Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of investigational drugs to learn whether the drug(s) works in treating a specific disease. As a basket study, the trial will enroll patients with NF2-SWN with associated progressive tumors of vestibular schwannomas (VS), non-vestibular schwannomas (non-VS), meningiomas, and ependymomas The MASTER STUDY is intended to enroll participants who will be allocated into different treatment arms (SUB-STUDIES) which will each have an additional consent and enrollment processes. MASTER STUDY \-- The research study procedures include screening for eligibility, randomization to an experimental treatment sub-study, if qualified, and observation for up to 10 years. * Participants who have tumors grow during a treatment sub-study will be permitted to enroll in a different experimental treatment sub-study if they are eligible. * Participants who are not eligible for enrollment in a different treatment sub-study will be permitted to remain under observation on the Master Study to understand the growth pattern of these tumors (natural history) * Participants will be eligible to remain on this Master study for up to 10 years. * It is expected that about 80 people will take part in the Master Study * The study will randomize a maximum of 40 patients to each of the experimental arms. The overall size of the trial is not fixed by design because it include arm-dropping rules for futility and allow for the possibility of arm addition by amendment. SUB-STUDY A (brigatinib) Drug Sub-study A will test the activity of brigatinib for treatment of NF2-related tumors. * Brigatinib is approved for the treatment of people with anaplastic lymphoma kinase (ALK)- positive metastatic non-small cell lung cancer (NSCLC) who have progressed or are intolerant to crizotinib. In preclinical models, brigatinib has shown evidence of activity against models of NF2-deficient tumors. * Forty (40) people will take part in the Brigatinib Sub-study. * The sub-study with brigatinib includes two stages. * In Stage 1, 20 subjects with any allowable tumor type will be accrued to each arm. A minimum of 2 subjects per tumor type (vestibular schwannoma, non-vestibular schwannoma, meningioma, and ependymoma) must be accrued in Stage 1. Interim analysis will be performed after Stage 1 to determine the radiographic response rate (RR) for each tumor types. Subsequently, in stage 2, another 20 subjects will be accrued into the 2 baskets with the most promising early results. If the results are equally promising for more than 2 baskets, subjects will be allocated to the appropriate number of baskets. SUB-STUDY B (neratinib) Collaborator: National Comprehensive Cancer Network (NCCN) through a grant provided by Puma Biotechnology Drug Sub-study B will test the activity of neratinib for treatment of NF2-related tumors. * Neratinib is approved for the treatment of people with early stage HER2-overexpressed/amplified breast cancer following treatment with trastuzumab-based therapy. In preclinical models, neratinib has shown evidence of activity against models of NF2-deficient tumors. \- It is expected that 20 people will take part in the Neratinib Sub-study. A minimum of 2 subjects per tumor type (vestibular schwannoma, non-vestibular schwannoma, meningioma, and ependymoma) must be accrued. Analysis will be performed to determine the radiographic response rate (RR) for each tumor types. * A subset of 5 participants will be enrolled into the PET imaging biomarker study. These participants will have additional PET scans performed just prior to the first dose of neratinib and after starting the treatment (witin 24 to 72 hours). SUB-STUDY C (retifanlimab plus bevacizumab) Collaborator: Funded by the Children's Tumor Foundation (CTF) and supported, in part, by Incyte Corporation. Drug sub-study C will test the activity of retifanlimab and bevacizumab on NF2-related tumors. * Retifanlimab is a humanized immunoglobulin G4 monoclonal antibody that targets programmed cell death protein 1. Retifanlimab is approved for the treatment of metastatic or recurrent locally advanced Merkel cell carinoma in adults. * Bevacizumab is a vascular endothelial growth factor inhibitor. Bevacizumab is approved for the treatment of metastatic colorectal cancer, non-small cell lung cancer, and glioblastoma. * It is expected that 20 participants will take part in the retifanlimab plus bevacizumab sub-study. A minimum of 2 participants per tumor type (vestibular schwannoma, non-vestibular schwannoma, meningioma, and ependymoma) must be accrued. Interim analysis will be performed to determine the radiographic response rate (RR) for each tumor type. If indicated based on this analysis, and with the support of Incyte, another 20 participants will be accrued into the 2 baskets with the most promising early results. If the results are equally promising for more than 2 baskets, participants will be allocated to the appropriate number of baskets.