SJ901: Evaluation of Mirdametinib in Children, Adolescents, and Young Adults With Low-Grade Glioma

NCT04923126 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: SJ901NCI-2021-05912
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

This is an open-label, multi-center, Phase 1/2 study of the brain-penetrant MEK inhibitor, mirdametinib (PD-0325901), in patients with pediatric low-grade glioma (pLGG).

Conditions

Progressive Low-Grade Glioma; Low-Grade Glioma; Recurrent Low-Grade Glioma

Keywords

Brain tumors in Adolescent; Brain tumors in Children; Brain tumors in Young Adults; Astrocytic tumor; Glioneuronal tumor; Neuroepithelial tumor, not otherwise specified (NOS); Neuroepithelial tumor, not elsewhere classified (NEC); Pilocytic astrocytoma; Pilomyxoid astrocytoma; Pleomorphic xanthroastrocytoma; Ganglioglioma; Gangliocytoma; Diffuse glioma; Diffuse astrocytoma; Oligodendroglioma; Oligoastrocytoma; Papillary glioneuronal tumor; Rosette-forming glioneuronal tumor; Diffuse leptomeningeal glioneuronal tumor; Central neurocytoma; Extraventricular neurocytoma; Angiocentric glioma; Dysembryoplastic neuroepithelial tumor (DNET); Septal Dysembryoplastic neuroepithelial tumor (DNET); Myxoid glioneuronal tumor; Tectal glioma; Desmoplastic infantile astrocytoma; Desmoplastic infantile ganglioglioma; Polymorphous low-grade neuroepithelial tumor of the young; Multinodular and vacuolating neuronal tumor

Outcome Measures

Primary Outcomes (8)

• Phase 1: Estimate the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma.

  The maximum tolerated dose (MTD) is empirically defined as the highest dose level at which six patients have been treated with at most one patient experiencing a dose-limiting toxicity (DLT) and the next higher dose level determined to be too toxic. The MTD estimate will not be available if the lowest dose level studied is too toxic or the highest dose level studied is considered safe. In the latter case, the highest studied safe dose may be considered as the recommended phase 2 dose (RP2D). The MTD estimation will be limited to evaluable patients and toxicity assessments from course 1 (28 days). We will require that at least 12 DLT evaluable subjects are assessed before the MTD/RP2D is declared.

  1 month after start of mirdametinib treatment

• Phase 1: Determine the safety and tolerability of mirdametinib dosed twice daily on a continuous schedule in pediatric patients with progressive or recurrent low-grade glioma.

  Incidence of adverse event data at least possibly related to treatment will be summarized in cohort specific tables by grade and attribution throughout treatment.

  Up to 25 months after start of mirdametinib treatment

• Characterize the maximum plasma concentration and area under the concentration-time curve (AUC0-8h) of mirdametinib.

  Mirdametinib plasma concentration will be provided and area under the curve (AUC0-8h) estimated based on course 1, days 1 and 15 PK samples

  Course 1: Days 1 and 15

• Phase 2, Cohort 1: Objective response rate observed anytime during active treatment and sustained for at least 8 weeks

  The response rate, defined as the rate of minor response, partial response (PR), major response, or complete response (CR) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., PR, major response, and CR). Subjects without an assessment will be considered non-responders.

  Up to 24 months after start of mirdametinib treatment

• Phase 2, Cohort 2: Objective response rate observed anytime during active treatment and sustained for at least 8 weeks

  The response rate, defined as the rate of minor response, partial response (PR), major response, or complete response (CR) will be calculated as the percentage of confirmed responders among all response assessable patients. These rates as well as their exact confidence intervals will be provided and will be summarized by each response category (i.e., PR, major response, and CR). Subjects without an assessment will be considered non-responders.

  Up to 24 months after start of mirdametinib treatment

• Phase 2, Cohort 3a: Estimate 1-year disease stabilization rate

  Rate of stable disease from start of treatment until the time of progression or time of last follow-up.

  Up to 12 months (slight departures from this timing allowed based on MRI screening) after start of mirdamentinib treatment

• Phase 2, Cohort 3b: Estimate 6-month disease stabilization rate

  Rate of stable disease from start of treatment until the time of progression or time of last follow-up.

  Up to 6 months (slight departures from this timing allowed based on MRI screening) after start of mirdametinib treatment

• Describe the toxicity profile of mirdametinib by cohort.

  Incidence of adverse event data at least possibly related to treatment will be summarized in cohort specific tables by grade and attribution throughout treatment.

  Up to 25 months after start of mirdametinib treatment

Secondary Outcomes (14)

• Progression-free survival (PFS) by cohort

  Up to 5 years after the last enrolled patient starts treatment

• Rates of Minor Response, by cohort

  Up to 5 years after the last enrolled patient starts treatment

• Rates of Partial Response (PR), by cohort

  Up to 5 years after the last enrolled patient starts treatment

• Rates of Major Response, by cohort

  Up to 5 years after the last enrolled patient starts treatment

• Rates of Complete Response (CR), by cohort

  Up to 5 years after the last enrolled patient starts treatment

Study Arms (5)

Phase I: Recurrent and/or progressive low-grade glioma without prior exposure to MEK inhibitors

EXPERIMENTAL

Participants will receive mirdametinib at one of the dose levels twice daily days 1-28. For the first cycle of treatment, participants will take mirdametinib tablets dissolved in water. After the first cycle of treatment, participants may receive the medicine the same way (dissolved in water) or may receive capsules. Treatment repeats every 28 days for up to 26 cycles of treatment (24 months) in the absence of disease progression or unacceptable toxicity.

