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) B-cell non-Hodgkin's lymphoma (NHL) CD19 and/or BCMA.
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 B-cell NHL 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 B-cell NHL who are positive for CD19 and/or BCMA expression.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
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
Biotherapeutic Department of Chinese PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGDose limited toxicity (DLT)
DLT is defined as any of the following adverse events (AEs) related to KSVCBD infusion occurring within 28 days after KSVCBD infusion
Time frame: Within 28 days post-infusion
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
AEs refer to any adverse medical events occurring in subjects from the initiation of KSVCBD administration during clinical trials. SAEs denote events involving death, life-threatening conditions, significant disability/incapacity, hospitalization or prolonged hospitalization arising after KSVCBD administration in subjects
Time frame: Within 24 months post-infusion
Incidence and severity of adverse events of special interest (AESI)
AESI including grade ≥ 3 Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), and infections
Time frame: Within 24 months post-infusion
Objective Response Rate (ORR)
ORR includes Complete Remission (CR) and Partial Remission (PR).
Time frame: Within 24 months post-infusion
Duration of Response (DOR)
Time from first documented PR or better to relapse or disease progression, or death from any cause
Time frame: Within 24 months post-infusion
Time to Response (TTR)
Time from administration to first documented PR or better.
Time frame: Within 24 months post-infusion
Progression-Free Survival (PFS)
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Time from administration to disease progression or death from any cause, whichever occurs first.
Time frame: Within 24 months post-infusion
Overall Survival (OS)
Time from administration to death from any cause.
Time frame: Within 24 months post-infusion
KSVCBD lentiviral particle concentration
KSVCBD lentiviral particle concentration in peripheral blood.
Time frame: Within 24 months post-infusion
Number of CAR-positive T cells
Number of CAR-positive T cells in peripheral blood.
Time frame: Within 24 months post-infusion
CAR gene copy number
CAR gene copy number in peripheral blood.
Time frame: Within 24 months post-infusion
Number of CD19-positive cells
Number of CD19-positive cells in peripheral blood.
Time frame: Within 24 months post-infusion
Number of BCMA-positive cells
Number of BCMA-positive cells in peripheral blood.
Time frame: Within 24 months post-infusion