In Vivo BCMA/GPRC5D Tandem Dual CAR-T Therapy for Relapsed/Refractory Plasma Cell Neoplasms

Официальное название

A Clinical Study on the Safety of in Vivo-CAR-T Cell Immunotherapy Targeting BCMA/GPRC5D for the Treatment of Relapsed/Refractory Plasma Cell Neoplasms

Обзор

This study aims to assess the safety profile of in vivo BCMA/GPRC5D-targeted CAR-T cell immunotherapy in patients with relapsed or refractory plasma cell neoplasms.

Подробное описание

This is a single-center, open-label, single-arm, prospective study designed to evaluate the safety of in vivo BCMA/GPRC5D-targeted CAR-T cell immunotherapy in patients with relapsed or refractory plasma cell neoplasms. The study employs a dose-escalation design to assess safety, tolerability, and preliminary efficacy. Safety assessments primarily focus on potential adverse events (AEs) following infusion of SL4903 injection, including the number of cases, incidence rates, and severity of cytokine release syndrome, immune effector cell therapy-related neurotoxicity, hematologic toxicity, organ toxicity, ect. Efficacy assessments will include overall objective response rate (ORR), event-free survival (EFS), overall survival (OS), progression-free survival (PFS), duration of complete remission, relapse rate, and mortality rate. Exploratory analyses will focus on characterizing the in vivo kinetics of CAR-T cells and the clonal evolution of plasma cell neoplasms during and after consolidation treatment.

Вмешательства

• Препарат In vivo BCMA/GPRC5D Tandem Dual CAR-T cell
  Administration of in vivo BCMA/GPRC5D tandem dual CAR-T cells. Three dose levels (dose A, dose B, dose C) will be evaluated using a standard 3+3 dose-escalation design.

Первичные конечные точки

• Number and incidence rate with Each Grade of Cytokine Release Syndrome (CRS) [Срок оценки: 1 month after treatment]
• Dose-limiting toxicities (DLTs) [Срок оценки: 1 month after treatment]
• Number and incidence rate of Each Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) [Срок оценки: 1 month after treatment]
• Number and incidence rate of Treatment-Associated Adverse Events (AEs) [Срок оценки: 1 years after treatment]

Вторичные конечные точки (9)

• Overall Objective Response Rate (ORR) [Срок оценки: Day 14, Day 28, Month 2 , Month 3, Month 6, Month 9, Month 12, Month 18, Month24 after the treatment]
• overall survival (OS) [Срок оценки: 2 years after treatment]
• progression free survival (PFS) [Срок оценки: 2 years after treatment]
• duration of response (DOR) [Срок оценки: 2 years after treatment]
• time to progression (TTP) [Срок оценки: 2 years after treatment]
• recurrence rate [Срок оценки: 2 years after treatment]
• Cmax of CAR-T Cells [Срок оценки: 1 month after treatment]
• Tmax of CAR-T Cells [Срок оценки: 1 month after treatment]
• AUC(0-28d) [Срок оценки: 1 month after treatment]

Критерии участия

Критерии включения

• Voluntary signing of informed consent by the subject or legally authorized representative, with willingness and ability to comply with scheduled visits, study treatment, laboratory tests, and other study procedures.
• Diagnosis of relapsed or refractory plasma cell neoplasms meeting the following criteria:

• Clonal plasma cells confirmed to be BCMA and/or GPRC5D positive by flow cytometry or immunohistochemistry;
• Previously treated with at least 2 lines of anti-plasma cell neoplasms therapy, with at least 1 complete treatment cycle for each line, and evidence of disease progression within 12 months after the most recent anti-plasma cell neoplasms treatment, or being refractory to both immunomodulatory drugs and proteasome inhibitors, with disease progression within 2 months after the most recent anti-plasma cell neoplasms treatment (according to the IMWG diagnostic criteria)
• Age 18 to 75 years (inclusive), male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Life expectancy > 3 months from the date of informed consent.
• Hemoglobin (HGB) ≥ 60 g/L (transfusion allowed).
• Adequate organ function (hepatic, renal, cardiac, and pulmonary):

• Creatinine ≤ 2 × ULN;
• Left ventricular ejection fraction (LVEF) ≥ 50%;
• Oxygen saturation > 90%;
• Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 2.5 × ULN.
• Willingness to use highly effective contraception from signing of informed consent until 1 year after SL4903 infusion.

Критерии исключения

• Severe cardiac dysfunction with left ventricular ejection fraction (LVEF) < 50%.
• History of severe pulmonary impairment.
• Concurrent diagnosis of another active malignancy.
• Uncontrolled active infection.
• History of severe autoimmune disease or primary immunodeficiency.
• Active hepatitis (defined as HBV DNA or HCV RNA above the lower limit of detection).
• Human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS), or active syphilis.
• History of severe hypersensitivity to biological products (including antibiotics).
• Allogeneic hematopoietic stem cell transplant recipients with ongoing acute graft-versus-host disease (GVHD) despite discontinuation of immunosuppressive therapy for at least one month prior to screening.
• Any other severe comorbidities or laboratory abnormalities that, in the investigator's opinion, would increase the risk to the subject or interfere with study results, rendering the subject unsuitable for participation.
• Pregnant or breastfeeding women (including women of childbearing potential who are pregnant or lactating).

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07586709 · 2026-172-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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