A Study to Evaluate the Efficacy and Safety of KW-0761 in Chinese Subjects With Mycosis Fungoides or Sézary Syndrome Previously Treated With Systemic Therapy

Inclusion Criteria:

1. Voluntarily signed and dated ethics committee (EC) approved informed consent form inaccordance with regulatory and institutional guidelines. Written informed consent mustbe obtained prior to performing any study-related procedure.
2. Male and female Chinese subjects ≥18 years of age at the time that written informedconsent is obtained.
3. Histologically confirmed diagnosis of MF or SS;
4. Stage IB, IIA, IIB, III, and IV.
5. Patients who have failed at least one prior systemic therapy. Systemic therapyincludes, for example, interferon, denileukin diftitox, retinoid, photopheresis,anti-neoplastic chemotherapy, methotrexate, and Histone deacetylase (HDAC) inhibitor.

• Ultraviolet light therapy (Psoralen plus ultraviolet A [PUVA], ultraviolet B [UVB]etc), systemic steroid monotherapy, topical steroid or other topical agents, and anyradiation are not considered to be a systemic therapy.

6. Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 1.
7. The subject has resolution of all clinically significant toxic effects of prior cancertherapy to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria forAdverse Events, version 5.0 (NCI-CTCAE, ver. 5.0) excluding the specificationsrequired in 8, 9, and 10 below.
8. Adequate hematological function:

• absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L;
• platelets ≥ 100.0 × 10^9/L;
• in subjects with known bone marrow involvement, ANC must be ≥ 1.0 × 10^9/L andplatelets ≥ 75.0 × 10^9/L.

9. Adequate hepatic function:

• Total bilirubin ≤ 1.5 times the specific institutional upper limit of normal (ULN);
• aspartate transaminase (AST) and alanine transaminase (ALT) each ≤ 2.5 × ULN or ≤ 5.0 × ULN in the presence of known hepatic involvement by CTCL.

10. Adequate renal function:

• serum creatinine (SCr) ≤ 1.5 × ULN, or calculated creatinine clearance (CCr)> 50mL/min using the Cockcroft-Gault formula. (CCr={((140-age) × body weight)/(72 × SCr)} × 0.85 (if female))

11. Patients with MF and a known history of non-complicated staphylococcusinfection/colonization are eligible provided they continue to receive stable doses ofprophylactic antibiotics.
12. Women of childbearing potential must have a negative pregnancy test within 7 daysprior to receiving study medication.
13. Women of childbearing potential (WOCBP)* and fertile men who consent to practicecontraception using highly effective methods during a period from the day providingher consent to the end of the study (for women) or from the start of IP administrationto the end of the study (for men). WOCBP shall have a negative pregnancy test resultin the screening examination and a negative pregnancy test result in the pre-doseexamination at Day 1.

• WOCBP do not include women who underwent permanent contraception, postmenopausalwomen (in the case of the absence of menstruation for 12 months or moreregardless of other medical reasons and serum follicle stimulating hormone (FSH)level >40 mIU/mL) and women who are anatomically incapable of becoming pregnant.

Exclusion Criteria:

1. Current evidence of large cell transformation (LCT). Patients with clinical featuressuggestive of LCT are recommended to have a biopsy performed within 4 months prior toCycle 1 Day 1 to rule out transformed disease. Patients with a history of LCT butwithout current aggressive disease and no current evidence of LCT on pathology in skinor lymph nodes are eligible.
2. Diagnosed with a malignancy other than MF/SS in the past 2 years from the time thatwritten informed consent is obtained. However, subjects with non-melanoma skincancers, melanoma in situ, localized cancer of the prostate with currentprostate-specific antigen of < 0.1 ng/mL, treated thyroid cancer or cervical carcinomain situ, or ductal/lobular carcinoma in situ of the breast within the past 2 years maybe enrolled as long as there is no current evidence of disease.
3. Clinical evidence of central nervous system metastasis.
4. Psychiatric illness, disability or social situation that would compromise thesubject's safety or ability to provide consent, or limit compliance with studyrequirements.
5. Significant uncontrolled intercurrent illness including, but not limited to:

• uncontrolled infection requiring antibiotics;
• clinically significant cardiac disease (Class III or IV of the New York HeartAssociation [NYHA] classification);
• unstable angina pectoris;
• angioplasty, stenting, or myocardial infarction within 6 months;
• uncontrolled hypertension (systolic blood pressure [BP] > 160 mmHg or diastolicBP>100 mmHg, found on 2 consecutive measurements separated by a 1-week period)despite 2 antihypertensive medications;
• clinically significant cardiac arrhythmia;
• uncontrolled diabetes.

6. Known or tests positive for human immunodeficiency virus (HIV) or history of HIVinfection, or hepatitis C disease or history of hepatitis C infection.
7. Tests positive for hepatitis B virus surface (HBs) antigen or both HBc antibody andhepatitis B virus (HBV)-DNA positive (over the lower limit of quantification);

• Patients with HBs antibody positive due to a hepatitis B vaccine will be allowed toparticipate in this trial.

8. Active herpes simplex or herpes zoster. Patients on prophylaxis for herpes who startedtaking medication at least 30 days prior to the pretreatment visit, have no signs ofactive infection, and whose last active infection was more than 6 months ago may enterthe study, and should continue to take the prescribed medication for the duration ofthe study.
9. Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins.
10. Known active autoimmune disease (e.g., Graves' disease; systemic lupus erythematosus;rheumatoid arthritis; Crohn's disease; psoriasis).
11. Is pregnant (confirmed by beta human chorionic gonadotrophin [β-HCG]) or lactating.
12. Prior treatment with mogamulizumab.
13. Have had any therapy directed against the subject's underlying cancer or anyinvestigational medications within 4 weeks of registration (skin directed treatments,including topicals and radiation within 2 weeks of registration treatment).
14. Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisoneequivalent) for at least 4 weeks prior to the registration may continue use althoughthe investigator should attempt to taper the use to the lowest dosage tolerable whileon study.
15. Subjects on a stable dose of medium or low potency topical corticosteroids for atleast 4 weeks prior to the registration may continue use at the same dose, althoughthe investigator should attempt to taper the use to the lowest dosage tolerable whileon study.
16. History of allogeneic transplant.
17. Autologous hematopoietic stem cell transplant within 90 days of the screening.
18. Patients on any immunomodulatory drug for concomitant or intercurrent conditions orwho have received any of these agents within 4 weeks of registration, including butnot limited to the following, will be excluded: low-dose or oral methotrexate,azathioprine, iv immunoglobulin, low-dose or oral cyclophosphamide, cyclosporine,mycophenolate, infliximab, etanercept, leflunomide, adalimumab, lenalidomide,abatacept, rituximab, anakinra, interferon-β, interleukin-2, and natalizumab.
19. Anyone otherwise considered unsuitable participation in the study by the investigatoror subinvestigator.