Clinical trial NCT06285370: 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
Official title: An Open-Label, Multicenter, Single Arm Study to Evaluate the Efficacy and Safety of Anti-CCR4 Monoclonal Antibody Mogamulizumab (KW-0761) in Chinese Subjects With Mycosis Fungoides or Sézary Syndrome Previously Treated With Systemic Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cutaneous T-Cell Lymphoma
Keywords: mycosis fungoides/sézary syndrome
Lead sponsor: Kyowa Kirin Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-02-29
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label, multicenter, single arm study.
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the efficacy and safety of mogamulizumab (KW-0761) in chinese subjects with mycosis fungoides or sézary syndrome previously treated with systemic therapy

Detailed description: This is an open-label, multicenter, single arm study. This study consists of three parts: the Pretreatment Period, the Treatment Period, and the Follow-up Period. Subjects who meet all of eligibility criteria by the screening examination will be enrolled into the study, and start treatment with mogamulizumab within 30 days after obtaining consent. Mogamulizumab will be administered at the dose of 1.0 mg/kg as an intravenous (iv) infusion over at least 1 hour on Days 1, 8, 15, and 22 of Cycle 1 and on Days 1 and 15 of subsequent cycles. Each treatment cycle is set as 28 days. Subjects will continue the treatment of mogamulizumab until any of the criteria for study withdrawal is met. After stopping treatment, the end-of treatment examination will be conducted within 30 days after the last dose.The primary efficacy analysis will be conducted once all subjects terminate treatment by the confirmation of PD/drug intolerance/unacceptable toxicity or 12 months after the date of the first mogamulizumab administration of the last subject of entire study, whichever comes first.

Eligibility criteria: Inclusion Criteria:

1. Voluntarily signed and dated ethics committee (EC) approved informed consent form in accordance with regulatory and institutional guidelines. Written informed consent must be obtained prior to performing any study-related procedure.
2. Male and female Chinese subjects ≥18 years of age at the time that written informed consent 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 therapy includes, 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 any radiation 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 cancer therapy to Grade ≤ 1 by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE, ver. 5.0) excluding the specifications 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 and platelets ≥ 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)\> 50 mL/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 staphylococcus infection/colonization are eligible provided they continue to receive stable doses of prophylactic antibiotics.
12. Women of childbearing potential must have a negative pregnancy test within 7 days prior to receiving study medication.
13. Women of childbearing potential (WOCBP)\* and fertile men who consent to practice contraception using highly effective methods during a period from the day providing her consent to the end of the study (for women) or from the start of IP administration to the end of the study (for men). WOCBP shall have a negative pregnancy test result in the screening examination and a negative pregnancy test result 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 months or more regardless 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 features suggestive of LCT are recommended to have a biopsy performed within 4 months prior to Cycle 1 Day 1 to rule out transformed disease. Patients with a history of LCT but without current aggressive disease and no current evidence of LCT on pathology in skin or lymph nodes are eligible.
2. Diagnosed with a malignancy other than MF/SS in the past 2 years from the time that written informed consent is obtained. However, subjects with non-melanoma skin cancers, melanoma in situ, localized cancer of the prostate with current prostate-specific antigen 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 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 the subject's safety or ability to provide consent, or limit compliance with study requirements.
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 Heart Association \[NYHA\] classification);
   * unstable angina pectoris;
   * angioplasty, stenting, or myocardial infarction within 6 months;
   * uncontrolled hypertension (systolic blood pressure \[BP\] \> 160 mmHg or diastolic BP\>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 HIV infection, or hepatitis C disease or history of hepatitis C infection.
7. Tests positive for hepatitis B virus surface (HBs) antigen or both HBc antibody and hepatitis 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 to participate in this trial.
8. Active herpes simplex or herpes zoster. Patients on prophylaxis for herpes who started taking medication at least 30 days prior to the pretreatment visit, have no 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.
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 any investigational 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 prednisone equivalent) for at least 4 weeks prior to the registration may continue use although the investigator should attempt to taper the use to the lowest dosage tolerable while on study.
15. Subjects on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to the registration may continue use at the same dose, although the investigator should attempt to taper the use to the lowest dosage tolerable while 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 or who have received any of these agents within 4 weeks of registration, including but not 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 investigator or subinvestigator.

Primary outcomes:
measure: Overall Response Rate
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
Secondary outcomes:
measure: Skin disease response rate;
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
measure: Lymth nodes response rate
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
measure: Visceral metastases response rate;
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
measure: Blood disease response rate;
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
measure: Progression Free Survival
timeFrame: Up to 32 months.
measure: Duration of response (DOR)
timeFrame: Up to 32 months.
measure: Time to response (TTR)
timeFrame: Up to 29 months.
measure: Response rate of lymph node evaluated by Lugano 2014.
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
measure: Response rate of viscera evaluated by Lugano 2014 criteria.
timeFrame: At the end of each cycle (each cycle is 28 days) until progression up to 29 months;
Other outcomes:
measure: To evaluate pharmacokinetics (plasma mogamulizumab concentration) of mogamulizumab.
timeFrame: Day 1 (Before infusion and at the end of the infusion), Day 8, Day 15, Day 22, Days 28 in Cycle 1; Day 15, Days 28 in Cycle 2 and 3; Days 28 in Cycle 4, 6, 8, 10, 12; Last visit. Each cycle is 28 days.
measure: To evaluate immunogenicity (anti-mogamulizumab antibody) of mogamulizumab.
timeFrame: Day 1, Days 28 in Cycle 1; Days 28 in Cycle 2, 3, 4, 6, 8, 10, 12; Last visit. Each cycle is 28 days.
measure: To evaluate the effects of skin disease on health-related Quality of Life (HRQoL) -Skindex 29.
timeFrame: Day 1, Days 28 in Cycle 1; Days 28 in odd cycles (Cycle 3, 5, 7, 9, 11, 13, 15…); Last visit. Each cycle is 28 days.
measure: The incidence and frequency of treatment-related adverse events (TEAEs) and drug-related TEAEs as assessed by CTCAE v5.0.
timeFrame: Information from the date of the subject's signing the ICF until 90 days after the last dose or initiation of alternative therapy, whichever comes first will be recorded.
Locations:
city: Beijing
country: China
facility: Cancer Hospital Chinese Academy of Medical Sciences
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital, Department of Dermatology and Venereology
state: Beijing
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center, Department of Medical Oncology
state: Guangdong
city: Harbin
country: China
facility: The 2nd Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Wuhan
country: China
facility: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Hohhot
country: China
facility: The Affiliated Hospital of Inner Mongolia Medical University
state: Inner Mongolia
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Hangzhou
country: China
facility: ZheJiang Cancer Hospital
state: Zhejiang
city: Henan
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Zhengzhou
Study officials:
affiliation: Chinese Academy of Medical Sciences
name: Yuankai Shi
role: PRINCIPAL_INVESTIGATOR
References: