A Phase 1 Study of IPI-926 in Patients With Advanced and/or Metastatic Solid Tumor Malignancies

Exclusion Criteria

• •1. Treatment with following therapies as indicated:
• •* Any chemotherapy (other than nitrosoureas or mitomycin C), radiation therapy, surgery, hormonal therapy, or investigational therapy within 4 weeks of the start of IPI-926 administration. Patients with luteinizing hormone releasing hormone therapy.
• •* Any tyrosine kinase inhibitor (e.g. erlotinib, imatinib) within 2 weeks of the start of IPI-926 administration
• •* Nitrosoureas o or mitomycin C within 6 weeks of the start of IPI-926 administration.
• •2. Inadequate hematologic function - neutrophil count (ANC) \<1,500 cells/mm3, platelet count \<100,000/mm3, or hemoglobin \<9.0 g/dL (may be increased to this level with transfusion as long as there is no evidence of active bleeding).
• •3. Inadequate hepatic function - aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \>2.5 x upper limit of normal (ULN); \>5 x ULN if attributable to liver metastases; total bilirubin \>1.5 x ULN.
• •4. Inadequate renal function - serum creatinine \>1.5 x ULN.
• •5. Uncontrolled hypomagnesemia or hypokalemia, defined as ≥ Grade 3 despite adequate electrolyte supplementation.
• •6. Baseline QTcF \>450 msec in men or \>470 msec in women.
• •7. Concurrent treatment with any agent known to prolong the QTc interval.
• •8. Prior surgery affecting drug absorption or any gastrointestinal dysfunction that could alter drug absorption (e.g. gastric bypass, Whipple procedure, gastrectomy).
• •9. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months.
• •10. Venous thromboembolic event (e.g. pulmonary embolism or deep vein thrombosis) requiring anticoagulation or who meet any of the following criteria are excluded:
• •* have been on a stable dose of anticoagulation for \<1 month
• •* have had a Grade 2, 3 or 4 hemorrhage in the last 30 days
• •* experiencing continued symptoms from venous thromboembolic event (e.g. continued dyspnea or oxygen requirement) \*Past venous thromboembolic event but do not meet any of the above three criteria are eligible for participation.
• •11. History of a seizure within the last 10 years or seizure disorder requiring anti-epileptic medications.
• •12. Concurrent treatment with medications known to lower the seizure threshold.
• •13. Concurrent administration of the medications or foods which are known to inhibit or induce CYP3A activity to a clinically relevant degree.
• •14. Presence of active infection or systemic use of antibiotics within 72 hours of treatment.
• •15. Significant co-morbid condition or disease which in the judgment of the Investigator would place the patient at undue risk or interfere with the study.
• •16. Known immunodeficiency virus (HIV) positivity.
• •17. Pregnant or lactating women.