The purpose of this study is to determine a maximum tolerated dose and/or recommended phase 2 dose of a combination of imatinib and BKM120 in the treatment of 3rd line GIST patients.

Inclusion criteria:

1. Male or female patients ≥ 18 years of age

2. WHO performance status (PS) of 0-2

3. Histologically confirmed diagnosis of GIST that is unresectable or metastatic

4. Available tissue specimen:

   • Dose-escalation cohorts: patients must have available archival tumor tissue which can be shipped during the course of the study
   • Dose-expansion cohort: patients must have available archival tumor tissue which can be shipped during the course of the study and must agree to a fresh pre-treatment biopsy.

5. Failed prior therapy with imatinib followed by sunitinib for the treatment of unresectable or metastatic GIST. Note the following specific criteria for the two phases of the trial:

   • Dose-escalation cohorts: patients who failed prior therapy with imatinib and then have failed therapy with sunitinib. Treatment failure may be due to either disease progression on therapy (both imatinib and sunitinib) or intolerance to therapy (sunitinib). Dose-escalation cohort patients may have had additional lines of therapy not limited to imatinib and sunitinib.
   • Dose-expansion cohort: patients must have documented disease progression on both imatinib and sunitinib. In addition, patients may have had no more than two lines of prior therapy (i.e. treatment with imatinib followed by treatment with sunitinib).
   • Adjuvant imatinib will not count as a prior course of imatinib for the purposes of this criterion

Exclusion Criteria:

1. Previous treatment with PI3-K inhibitors

2. A medical history of any of the following mood disorders as judged by the Investigator or a psychiatrist:

   • Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or thoughts, or homicidal thoughts (immediate risk of doing harm to others)
   • ≥ CTCAE grade 3 anxiety

3. When completing the patient questionnaires at screening:

   • Meets the cut-off score of ≥ 10 in the nine item depression scale of the Patient Health Questionnaire (PHQ-9) or a cut-off of ≥ 15 in the Generalized Anxiety Disorder Assessment (GAD 7) mood scale respectively, or
   • Selects positive response of 1, 2, 3 to question number 9 regarding potential for suicidal thoughts or ideation in the PHQ-9 (independent of the total score of the PHQ-9)

4. Severe and/or uncontrolled concurrent medical condition that, in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g. acute or chronic liver, pancreatic, severe renal disease considered unrelated to study disease, chronic pulmonary disease including dyspnea at rest from any cause).

5. Poorly controlled diabetes mellitus (defined as HbA1c > 8%)

Other protocol-defined inclusion/exclusion criteria may apply.