like Noonan Syndrome or schwannomatosis.

Inclusion Criteria

Participants should have a minimum of seven measurable CN.

Participant must be able and willing to undergo serial 2-D and where available 3-D photography as well as caliper measurements.

Participant must have an international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤ 1.5 x ULN.

Exclusion Criteria

Participant has specific ophthalmic abnormalities.

Participant has participated in another interventional clinical study within 28 days of starting PAS-004.

Participant is pregnant or lactating.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment Part A

Participants receive PAS-004 in sequential dose escalation: 4 mg, 8 mg, 12 mg, and 18 mg to evaluate safety and tolerability

4 weeks

Regular visits for tests and exams, including blood draws and MRIs

Treatment Part B

Two parallel cohorts dosing at 2 levels selected based on Part A safety results, continuing PAS-004 for up to 6 months

24 weeks

Regular visits for tests and exams, including blood draws and MRIs

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PAS-004

Trial Overview The trial tests PAS-004 tablets on people with NF1-related tumors. It has two parts: Part A finds tolerable doses and observes side effects; Part B continues testing selected doses from Part A for their impact on the tumors. Participants take daily oral PAS-004 in cycles, undergo regular health checks, blood draws, MRIs, and keep a drug diary.

How Is the Trial Designed?

Group I: Part B Experimental Treatment 1 Intervention

Two parallel cohorts dosing at 2 levels selected based on Part A safety results

Group II: Part A Experimental Treatment 1 Intervention

Sequential dose escalation: 4 mg, 8 mg, 12 mg, and 18 mg

Who Is Running the Clinical Trial?

Pasithea Therapeutics Corp.

Lead Sponsor

Trials

1

Recruited

50+

Novotech (Australia) Pty Limited

Industry Sponsor

Trials

76

Recruited

7,800+

Dr. John Moller

Novotech (Australia) Pty Limited

Chief Executive Officer

MD and MBA from the University of Oxford

Dr. Judith Ng-Cashin

Novotech (Australia) Pty Limited

Chief Medical Officer since 2023

MD

Citations

1. ir.pasithea.com ir.pasithea.com/news-events/press-releases/detail/131/pasithea-therapeutics-announces-positive-pas-004-tablet

Press Releases Pasithea Therapeutics Announces Positive PAS-004 Tablet Pharmacokinetic (PK) Data in Ongoing Phase 1/1b Trial in Adult NF1 Patients · AUC: 2,290 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06961565

PAS-004 in Adults Who Have Neurofibromatosis Type 1 ... The main purpose of this clinical trial is to test PAS-004 in people with at least one symptomatic plexiform neurofibroma due to Neurofibromatosis Type 1 (NF1).

3. cancernetwork.com cancernetwork.com/view/novel-agent-yields-promising-results-in-mapk-associated-solid-tumors

Novel Agent Yields Promising Results in MAPK-Associated ... Partial responses and stable disease were observed with PAS-004 in patients with advanced solid tumors harboring RAS, NF1, or RAF mutations.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.3126

PAS-004: A novel macrocyclic MEK inhibitor to inhibit ... In the HCC xenograft study the highest dose of PAS-004 completely prevented tumor growth and the same dose caused a 69% reduction in tumor ...

5. biospace.com biospace.com/press-releases/pasithea-therapeutics-announces-positive-phase-1-data-including-partial-response-demonstrating-monotherapy-clinical-activity-and-favorable-safety-profile-for-pas-004-in-advanced-cancer-study

Pasithea Therapeutics Announces Positive Phase 1 Data ... Interim Phase 1 Results for PAS-004: Initial Signals of Clinical Activity. Among 21 efficacy evaluable patients (as per RECIST1.1):. Partial ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.3125

Phase I dose-escalation study of the safety and ... Conclusions: To date, PAS-004 is shown to be a safe and well-tolerated novel MEK inhibitor, with dose-dependent PK profile and preliminary ...

7. biospace.com biospace.com/press-releases/pasithea-therapeutics-announces-completion-of-cohort-7-in-ongoing-phase-1-trial-of-pas-004-in-advanced-cancer-patients-with-positive-safety-pharmacokinetic-pk-and-pharmacodynamic-pd-data

Pasithea Therapeutics Announces Completion of Cohort 7 ... PAS-004 was safe and well tolerated with no dose limiting toxicities ... At steady-state, individual patient plasma data showed PAS-004 ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06299839

PAS-004 in Patients With Advanced Solid Tumors The main purpose of this clinical trial is to test PAS-004 in people with advanced solid tumors with rat sarcoma virus (RAS), neurofibromatosis type I (NF1) ...