Study of NK012 in Patients With Refractory Solid Tumors

• Toxicity profile of NK012 in all patients [ Time Frame: Minimum of 30 days after the last dose of study drug and followed for any unresolved adverse events ] [ Designated as safety issue: No ]
• Antitumor activity of NK012 according to RECIST criteria in all patients [ Time Frame: Measured every 6 weeks (i.e., every 2 cycles) while receiving study drug ] [ Designated as safety issue: No ]
• Limited pharmacokinetics of NK012 [ Time Frame: Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable ] [ Designated as safety issue: No ]

• Toxicity profile of NK012 in all patients [ Time Frame: Minimum of 30 days after the last dose of study drug and followed for any unresolved adverse events ]
• Antitumor activity of NK012 according to RECIST criteria in all patients [ Time Frame: Measured every 6 weeks (i.e., every 2 cycles) while receiving study drug ]
• Limited pharmacokinetics of NK012 [ Time Frame: Sampling during Cycle 1 (first 3 weeks) and up to Day 3 of Cycle 2, if applicable ]

The purpose of this study is to determine whether NK012 is safe and effective in the treatment of refractory solid tumors

This is a Phase I dose-escalation study of the intravenous administration of NK012 in patients with refractory solid tumors. Patients will receive NK012 as an intravenous infusion over 30 minutes on Day 1 followed by a 20-day observation period for a total of 21 days (3 weeks) per cycle. Two patient populations will be evaluated separately: patients with UGT1A1*28 genotype homozygous wild type (wt/wt) and heterozygous (wt/*28) variants as one group, and patients with UGT1A1*28 homozygous variant (*28/*28) as another group.

Inclusion Criteria:

• Histologically confirmed malignant solid tumor for which there are no known regimens or protocol treatments of higher efficacy or priority
• Failed conventional therapy for the cancer or have a malignancy for which a conventional therapy does not exist
• Recovered from all acute adverse effects of prior therapies, excluding alopecia (hair loss)
• Life expectancy of at least 12 weeks and an EOCG performance status of 0 or 1
• 18 years of age or older
• Adequate kidney, liver, and bone marrow function
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or have not recovered from adverse effects due to agents administered more than 4 weeks earlier
• Receiving any other investigational agent
• History of brain metastases or spinal cord compression, unless irradiated a minimum of 4 weeks before study entry and stable without requirement for corticosteroids for > 1 week
• History of allergic reactions attributed to compounds of similar chemical composition to NK012
• Concurrent serious infections (i.e., requiring an intravenous antibiotic)
• Pregnant women or women of childbearing potential who are not using methods to avoid pregnancy; a negative pregnancy test (urine or serum) must be documented at baseline and before every NK012 administration for women of childbearing potential; no breast-feeding while on study
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, unstable angina pectoris or psychiatric illness/social situations that would limit compliance with study requirements
• Significant cardiac disease
• History of serious ventricular arrhythmia
• Positive for anti-HbsAg, anti-HCV, anti-HIV, or anti-syphilis antibodies