Study of KW-0761 Versus Vorinostat in Relapsed/Refractory CTCL

Phase 3 randomized study to compare the progression free survival of subjects with
relapsed/refractory CTCL who receive KW-0761 versus those who receive vorinostat. Subjects
who progress on vorinostat will be allowed to cross over to KW-0761 upon progression.

Inclusion Criteria:

- Males and female subjects ≥ 18 years of age at the time of enrollment, except in Japan
where subjects must be ≥ 20 years of age at the time of enrollment

- Histologically confirmed diagnosis of mycosis fungoides (MF) or Sezary Syndrome (SS)

- Stage IB, II-A, II-B, III and IV

- Subjects who have failed at least one prior course of systemic therapy. Psoralen plus
ultraviolet light therapy (PUVA) is not considered to be a systemic therapy

- Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1 at study
entry

- Resolution of all clinically significant toxic effects of prior cancer therapy to
grade ≤1 by the National Cancer Institute Common Terminology Criteria for Adverse
Events, version 4.0 (NCI-CTCAE, v.4.0)

- Adequate hematological, renal and hepatic function

- Subjects previously treated with anti-CD4 antibody or alemtuzumab are eligible
provided their CD4+ cell counts are ≥ 200/mm3

- Subjects with mycosis fungoides (MF) and a known history of non-complicated
staphylococcus infection/colonization are eligible provided they continue to receive
stable doses of prophylactic antibiotics

- Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7
days of receiving study medication

- WOCBP and male subjects as well as their female partners of childbearing potential
must agree to use effective contraception throughout the study and for 6 months after
the last dose of KW-0761

Exclusion Criteria:

- Prior treatment with KW-0761 or vorinostat.

- Large cell transformation. However, subjects with a history of LCT but without current
aggressive disease and no current evidence of LCT on pathology in skin and lymph nodes
would be eligible.

- Diagnosed with a malignancy in the past two years. However, subjects with non-melanoma
skin cancers, melanoma in situ, localized cancer of the prostate with current PSA of
<0.1 ng/mL, treated thyroid cancer or cervical carcinoma in situ or ductal/lobular
carcinoma in situ of the breast within the past two years may enroll as long as there
is no current evidence of disease.

- Clinical evidence of central nervous system (CNS) metastasis.

- Psychiatric illness, disability or social situation that would compromise the
subject's safety or ability to provide consent, or limit compliance with study
requirements.

- Significant uncontrolled intercurrent illness

- Known or tests positive for human immunodeficiency virus (HIV), human T-cell leukemia
virus (HTLV-1), hepatitis B or hepatitis C.

- Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes who started
taking medication at least 30 days prior to study entry, and have no active signs of
active infection, and whose last active infection was more than 6 months ago, may
enter the study, and should continue to take the prescribed medication for the
duration of the study.

- Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.

- Known active autoimmune disease will be excluded. (For example, Grave's disease;
systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease; psoriasis).

- Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.