Mirdametinib Monotherapy in Adults With Neurofibromatosis 1 (NF1) and Cutaneous Neurofibromas (cNF).

NCT06159166 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB00365255J23129
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1/2a, open-label, non-randomized, multi-dose study of mirdametinib monotherapy in adults with NF1 and cNF. In both Phases of the study, participation in the study will comprise three periods: screening, treatment and post-study safety follow-up to be performed at the NF1 and cNF specialty center: Johns Hopkins University.

Conditions

NF1; Cutaneous Neurofibroma; Monotherapy

Keywords

Mirdametinib

Outcome Measures

Primary Outcomes (3)

• Assess the safety of continuous and three week on-one week off dosing of mirdametinib in adults with NF1 and cutaneous neurofibromas (cNFs).

  Phase 1 will test the safety and tolerability of multiple dose regimens of mirdametinib, in order to identify the recommended phase 2 dose(s) for phase 2a. The study will continue until one of the stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety The study will continue until one of the following stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety

  Up to 28 days

• Define the recommended phase 2 dose (RP2D) of mirdametinib in adults with NF1 and cNF.

  Phase 2a of the study will test the efficacy and safety of a maximum of two RP2Ds in adults with NF1 and cNF.

  Up to 28 days

• • Evaluate the preliminary anti-tumor activity of mirdametinib monotherapy in adults with NF1 and cNFs.

  Evaluate the efficacy of mirdametinib monotherapy at the RP2D in adults with NF1 and cNF. We will determine efficacy of Anti-tumor activity with 3D photography (Sum of the surface area, sum of the tumor volume, sum of the longest diameter) and Digital Caliper (Sum of the longest diameter).

  Up to 28 days

Study Arms (2)

Phase 1

EXPERIMENTAL

For the Phase 1 portion, treatment will be administered continuously (Dose regimens 1, 2, 4) or intermittently (Dose regimen 3; 3 weeks on/1 week off) in 28-day cycles). All participants will receive study drug until: 1. cessation of study treatment due to death, intolerance, or withdrawal of consent from the study; 2. completion of 24 cycles of treatment (unless the investigator's benefit-risk assessment supports continued treatment); 3. participants enroll in the phase 2a portion of the study; 4. disease progression; or 5. Investigator's decision. Treatment period ends with the administration of the last dose. The study ends 30 days after the last dose

Drug: Mirdametinib

Phase 2

EXPERIMENTAL

For the Phase 2 portion, treatment will be administered based on recommended RP2D from Phase 1. All participants will receive study drug until: 1. cessation of study treatment due to death, intolerance, or withdrawal of consent from the study; 2. completion of 24 cycles of treatment (unless the investigator's benefit-risk assessment supports continued treatment; 3. disease progression; or 4. Investigator's decision. Treatment period ends with the administration of the last dose. The study ends 30 days after the last dose.

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

This study is designed to assess Mirdametinib safety and efficacy in two phases: phase 1 tests the safety of up to four dose regimens of Mirdametinib, administered continuously or intermittently (3 weeks on/1 week off) to identify up to two recommended phase 2 doses. Phase 2a of the study will test the safety and efficacy of the recommended phase 2 dose(s) in adults with NF1 and cNF. The following dosing strategy will be assessed in participants ≥ 18 years old with NF1 and a minimum of 12 measurable cNF who desire systemic treatment of their cNF due to disfigurement, pain or itching. Each treatment cycle in this study is 28 days.treatment cycle in this study is 28 days.

Phase 1; Phase 2

Eligibility Criteria

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

You may qualify if:

