Open-label Phase 1b Study of ARQ 092 in Combination With Anastrozole

Exclusion Criteria

• •1. Anti-cancer therapy, such as chemotherapy, immunotherapy, targeted and hormonal/endocrine therapy, or investigational agents within five half-lives or two weeks (whichever is shorter) for oral drugs, five half-lives or four weeks (whichever is shorter) for intravenous drugs, and six weeks for nitrosoureas, mitomycin C, or bevacizumab prior to administration of the first dose of study drug
• •* To be eligible for study treatment, toxicity from prior treatment must recover to Grade ≤ 1, except for alopecia
• •* Concurrent systemic high-dose corticosteroids when used intermittently in an antiemetic regimen for central nervous system (CNS) metastases management or as a part of the premedication regimen are allowed
• •* Prior hormonal therapy (including, but not limited to, tamoxifen, megestrol acetate, fulvestrant, and GnRH analogs) for the treatment of recurrent/advanced endometrial cancer are not allowed
• •2. Radiation therapy within four weeks prior to administration of the first dose of study drug
• •• To be eligible for study treatment, radiation therapy-related toxicity must recover to Grade ≤ 1 prior to administration of the first dose of study drug. Concurrent palliative radiotherapy for local pain-control may be allowed, provided the subject does not meet criteria of progressive disease and treated lesions will not be included in the target/non-target lesion assessment.
• •3. Major surgical procedure within four weeks prior to administration of the first dose of study drug
• •• To be eligible for study treatment, all surgical wounds must be fully healed and any surgery-related adverse events (AE) must recover to Grade ≤ 1
• •4. Previous treatment with AKT inhibitors (e.g., MK-2206, GSK2141795, AZD5363)
• •5. Contraindications to treatment with anastrozole defined by the Investigator based on institutional Standard of Care (SOC), scientific evidence, expert medical judgment, or published literature
• •6. History of allergic reaction attributed to compound(s) of similar chemical or biologic composition as ARQ 092 or anastrozole
• •7. Unable or unwilling to swallow ARQ 092 or anastrozole
• •8. Known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis
• •• To be eligible for the study treatment, subjects must have stable disease ≥ 3 months, confirmed by magnetic resonance imaging (MRI) or computed tomography (CT) scan, and have CNS metastases well controlled by low-dose steroids, anti-epileptics, or other symptom-relieving medications
• •9. History of myocardial infarction (MI) or congestive heart failure defined as Class II to IV per the New York Heart Association (NYHA) classification within 6 months of the first dose of ARQ 092 (MI that occurred \> 6 months prior to the first dose of ARQ 092 will be permitted)
• •10. History of Type 1 or 2 diabetes mellitus requiring regular medication (other than oral hypoglycemic agents including metformin) or fasting glucose ≥ 160 mg/dL
• •11. Significant gastrointestinal disorder(s), that could in the opinion of the Investigator, interfere with the absorption, metabolism, or excretion of ARQ 092 (e.g., Crohn's disease, ulcerative colitis, extensive gastric resection)
• •12. Previous malignancy within 2 years of the first dose of study drugs, except tumors totally resected and/or not requiring therapy
• •13. Concurrent uncontrolled illness not related to cancer, including but not limited to:
• •• Ongoing or active infection, including human immunodeficiency virus (HIV), hepatitis B (HBV) (hepatitis B surface antigen \[HBsAg\] positive; subjects with documented laboratory evidence of HBV clearance may be enrolled) or hepatitis C (HCV) (positive HCV antibody), or bleeding
• •14. Psychiatric illness, substance abuse, and/or social situation that would limit compliance with study requirements
• •15. Blood transfusion within 5 days of the blood draw being used to confirm eligibility
• •16. Pregnant or breastfeeding