Phototherapy and Mogamulizumab in Early Stage MF (PLIGHT)

Inclusion Criteria:

• Be willing and able to provide written informed consent/assent for the trial.

• Be at least 18 years of age on day of signing informed consent.

• Able to adhere to the study visit schedule and other protocol requirements.

• Diagnosis of mycosis fungoides (MF) based on a combination of histological,clinical, and immunophenotypical criteria. The histological criteria will be basedon skin biopsy from the most representative skin area.

• CTCL (Mycosis fungoides) stage IA-IIA (early stage) at the time of screening witheither B0 blood involvement with a positive T-cell receptor (TCR) gene rearrangementor B1 blood involvement with positive TCR gene rearrangement. The TNMB system willbe used to classify the stage of disease.

• Any number of prior therapies is allowed.

• Patients must have stable disease (SD), partial response (PR) or disease progression (PD) after 3 or more months prior to date of consent of one of the followingtreatments: Phototherapy [narrow-band ultraviolet B (nb-UVB) or Psoralen ultravioletA (PUVA)] alone or PUVA in combination with topical therapy such as nitrogenmustard, steroids, or bexarotene gel progression of skin disease on long-termmaintenance phototherapy.

• A minimum washout period of 14 days prior after previous CTCL therapy before thefirst day of treatment.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.

• Subjects on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisoneequivalent) for at least 4 weeks prior to day 1 of treatment may continue use.Investigator should attempt to taper the use to the lowest dosage tolerable while onstudy. Initiation of treatment with systemic corticosteroids or increase in dosewhile on study is not permitted except to treat an infusion reaction. Subjects mayreceive intra-articular corticosteroid injections, intraocular corticosteroid drops,inhalation or nasal corticosteroids and replacement doses of systemiccorticosteroids as needed.

• Subjects on a stable dose of topical calcineurin inhibitors, medium or low potencytopical corticosteroids for at least 4 weeks prior to the consent date may continueuse at the same dose, although the investigator should attempt to taper the use tothe lowest dosage tolerable while on study. Initiation of treatment with topicalcorticosteroids while on study is not permitted except to treat an acute rash.

• Resolution of all clinically significant toxic effects of prior cancer therapy toGrade ≤ 1 by the National Cancer Institute Common Terminology Criteria for AdverseEvents, version 5.0 (NCI-CTCAE, v.5.0).

• Laboratory parameters required to be met prior to the initiation of each cycle: A)Adequate hepatic and kidney function defined as Serum bilirubin less than 1.5x upperlimit of normal (ULN), AST and ALT must be less than 2.5x ULN, Serum creatinine < 1.5x upper limit of normal (ULN) OR calculated creatinine clearance ≥ 60 mL/minusing the Cockcroft-Gault formula. B) Adequate hematological function defined asSerum Platelets greater than or equal to 100,000/mm3, Hemoglobin greater than orequal to 9g/dL without transfusion support and Absolute neutrophil count (ANC)greater than or equal to 1,500 cells/μL (greater than or equal to 1,500/mm3).

• Subjects previously treated with POTELIGEO (mogamulizumab-kpkc) are eligible if theyachieved complete response on mogamulizumab and the last treatment was over 1 yearago.

• Female of childbearing potential (FCBP) must have a negative pregnancy test within 7days of receiving study medication.

• Male subjects and their female partners of childbearing potential must be willing touse an appropriate method of contraception defined as oral contraceptives, doublebarrier method (condom plus spermicide or diaphragm plus spermicide) or practicetrue abstinence from sexual intercourse (periodic abstinence, e.g., calendar,ovulation, symptothermal, post-ovulation methods and withdrawal are not acceptablemethods of contraception) during the study and for 3 months after the last dose.

Exclusion Criteria:

• Current evidence of large cell transformation (LCT) on biopsy. Subjects withclinical features suggestive of LCT must have a biopsy performed within 4 monthsprior to Cycle

1 Day 1 to rule out transformed disease. Subjects with a history of LCT but withoutcurrent aggressive disease and no current evidence of LCT on pathology in skin orlymph nodes would be eligible.

• Has a history or current evidence of any condition, therapy, or laboratoryabnormality that might confound the results of the trial, interfere with thesubject's participation for the full duration of the trial, or is not in the bestinterest of the subject to participate, in the opinion of the treating investigator (including but not limited to severe dermatitis). Any active infection requiringsystemic therapy, including human immunodeficiency virus (HIV), human T-celllymphotropic virus (HTLV), Hepatitis B, and/or Hepatitis C.

• Active herpes simplex or herpes zoster. Subjects on prophylaxis for herpes whostarted taking medication at least 30 days prior to consent, and have no activesigns of active infection, and whose last active infection was more than 6 monthsago, may enter the study, and should continue to take the prescribed prophylacticmedication for the duration of the study.

• Any major surgery or radiation therapy within four weeks.

• Diagnosed with a malignancy in the past 2 years except nonmelanoma skin cancers,melanoma in situ, localized cancer of the prostate with current prostate-specificantigen of less than 0.1 ng/mL, treated thyroid cancer, cervical carcinoma in situor ductal/lobular carcinoma in situ of the breast with in the past 2 years mayenroll as long as there is no current evidence of active disease.

• If pregnant or breastfeeding or expecting to conceive or father children within theprojected duration of the trial, starting with consent through 30 after the lastdose of trial treatment.

• Significant uncontrolled intercurrent illness including, but not limited to:uncontrolled infection requiring systemic antibiotics; clinically significantcardiac disease (class III or IV of the New York Heart Association [NYHA]classification); unstable angina pectoris; angioplasty, stenting, or myocardialinfarction within 6 months; uncontrolled hypertension (systolic blood pressure (BP)greater than 160 mm Hg or diastolic BP greater than 100 mm Hg, found on 2consecutive measurements separated by a 1-week period) despite 2 anti-hypertensivemedications; clinically significant cardiac arrhythmia or uncontrolled diabetes.

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

• Documented prior hypersensitivity (i.e., allergic reaction) to POTELIGEO (mogamulizumab-kpkc) with a severity of Grade 2 or higher.

• Experienced allergic (does not include a grade 1-2 infusion-related) reactions tomonoclonal antibodies or other therapeutic proteins.

• History of allogeneic transplant or autologous hematopoietic stem cell transplant.

• Subjects on any immunomodulatory drug for concomitant or intercurrent conditionsother than T-cell lymphoma or who have received any of these agents within 4 weeksof treatment, including but not limited to the following, will be excluded: low doseor oral methotrexate; azathioprine; iv immunoglobulin; low dose or oralcyclophosphamide; cyclosporine; mycophenolate; infliximab; etanercept; leflunomide;adalimumab; lenalidomide; abatacept; rituximab; anakinra; interferon-β; IL-2 andnatalizumab.

• Currently taking potential photosensitizing medications.

• Known or symptoms of photosensitivity disorders, including porphyria, lupuserythematosus, xeroderma pigmentosum, vitiligo, etc.

• History of phototoxic eruptions, photoallergic eruptions or PMLE (polymorphous lighteruption).