A Phase 1, Multicenter, Open-label, Prospective, First-in-human Dose-escalation Clinical Trial of Domain Therapeutics' Anti-CCR8 Monoclonal Antibody (DT-7012) in Patients With Relapsed or Refractory Cutaneous T-cell Lymphomas (CTCL)

NCT07213882 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: APHP240605
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Cutaneous T Cell Lymphoma (CTCL); Mycosis Fungoides; Sezary Syndrome

Keywords

Cutaneous T Cell Lymphoma; Mycosis Fungoides; Sezary Syndrome

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 12 months

Secondary Outcomes (26)

• Incidence of Adverse events

  Up to 12 months

• Objective Response Rate

  At 3 months

• Complete Response (CR)

  At 3 months

• Partial Response (PR)

  At 3 months

• Maximum concentration (Cmax) of DT-7012

  Up to 12 months

Other Outcomes (12)

• Percentage of of positive cells within the infiltrate by immunohistochemistry

  At baseline

• Percentage of of positive cells within the infiltrate by immunohistochemistry

  At 3 months

• CCR8 mean fluorescence intensity by flow cytometry in peripheral blood

  At baseline

Study Arms (1)

single agent DT-7012

EXPERIMENTAL

Drug: DT-7012

Interventions

DT-7012 DRUG

This 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.

single agent DT-7012

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• ECOG performance status 0-1
• Adequate liver function:
• Total bilirubin ≤ 1.5 xULN, or Direct bilirubin ≤ 1.5xULN if total bilirubin is \>1.5xULN, or total bilirubin \>1.5 xULN if elevated total bilirubin is attributed to Gilbert's syndrome or to histologically-proven liver involvement by CTCL
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2,5 x ULN, unless elevated to up to 5 x ULN due to CTCL
• Adequate hematological function:
• Absolute neutrophil count of ≥ 1.5 G/L without G-CSF support for at least 7 days
• Platelet count of ≥ 75 G/L without platelet transfusion within 7 days
• Hemoglobin ≥ 9 g/dL without RBC transfusion within 7 days
• Adequate renal function: creatinine clearance calculated by Cockcroft \& Gault formula of ≥ 50 mL/min
• HBV: negative blood HBs Ag or blood HBV DNA. Vaccinated patients may be included. Patients with HBc antibody may be included if HBV DNA is negative
• HCV: negative HCV serology, or negative HCV RNA if HCV serology is positive

You may not qualify if:

• Known central nervous system involvement by CTCL
• Participation in any study of a health product within 30 days prior to study entry
• 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
• Any severe acute or chronic medical or psychiatric condition
• Patients with immunodeficiency
• Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 1 week prior to first study drug dose
• Chronic use of systemic corticosteroids of prednisone or equivalent \>10 mg prednisone equivalent/day for a chronic condition (washout of 8 days from start of treatment is accepted)
• Other immunosuppressive therapies are also excluded, (washout of 7 days from start of treatment is accepted)
• Autologous Hematopoietic Stem Cell Transplantation (HSCT) within 100 days prior to DT-7012 infusion
• Prior allogeneic HSCT
• Prior solid organ transplantation
• Patient with history of confirmed progressive multifocal leukoencephalopathy
• Known or suspected allergies, hypersensitivity, or intolerance to DT-7012 or its excipients
• Pregnant or breast-feeding woman, or desire (for both man and woman participant) to conceive a child within 6 months after end of treatment
• Patient under guardianship or curatorship and protected adults or unable to consent

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Domain Therapeutics SA: collaborator

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Caroline RAM WOLFF, MD

CONTACT

+33142499961; caroline.ram-wolff@aphp.fr

Jérôme Lambert, MD PhD

CONTACT

+33142499742; jerome.lambert@u-paris.fr

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm, open-label, multicenter prospective phase 1 dose-escalation study

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 9, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: October 9, 2025

Record last verified: 2025-10