A Phase 1, Open-Label, Dose-Escalation Study of NEV801, Administered to Patients With Advanced Cancers

Inclusion Criteria

• Male or female at least 18 years of age
• Willing and able to provide written informed consent and comply with the requirements of the study
• Pathologically confirmed advanced malignancy for which standard therapy proven to provide clinical benefit does not exist or is no longer effective
• Part A only: Evaluable disease, measurable either on physical examination or by imaging according to RECIST v1.1 or by informative tumor marker(s)
• Part B only: Selected tumor type(s), as determined by results of Part A
• Part B only: Measurable disease, using RECIST v1.1
• ECOG performance status of 0 or 1

Exclusion Criteria

• Receipt of more than 5 prior regimens of cytotoxic chemotherapy (unless prior approval is granted by the Sponsor)
• Any chemotherapy, immunomodulatory drug therapy, antineoplastic hormonal therapy, immunosuppressive therapy, corticosteroids > 20 mg/day prednisone or equivalent (unless administered to prevent contrast material reactions during radiographic procedures), or growth factor treatment (e.g., erythropoietin) within 14 days before first NEV801 dose
• Presence of an acute or chronic toxicity of prior chemotherapy, with the exception of alopecia, that has not resolved to ≤ Grade 1, according to the NCI CTCAE v4.03
• Radiotherapy within 28 days before the first NEV801 dose
• Use within 7 days of the first NEV801 dose, or anticipated use, of agents that are strong inhibitors of CYP3A4, CYP1A2 and CYP2D6 enzymes (unless approved by the Sponsor) - see Section 5.6 for a list of strong CYP3A4, CYP1A2 and CYP2D6 inhibitors
• Use of any investigational agents within 28 days of the first NEV801 dose
• Major surgery within 28 days before the first NEV801 dose
• Life expectancy < 12 weeks
• Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), angina, myocardial infarction, cerebrovascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism within 3 months before the first NEV801 dose
• History of or ongoing cardiac dysrhythmias requiring treatment, atrial fibrillation of any grade, or persistent prolongation of the QT corrected by the Fridericia formula (QTcF) interval to > 450 msec for males or > 470 msec for females
• Previous malignancy other than non-squamous-cell carcinoma of skin or carcinoma in situ of the uterine cervix (unless the tumor was treated with curative intent more than 2 years before the first NEV801 dose)
• Active bacterial, viral, or fungal infection requiring systemic therapy.
• Known HIV infection or AIDS-related illness
• Known active viral hepatitis
• Presence of genetic polymorphism of UGT1A1 leading to reduced glucuronidation
• Pregnant or lactating female
• Women of childbearing potential, unless they agree to use 2 contraceptive methods which, in the opinion of the Investigator, are effective and adequate for that subject's circumstances while on study drug and for 3 months afterward
• Men who partner with a woman of childbearing potential, unless they agree to use 2 effective contraceptive methods (i.e., a condom, female partner using oral, injectable, or barrier method) while on study drug and for 3 months afterward
• Any severe, acute, or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or NEV801 administration; that may interfere with the informed consent process or with compliance with the requirements of the study; or that may interfere with the interpretation of study results and, in the Investigator's opinion, would make the subject inappropriate for entry into this study