This is a multi-arm phase II platform-basket screening study designed to test multiple experimental therapies simultaneously in patients with NF2-related schwannomatosis (NF2-SWN, formerly known as neurofibromatosis type 2) with associated progressive tumors of vestibular schwannomas (VS), non-vestibular schwannomas (non-VS), meningiomas, and ependymomas.
This Master Study is being conducted as a "basket" study that may allow people with multiple tumor types associated with NF2-SWN to receive new drugs throughout this study. Embedded within the Master Study are individual drug substudies.
* Investigational Drug Sub-study A: Brigatinib * Investigational Drug Sub-study B: Neratinib * Investigational Drug Sub-study C: Retifanlimab plus bevacizumab
Bilateral vestibular schwannomas, OR
First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity.
Bilateral vestibular schwannomas, OR
First-degree relative with NF2 and EITHER unilateral eighth nerve mass OR two of the following: neurofibroma, meningioma, glioma, schwannoma, juvenile posterior subcapsular lenticular opacity, OR
Participants who have had chemotherapy within a minimum of 4 weeks prior to Master Study registration (or a minimum of 5 half-lives and resolution to baseline of toxicities unless there are irreversible toxicities from prior drug that do not influence risk of next drug).
Participants who have received radiation to the target tumor within the last 3 years prior to Master study registration.
Participants who are receiving any other investigational agents.
Participants with target or non-target nervous system tumors that, in the opinion of the treating investigator, are likely to require active treatment (including surgery) within 6 months of registration to the Master Study.
Parallel
Brigatinib
DrugOral daily per predetermined dosage per protocol.
Neratinib
DrugOral daily per predetermined dosage per protocol.
Retifanlimab
DrugEvery 3 weeks by IV per predetermined dose in protocol.
Bevacizumab
DrugEvery 3 weeks by IV per predetermined dose in protocol.
Radiographic response rate (for each drug substudy)
Radiographic response rates in target tumors according to tumor-associated criteria: * VS, non-VS, and meningiomas: Dombi criteria (2013) * Ependymomas: RECIST 1.12
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability
Number of Participants with Treatment Emergent Adverse Events as Assessed CTCAE v5.0
Click on the lead sponsor to view all of their trials.
Scott R. Plotkin, MD, PhD
Lead sponsor
Massachusetts General Hospital
Sponsor institution
Takeda
Collaborator
The Children's Tumor Foundation
Collaborator
National Comprehensive Cancer Network
Collaborator
Incyte Corporation
Collaborator