• Meet the diagnostic criteria for NF12
• ≥ 18 years of age
• Have a minimum of 24 measurable cNF (2 target areas of ≥6 measurable cNF)
• a. Measurable is defined as: i. non-pedunculated (no stalk) ii. surrounded by uninvolved skin and not adjacent to another cNF lesion iii. measuring ≥ 0.5 cm in the longest diameter and ≥ 0.5 cm in height iv. the 24 cNF must be located in two Target Areas. One target area must be located on the back and must have at least 6 measurable cNF. The second target area can be in any of the following body regions with at least 6 cNF: head and neck; upper extremities; anterior chest wall, anterior abdominal wall; pelvic region/gluteal region; lower extremities.
• Participants must have cNF that meet eligibility criteria located within the two study designated target areas or outside of the target areas amenable to biopsy. If biopsy is taken within the target area there must be a minimum of 6 cNF remaining for long term surveillance after biopsy. Participants must be willing to undergo pre-, and on-treatment tumor biopsies providing fresh tumor tissue; there should be no contraindication for serial biopsy
• Karnofsky performance level of ≥ 80%.
• Adequate organ and bone marrow function as defined by the following Screening laboratory values:
• Absolute neutrophil count ≥ 1500 cells/µL;
• Platelets ≥ 100 x 103/µL;
• Hemoglobin ≥ 9.5 g/dL;
• Serum albumin ≥ 2.8 g/dL;
• Calculated creatinine clearance at Screening ≥ 60 mL/min (by Cockcroft-Gault formula) OR a normal serum creatinine.
• Participant is willing and able to comply with all aspects of the protocol
• Ability to understand and the willingness to sign written informed consent document(s).
• Women of childbearing potential (WOCBP) must not be pregnant or breastfeeding during any portion of the study and must use an adequate method to avoid pregnancy during the study period and for 6 months after treatment conclusion and agrees not to donate eggs (ova, oocytes) for the purpose of reproduction during the study and for a period of 6 months after last dose of study treatment. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study treatment (see the Approved Methods of birth control listed below).

You may not qualify if:

• Participant has a altered screening values:
• alanine transaminase (ALT) value of \> 2.0 x upper limit of normal (ULN);
• total bilirubin value of \> 1.5 x ULN (isolated bilirubin \> 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin \< 35%);
• Participant has a history of malignancy associated hypercalcemia;
• Participant has an active parathyroid disorder, hyperphosphatemia at Screening (serum phosphorus \> 1 x ULN), or serum calcium (mg/dL) x serum phosphorus (mg/dL) product \> 70 at Screening;
• Any clinically significant active or known history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
• Hepatitis serology will be tested at Screening. Participants who are hepatitis B surface antigen (HBsAg) positive or hepatitis C virus (HCV) antibody positive at Screening must not be enrolled until further definite testing with hepatitis B virus (HBV) deoxyribonucleic acid (DNA) titers is \< 500 IU/mL or HCV ribonucleic acid (RNA) polymerase chain reaction test is negative;
• Lymphoma, leukemia, or any malignancy (including malignant glioma or MPNST) within the past 5 years except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 years;
• Breast cancer within the past 3 years;
• Active optic glioma or other low-grade glioma requiring treatment with chemotherapy or radiation therapy.
• a. Participants not requiring treatment are eligible. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor or strabismus) or long-standing orbito-temporal PN (such as visual loss, strabismus) will NOT be considered a significant abnormality for the purposes of the study;
• Abnormal QT interval corrected by Fridericia's formula (\> 450 msec for male participants, \> 470 msec for female participants, or \> 480 msec for participants with known bundle branch block), calculated from triplicate ECG readings taken approximately 2 to 3 minutes apart and averaged at Screening;
• Participant has experienced any of the following within 6 months (24 weeks) of signing informed consent/assent: clinically significant cardiac disease, myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism;
• A recorded LVEF \< 55% at screening or within 3 years of signing informed consent/assent, OR has a history of congestive heart failure;
• Participants with 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:

Sponsors & Collaborators

• Johns Hopkins University: lead
• Neurofibromatosis Therapeutic Acceleration Program: collaborator
• SpringWorks Therapeutics, Inc.: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

MeSH Terms

Interventions

mirdametinib

Study Officials

• Carlos Romo, MD

  Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carlos Romo, MD

CONTACT

(410) 955-6827; cromo1@jhmi.edu

Joshua Roberts

CONTACT

4109558837; jrobe112@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase 1 will test the safety of multiple dose regimens of mirdametinib, in order to identify a recommended phase 2 dose(s) for phase 2a. The phase 1 portion will enroll participants in dose regimens 1 to 3 concurrently. Enrollment of participants to dose regimen 4 will be conducted only if no DLT occurred in any of the three previous regimens within at least, the first three cycles. The study will continue until one of the following stopping conditions is met. * The RP2D(s) have been identified with sufficient accuracy (The dose regimen(s) selected as the RP2D have been fully enrolled with at least 3 cycles of treatment completed for all participants) * All dose regimens are deemed to have unacceptable safety

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: December 6, 2023
• Study Start: February 12, 2024
• Primary Completion (Estimated): November 15, 2027
• Study Completion (Estimated): November 15, 2028
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)