Trial in Progress: A Phase 4 Multicenter Study of Brentuximab Vedotin Treatment in Chinese Patients with CD30-Positive Cutaneous T-Cell Lymphoma

Background: Cutaneous T-cell lymphomas (CTCLs) are rare, heterogenous group of extranodal non-Hodgkin's lymphomas represented by cutaneous infiltration of malignant T lymphocytes (1). Mycosis fungoides (MF) and CD30+ primary cutaneous anaplastic large cell lymphoma (pcALCL) are common subtypes of CTCLs (2). CD30+MF cells can morphologically transform to high-grade large cell lymphoma which is associated with more aggressive disease course. Currently available systemic therapies offer suboptimal outcomes with few durable responses for patients with advanced stage disease, which necessitates development of new targeted therapeutic options (3). Recently, results from phase 3 ALCANZA trial (ClinicalTrials.gov Identifier: NCT01578499) showed that brentuximab vedotin, an anti-CD30 antibody-drug conjugate significantly improved Objective Response Rate lasting at least 4 months (ORR4) in patients with CD30+ CTCLs in comparison to common conventional therapies according to independent review. Based on the results of this global pivotal study, China's National Medical Products Administration (NMPA) has approved brentuximab vedotin treatment in patients with CD30+ MF or pcALCL who have received prior systemic treatment. This post approval study is currently in progress in China. Study Design and Methods: Brentuximab Vedotin is being evaluated in phase 4, open-label, single-arm, multicenter study (NCT05442554) in patients with CD30+ MF or pcALCL conducted in up to 5 investigative sites across China. Approximately ten patients aged 18 years and above, diagnosed with MF or pcALCL, and histologically confirmed ≥10% CD30 expression who received at least 1 prior systemic therapy or radiation therapy (only for patients with pcALCL) with Eastern Cooperative Oncology Group (ECOG) performance status of ≤2 and with adequate bone marrow reserve and renal and hepatic function will be enrolled in the study. Key exclusion criteria were concurrent diagnosis of systemic anaplastic large cell lymphoma (ALCL), or another non-Hodgkin lymphoma (excluding lymphomatoid papulosis), or history of known active cerebral/meningeal disease, or treatment with corticosteroid therapy or oral retinoid therapy within 3 weeks of first dose of study drug. Eligibility and baseline assessment will be completed within 28-day screening period, thereafter 1.8 mg/kg dose of brentuximab vedotin monotherapy will be administered by intravenous (IV) infusion on day 1 of each 21-day cycle for up to 16 cycles or until disease progression. The primary end point to be assessed is ORR4 with brentuximab vedotin in Chinese patients with CD30+ MF or pcALCL. Secondary endpoints are Complete Response (CR) rate, ORR and Duration of response (DOR). A global response score (GRS) defined treatment response will be assessed based on sequential tumour burden assessments which consists of skin evaluation (a modified severity weighted assessment tool [mSWAT]), nodal and visceral radiographic assessment, and detection of circulating Sezary cells for MF only at 3-cycles intervals and End of Treatment (EOT) visit. Safety endpoints to be assessed are change from baseline in the patient's vital sign and clinical laboratory measurements, incidence of treatment-emergent adverse events and serious adverse events, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 5.0. Safety analysis set will consist of all enrolled patients who will receive at least 1 dose of study drug. Descriptive summaries and analyses will be performed for all efficacy and safety assessments.