In Vivo PICX CAR-T Therapy for R/R Multiple Myeloma

This is a prospective, open-label, single-arm clinical investigation to assess the safety and efficacy of in vivo CAR-T cell therapy in patients with relapsed or refractory multiple myeloma.

Eligible subjects will be treated with PICX Injection as a single intravenous infusion. Post-infusion, subjects will remain hospitalized for close observation and undergo serial evaluations for adverse events and treatment response. Long-term follow-up will continue for up to 2 years to assess disease status and durability of response.

Inclusion criteria

• Age ≥ 18 years, male or female;
• Confirmed diagnosis of multiple myeloma meeting at least one of the following criteria:

• Disease progression after at least 2 prior standard treatment regimens; or poor response to primary therapeutic agents (e.g., immunomodulatory agents, proteasome inhibitors)
• Disease progression within 18 months after first-line therapy
• Presence of features associated with high risk of disease relapse or progression (e.g., high-risk cytogenetic abnormalities);
• At least one measurable disease indicator:

• Serum M-protein ≥ 0.5 g/dL
• Urine M-protein ≥ 200 mg/24 hours
• Involved serum free light chain (sFLC) ≥ 10 mg/dL with an abnormal serum free light chain κ/λ ratio
• No evidence of extramedullary plasmacytoma (soft tissue plasmacytoma);
• ECOG performance status score 0-2;
• Expected survival period ≥ 3 months;
• Adequate bone marrow function within 1 month prior to screening:

• Hemoglobin ≥ 60 g/L;
• Absolute neutrophil count (ANC) ≥ 0.5 × 10⁹/L;
• Platelet count (PLT) ≥ 50 × 10⁹/L;
• Lymphocyte count ≥ 0.5 × 10⁹/L;
• CD3-positive T-cell absolute count ≥ 0.15 × 10⁹/L;
• Adequate vital organ function within 1 month prior to screening:

• Renal function: creatinine clearance rate (CrCl) ≥ 30 mL/min (calculated using the Cockcroft-Gault formula), or serum creatinine (Scr) ≤ 2.0 × upper limit of normal (ULN);
• Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3.0 × ULN; total bilirubin (TBIL) ≤ 2.0 × ULN (except for patients with congenital hyperbilirubinemia such as Gilbert's syndrome, in which case direct bilirubin may be ≤ 1.5 × ULN);
• Cardiac function: left ventricular ejection fraction (LVEF) ≥ 40%; no clinically significant pericardial effusion; and no clinically significant electrocardiogram (ECG) abnormalities (e.g., severe arrhythmia, myocardial ischemia, conduction block);
• Pulmonary function: blood oxygen saturation (SpO₂) ≥ 90% without supplemental oxygen;
• Women of childbearing potential must have a negative pregnancy test during the screening period and before study drug administration, and must not be lactating during the study;
• Men and women of childbearing potential must agree to use effective contraceptive measures (excluding unreliable methods such as rhythm method) from the time of signing the informed consent form until 1 year after the last dose of study drug, and must agree not to donate sperm or eggs;
• The subject or their legally authorized representative has signed the informed consent form (ICF), indicating understanding of the study purpose and procedures and voluntary participation.

Exclusion criteria

• Prior treatment with CAR-T therapy or other gene-modified cell therapy before screening;
• Presence of active central nervous system (CNS) involvement at screening (including brain parenchymal, meningeal, or spinal meningeal involvement, or positive cerebrospinal fluid for tumor cells), or other CNS diseases;
• Received the following anti-tumor therapies prior to PICX Injection infusion:

• Chemotherapy, combination therapy with proteasome inhibitors and immunomodulatory agents, or other systemic anti-tumor drug therapy within 14 days or at least 5 half-lives before infusion (excluding intrathecal chemotherapy, which must be discontinued at least 1 week prior to infusion);
• Radiotherapy to non-hematopoietic sites within 7 days, or to hematopoietic sites within 14 days before infusion;
• BCMA-targeting antibody-based therapy within 3 months before infusion;
• Active or uncontrolled infection requiring systemic treatment at screening (including bacterial, viral, fungal, or other infections);
• Presence of any of the following cardiac conditions:

• New York Heart Association (NYHA) Class III or IV congestive heart failure;
• Myocardial infarction, or coronary artery bypass grafting (CABG), or coronary stent placement within 6 months prior to screening;
• Clinically significant ventricular arrhythmia, or history of syncope of unknown cause (excluding vasovagal or dehydration-related);
• History of severe non-ischemic cardiomyopathy;
• Presence of other clinically significant diseases or conditions, including:

• Primary immunodeficiency disease;
• Cerebrovascular accident or seizure within 6 months prior to screening;
• Definite cognitive impairment or psychiatric/behavioral abnormalities (e.g., dementia, altered mental status), or severe psychiatric disorders;
• Parkinson's disease, Parkinsonism, or other movement disorders;
• Grade 2-4 acute graft-versus-host disease (GVHD) or moderate to severe chronic GVHD within 4 weeks prior to screening;
• History of other malignancies other than multiple myeloma prior to screening, except for:

• Malignancies treated with curative intent with no known active disease for ≥ 2 years prior to enrollment;
• Adequately treated cervical carcinoma in situ, basal cell or squamous cell skin carcinoma, localized prostate cancer after radical surgery, or ductal carcinoma in situ after radical surgery;
• Vaccination with live-attenuated vaccine within 4 weeks prior to screening;
• Known severe hypersensitivity to PICX Injection or any of its formulation components;
• Inability to establish venous access;
• Other conditions deemed by the investigator to be unsuitable for participation in the study.