Safety, Tolerability, and Immunoregulatory Activity of Mogamulizumab (KW-0761) in Subjects With Advanced and/or Metastatic Solid Tumors

Inclusion criteria

• Informed Consent form signed by the subject.
• Males and females 18 years or older at the time of dose initiation.
• Histologically confirmed unresectable solid tumor malignancy with at least 1 measurable lesion. In the expansion phase, eligibility will be limited to metastatic triple negative breast cancer that has received prior taxane and anthracycline therapy; Metastatic NSCLC that is not ALK+ and does not have a EGFR sensitizing mutation; and metastatic gastric cancer
• Previously treated for an advanced cancer and there are no curative therapy options available
• Karnofsky Performance Status ≥70 in the 30 day baseline period immediately prior to dosing.
• Evidence of adequate organ function by standard laboratory tests:

• Serum creatinine (Cr) ≤1.5 X upper limit of normal (ULN)
• Serum total and (T -Bil ) ≤1.5 X ULN (prior diagnosis or past history consistent with Gilbert's syndrome is an exception)
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 X ULN
• Platelets (Plts) ≥ 100,000/μl
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥1000/mm3
• All female subjects of childbearing age must be either surgically sterile, postmenopausal for at least 1 year, or using an acceptable method of contraception. Examples of adequate methods of contraception include abstinence, intrauterine device, hormonal contraception, use of spermicide and a condom by sexual partner, or partner with a vasectomy. Adequate contraception must be used from the beginning of the screening period until at least 16 weeks after the last dose of KW-0761. Male subjects with partners of childbearing potential must use a barrier method of contraception from the day of the first dose of KW-0761 until at least 16 weeks after the last dose.
• Life expectancy > 12 weeks
• Previously treated for advanced cancer with no additional therapy options available known to prolong survival.

Exclusion criteria

• Evidence of clinically significant of central nervous system (CNS) metastases or symptomatic CNS metastases within 30 days prior to dosing.

History of autoimmune disease, except for vitiligo, diabetes, and autoimmune thyroiditis.

• A history of any major surgery within 6 weeks prior to dosing.
• Any history of systemic anticancer therapy (standard or experimental) completed within 30 days prior to dosing, with the exception of palliative ablation of lesion(s) as long as measurable disease lesion(s) remain for evaluation of exploratory endpoints.
• Any concomitant serious physical illness other than cancer (i.e., immune deficiency disease, bleeding disorder, etc.) within 1 year prior to dosing.
• Any history of Stevens-Johnson syndrome.
• Clinically significant heart disease, defined as NYHA Class III or IV.
• Any allergic reaction to a previously administered monoclonal antibody or other therapeutic protein.
• Any significant systemic infection within 4 weeks prior to dosing.
• Pregnancy or breast-feeding.
• An existing diagnosis of HIV, hepatitis B, hepatitis C, or any current laboratory findings or clinical signs and symptoms that suggest these conditions.
• Subjects with active herpes simplex or herpes zoster. Subjects with a history of herpes zoster who have had an outbreak within the last year will also be excluded. Subjects on prophylaxis for herpes who started taking medication at least 30 days prior to study entry, should continue to take the prescribed medication for the duration of the study.
• Unresolved immune- related adverse events following prior biological therapy
• Use of any investigational drugs within 30 days prior to dosing.
• Any condition that requires or is likely to require treatment with systemic corticosteroids within the Core Study Period and short term follow-up.
• Subjects that have had a myocardial infarction within the last 6 months.
• Subjects on any immunomodulatory drug.