Oral STAT3 Inhibitor, TTI-101, in Patients with Advanced Cancers

Exclusion Criteria

• •1. Previous therapy with:
• •1. Standard therapy including chemotherapy, immunotherapy, biologic therapy, or any other anticancer therapy within 28 days (or five elimination half-lives for non-cytotoxic drugs, whichever is shorter) of Day 1 of trial drug treatment (6 weeks for nitrosureas or mitomycin);
• •2. Any investigational agent within 28 days of Day 1 of trial drug treatment or 5 half-lives for a small molecule/targeted therapy;
• •2. Extensive prior radiotherapy on more than 30% of bone marrow reserves, or prior bone marrow/stem cell transplantation within 5 years from enrollment; Ongoing toxicity (except alopecia) due to a prior therapy, unless returned to baseline or Grade 1 or less;
• •3. Major surgical intervention or participation in a therapeutic clinical trial within 28 days from Day 1 of the first dose of TTI-101;
• •4. Significantly impaired cardiac function such as unstable angina pectoris, congestive heart failure with New York Heart Association (NYHA) class III or IV, myocardial infarction within the last 12 months prior to trial entry; signs of pericardial effusion, serious arrhythmia (including QTc prolongation of \>470 ms and/or pacemaker) or prior diagnosis of congenital long QT syndrome or left ventricular ejection fraction \<50% on screening echocardiogram;
• •5. History of cerebral vascular accident or stroke within the previous 2 years;
• •6. Uncontrolled hypertension (\>160/100mm Hg);
• •7. History of Grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition as TTI-101 (hydroxyl-naphthalene sulfonamides);
• •8. Known active metastases in the central nervous system (unless stable by brain imaging studies for at least 1 month without evidence of cerebral edema and no requirements for corticosteroids or anticonvulsants);
• •9. History of difficulty swallowing, malabsorption, or other chronic gastrointestinal disease or conditions that may hamper compliance and/or absorption of the investigational product;
• •10. Known human immunodeficiency virus (HIV);
• •11. Subjects with chronic hepatitis B virus (HBV) infection, unless screening viral load \<100 IU/mL on stable doses of antiviral therapy. Note: Subjects with chronic HCV infection are allowed to enroll in the study but do not have a defined maximum viral load requirement for study entry;
• •12. Legal incapacity or limited legal capacity;
• •13. Pregnant or lactating women;
• •14. Any other condition, which in the opinion of the investigator, might impair the subject's tolerance of trial treatment, the safety of the individual subject, or the outcome of the trial;
• •15. Previous treatment of the current malignancy with a STAT inhibitor.