CAR-T Cell Efficacy With Molecular Imaging in Multiple Myeloma

Official title

Visualizing CAR-T Cell Therapy in Multiple Myeloma Using a BCMA-Targeted PET Probe

Overview

⁶⁸Ga-NOTA-BCMA is a novel, targeted PET tracer under clinical investigation. It is designed to provide a non-invasive method for monitoring the biodistribution and persistence of BCMA CAR-T cells in patients. Preclinical data robustly support its specific binding, favorable pharmacokinetics, and excellent safety profile, warranting its advancement into clinical studies.

Detailed description

⁶⁸Ga-NOTA-BCMA is an investigational PET radiopharmaceutical designed for targeted in vivo tracking of BCMA-directed CAR-T cells. Its molecular design incorporates a BCMA-derived peptide, specific for the CAR's scFv, conjugated to the ⁶⁸Ga-chelator NOTA. Preclinical data confirm high target affinity, rapid renal clearance (t₁/₂α=3.30 min, t₁/₂β=33.27 min), and an excellent safety profile with no drug-related toxicities in murine models. The agent is administered as a single IV bolus (4 mCi/80 μg) and must be used within 4 hours of GMP-compliant, on-site radiolabeling.

Interventions

• Other BCMA-Targeting CAR-T Cell Therapy
  Patient T-cells are harvested and genetically engineered to express chimeric antigen receptors (CARs) targeting B-cell maturation antigen (BCMA). These modified CAR-T cells specifically recognize and eliminate multiple myeloma cells expressing BCMA. Following reinfusion, the CAR-T cells undergo antigen-stimulated proliferation, establishing sustained antitumor immune activity.
• Device PET/CT Imaging
  A low-dose PET/CT scan will be performed 60 minutes post-administration of the agent. Low-dose CT is only utilized for anatomic localization and PET attenuation correction, and the radiation dose involved is substantially lower than that of conventional CT.

Primary outcome measures

• Biodistribution of 68Ga-NOTA-BCMA [Time frame: Baseline (pre-CAR-T), and at Day 6±2, Day 11±2, Day 21±2 post-CAR-T infusion (Scan at 60 minutes post-injection). For the first 3 subjects, additional scans at 30 and 120 minutes post-injection will be performed at baseline.]
• Pharmacokinetic assessment of 68Ga-NOTA-BCMA: measurement of elimination half-life (t1/2) [Time frame: Baseline: pre-injection, and at 2, 5, 10, 15, 30, 60, 90, 120 minutes post-injection of 68Ga-NOTA-BCMA. (May be omitted for subsequent subjects based on results from the first 5 subjects).]

Secondary outcome measures (3)

• CAR-T Cell Expansion and Persistence [Time frame: Day 6±2 and Day 11±2 post-CAR-T infusion.]
• Safety and Tolerability of 68Ga-NOTA-BCMA [Time frame: Vital signs: pre-injection and 2 hours (±1h) post-injection of 68Ga-NOTA-BCMA. Other safety assessments: throughout the study, with a follow-up at Day 28±2 after the last tracer dose.]
• CAR-T Cell Immunophenotyping [Time frame: Day 6±2 and Day 11±2 post-CAR-T infusion.]

Eligibility criteria

Inclusion criteria

• \*\*Inclusion Criteria\*\*

• Subjects must voluntarily sign the informed consent form and be able to complete the trial per the protocol requirements.
• Age 18 years or older, regardless of gender.
• Diagnosed with multiple myeloma and scheduled to receive anti-BCMA CAR-T cell therapy.
• ECOG performance status of 0-2; with a life expectancy of not less than 3 months.
• Female subjects of childbearing potential must have a negative serum pregnancy test prior to enrollment.
• For female subjects of childbearing potential or male subjects with partners of childbearing potential, agreement to remain abstinent or use one or more forms of contraception with a failure rate of <1% per year during the study period and for at least one year after the study completion.

Exclusion criteria

• \*\*Exclusion Criteria\*\*

• Participation in another interventional clinical trial, concurrently or within 28 days prior to the first dose in this study. Participation in non-interventional trials is permitted.
• History of hypersensitivity to any component of the imaging agent or antibodies, or a known allergic predisposition.
• Inability to undergo PET/CT imaging, such as due to claustrophobia or emotional instability.
• Current use of anticoagulant therapy or anticipated requirement for such therapy during the study period.
• Known allergic or hypersensitivity reactions to biological products or any excipient of the 68Ga-NOTA-BCMA molecular probe.
• Active hepatitis B or C infection, or seropositivity for human immunodeficiency virus (HIV) antibody or Treponema pallidum antibody.
• Pregnancy, lactation, or intention to become pregnant during the trial period.
• Any other condition deemed by the investigator to render the subject unsuitable for trial participation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07280793 · XYFY2025-KL519-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