Safety and Efficacy of KSVCBD Injection in Multiple Myeloma Expressing CD19 and/or BCMA

Официальное название

A Multicenter Clinical Study on the Safety and Efficacy of KSVCBD Injection in the Treatment of Multiple Myeloma With Positive Expression of CD19 and/or BCMA

Обзор

KSVCBD injection is an in vivo Chimeric Antigen Receptor T-Cell (CAR-T cell) therapy product. This multicenter, single-arm, open-label, early exploratory clinical study is designed to evaluate the preliminary safety and efficacy of KSVCBD injection in patients with relapsed or refractory (r/r) multiple myeloma(MM) expressing CD19 and/or BCMA.

Подробное описание

A structurally modified, third-generation, self-inactivating lentiviral vector was used in KSVCBD injection. This modified vector exhibits reduced immunogenicity and enables efficient T-cell targeting, thereby facilitating the in vivo generation of CD19/BCMA CAR T cells from endogenous T cells. Simultaneously targeting BCMA to eliminate plasma cells producing anti-lentivirus and anti-CD19 scFv antibodies enables repeated infusion. The safety and efficacy of CD19/BCMA dual-target autologous CAR-T therapy for the treatment of r/r MM have already been validated in clinical studies. In this study, dose-escalation research will be conducted to explore the safety and preliminary efficacy of CD19/BCMA dual-target in vivo CAR-T therapy in patients with r/r MM who are positive for CD19 and/or BCMA expression.

Вмешательства

• Биопрепарат KSVCBD injection
  KSVCBD injection is an in vivo CAR-T therapy targeting CD19/BCMA. Three dose levels are predefined, and KSVCBD will be dose-escalated per the protocol-specified doses

Первичные конечные точки

• Dose limited toxicity (DLT) [Срок оценки: Within 28 days post-infusion]
• Incidence and severity of AEs and serious adverse events (SAEs) [Срок оценки: Within 24 months post-infusion]
• Incidence and severity of adverse events of special interest (AESI) [Срок оценки: Within 24 months post-infusion]

Вторичные конечные точки (12)

• Objective Response Rate (ORR) [Срок оценки: Within 24 months post-infusion]
• Minimal Residual Disease (MRD) negativity rate [Срок оценки: Within 24 months post-infusion]
• ≥ CR rate [Срок оценки: Within 24 months post-infusion]
• Duration of Response (DOR) [Срок оценки: Within 24 months post-infusion]
• Time to Response (TTR) [Срок оценки: Within 24 months post-infusion]
• Progression-Free Survival (PFS) [Срок оценки: Within 24 months post-infusion]
• Overall Survival (OS) [Срок оценки: Within 24 months post-infusion]
• KSVCBD lentiviral particle concentration [Срок оценки: Within 24 months post-infusion]
• Number of CAR-positive T cells [Срок оценки: Within 24 months post-infusion]
• CAR gene copy number [Срок оценки: Within 24 months post-infusion]
• Number of CD19-positive cells [Срок оценки: Within 24 months post-infusion]
• Number of BCMA-positive cells [Срок оценки: Within 24 months post-infusion]

Критерии участия

Критерии включения

• Age 18-75 years (inclusive), any gender.
• Subjects must meet the following diagnostic and treatment criteria:

2.1 According to the IMWG 2014 diagnostic criteria, subjects must have a confirmed diagnosis of multiple myeloma and be in a relapsed or refractory state at screening, while meeting all of the following conditions:

• Must have received at least 3 prior lines of MM therapy (including a proteasome inhibitor and an immunomodulatory agent). consecutive cycles of induction chemotherapy, hematopoietic stem cell transplantation, and maintenance therapy are considered as one line of therapy if no disease progression occurs between these treatments. each line of therapy must consist of at least one complete treatment cycle, unless the best response to that regimen was disease progression.
• Must have experienced disease progression during or within 12 months after the most recent anti-myeloma therapy. or the subject must have experienced disease progression within the last 6 months and subsequently shown no response to the most recent line of therapy. Lack of response is defined as failure to achieve at least a minimal response (MR) or experiencing disease progression (PD) during treatment.

2.2 Subjects judged by the investigator to be intolerant to standard therapy may also be included in the study.

• Presence of measurable lesions at screening as determined by any of the following criteria:

• Serum monoclonal paraprotein (M-protein) level ≥ 1.0 g/dL, or urinary M-protein level ≥ 200 mg/24 hours. or
• For light chain multiple myeloma without measurable lesions in serum or urine: serum immunoglobulin free light chain level ≥ 10 mg/dL and an abnormal serum immunoglobulin κ/λ free light chain ratio.
• Positive expression of CD19 and/or BCMA in tumor tissue confirmed by flow cytometry and/or histopathology (previous pathology or flow cytometry diagnosis of CD19 and/or BCMA in the patient, as confirmed by the investigator, is acceptable). For subjects who have previously received anti-CD19 and/or anti-BCMA therapy, a tumor biopsy should be performed to confirm current positive expression of CD19 and/or BCMA.
• Toxicities from any prior therapy must be stable and have resolved to ≤ Grade 1 (excluding hematologic toxicities and clinically insignificant toxicities such as alopecia).
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.

Критерии исключения

• Expected survival < 3 months.
• History of or concurrent active malignancy. Exceptions include: carcinoma in situ of the cervix that has been cured or with no recurrence for at least 3 years, non-invasive basal cell or squamous cell skin cancer, locally advanced prostate cancer that has received curative treatment, or ductal carcinoma in situ after radical surgery.
• Prior allogeneic hematopoietic stem cell transplantation (allo-HSCT) or autologous HSCT within 3 months prior to KSVCBD infusion.
• Solitary extramedullary soft tissue plasmacytoma.
• Diagnosis of plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.
• Presence of CNS metastasis or symptoms of CNS metastasis.
• Receipt of anti-tumor therapy that is still within 5 half-lives prior to the planned KSVCBD infusion.
• Presence of uncontrolled active infections.
• Positive for human immunodeficiency virus (HIV) antibody, positive for Treponema pallidum antibody, positive for hepatitis B surface antigen (HBsAg) or positive for hepatitis B core antibody (HBcAb) with detectable peripheral blood HBV DNA, or positive for hepatitis C virus (HCV) antibody with detectable HCV RNA. except for infections that the investigator judges can be prevented or controlled with medication.
• Known active autoimmune disease requiring systemic treatment.
• Known severe allergy to the study drug or any of its components.
• Pregnant or breastfeeding women.
• Receipt of a live vaccine within 6 weeks prior to enrollment.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 3 центра

• Biotherapeutic Department of Chinese PLA General Hospital — Пекин
• Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University — Пекин
• National Clinical Research Center for Blood Diseases, State Key Laboratory of Experimental — Тяньцзинь

Идентификаторы

NCT: NCT07620275 · KSVCBD-R101-1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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