A Phase 1/2 Study of a Fully Human BCMA-targeting CAR (CT103A) in Patients With Relapsed/Refractory Multiple Myeloma (FUMANBA-1)

Inclusion Criteria: Subjects must satisfy all the following criteria to be enrolled in the study:

1. age 18 to 70 years old, male or female.
2. Subjects with diagnosed relapsed or refractory MM according to IMWG criteria and havehad at least 3 prior lines of therapy including chemotherapy based on proteasomeinhibitors (PIs) and immunomodulatory agents (IMiDs). Disease progression must bedocumented during or within 12 months following the most recent anti-myelomatreatment.
3. Evidence of cell membrane BCMA expression, as determined by a validatedimmunohistochemistry (IHC) or flow cytometry of tumor tissue (e.g., bone marrowbiopsies, or plasmacytoma).
4. The subjects should have measurable disease based on at least one of the followingparameters:

• The proportion of primitive immature or monoclonal plasma cells detected by bonemarrow cytology, bone marrow biopsy, or flow cytometry is ≥ 5%.
• Serum M-protein ≥ 0.5 g/dL.
• Urine M-protein ≥ 200 mg/24 hrs.
• For those whose Serum or Urine M-protein does not meet the measurable criteriabut the light chain type, serum free light chain (sFLC): involved sFLC level ≥ 10mg/dL (100 mg/L) provided serum FLC ratio is abnormal.

5. ECOG performance score 0-1.
6. Estimated life expectancy ≥ 12 weeks.
7. Patients should have adequate organ function:

• Hematology: Absolute neutrophil count (ANC) ≥1×10^9 /L (prior use of growthfactor support is permitted, but subjects must not have received supportivetreatment within 7 days prior to laboratory examination); absolute lymphocytecount (ALC) ≥0.3×10^9 /L; platelets ≥50×10^9 /L (subjects must not have receivedblood transfusion support within 7 days prior to laboratory examination);hemoglobin ≥60 g/L (subjects must not have received transfusion of red bloodcells [RBC] within 7 days prior to laboratory examination; the use of recombinanthuman erythropoietin is permitted).
• Liver function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×upper limit of normal (ULN); total serum bilirubin ≤ 1.5×ULN.
• Renal function: Creatinine clearance rate (CrCl) calculated according toCockcroft-Gault formula ≥ 40 ml/min.
• Coagulation function: Fibrinogen ≥ 1.0 g/L; activated partial thromboplastin time (APTT) ≤ 1.5×ULN, prothrombin time (PT) ≤ 1.5×ULN.
• SpO2 > 91%.
• Left ventricular ejection fraction (LVEF) ≥ 50%.

8. The subject and his/her spouse agree to use an effective contraceptive tool ormedication (excluding safety period contraception) for one year from the date of thesubject's informed consent to the date of CAR T cell infusion.
9. Subject must sign the informed consent form approved by ethics board in person beforestarting any screening procedure.

Exclusion Criteria: The presence of any of the following will exclude a subject from enrollment:

1. Subjects who are known to have GVHD or need long-term immunosuppressive therapy.
2. Subjects have received an autologous hematopoietic stem cell transplantation (auto-HSCT) within 12 weeks before leukapheresis or have a previous history of twotimes of allo-HSCT or previous history of an allogeneic hematopoietic stem celltransplantation (allo-HSCT).
3. Insufficient mononuclear cells for CAR T cell production.
4. Subjects have received any anti-cancer treatment as follows: targeted therapies,epigenetic therapy or invasive experimental instruments therapy within 14 days or atleast 5 half-lives before leukapheresis (according to the longer time), or monoclonalantibody for treating multiple myeloma within 21 days before leukapheresis, orcytotoxic therapy or proteasome inhibitors within 14 days before leukapheresis, orimmunomodulatory agents within 7 days before leukapheresis.
5. Subjects who were receiving a used therapeutic dose of corticosteroid treatment (defined as prednisone or equivalent > 20mg) within 7 days prior to screening, exceptfor physiological alternatives, inhalation, or topical use.
6. Subjects with serious heart disease: including but not limited to unstable angina,myocardial infarction (within 6 months prior to screening), congestive heart failure (NYHA classification ≥III), and severe arrhythmias.
7. Subjects with systemic diseases that the investigator determined to be unstableinclude, but are not limited to, severe liver and kidney or metabolic diseasesrequiring medical treatment.
8. Subjects with second malignancies in addition to MM within the past 5 years before thescreening, exceptions to this criterion: successfully treated cervical carcinoma insitu and non-metastatic basal or squamous cell skin carcinoma, local prostate cancerafter radical surgery, and ductal carcinoma in situ of the breast after radicalsurgery.
9. Subjects with a history of organ transplantation.
10. Subjects have central nervous system (CNS) involvement (including cranial neuropathiesor mass lesions and leptomeningeal disease).
11. Subjects with extramedullary lesions (except for a single extramedullary lesion with amaximum transverse diameter of 3 cm).
12. Subjects with plasma cell leukemia.
13. Subjects have received major surgery within 2 weeks prior to leukapheresis or plan toreceive surgery during the study or within 2 weeks after the study treatment (excluding local anesthesia).
14. Subjects participated in another interventional clinical study 3 months before signingthe informed consent (ICF);
15. Subjects with any uncontrolled active infection needed to receive systemic therapywithin 7 days before leukapheresis collection (excluding < CTCAE grade 2 urogenitalinfection and upper respiratory infection).
16. Positive for any of the following tests:

• Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B coreantibody-positive and detectable HBV DNA in peripheral blood
• Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood
• Human immunodeficiency virus (HIV) antibody
• Cytomegalovirus (CMV) DNA
• Treponema Pallidum antibody

17. Pregnant or lactating women.
18. Subjects with mental illness or consciousness disorder or disease of the centralnervous system
19. Subjects who haven't recovery to Grade 1 or baseline of any toxicities due to priortreatments, excluding alopecia.
20. Other conditions that researchers consider inappropriate for inclusion.