Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol;

Patients must have a tumor that harbors an inactivating mutation in NF2;

Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block);

Patients with known left ventricular dysfunction must have echocardiogram (ECHO) or a nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN). If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible;

Patients with history of hypertension should be adequately controlled (blood pressure [BP] < 140/90) with appropriate anti-hypertensive therapy or diet

Patients must not have known hypersensitivity to VS-6063 (defactinib) or compounds of similar chemical or biologic composition;

Patients must not have a history of upper gastrointestinal (GI) bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug;

Patients must not have known history of Gilbert's syndrome;

Patient must not have a known history of stroke or cerebrovascular accident within 6 months prior to the first dose of VS-6063 (defactinib);

Patients must not have prior treatment with a FAK inhibitor (e.g., VS-6063 [defactinib] or GSK2256098) and must not be participating or have participated in the COMMAND trial of maintenance therapy of VS-6063 (defactinib) versus (vs.) placebo, for mesothelioma

• Hematology

• Oncology (Adult)

• National Cancer Institute (NCI)