CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria

1. Male and female participants of age 18 years and above.
2. Patients with a confirmed diagnosis of multiple myeloma according to IMWG diagnostic criteria.
3. Received at least 3 prior multiple myeloma treatment lines of therapy or are double refractory to an IMiD and PI (refractory multiple myeloma as defined by IMWG consensus criteria). Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single line of therapy.
4. Measurable disease at Screening as per IMWG criteria.
5. ECOG Performance Status grade of 0 to 2.
6. Adequate organ function: ANC/platelets thresholds (unless cytopenias attributable to MM), LVEF ≥45%, adequate oxygenation; hepatic/renal criteria specified in Section 10.
7. Negative pregnancy test for women of childbearing potential; agreement to effective contraception.
8. Patients giving written informed consent to participate in the study after a full understanding of the implications and constraints of the study protocol.
9. Understand the content of the ICF, and voluntarily sign the ICF (If the participant is unable to sign the ICF on their own due to illiteracy, an impartial witness is needed).
10. The subject can understand the research process and is willing and able to comply with all research proposals and other requirements of the study.
11. Willing and able to adhere to the prohibitions and restrictions specified in this protocol.

Exclusion Criteria

1\. Patients who will meet any of the following criteria will not be eligible to participate in the study.

1. Prior treatment with CAR-T therapy directed at any target. Any therapy that is targeted to BCMA.
2. Known active, or prior history of central nervous system (CNS) involvement, or exhibits clinical signs of meningeal involvement of multiple myeloma.
3. Stroke or seizure within 6 months of signing the ICF.
4. Uncontrolled active infection, including uncontrolled bacterial or fungal infection; active uncontrolled HBV/HCV/HIV.
5. Clinically significant cardiac disease (e.g., NYHA III/IV, recent MI), or severe pulmonary disease.
6. Recent allogeneic HSCT with active GVHD or ongoing immunosuppression.
7. Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 1 year after receiving study treatment.
8. Any other circumstances that would impair the ability of the participant to receive or tolerate the planned treatment at the investigational site, to understand informed consent, or any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (e.g., compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.

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   Exclusion Criteria:

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主要终点：Assess Safety /tolerability and feasibility of manufacturing and delivering the product · incidence/severity of AEs including CRS/ICANS (ASTCT grading), DLTs through Day +28 · From enrolment to 1 years after infusion of the product

• CAR-T arm · OTHER · 6.2. Screening Phase During the Screening period, all participants will be asked to provide written consent for study participation and will be screened for study eligibility within 28 days before apheresis. Safety criteria that must be met before starting apheresis are presented in Section 8.1.1. If an assessment was performed as part of the participant's routine clinical evaluation and not specifically for this study, it does not need to be repeated after signed informed consent has been obtained, provided the assessments fulfill the study requirements and are performed within the specified timeframe before the first dose of study treatment. Retesting of abnormal screening values that lead to exclusion is allowed only once during the screening phase (to reassess eligibility). The last result obtained before apheresis will be used to determine eligibility. Subjects who do not meet all inclusion criteria or who meet an exclusion criterion may, at the discretion of the investigator,

The treatment options for multiple myeloma have evolved significantly over the years, providing patients with a range of therapies tailored to their specific circumstances. The choice of treatment often hinges on various factors, including the aggressiveness of the disease, individual prognostic indicators like genetic markers, the overall physical condition of the patient, and any pre-existing health issues that may affect treatment decisions. Current therapeutic strategies include several classes of drugs, each working through different mechanisms. Proteasome inhibitors (PIs) disrupt the protein degradation process within myeloma cells, thereby promoting their death. Immunomodulatory drugs (IMiDs) modulate the immune system and inhibit tumor growth by enhancing the body's natural anti-cancer responses. Monoclonal antibodies specifically target cancer cells, marking them for destruction by the immune system. In cases where patients are eligible, autologous stem cell transplantation remains a viable option, offering the potential for long-term remission by replacing damaged bone marrow with healthy stem cells from the patient's own body. Despite these advancements, multiple myeloma continues to present significant challenges, as it often recurs even after initial successful treatment and remains an incurable disease. This highlights the urgent need for innovative therapeutic strategies that can effectively address resistance to existing treatments, ultimately aiming to improve patient outcomes and survival rates.