New platform trial takes on NF2 tumors with multiple drug strategies

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Eligibility Specific For MASTER STUDY Inclusion Criteria: Subjects must satisfy all of the following criteria to be enrolled into the main study natural history observation cohort: (1) Must meet the 2022 International Consensus Criteria for NF2-SWN, defined by having at least one of the following: 1. Bilateral vestibular schwannomas (VS) 2. An identical NF2 pathogenic variant in at least 2 anatomically distinct NF2-related tumors (schwannoma, meningioma, and/or ependymoma). (Note: if the variant allele fraction (VAF) in unaffected tissues such as blood is clearly \<50%, the diagnosis is mosaic NF2-related schwannomatosis) 3. Either 2 major or 1 major and 2 minor criteria as described in the following: Major criteria: * Unilateral VS * First-degree relative other than sibling with NF2-related schwannomatosis * 2 or more meningiomas (Note: single meningioma qualifies as minor criteria). * NF2 pathogenic variant in an unaffected tissue such as blood (Note: if the VAF is clearly \<50%, the diagnosis is mosaic NF2-related schwannomatosis) Minor criteria: Can count \>1 of a type (eg, 2 distinct schwannomas would count as 2 minor criteria) * Ependymoma, meningioma (Note: multiple meningiomas qualify as a major criteria), schwannoma (Note: if the major criterion is unilateral VS, at least 1 schwannoma must be dermal in location) Can count only once (eg, bilateral cortical cataracts count as a single minor criterion) * Juvenile subcapsular or cortical cataract, retinal hamartoma, epiretinal membrane in a person aged \<40 years, meningioma (2) Presence of at least one evaluable lesion: Vestibular schwannoma, meningioma, or non-vestibular schwannoma: clearly identifiable lesion on contrast-enhanced T1-weighted MRI; Ependymoma: clearly identifiable lesion on contrast-enhanced T1-weighted or T2/FLAIR sequences; (3) Expected ability to complete at least 12 months of follow-up assessments; (4) Ability to understand and voluntarily sign a written informed consent form, or a legally authorized guardian signs the informed consent form together ; (5) Sub-study-specific criteria (for intervention arms only): If the subject intends to enter an interventional sub-study, in addition to meeting the above main study criteria, the subject must also satisfy the specific inclusion criteria specified in that sub-study protocol (e.g., organ function, prior treatment restrictions, washout periods, etc.), as determined by the drug characteristics. Exclusion Criteria: Subjects meeting any of the following criteria will not be permitted to enter the main study: 1. Coexisting other genetic syndromes that may cause multiple intracranial tumors (e.g., SMARCB1/LZTR1-related schwannomatosis, Cowden syndrome); 2. Expected survival \<12 months; 3. Presence of severe psychiatric disorders or cognitive impairment that precludes cooperation with imaging or hearing assessments; 4. Extreme social or geographic factors that, in the investigator's judgment, may impede follow-up for more than 12 months; 5. Sub-study-specific exclusion criteria (for intervention arms only): If the subject intends to enter an interventional sub-study, the subject must also satisfy the specific exclusion criteria specified in that sub-study protocol (e.g., specific organ dysfunction, active infection, pregnancy, etc.).