Cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of lymphomas characterized by a primary involvement of the skin. Among them, mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes. SS is defined as erythroderma (erythema of the entire skin surface), and circulating tumor blood cells. The circulating tumor T cells express CD4 and may lose expression of CD7 and CD26, while exhibiting in most cases aberrant expression of CD158k (KIR3DL2), which is a surface marker of Sézary cells. CCR8 is a surface marker of tumor-infiltrating regulatory T cells. It has recently be observed that CCR8 was expressed by tumor cells in CTCL and other peripheral T-cell lymphomas. CCR8 is expressed by skin resident-memory T cells which are believed to be the tumor cell-of-origin in mycosis fungoides. Domain Therapeutics (DT) showed the in vitro efficacy of their proprietary anti-CCR8 mAb DT7012 in the depletion of CTCL cells. Therapeutic depletion of CCR8-expressing cells by DT-7012 could eliminate tumor cells and activate the anti-tumor immunity in CTCL. We hypothesize that treatment with DT-7012 is effective in the treatment of relapsed or refractory (R/R) CTCL as advanced MF and SS.
Adult Patients (≥18 years) with no upper age limit
Confirmed diagnosis of mycosis fungoides or Sezary syndrome
Stage IB to IVB in the ISCL / EORTC classification
Relapsed or refractory (no response) after at least two systemic treatments
Known central nervous system involvement by CTCL
Participation in any study of a health product within 30 days prior to study entry
Patients with a history of other malignancies during the past three years (except for: non-melanoma skin cancer, lymphomatoid papulosis, curatively treated localized prostate cancer, curatively treated localized breast cancer, resected thyroid cancer, biopsy proven cervical intraepithelial neoplasia or cervical carcinoma in situ, which are not considered exclusion criteria).
Uncontrolled congestive heart failure (New York Heart Association Classification 3 or 4), or angina, myocardial infarction, cerebrovascular accident, transient ischemic attack within 6 months prior to study entry
Single group
DT-7012
DrugThis study use the Bayesian one-stage time-to-event continual reassessment method (TITE-CRM) design for dose finding phase I clinical trials, using an empirical dose-toxicity model with linear weights. A maximum total of 30 patients with CTCL, given 4 candidate dose levels (0.3; 1.0; 3.0; 10.0 mg/kg) will be dose-assigned starting from 1mg/kg dose level, in cohorts of 1 patient and including safety rules notably to ensure staggered accrual.
Dose limiting toxicity (DLT) defined by any treatment-emergent adverse event (TEAE) not attributable to the disease or disease-related processes
Any Grade ≥ 3 non-hematologic toxicity lasting at least 7 days is considered DLT, EXCEPT for: * Isolated laboratory findings with no clinical signs or symptoms, * Grade 3 fatigue, nausea, vomiting, diarrhea, or other manageable constitutional symptom that is responsive to supportive therapy and resolves to Grade ≤ 2 (or baseline if baseline is Grade ≥ 2) within 72 hours Any Grade ≥ 3 hematologic toxicity is considered DLT, EXCEPT for: * Grade 3 neutropenia (without fever and not requiring growth factor support) lasting for less than 7 days, * Grade 3 thrombocytopenia without clinically significant bleeding or requiring platelet transfusion, * Grade 3 leukopenia/lymphopenia, * Grade 3 anemia that does not require transfusion.
Incidence of Adverse events
Adverse Events (AEs), Serious Adverse Events (SAEs), Drug related AEs, Drug related SAEs, Adverse Events of Special Interest (AESI)
Objective Response Rate
Complete Response (CR)
Partial Response (PR)
Percentage of of positive cells within the infiltrate by immunohistochemistry
Expression of CCR8, on tumor and reactive cells, in skin and blood
Percentage of of positive cells within the infiltrate by immunohistochemistry
Expression of CCR8, on tumor and reactive cells, in skin and blood
CCR8 mean fluorescence intensity by flow cytometry in peripheral blood
CCR8 mean fluorescence intensity by flow cytometry in peripheral blood
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Assistance Publique - Hôpitaux de Paris
Lead sponsor
Domain Therapeutics SA
Collaborator
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