Efficacy and Safety of Brentuximab Vedotin Combined With Lisaftoclax in CD30+ Cutaneous T-cell Lymphoma (CTCL)

Inclusion criteria

• Age greater than or equal to 18 years.
• Confirmed diagnosis of mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL).
• CD30 positive confirmed by skin biopsy (at least 2 lesion biopsies for MF patients, and at least 1 lesion biopsy for pcALCL patients). CD30 positivity is defined as greater than or equal to 10% of target lymphocytes showing CD30 membrane, cytoplasmic, and/or Golgi-like staining, with a staining intensity higher than the background staining of the corresponding negative control.
• Prior treatment requirements:

• pcALCL: Must have received ≥ 1 prior systemic therapy or radiotherapy.
• MF: Must have received ≥ 1 prior systemic therapy.
• Note: Patients must be chemotherapy-naïve.
• Eastern Cooperative Oncology Group (ECOG) performance status score of less than or equal to 2.
• Adequate hepatic, renal, and hematopoietic function.
• Females of childbearing potential must be willing to use highly effective methods of contraception during the study and for 6 months after the last dose of study drug; or must be postmenopausal for greater than or equal to 1 year, or surgically sterile.
• Males, even if surgically sterilized (i.e., post-vasectomy), must agree to use highly effective methods of contraception during the study and for 6 months after the last dose of study drug.
• No cognitive or communication barriers; capable of understanding and willing to sign a written informed consent form (ICF), and willing to comply with the study visits and procedures.
• Good venous access for required blood sampling.

Exclusion criteria

• Concomitant diagnosis of systemic anaplastic large cell lymphoma (sALCL), other non-Hodgkin lymphomas (except lymphomatoid papulosis), Sézary syndrome, or stage B2 disease.
• Active central nervous system (CNS) involvement of lymphoma.
• Prior treatment with chemotherapy, allogeneic or autologous stem cell transplantation.
• Prior treatment with brentuximab vedotin or any B-cell lymphoma 2 (BCL-2) inhibitors.
• Receipt of corticosteroids for cutaneous T-cell lymphoma (CTCL) or skin-directed therapies within 3 weeks prior to the first dose of study drug.
• Receipt of antibody-directed therapy, immunoglobulin therapy, or other monoclonal antibodies within 12 weeks prior to the first dose of study drug.
• History of other primary malignancies not in complete remission for greater than or equal to 3 years (exceptions: adequately treated carcinoma in situ of the cervix, non-melanoma skin cancer, squamous intraepithelial lesions, or localized prostate cancer with no evidence of recurrence based on prostate-specific antigen (PSA) levels).
• Presence of severe organ dysfunction or history of major organ diseases, including:

• Cardiac: Left ventricular ejection fraction (LVEF) less than 50%; unstable angina; acute myocardial infarction within the past 6 months; New York Heart Association (NYHA) class III-IV congestive heart failure; clinically significant arrhythmias.
• Renal: Creatinine clearance ≤ 50 mL/min.
• Hepatic: Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase > 3 × Upper Limit of Normal (ULN), or Total Bilirubin > 1.5 × ULN.
• Active liver or biliary disease (exceptions: Gilbert's syndrome, asymptomatic gallstones, liver involvement by lymphoma, or stable chronic liver disease assessed by the investigator).
• History of severe cerebrovascular disease within the past 6 months, or current presence of symptomatic/sequelae cerebrovascular events.
• History of pancreatitis or high-risk factors for pancreatitis.
• Uncontrolled systemic bacterial, fungal, viral, or other severe infections.
• Positive test for Human Immunodeficiency Virus (HIV) or Hepatitis B virus (positive HBsAg or HBcAb).
• Known hypersensitivity to recombinant proteins, murine proteins, or any excipients of the study drugs.
• Female patients who are pregnant, lactating, or planning to become pregnant within 6 months.
• Presence of severe concurrent medical/psychiatric conditions that may compromise patient safety or compliance, or interfere with informed consent, study participation, or interpretation of results.
• Any other conditions that, in the opinion of the investigator, make the patient unsuitable for study participation.