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 consentmust be 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 priorcancer therapy to Grade ≤ 1 by the National Cancer Institute Common TerminologyCriteria for Adverse Events, version 5.0 (NCI-CTCAE, ver. 5.0) excluding thespecifications required 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. To calculate CCr, the body weight and SCrresults on the same day should be used.

11. Patients with MF and a known history of non-complicated staphylococcusinfection/colonization are eligible provided they continue to receive stable dosesof prophylactic 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 IPadministration to the end of the study (for men). WOCBP shall have a negativepregnancy test result in the screening examination and a negative pregnancy testresult in the pre-dose examination at Day 1.

• WOCBP do not include women who underwent permanent contraception,postmenopausal women (in the case of the absence of menstruation for 12 monthsor more regardless of other medical reasons and serum follicle stimulatinghormone (FSH) level >40 mIU/mL) and women who are anatomically incapable ofbecoming 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 priorto Cycle 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 inskin or 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 cervicalcarcinoma in situ, or ductal/lobular carcinoma in situ of the breast within the past 2 years may be 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 allowedto participate in this trial.

8. Active herpes simplex or herpes zoster. Patients on prophylaxis for herpes whostarted taking medication at least 30 days prior to the pretreatment visit, have nosigns of active infection, and whose last active infection was more than 6 monthsago may enter the study, and should continue to take the prescribed medication forthe duration of the study.

9. Experienced allergic reactions to monoclonal antibodies or other therapeuticproteins.

10. Known active autoimmune disease (e.g., Graves' disease; systemic lupuserythematosus; 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 directedtreatments, including topicals and radiation within 2 weeks of registrationtreatment).

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 tolerablewhile on 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 tolerablewhile on 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 theinvestigator or subinvestigator.