CELL INTELLIGENCE · 肿瘤细胞治疗研究

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:

  1. Clonal plasma cells confirmed to be BCMA and/or GPRC5D positive by flow cytometry or immunohistochemistry;
  2. 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):

  1. Creatinine ≤ 2 × ULN;
  2. Left ventricular ejection fraction (LVEF) ≥ 50%;
  3. Oxygen saturation \> 90%;
  4. 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).

主要终点：Number and incidence rate with Each Grade of Cytokine Release Syndrome (CRS) · CRS severity will be graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading. The grade ranges from 1 to 4, where a higher grade indicates a worse outcome. · 1 month after treatment；Dose-limiting toxicities (DLTs) · Dose limiting toxicity will be assessed after injection · 1 month after treatment；Number and incidence rate of Each Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) · ICANS severity is graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading, which incorporates the Immune Effector Cell-Associated Encephalopathy (ICE) assessment. The ICE score ranges from 0 to 10, with higher scores indicating better cognitive function. ICANS grade ranges from 1 to 4, where a higher grade indicates a worse outcome. · 1 month after treatment；Number and incidence rate of Treatment-Associated Adverse Events (AEs) · All other AEs would be assessed according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0). · 1 years after treatment
次要终点：Overall Objective Response Rate (ORR)；overall survival (OS)；progression free survival (PFS)；duration of response (DOR)；time to progression (TTP)；recurrence rate；Cmax of CAR-T Cells；Tmax of CAR-T Cells

• In vivo BCMA/GPRC5D Tandem Dual CAR-T · EXPERIMENTAL · Participants receive treatment of In vivo BCMA/GPRC5D Tandem Dual CAR-T cell following a 3+3 dose-escalation design.

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.