CBG002 CAR-T（CAR-T 细胞）治疗多发性骨髓瘤：I 期临床试验

Inclusion Criteria:

* 18 years old≤ subjects \< 75 years old, all genders;
* Patients volunteered to participate in the study, and they or their legal guardians signed informed consent form (ICF);
* According to the diagnostic criteria of the "The Guidelines for Diagnosis and Treatment of Multiple Myeloma in China (2022)", patients with multiple myeloma are clearly diagnosed;
* Patients without indications for hematopoietic stem cell transplantation；
* Meet the definition criteria of relapsed or refractory multiple myeloma. Patients failed at least 3-line of anti-multiple myeloma therapy have at least 2 complete treatment cycles per line, unless the best response to the therapy was recorded as disease progression; Must have a record of disease progression during or within 12 months after the last treatment;
* Applicable only in the dose expansion phase: the surface BCMA positive percentage of plasma cells of bone marrow samples by flow cytometry is ≥ 50 %;
* Patient has one or more measurable multiple myeloma lesions；
* Patients must have appropriate organ function;
* Patients had no contraindications to peripheral blood mononuclear cell collection;
* ECOG score 0-2;
* Expected survival ≥ 12 weeks;
* Female subjects of childbearing potential must have a negative blood pregnancy test within 7 days prior to cell therapy and not be lactating.

Exclusion Criteria:

* Have a history of allergies to cyclophosphamide, fludarabine, or any component of the cell product;
* Severe cardiovascular and cerebrovascular diseases;
* Severe comorbidities or diseases that the researchers believe will put the patients at inappropriate risk or interfere with the study;
* Have a history of allogeneic hematopoietic stem cell transplantation, or received autologous hematopoietic stem cell transplantation (ASCT) within 12 weeks prior to signing the ICF;
* Central nervous system (CNS) involvement or symptoms of CNS involvement or CNS metastases;
* Stroke or seizure occurred within 6 months prior to signing the ICF;
* Previous plasma cell leukemia;
* Multiple myeloma with extramedullary lesions;
* Previous or screening examination showing amyloidosis;
* Malignant tumor cells with T cell origin revealed by previous pathological examination;
* Having autoimmune disease, immunodeficiency or other disease that requires immunosuppressant therapy;
* Within 5 years prior to signing the ICF, patients with malignancies other than multiple myeloma;
* Uncontrolled active infection;
* Systemic disease judged by the investigator to be unstable;
* More than 5 mg/day of prednisone (or equivalent amounts of other corticosteroids) within 1 week prior to apheresis;
* Have used any CAR-T cell products or other genetically modified T cell therapies;
* Previously received anti-tumor therapy against BCMA targets, including but not limited to antibodies, ADCs or CAR-T;
* History of live vaccination (including live attenuated vaccines) within 4 weeks prior to signing the ICF;
* Any non-hematologic toxicity due to prior therapy that cannot be restored to Grade ≤1 or baseline;
* Patients with grade ≥2 acute graft-versus-host disease (GVHD) (Glucksberg criteria) or extensive chronic GVHD (Seattle criteria) requiring treatment within 4 weeks prior to enrollment, or those who may need to receive anti-GVHD treatment during the trial as judged by the investigator;
* History of alcoholism, drug abuse or mental illness requiring drug intervention within 1 year prior to signing the ICF, which may affect the safety evaluation or compliance as judged by the investigator;
* Other conditions that are considered inappropriate by the investigator to participate in this study.

主要终点：AEs. · The severity and incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), and serious adverse events (SAEs). · 2 years post infusion；DLT · The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and are specifically defined in study protocol. · 28 days post infusion
次要终点：Overall Response Rate (ORR)；Progression free survival (PFS)；Overall survival (OS)；Duration of remission (DOR)

• CBG002 CAR-T Cell Suspension · EXPERIMENTAL · Single dose of CAR+ T cells will be infused, and classic "3+3" dose escalation will be applied.

This is a single arm study to evaluate the efficacy and safety of BCMA-targeted CAR-T cells therapy for patients with relapsed/refractory Multiple Myeloma.