Inclusion Criteria:

• Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations.
• Age >18 years at the time of informed consent.
• Pathologically confirmed GIST refractory to, intolerant of, or not a candidate for imatinib and sunitinib therapy.
• FDG PET standard uptake value (SUVmax; averaged over a maximum of 5 lesions) <2 at screening.
• ECOG performance status of <2.

• Required laboratory values:

  • Absolute neutrophil count (ANC) >1500 cells/mm3, platelet count >100,000 cells/mm3, hemoglobin >9 gm/L.
  • Bilirubin <1.5 x upper limit of normal (ULN), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) <2.5 x ULN; except in subjects with known hepatic metastasis, where AST or ALT can be <5.0 X ULN.
  • Serum creatinine <2.0 x ULN.
  • International Normalized Ratio (INR) <1.5.
  • Glucose ≥3.3 mmol/L, sodium ≥130 mmol/L, calcium ≥2.0 mmol/L
• Plasma cortisol and adrenocorticotropic hormone (ACTH) levels that are not suggestive of adrenal insufficiency.
• Female subjects of childbearing potential must have a negative pregnancy test during screening.

• Male and female subjects of childbearing potential must practice effective double barrier contraception during the study and continue contraception for 3 months after their last dose of study drug. Male subjects must agree to not have intercourse with pregnant or nursing women during the study and for 3 months after their last dose of study drug, unless using double-barrier contraception. The only exceptions to double-barrier contraception are:

  • Subject or partner is surgically sterile
  • Female subject is postmenopausal for at least 1 year before screening
  • Subject abstains from sexual intercourse, at the discretion of the Investigator
• Subject must be willing to provide formalin fixed, paraffin embedded (FFPE) sections of prior tumor biopsy for SNP analysis and exploratory biomarkers.

Exclusion Criteria:

• Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of enrollment.
• Pregnant or nursing women.
• Prior treatment with imatinib, sunitinib, or sorafenib within 14 days of Day 1.
• Prior treatment with Hsp90 inhibitors at any time.
• Prior antitumor therapies including prior experimental agents, approved antitumor small molecules (excluding imatinib, sunitinib, and sorafenib) and biologics, or radiotherapy within 28 days or <3 half lives (whichever is longer) before start of BIIB021 treatment.
• Diabetes treated with insulin and/or concurrent severe or uncontrolled other medical disease (i.e., systemic infection, hypertension, coronary artery disease, congestive heart failure).
• Unstable cardiac disease, including poorly controlled angina, congestive heart failure, arrhythmias, myocardial infarction (within 1 year), or electrocardiogram (ECG) evidence of acute ischemia or significant conduction abnormality (bifascicular block, defined as left anterior hemiblock in the presence of right bundle branch block, or 2nd or 3rd degree atrioventricular block).
• Active symptomatic fungal, bacterial, and/or viral infection including active HIV or viral (A, B, or C) hepatitis.
• Problems with swallowing or malabsorption.
• Total gastrectomy.
• Chronic diarrhea (excess of 2 to 3 stools/day above normal frequency). Inflammatory gastrointestinal diseases including gastritis, ulcerative colitis, Crohn's disease, or hemorrhagic coloproctitis.
• History of adrenal insufficiency.
• Major surgery within 28 days of first administration of study treatment.
• Active or untreated brain metastasis.
• Medications that may affect the metabolism of BIIB021 including all proton pump inhibitors or drugs known to affect CYP2C19 during the study and within 14 days of first administration of study treatment (7 days for proton pump inhibitors).
• Previous head trauma.
• History of seizures.
• History of central nervous system metastasis.
• Drug or alcohol abuse.
• Use of epileptogenic medications.
• Abrupt discontinuation of benzodiazepines.