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

NCT07717580 | Not Yet Recruiting Phase 2

• 2 other identifiers: CTCL00182425050
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, single-center, open-label, randomized, controlled phase II clinical trial. The main purpose of this study is to evaluate the efficacy and safety of combining brentuximab vedotin (an anti-CD30 antibody-drug conjugate, ADC) with lisaftoclax (APG-2575, a novel B-cell lymphoma 2 (BCL-2) inhibitor) in patients with CD30-positive cutaneous T-cell lymphoma (CTCL), specifically including mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL). Previous studies suggest that the overexpression of the anti-apoptotic protein BCL-2 may contribute to brentuximab vedotin resistance in CTCL. Researchers hypothesize that adding a highly selective BCL-2 inhibitor (lisaftoclax) can reverse this drug resistance, enhance tumor cell apoptosis, and improve clinical outcomes. In this study, approximately 46 eligible patients will be randomly assigned in a 1:1 ratio to one of two treatment arms: Monotherapy arm (control): Patients will receive brentuximab vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles. Combination arm (experimental): Patients will receive the same brentuximab vedotin regimen. Additionally, starting from the 6th cycle, patients will receive oral lisaftoclax. To mitigate the risk of tumor lysis syndrome (TLS), a daily dose ramp-up will be implemented in the first cycle of lisaftoclax. Subsequently, lisaftoclax will be administered at a targeted dose of 600 mg daily on days 1 to 10 of each 21-day cycle, for a total of 9 combination cycles. The primary endpoint of the study is the objective response rate (ORR) evaluated at the end of the 16 cycles. Secondary endpoints include the improvement of skin lesions (evaluated by modified severity-weighted assessment tool (mSWAT) score), pruritus relief (visual analog scale (VAS) score), and the incidence of adverse events (AEs). Independent, blinded assessors will be utilized to evaluate the clinical responses to reduce bias.

Conditions

Cutaneous T-Cell Lymphoma/Mycosis Fungoides; Primary Cutaneous Anaplastic Large Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  The percentage of participants who achieve a complete response (CR) or partial response (PR) at the end of the treatment, evaluated by independent blinded assessors based on clinical skin assessments and radiological imaging.

  At the end of 16 treatment cycles (up to approximately 48 weeks)

Study Arms (2)

Brentuximab Vedotin Monotherapy

ACTIVE COMPARATOR

Patients will receive Brentuximab Vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.

Drug: Brentuximab Vedotin (Bv)

Brentuximab Vedotin + Lisaftoclax

EXPERIMENTAL

Patients will receive brentuximab vedotin at 1.8 mg/kg intravenously every 3 weeks for 16 cycles. Starting from cycle 6, oral lisaftoclax will be added at 600 mg daily on days 1-10 of each 21-day cycle for 9 cycles, with a daily dose ramp-up during the first cycle of lisaftoclax administration. Lisaftoclax is provided by Ascentage Pharma.

Drug: Brentuximab Vedotin (Bv); Drug: Lisaftoclax (APG-2575)

Interventions

Brentuximab Vedotin (Bv) DRUG

Patients will receive brentuximab vedotin intravenously at a dose of 1.8 mg/kg every 3 weeks for a total of 16 cycles.

Brentuximab Vedotin + Lisaftoclax; Brentuximab Vedotin Monotherapy

Lisaftoclax (APG-2575) DRUG

Patients will receive Brentuximab Vedotin (1.8 mg/kg, IV, q3w, 16 cycles). Starting from cycle 6, oral Lisaftoclax will be added (600 mg daily on days 1-10 of each 21-day cycle, for 9 cycles, with a daily dose ramp-up in the first cycle).

Brentuximab Vedotin + Lisaftoclax

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Peking University First Hospital: lead
• Ascentage Pharma: collaborator

Study Sites (1)

Peking University First Hospital

Beijing, Beijing Municipality, 100034, China

Location

MeSH Terms

Conditions

Mycosis Fungoides; Lymphoma, Primary Cutaneous Anaplastic Large Cell

Interventions

Brentuximab Vedotin; Lisaftoclax

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell, Cutaneous; 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

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 21, 2026
• Study Start: July 31, 2026
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2028
• Last Updated: July 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: De-identified IPD and supporting documents will become available 12 months after the publication of the primary study results and will remain accessible indefinitely to eligible researchers upon approved application.
• Access Criteria: Qualified researchers may submit a formal research proposal and data use agreement to the study principal investigator. Proposals will be reviewed for scientific validity prior to data access approval.

Locations

CN (1)