Drug: Mirdametinib

Phase 2, Cohort 1: Newly diagnosed and/or previously untreated (except surgery)

EXPERIMENTAL

Participants will receive the RP2D of mirdametinib. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Drug: Mirdametinib

Phase 2, Cohort 2: Recurrent and/or Progressive without prior exposure to MEK inhibitors

EXPERIMENTAL

Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Drug: Mirdametinib

Phase 2, Cohort 3a:

EXPERIMENTAL

Participants with recurrent and/or progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants with previous exposure to mirdametinib may receive a starting dose lower than the RP2D, depending on the dose they tolerated during their previous exposure. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Drug: Mirdametinib

Phase 2, Cohort 3b:

EXPERIMENTAL

Participants with recurrent and/or progressive low-grade glioma who previously received ≥ 6 courses MEK inhibitor (including mirdametinib) and did not progress while on active MEKi therapy. Participants will receive the RP2D of mirdametinib. Participants may take mirdametinib tablets dissolved in water, or receive capsules. Therapy will be administered in cycles of 28 days and may be continued for up to 24 months (26 cycles) in absence of disease progression or unacceptable toxicity.

Drug: Mirdametinib

Interventions

Mirdametinib DRUG

By mouth, nasogastric (NG) tube or gastrostomy tube (G-tube) BID, days 1-28

Also known as: PD-0325901

Phase 2, Cohort 1: Newly diagnosed and/or previously untreated (except surgery); Phase 2, Cohort 2: Recurrent and/or Progressive without prior exposure to MEK inhibitors; Phase 2, Cohort 3a:; Phase 2, Cohort 3b:; Phase I: Recurrent and/or progressive low-grade glioma without prior exposure to MEK inhibitors

Eligibility Criteria

• Age: 2 Years - 24 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants with histologically confirmed or suspected low-grade glioma, including neuronal and mixed neuronal-glial tumors
• Participant must have adequate tumor tissue from primary and/or relapsed tumor for central pathology review
• For Phase 1: Projected to be ≥ 2 years and \< 25 years at the time of study enrollment
• Participant's body surface area (BSA) at time of study enrollment must fall within the range outlined in the protocol for the specific dose level under evaluation:
• Phase 1: Dose Finding/Dose-escalation
• For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation.
• Phase 2: All Cohorts:
• For Phase 2 of the study the upper BSA restrictions will be removed.
• Participant and/or guardian can understand and is willing to sign a written informed consent document according to institutional guidelines

You may not qualify if:

• Participants with known current retinal pathology that is consistent with or a precursor for central serous retinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration
• Participants with a known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of mirdametinib (e.g., gastric bypass, lap band, or other gastric procedures)
• Participant with a known history of liver disease or known hepatic or biliary abnormalities (except for Gilbert's syndrome or asymptomatic gallstones)
• Participants with a clinically significant history of chronic interstitial lung disease (such as bronchopulmonary dysplasia, chronic bronchiolitis, obliterative bronchiolitis, chronic aspiration pneumonia, surfactant protein disorder, or other serious chronic pulmonary condition). Participants with a history of asthma, reactive airways disease, or viral pneumonitis are not to be excluded if disease has resolved or is well-controlled.
• Participant must be ≥ 2 years and \< 25 years of age at the time of enrollment
• Participant's BSA at time of study enrollment must fall within the range outlined below for the specific dose level under evaluation:
• Phase 1: Dose-finding/Dose-escalation
• For Phase 1 participant's BSA must fall within the range specified in the protocol for the specific dose level under evaluation.
• Phase 2: All Cohorts
• For Phase 2 of the study the upper BSA restrictions will be removed.
• Participant must have confirmation of one of the following diagnosis per St. Jude Children's Research Hospital central pathology review of primary and/or relapsed tumor:
• Eligible tumors include:
• Low-grade glioma/astrocytic tumor/glioneuronal tumor/neuroepithelial tumor, not otherwise specified (NOS) or not elsewhere classified (NEC)
• Pilocytic astrocytoma
• Pilomyxoid astrocytoma

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• SpringWorks Therapeutics, Inc.: collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude
• St. Jude Brain Tumor Studies

MeSH Terms

Conditions

Astrocytoma; Neoplasms, Neuroepithelial; Ganglioglioma; Ganglioneuroma; Oligodendroglioma; Neurocytoma

Interventions

mirdametinib

Condition Hierarchy (Ancestors)

Glioma; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Giles W. Robinson, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

• Anna Vinitsky, MD, MS

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tabatha E. Doyle, RN

CONTACT

901-595-2544; tabatha.doyle@stjude.org

Study Design

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

Study Record Dates

• First Submitted: May 27, 2021
• First Posted: June 11, 2021
• Study Start: June 21, 2021
• Primary Completion (Estimated): June 1, 2031
• Study Completion (Estimated): June 1, 2031
• Last Updated: February 4, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)