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

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Drug 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.

Primary outcome measures

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

Secondary outcome measures (9)

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

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07586709 · 2026-172-02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