A Study of Avutometinib for People With Solid Tumor Cancers (NCT06104488)

Check every box below. If you can check all of them, you may meet the study's basic screening requirements (final eligibility is confirmed by the site team).

1. Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
2. Age ≥ 3 year and ≤ 30 years at the time of informed consent. \*Patients over 18 years of age will be treated at the adult RP2D. The accrual for patients \>18 and ≤ 30 years will be limited to no more than 5 patients overall and will not participate in the dose escalation.
3. All patients and/or their parents or legally authorized representatives must sign a written informed consent. Assent, when appropriate, will be obtained according to institutional guidelines.
4. Karnofsky ≥ 50% for patients \> 16 years of age and Lansky ≥ 50 for patients ≤ 16 years of age.
5. Participants must have one of the following:
6. Histologically confirmed diagnosis of a pediatric tumor including CNS tumors with activating MAP kinase pathway alterations including but not limited to BRAF/ARAF/CRAF fusions or mutations, KRAS/NRAS/HRAS alterations, PTPN11 or SOS1/2 mutations and/or loss of function alterations in NF1. This will be performed at the enrolling institution and central review is not required OR
7. Participants with a clinical or molecularly confirmed (germline alteration positive) diagnosis of NF1 with symptomatic inoperable plexiform neurofibromas and recurrent/progressive low-grade gliomas are eligible and may enroll without tissue/biopsy confirmation. OR
8. Patients with recurrent optic pathway gliomas are eligible if they have clinical progression (defined as new or worsening neurologic symptoms including visual dysfunction, as defined below):
9. Visual worsening, defined as worsening of visual acuity (VA) or visual fields (VF) documented within the past year (by examination or history); OR - Significant visual dysfunction (defined as VA worse than normal for age by 0.6 logMAR \[20/80, 6/24, or 2.5/10\] or more in one or both eyes). OR d) Participants with a confirmed diagnosis of neurofibromatosis 2 schwannomatosis (NF2-SWN) based on revised consensus 2021 criteria \[61\] with a target NF2-related tumor (vestibular schwannoma, non-vestibular schwannoma, meningioma) with documented radiographic progression defined as either:
10. ≥ 20% increase in volume of enhancing tumor
11. ≥ 2mm increase in greatest linear dimension of enhancing tumor Participants with diagnosis of NF2-SWN may enroll without tissue/biopsy confirmation. Genetic variants are classified as benign (B), likely benign (LB), likely pathogenic (LP), pathogenic (P), or variant of uncertain clinical significance (VUS) according to the standards and guidelines developed by the American College of Medical Genetics and Genomics, the Association for Molecular Pathology, and the College of American Pathologists \[62\]. Only patients with pathogenic and likely pathogenic variants in NF2 will be permitted to enroll \[61\]. Molecular testing requirements: Genetic alterations (SNVs or fusions) may be identified through local testing in a Clinical Laboratory Improvement Amendments (CLIA) laboratory in the US or equivalently accredited diagnostic lab outside the United States (US) (CLIA certified) by using molecular assays on any tumor samples (either at initial diagnosis or recurrence). Only the following test modalities are permitted:
12. Tissue-based or liquid biopsy NGS or quantitative polymerase chain reaction (qPCR) or RNA based fusion detection (ARCHER or other similar platform). The reports should be collected for any participants who have completed Next Generation Sequencing (NGS) at any point prior to or during study participation

🔍 Extracted verbatim from the official NIH eligibility criteria. Always confirm with the study coordinator.

📍 All Participating Trial Locations (2 Sites)

• Children's Healthcare of Atlanta (Data Collection Only) — Atlanta, Georgia
• Memorial Sloan Kettering Cancer Center (All Protocol Activities) — New York, New York

💰 Cost, Insurance & Patient Rights

• 100% Free Items: The investigational treatment and protocol-required procedures are supplied at zero cost by the sponsor.
• Routine Patient Care: Under federal law (ACA § 2709) and many state statutes, routine care costs are covered during participation.
• Voluntary Participation: You may withdraw at any time without affecting your standard medical care.