Phase 2 Study to Evaluate the Efficacy of Regorafenib in Specific GIST Mutation Subsets (KIT Exon 17, 18, or 14 Mutation and SDHB Deficient GIST) in the Post-imatinib Second-line Setting.

To learn if regorafenib can help to control the disease.

Inclusion Criteria: Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for nonnodal lesions and short axis for nodal lesions) as≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam. * Age ≥18 years. * Histologic diagnosis of GIST with presence of KIT exon 17, 18, or 14 mutation, or SDHB deficiency on tumor biopsy and/ or liquid biopsy. * Participants must have unresectable or metastatic GIST and radiologic progression on imatinib treatment. Imatinib treatment must have been discontinued at least 5 days prior to the first dose of study drug. All imatinib treatment will be counted as 1 line of therapy. * ECOG performance status ≤2 (Karnofsky ≥60%) at screening. * Life expectancy of at least 12 weeks (3 months). * Subjects must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trialspecific procedure. * Patients must have adequate organ and marrow function as definedbelow: Hemoglobin ≥8 g/dL Absolute neutrophil count ≥1,000/mcL Platelets ≥100,000/mcL Total bilirubin ≤2 x institutional upper limit of normal (ULN) or \