Mogamulizumab Every 4 Week dosing in Participants with R/R CTCL

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Kyowa Kirin Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

13 Jan 2021 → 11 Apr 2025

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Kyowa Kirin Inc.

External identifiers

EU CT number

2024-515921-27-00

EudraCT number

2020-004537-20

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Pharmacodynamic, Others, Efficacy

To evaluate the safety and tolerability of mogamulizumab given every 4
weeks in participants with relapsed/refractory mycoses fungoides (MF)
or Sézary syndrome (SS) subtypes of CTCL.

Secondary objectives 1

1. • To characterize the pharmacokinetics (PK) of mogamulizumab following 2 mg/kg Q4W IV administration. • To evaluate the anti-tumor activity of mogamulizumab in participants with relapsed/refractory MF and SS (overall response rate [ORR] and duration of response [DOR]) as assessed by Investigators. • To characterize the immunogenicity of mogamulizumab following 2 mg/kg Q4W IV administration. • To evaluate the pharmacodynamic (PDyn) profile. Exploratory Objectives: • To further evaluate the PDyn profile. • To further evaluate the anti-tumor activity of mogamulizumab utilizing time to next treatment (TTNT).

Conditions and MedDRA coding

Mycosis fungoides/Sezary syndrome recurrent

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 3

1. 1) Voluntarily signed and dated IRB / EC approved informed consent obtained prior to performing any study-related procedure in accordance with regulatory and institutional guidelines. 2) Male and female participants equal to or more than 18 years of age at the Pre-treatment Visit. 3) Histologically confirmed diagnosis of MF or SS. - Stage IB, II-A, II-B, III, or IV (Olsen, 2011); 4) Participants who have failed at least one prior course of systemic therapy (e.g., interferon, bexarotene, photopheresis, anti-neoplastic chemotherapy). Psoralen plus UVA is not considered a systemic therapy. 5) Eastern Cooperative Oncology Group performance status score of ≤ 1. 6) The participant has resolution of all clinically significant toxic effects of prior cancer therapy to Grade ≤ 1 according to NCI-CTCAE (v.5.0), excluding the specifications required in criteria 7, 8, and 9 below.
2. 7) Adequate hematological function, defined as: a) ANC ≥ 1000 cells/μL (≥ 1000/mm3 ) and b) Platelets ≥ 75,000 cells/μL (≥ 75,000/mm3 ); 8) Adequate hepatic function, defined as: a) Bilirubin ≤ 1.5 times the specific institutional ULN, except for participants with Gilbert's syndrome. b) Aspartate transaminase/serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase/serum glutamic-pyruvic transaminase (ALT/SGPT) each ≤ 2.5 × ULN or ≤ 5.0 × ULN in the presence of known hepatic involvement by CTCL. 9) Adequate renal function, defined as calculated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula. 10) Participants previously treated with anti-CD4 antibody or alemtuzumab are eligible, provided their CD4+ cell counts are ≥ 200/mm3. 11) Participants with MF and a known history of non-complicated staphylococcus colonization/infection are eligible, provided they continue to receive stable doses of prophylactic antibiotics.
3. 12) Women of childbearing potential must have a negative pregnancy test within 7 days prior to receiving study medication. 13) Women of childbearing potential must agree to use effective contraception, defined as oral contraceptives, double barrier method (condom plus spermicide or diaphragm plus spermicide) or practice true abstinence from sexual intercourse (periodic abstinence, e.g., calendar, ovulation, symptothermal, post-ovulation methods, and withdrawal, are not acceptable methods of contraception) during the study and for 6 months after the last dose. • Women of childbearing potential includes any female who has experienced menarche and who has not undergone successful surgical sterilization or is not postmenopausal (defined as amenorrhea ≥ 12 consecutive months without an alternative medical cause).

