Phase II Study of Ilorasertib (ABT348) in Patients With CDKN2A Deficient Solid Tumors

Inclusion Criteria: 1. Patients with histologically confirmed, advanced or metastatic cancer for which standard curative or palliative measures do not exist or are no longer effective. 2. Patients must have CDKN2A-deficient tumor (deletion or mutation). Definition of CDKN2A deficient tumor: #1. CDKN2A deletion or mutation by any CLIA-certified sequencing OR #2. \>/= 30% of tumor cells with (at least) hemizygous deletion by FISH. Status will be determined from archived tissue. 3. Patients must have measurable disease by RECIST 1.1. 4. Patients must be \>/=18 years of age. 5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2. 6. Subject has adequate renal function as demonstrated by serum creatinine value of \</= 1.5 times the upper limit of normal (ULN) and either an estimated creatinine clearance value of \>/= 50 mL/min as determined by the Cockcroft-Gault formula or a creatinine clearance value of \>/= 50 mL/min based on a 24 hour urine collection. 7. Subject has adequate liver function as demonstrated by serum bilirubin \</= 2 x ULN and AST and ALT \</= 2.5 x ULN. For subjects with liver metastasis, adequate liver function is demonstrated by serum bilirubin \</= 2 x ULN and AST/ALT \</= 5.0 x ULN. 8. Subject has adequate bone marrow as demonstrated by absolute neutrophil count (ANC) \>/= 1,500/mm3 (1.5 x 10\^9/L); Platelets \>/= 100,000/mm2 (100 x 10\^9/L); Hemoglobin \>/= 9.0 g/dL (1.4 mmol/L). 9. Subject has QTc interval \< 500 msec on baseline electrocardiogram. 10. The subject has a documented Left Ventricular Ejection Fraction \> 50%. 11. Women of child-bearing potential and men must agree to use adequate contraception (one of the following listed below) prior to the study entry, for the duration of study participation and up to 3 months following completion of therapy. Women of child-bearing potential must have a negative pregnancy test within 7 days prior to initiation of treatment and/or post menopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential. -Total abstinence from sexual intercourse (minimum one complete menstrual cycle) -Vasectomized male subjects or vasectomized partner of female subjects -Intrauterine device -Double-barrier method (condoms, contraceptive sponge, diaphragm or vaginal ring with spermicidal jellies or cream) -Additionally, male subjects (including those who are vasectomized) whose partners are pregnant or might be pregnant must agree to use condoms for the duration of the study and for 3 months following completion of therapy. 12. Ability to understand and willingness to sign informed consent form prior to initiation of the study and any study procedures. 13. Signed informed consent approved by the Institutional Review Board prior to patient entry Exclusion Criteria: 1. Patients with CDKN2A wild type by a CLIA-certified laboratory 2. Subject has known active CNS involvement. The subject has untreated brain or meningeal metastases. CT scans are not required to rule out brain or meningeal metastases unless there is a clinical suspicion of central nervous system disease. Subjects with treated brain metastases that are radiographically or clinically stable for at least 4 weeks after therapy and have no evidence of cavitation or hemorrhage in the brain lesion(s) are eligible, providing that they are asymptomatic, and do not require corticosteroids (must have discontinued steroids at least 1 week prior to study drug administration). 3. Subject has received anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, hormonal, biologic or any investigational therapy within a period of 21 days or 5 half-lives (whichever is shorter) prior to Study Day 1. 4. Subject has unresolved toxicities from prior anti-cancer therapy, defined as any Common Terminology Criteria for Adverse Events (NCI CTCAE v 4.0) grade 2 or higher clinically significant toxicity (excluding alopecia). 5. Subject has had major surgery within 28 days prior to Study Day 1. 6. Subject currently exhibits symptomatic or persistent, uncontrolled hypertension defined as diastolic blood pressure \> 90 mmHg or systolic blood pressure \> 140 mmHg. Subjects may be re-screened if blood pressure is shown to be controlled with or without intervention. 7. Subject has proteinuria defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 4.0) grade \> 1 at baseline as measured by a urine dipstick (2+ or greater) and confirmed by a 24 hour urine collection (\>/= 1 g/24 hrs). Subjects may be re-screened if proteinuria is shown to be controlled with or without intervention. 8. Subject is receiving therapeutic anticoagulation therapy. Low dose anti-coagulation (e.g., low dose heparin or warfarin) for catheter prophylaxis will be permitted. Use of Aspirin for treatment of Atrial Fibrillation will also be permitted. 9. Patients with another primary malignancy within 3 years prior to starting study treatment with the exception of adequately treated basal cell carcinoma, squamous cell carcinoma or other non-melanomatous skin cancer, or in-situ carcinoma of the uterine cervix. 10. Clinically significant uncontrolled condition(s) including but not limited to: Active uncontrolled infection, Symptomatic congestive heart failure, Unstable angina pectoris or cardiac arrhythmia (subjects with stable atrial fibrillation are not excluded), History of adrenal insufficiency. 11. Psychiatric illness/social situation that would limit compliance with study requirements. 12. Subject has a known infection with HIV, Hepatitis B or Hepatitis C. 13. Subject is known to have poorly controlled diabetes mellitus defined as HbA1c \> 7%; subjects with a history of transient glucose intolerance due to corticosteroid administration are allowed in this study if all other inclusion/exclusion criteria are met. 14. Any medical condition which in the opinion of the study investigator places the subject at an unacceptably high risk for toxicities. 15. Subject is unable to swallow or absorb oral tablets normally 16. Female subject who is lactating or pregnant. 17. Subject takes CYP3A Inhibitors/Inducers within 7 days prior to the study drug administration.