Preliminary results from the dose-escalation stage of a phase I trial of an anti-CCR8 antibody in patients with relapsed/refractory cutaneous T-cell lymphoma (R/R CTCL).

2514 Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common cutaneous T-cell lymphomas (CTCL). CCR8 is expressed in the skin resident memory T cells. ICP-B05 (CM369) is a humanized monoclonal antibody against CCR8 with potent ADCC activity. Here we report safety, efficacy and PK/PD findings for ICP-B05 during the dose-escalation stage of a Phase I study. Methods: Patients with R/R CTCL received ICP-B05 at 150 mg, 300 mg, 450 mg and 600 mg I.V. Q2W. Patients with R/R CTCL who failed at least 1 prior standard systemic regimen. Primary objectives included safety and tolerability of ICP-B05, MTD and RP2D. Secondary Objectives included the PK/PD and objective response per investigator. Results: By the cutoff date of 6 th Jan, 2025, a total of 13 patients with R/R CTCL were treated, with 4 patients in 150 mg, and 3 patients each in 300 mg, 450 mg and 600mg, respectively. Eleven patients had a diagnosis of MF, one had SS and one had pcALCL. The median age was 46 years, and the median prior lines of therapy were 3 (2-6). There were 10/13 (76.9%) patients had lymph nodes involvement and 1/13 (7.7%) patient with SS had above 90% Sézary cells in peripheral blood at baseline. TEAEs occurred in 12 (92.3%) patients, and ≥Grade 3 TEAEs occurred in 6(46.2%) patients. The most common≥Grade 3 TEAEs is hematological AEs, including lymphopenia (8.3%), neutropenia (8.3%) and thrombocytopenia (8.3%). Two patients (16.7%) reported serious TEAEs, including edema and cardiac failure reported by the SS patient which was assessed as not related to ICP-B05, and thrombocytopenia and anemia reported by a MF patient. There was no fatal TEAE reported. There were 12 patients received at least one skin lesion assessment followed the mSWAT. 4/12 patients (33.3%) achieved PR, and 7patients (7/12, 58.3%) were assessed as SD with reduction (medium: - 27%) in skin lesion. The 6-month PFS rate was 82.5% (95% CI: 46.1%-95.3%). At baseline, CCR8+ in skin lesions (medium: 8.38%, range: 3.22–49.6%) was assessed in 11 out of 13 patients. Among the five patients with CCR8+ levels exceeding 10%, four (80%) achieved PR. PK analysis showed that serum exposure (C max and AUC 0-14D ) increased with dose escalation. PD analysis demontrated significant depletion of CCR8-expressing cells in CTCL skin lesions. Significant reduction of CCR8+ malignant T cells (-80%) and CCR8+ regulatory T cells (Treg, -68%) were observed at C3D1 compared with baseline in the skin lesion. Similar PD effects were observed in the peripheral blood as well with an average decrease of 91% in CCR8+ malignant T cells and 16% in Treg at C3D1 when compared with baseline. Conclusions: The current study is the first and only report on the preliminary efficacy data of anti-CCR8 targeted therapy for CTCL patients. The effectiveness of ICP-B05 was supported by the PD effects in both skin lesions and peripheral blood in the depletion of CCR8+ cells. ICP-B05 is safe and well tolerated and its safety profile made it a good candidate for combo therapies for CTCL patients with lymph node and other organ involvement. Clinical trial information: NCT05690581 .