Exclusion criteria 4

1. 1) Current evidence of large cell transformation (LCT). Participants with clinical features suggestive of LCT must have a biopsy performed within 4 months prior to Cycle 1 Day 1 to rule out transformed disease. Participants with a history of LCT but without current aggressive disease and no current evidence of LCT on pathology in skin or lymph nodes would be eligible. 2) Diagnosed with another malignancy in the past 2 years. However, participants 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 enroll as long as there is no current evidence of disease. 3) Clinical evidence of CNS metastasis. 4) Psychiatric illness, disability, or social situation that would compromise the participant's safety or ability to provide consent, or limit compliance with study requirements.
2. 5) Significant uncontrolled intercurrent illness including, but not limited to: a) uncontrolled infection requiring antibiotics; b) clinically significant cardiac disease (class III or IV of the NYHA classification); c) unstable angina pectoris; d) angioplasty, stenting, or myocardial infarction within 6 months; e) uncontrolled hypertension (systolic BP > 160 mmHg or diastolic BP > 100 mmHg, found on two consecutive measurements separated by a one week period) despite the use of two anti-hypertensive medications; f) clinically significant cardiac arrhythmia; or g) uncontrolled diabetes.
3. 6) Active HIV, HTLV-1, hepatitis B, or hepatitis C disease. 7) Active herpes simplex or herpes zoster. Participants on prophylaxis for herpes may enter the study and should continue to take the prescribed medication for the duration of the study if they started taking medication at least 30 days prior to the Pre-treatment Visit, have no signs of active infection, and their last active infection was more than six months ago. 8) Experienced allergic reactions to monoclonal antibodies or other therapeutic proteins. 9) Hypersensitivity to the active substance or to any of the excipients. 10) Known active autoimmune disease (i.e., Graves' disease; systemic lupus erythematosus; rheumatoid arthritis; Crohn's disease; psoriasis). 11) Is pregnant (confirmed by beta human chorionic gonadotropin) or lactating. 12) Prior treatment with mogamulizumab. 13) Have had any therapy directed against the participant's underlying cancer or any investigational medications within 4 weeks of enrollment (skin directed treatments, including topicals and radiation within 2 weeks of enrollment). However, participants with rapidly progressive malignant disease may be enrolled prior to this period after discussion with and approval from the Medical Monitor.
4. 14) Participants on a stable dose of a low dose systemic corticosteroid (≤ 20 mg prednisone equivalent) for at least 4 weeks prior to the Cycle 1 Day 1 may continue use, although the Investigator should attempt to taper the use to the lowest dosage tolerable while on study. Initiation of treatment with systemic corticosteroids or increase in dose while on study is not permitted except to treat an infusion reaction. Participants may receive intra-articular corticosteroid injections, intraocular corticosteroid drops, inhalation or nasal corticosteroids, and replacement doses of systemic corticosteroids as needed. 15) Participants on a stable dose of medium or low potency topical corticosteroids for at least 4 weeks prior to the Cycle 1 Day 1 may continue use at the same dose, although the Investigator should attempt to taper the use to the lowest dosage tolerable while on study. Initiation of treatment with topical corticosteroids while on study is not permitted except to treat an acute rash. 16) History of allogeneic transplant. 17) Autologous hematopoietic stem cell transplant within 90 days of the Pre-treatment Visit. 18) Participants will be excluded if on any immunomodulatory drug for concomitant or intercurrent conditions other than T-cell lymphoma or who have received any of these agents within four weeks of treatment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. •Percentage of participants experiencing treatment-emergent adverse events. • Changes in laboratory analyses, physical examinations, vital signs, and ECGs.

Secondary endpoints 2

1. • Serum concentrations of mogamulizumab and other PK parameters. • ORR and compartment response will be assessed as described by Olsen (2011). • DOR will be calculated from first response to progression or death • Detection of anti-drug antibodies (ADAs) to mogamulizumab and incidence of ADAs. • Tissue samples will be assessed for changes in CCR4, CD4, and CD8 expression.
2. • Blood samples will be assessed for circulating malignant T-cells

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Kyowa Kirin Inc.

Sponsor organisation

Kyowa Kirin Inc.

Address

510 Carnegie Center Suite 600

City

Princeton

Postcode

08540-6241

Country

United States

Scientific contact point

Organisation

Kyowa Kirin Inc.

Contact name

Clinical Trial Information

Public contact point

Organisation

Kyowa Kirin Inc.

Contact name

Clinical Trial Information

Third parties 14

Locations

2 EU/EEA countries · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 9 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications