Mirdametinib in Patients With Advanced NF1-mutant Melanoma

NCT07237100 | Recruiting Phase 2 FDA Drug

• 1 other identifier: CPMC24-MEL01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate clinical efficacy of mirdametinib in patients with advanced NF1-mutant melanoma whose disease has progressed while on or after previous immunotherapy. The main questions this study aims to answer are:

• To evaluate the feasibility of conducting a prospective single-center clinical trial of mirdametinib in patients with advanced NF1-mutant melanoma whose disease progresses during or after PD-1 antibody-based checkpoint inhibitor therapy.
• To evaluate preliminary clinical efficacy of mirdametinib in patients with advanced NF1-mutant melanoma whose disease has progressed while on or after previous immunotherapy
• To evaluate the safety profile of mirdametinib in patients with advanced NF1-mutant melanoma

Conditions

Advanced Unresectable Melanoma; Metastatic Melanoma

Keywords

Neurofibromin 1 (NF1) mutation; advanced unresectable melanoma; Metastatic Melanoma; Melanoma; Mirdametinib

Outcome Measures

Primary Outcomes (1)

• To evaluate the feasibility of conducting a prospective single-center clinical trial of mirdametinib in patients with advanced NF1-mutant melanoma whose disease progresses during or after PD-1 antibody-based checkpoint inhibitor therapy.

  This is a small pilot study to evaluate a feasibility of conducting a prospective single-center clinical trial of mirdametinib in patients with advanced NF1-mutant melanoma whose disease progresses during or after PD-1 antibody-based checkpoint inhibitor therapy. The primary endpoint is to enroll and treat 10 patients over a 12 month period. If there are at least 2 clinical responses among the 10 patients, the preliminary efficacy will be considered promising. Further discussions with the funding agency to expand the cohort to a total of 29 patients will then be planned.

  12 months

Secondary Outcomes (2)

• To evaluate the safety profile of mirdametinib in patients with advanced NF1-mutant melanoma

  2 years

• To evaluate preliminary clinical efficacy of mirdametinib in patients with advanced NF1-mutant melanoma whose disease has progressed while on or after previous immunotherapy

  12 months

Study Arms (1)

Mirdametinib

EXPERIMENTAL

Patients receive mirdametinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

Mirdametinib is a kinase inhibitor. It is taken by mouth twice a day

Also known as: PD-0325901

Mirdametinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with unresectable or metastatic melanoma with an NF1 mutation; Variance of NF1 of unknown/ uncertain significance will not be eligible; The genetic analysis for somatic mutations must be performed in a lab that has obtained CLIA certification.
• Patients must have a report of NF1 sequencing analysis performed at CLIA-certified laboratory (by either tissue-based sequencing or liquid biopsy)
• Must have been previously treated with
• anti PD-1/PD-L1 antibody; AND anti CTLA-4 antibody and/or anti LAG3 antibody;
• UNLESS these standard checkpoint inhibitors are not clinically indicated or suitable (for example, comorbid conditions, such as autoimmune disease, or significant toxicity with prior checkpoint inhibitor treatment)
• Tumors must be progressing at the time of the enrollment
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Patients must be ≥ 18 years of age
• Patients must have measurable metastatic disease according to RECIST 1.1
• Patients must have adequate organ function, defined as follows:
• Absolute neutrophil count ≥ 1,500/μL
• Platelets ≥ 100,000/μL
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation. Estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (Grade ≤1). • Total bilirubin ≤ 1.5 x ULN OR direct bilirubin ≤ 1 x ULN (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)
• Aspartate aminotransferase and alanine aminotransferase ≤ 3.0 x ULN (Grade ≤1) unless liver metastases are present, in which case they must be ≤ 5 x ULN (Grade ≤2).

You may not qualify if:

• Patients who were previously treated with MEK, ERK or RAF inhibitor therapy
• Patients with symptomatic brain metastasis or active brain lesions ≥ 6 mm size or those who require steroid treatment for brain lesions or leptomeningeal disease
• No systemic cancer therapy within 28 days of the study drug administration,
• Patients must not be simultaneously enrolled in any therapeutic clinical trial
• Patients must not have had investigational therapy administered ≤ 4 weeks, or within a time interval less than at least 5 half-lives of the investigational agent, whichever is longer, prior to the first scheduled day of dosing in this study.
• Patient has a history of, or evidence of, retinal pathology on ophthalmologic examination that is considered a risk factor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration. Participants will be excluded from study participation if they have any of the following risk factors for RVO at Screening:
• Intraocular pressure \> 21 mmHg;
• Serum cholesterol \> 300 mg/dL;
• Serum triglycerides \> 300 mg/dL;
• Hyperglycemia (fasting blood glucose \> 125 mg/dL or random blood glucose \> 200 mg/dL);
• History or current evidence of glaucoma or clinically significant abnormalities on the ophthalmological exam, including but not limited to cataract limiting the ability to examine the retina or any optical coherence tomography (OCT) finding that could be a significant risk factor for RVO, retinopathy or neovascular macular degeneration.
• o Note: Mild and controlled/stable age-related macular degeneration or non-proliferative diabetic retinopathy may be acceptable at the investigator's discretion after consultation with the ophthalmologist.
• History (within 6 months before the start of the study treatments) of clinically significant cardiac disease (New York Heart Association Class III or IV), myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, clinically significant transient ischemic attack, symptomatic pulmonary embolism, unexplained syncope, or long QT syndrome.
• Patient who is pregnant or breastfeeding.
• Patient with active bacterial, fungal, or viral infection, including but not limited to the use of antibiotics, antifungals, or antiviral agents at the time of Screening;

Sponsors & Collaborators

• Kevin Kim, MD: lead

Study Sites (1)

California Pacific Medical Center - Sutter Health

San Francisco, California, 94115, United States

RECRUITING

MeSH Terms

Conditions

Melanoma; Neurofibromatoses

Interventions

mirdametinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neurofibroma; Nerve Sheath Neoplasms; Neoplastic Syndromes, Hereditary; Neurocutaneous Syndromes; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Central Study Contacts

Clinical Research at Sutter Health

CONTACT

415-600-1544; clinicalresearch@sutterhealth.org

Andrea Davila

CONTACT

andrea.davila@sutterhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Medical Director of Melanoma Clinical Research Program

Model Details: The dosing schedule: • 4 mg BID for administered continuously (1 cycle = 28 days).

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 19, 2025
• Study Start: October 13, 2025
• Primary Completion (Estimated): October 13, 2027
• Study Completion (Estimated): October 13, 2030
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Upon publication.

Locations

US (1)