Clinical Trials

Inclusion Criteria:

•  Have a histologically confirmed diagnosis of advanced metastatic or progressive solid tumor:
  • who are refractory to, or intolerant of, established therapy known to provide clinical benefit for their condition (Monotherapy Arm);
  • that are eligible for standard of care treatment with ipilimumab and nivolumab according to the Prescribing Information in the Label (Combination Arm).  
• Naïve to prior treatment with any PD1 or CTLA-4 inhibitor (Combination Arm Only).
• Have one or more tumors measurable as outlined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1.
• Have a life expectancy ≥ 3 months.
• ≥ 18 years of age.
• Have a negative pregnancy test (if female of childbearing potential).
• Have acceptable liver function:  
  • Bilirubin ≤ 1.5 x upper limit of normal (ULN) (unless associated with Gilbert syndrome);
  • Aspartate aminotransferase (AST/SGOT), alanine aminotransferase (ALT/SGPT) and alkaline phosphatase ≤ 2.5 x ULN*. 
  • *If liver metastases are present, then ≤ 3 x ULN is allowed.
• Have acceptable renal function: calculated creatinine clearance ≥ 30 mL/min.
• Have acceptable hematologic status:  
  • Granulocyte ≥ 1500 cells/mm^3;
  • Platelet count ≥ 100,000 (plt/mm3);  
  • Hemoglobin ≥ 8 g/dL.   

• Have acceptable coagulation status:  
  • Prothrombin time (PT) within 1.5 x normal limits;
  • Activated partial thromboplastin time (aPTT) within 1.5 x normal limits.  
• Be nonfertile or agree to use an adequate method of contraception. Sexually active patients and their partners must use an effective method of contraception (hormonal or barrier method of birth control; or abstinence) prior to study entry and for the  duration of study participation and for at least 3 months (males) and 6 months  (females) after the last study drug dose.  Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.  
• Have read and signed the Institutional Review Board (IRB)-approved informed consent  form (ICF) prior to any study-related procedure. (In the event that the patient is rescreened for study participation or a protocol amendment alters the care of an  ongoing patient, a new ICF must be signed). 

Exclusion Criteria:

• Contraindications to ipilimumab or nivolumab treatment (Combination Arm only).
• New York Heart Association Class III or IV cardiac disease, or myocardial infarction,  severe unstable angina, coronary/peripheral artery bypass graft, congestive heart failure within the past 6 months or evidence of ischemia on electrocardiogram (ECG) within 14 days prior to Cycle 1/Day 1.
• Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of > 450 msec in men and > 470 msec in women.
• Have a seizure disorder requiring anticonvulsant therapy.
• Presence of symptomatic central nervous system metastatic disease or disease that  requires local therapy such as radiotherapy, surgery, or increasing dose of steroids  within the prior 2 weeks.
• Have severe chronic obstructive pulmonary disease with hypoxemia (defined as resting O2 saturation of ≤ 90% breathing room air).
• Have undergone major surgery within 2 weeks prior to Cycle 1/Day 1.
• Have active, uncontrolled bacterial, viral, or fungal infections, requiring systemic  therapy.
• Are pregnant or nursing.
• Received treatment with radiation therapy, surgery, chemotherapy, or investigational  therapy within 28 days or 5 half-lives, whichever occurs first, prior to study entry (6 weeks for nitrosoureas or mitomycin C).
• Contraindications to an FDG PET Scan.
• Are unwilling or unable to comply with procedures required in this protocol.
• Have known infection with human immunodeficiency virus, hepatitis B, or hepatitis C.  Patients with history of chronic hepatitis that is currently not active are eligible.
• Have a serious nonmalignant disease (e.g., hydronephrosis, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the  Investigator and/or the Sponsor.
• Are currently receiving any other investigational agent.
• Have exhibited allergic reactions to a similar structural compound, biological agent,  or formulation.
• Have malabsorption conditions (e.g., Crohn's disease, etc.) or have undergone significant  surgery to the gastrointestinal tract that could impair absorption or that could  result in short bowel syndrome with diarrhea due to malabsorption.
• Systemic corticosteroids greater than the equivalent of 10mg of prednisone or equivalent alternative steroid (except physiologic dose for adrenal replacement  therapy) or other immunosuppressive agents (e.g., cyclosporine or methotrexate).