CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

* Voluntarily participate in the trial; fully understand and sign the informed consent form (ICF); willing and able to comply with all trial procedures.
* Age ≥ 18 years, male or female.
* Patients with relapsed/refractory multiple myeloma (R/R MM) who have received at least 3 prior lines of therapy, including at least one proteasome inhibitor (PI), at least one immunomodulatory agent (IMiD), and at least one anti-CD38 monoclonal antibody.
* Relapsed/refractory disease defined per IMWG 2016 response criteria,.
* Must have measurable disease:
* Life expectancy ≥ 12 weeks.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Must have Adequate organ function
* Female participants of childbearing potential must have a negative pregnancy test at screening and prior to lymphodepletion, and must agree to use highly effective contraception for at least 1 year after CT0596 infusion, and absolutely refrain from oocyte donation. Male participants with active sexual life with WOCBP must agree to use highly effective contraception for at least 1 year after infusion and absolutely refrain from sperm donation。

Exclusion Criteria:

* Pregnant or lactating women.
* Positive for HIV, syphilis, active hepatitis B (HBV-DNA above LLoD), or active hepatitis C (positive for both HCV antibody and HCV-RNA).
* Presence of any uncontrolled active infection, including but not limited to active tuberculosis (per investigator), active CMV and/or EBV infection, etc.
* Toxicity from prior therapy not recovered to ≤ Grade 1 per Common Terminology Criteria for Adverse Events(CTCAE) V5.0 (except alopecia and other events deemed tolerable by the investigator).
* Prior BCMA-targeted therapy (refer to the protocol for exceptions).
* Prior allogeneic stem cell transplantation; or autologous SCT within 3 months prior to signing ICF; or planned Hematopoietic Stem Cell Transplantation(HSCT) during the trial.
* Received disease-directed therapy within 14 days or 5 half-lives (whichever is shorter) prior to lymphodepletion.
* Received any cell therapy within 6 months prior to ICF; or prior CAR-T with best response \< PR.
* Received systemic corticosteroids equivalent to \> 15 mg/day of prednisone within 7 days prior to lymphodepletion (excluding topical use).
* Received live-attenuated, inactivated, or RNA vaccines within 4 weeks prior to lymphodepletion.
* Major surgery within 2 weeks prior to lymphodepletion, or planned major surgery during trial or within 4 weeks after treatment (excluding local anesthesia surgeries).
* Allergy or intolerance to lymphodepletion agents, tocilizumab, or any component of infusion (e.g., DMSO); or history of severe allergy such as anaphylactic shock.
* Diagnosed with secondary plasma cell leukemia, solitary extramedullary plasmacytoma, Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at screening.
* Severe cardiac diseases within 6 months prior to screening.
* Severe pulmonary disease that may jeopardize the patient's life per investigator.
* Inability to tolerate an adequate lymphodepletion regimen.
* Secondary primary malignancy requiring treatment or not in complete remission within 2 years prior to screening, except for successfully treated non-metastatic basal/squamous cell skin carcinoma, non-metastatic prostate cancer, carcinoma in situ (breast/cervix), non-muscle-invasive bladder cancer, or low-grade thyroid cancer.
* Known symptomatic central nervous system (CNS) disease or suspected CNS metastasis.
* Patients assessed by the investigator as unable or unwilling to comply with protocol requirements, or otherwise unsuitable for participation.

主要终点：Phase I:Adverse Events (AE) after CT0596 infusion · An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria. · 24months after CT0596 infusion；Phase I:Maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) · Evaluate Dose limited toxicity and recommended dosage range after CT0596 infusion. · 28 days after CT0596 infusion；Phase II:Overall response rate (ORR) · Overall response rate (ORR) at Week 12 post-infusion, assessed by an Independent Review Committee (IRC) per IMWG 2016 criteria. · Week 12 after CT0596 infusion
次要终点：Overall response rate (ORR) as assessed by IRC and investigator；Complete response/stringent complete response (CR/sCR) rate；Rate of very good partial response (VGPR) and above；Duration of response (DOR)；Minimal residual disease (MRD) negative rate；Time to response (TTR)；Progression-free survival (PFS)；Overall survival (OS)

• CAR-T cells · EXPERIMENTAL · chimeric antigen receptor T cells

This is a Phase I/II, single-arm, open-label, multicenter clinical trial in patients with relapsed/refractory multiple myeloma (R/R MM). The study aims to evaluate the safety, tolerability, efficacy, cellular kinetics, and immunogenicity of CT0596.