NCT Number: NCT06385652
Multiple myeloma (MM) predominantly affects the elderly, often presenting insidiously and with a rising incidence rate. Current diagnostic methods primarily rely on invasive bone marrow biopsies, which can lead to false-negative results if the biopsy site is improperly chosen. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for this disease.
Addressing the limitations in specificity and sensitivity of traditional PET imaging agents, this project is dedicated to developing a new type of nanobody PET/CT imaging probe, 68Ga-NB381, which possesses high affinity and targets CD38. This probe, which is an intellectual property of our institution, aims to enhance the accuracy and specificity of early MM diagnosis. In terms of clinical evaluation, the project will implement a comprehensive assessment process including case selection, collection of baseline information, high-precision imaging, expert-level image interpretation, and follow-up studies, comparing directly with traditional 18F-FDG imaging to thoroughly verify the specificity and safety of 68Ga-NB381. This lays the groundwork for the clinical translation of this radiopharmaceutical in China. Furthermore, the project contributes to formulating more effective precision treatment plans based on CD38 expression levels and provides evidence for monitoring the therapeutic effects of daratumumab, a drug also targeting CD38. This makes the project of significant academic value and clinical importance, thus promoting the development of personalized treatment strategies.
Interested in participating?
Request Info18 year–90 year
All sexes
Interventional
Early Phase 1
Beijing, Beijing Municipality, 100000, China
Location status: Recruiting
Lei Kang, MD
PRINCIPAL_INVESTIGATOR
Ronghui Yu, Master
CONTACT
TIANYAO Wang, PhD
PRINCIPAL_INVESTIGATOR
Yongkang Qiu, Master
SUB_INVESTIGATOR
Zhenghao Tong, MD
SUB_INVESTIGATOR
Multiple myeloma (MM) commonly occurs in the elderly and often remains undetected until it reaches an advanced stage. With the aging population in China, the incidence of MM is on the rise, now surpassing that of acute leukemia. Clinically, MM is characterized by bone destruction and lacks specificity; diagnosis primarily relies on bone marrow biopsies that detect an increase in clonal plasma cells, which are invasive and can yield false-negative results if the biopsy site is improperly selected. CD38 is significantly overexpressed on the surface of malignant plasma cells in MM, making it a characteristic tumor biomarker for MM.
As the incidence of malignant tumors in China continues to increase, so does the clinical demand for radiopharmaceuticals. Addressing the limitations in the targeting of 18F-FDG in PET imaging, the development of new targeted nuclear medicine molecular probes is of significant academic value and clinical importance, particularly in monitoring the therapeutic effects of the CD38-targeted nanobody NB381, which offers unique advantages. This project uses a nanobody with high affinity for CD38 as the targeting moiety for the radiopharmaceutical, exploring the diagnostic efficiency of 68Ga-NB381 in patients with MM exhibiting high CD38 expression. This not only provides a basis for the early diagnosis of MM but also allows for the formulation of effective precision treatment strategies based on the CD38 expression profile in MM patients.
68Ga-NB381, a new CD38-targeted molecular probe labeled with 68Ga, can be used for the diagnosis and research of various malignancies expressing high levels of CD38, including MM. The probe is conjugated with 68Ga3+ using TOHP as a bifunctional chelator, with a simple labeling process that does not require purification, offering high in-vivo stability and significant radioactive accumulation in tumor sites in mouse models, resulting in superior imaging outcomes. This project will complete the automation of the 68Ga-NB381 labeling process and conduct quality control studies on the resulting radiopharmaceutical injection solution, establishing quality standards for this new PET probe and laying the foundation for its clinical translation in China. The project aims to provide 68Ga-NB381 PET/CT imaging studies to support the early diagnosis of CD38 high-expression malignancies, the formulation of treatment plans, and the assessment of therapeutic efficacy.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Lei Kang from Peking University First Hospital and Bing Jia's team from the School of Basic Medical Sciences at Peking University have developed a targeted CD38 nanobody sequence using genetic engineering technology. They have optimized its structure, functionalized it with labeling, and conducted imaging and other evaluations, ultimately producing the CD38-targeted nuclear medicine small molecule diagnostic and therapeutic agent-68Ga-labeled nanobody NB381. The post-labeling quality control of the drug meets clinical trial requirements with a radiochemical purity (PCR) greater than 98% and in vitro stability not less than 90%.
Preliminary PET imaging results of 68Ga-NB381 indicate that the nanobody is primarily concentrated in the kidneys, bladder, and MM.1S and Ramos or H929 tumors (CD38+). Additionally, the cold antibody NB381 significantly inhibits the uptake of 68Ga-NB381 in tumors, confirming the high specificity of this nanobody's binding to the CD38 protein.
Other names: 18F-FDG
Time frame: For a single patient, imaging and analysis will be conducted within 24 hours post-injection; follow-up assessments for stability and biodistribution will be conducted at 1 week post-injection.
Evaluate the specificity and binding efficiency of 68Ga-labeled NB381 nanobody in targeting CD38 positive tumors using PET imaging. The measure involves comparing the uptake of 68Ga-NB381 in CD38 positive tumors to non-target areas and assessing the ability of cold antibody NB381 to inhibit this uptake, thus confirming the high specificity of the nanobody for CD38 protein.
Time frame: Baseline (within 28 days prior to first dose of study intervention)
Baseline bone marrow pathological assessments will be performed, including: (1) histopathological evaluation of plasma cell infiltration; (2) flow cytometry to quantify the proportion of malignant plasma cells and CD38-positive cells; and (3) immunohistochemical profiling for relevant markers (e.g., CD138, κ/λ light chain restriction). Results will be summarized descriptively for baseline disease characterization.
Time frame: Baseline (within 28 days prior to first dose of study intervention)
Baseline disease characteristics of enrolled participants will be documented, including: (1) International Staging System (ISS) stage (I, II, or III), determined by serum β2-microglobulin and albumin levels per International Myeloma Working Group (IMWG) criteria; and (2) Immunofixation electrophoresis (IFE) type identifying the monoclonal protein isotype (e.g., IgG κ, IgG λ, IgA κ, IgA λ, IgD, free light chain-only, or non-secretory disease). These baseline stratification factors will be summarized descriptively and may be used for pre-specified subgroup analyses to evaluate treatment effect consistency across disease risk profiles.
Time frame: Baseline (within 28 days prior to first dose of study intervention)
Baseline laboratory parameters will be collected, including complete blood count, clinical chemistry (renal/hepatic function, electrolytes, LDH), serum immunoglobulins, serum and urine M-protein quantification, serum free light chains with κ/λ ratio, and urine immunofixation electrophoresis. Results will be summarized descriptively and may be used for baseline characterization and subgroup analyses.
Time frame: End of Cycle 2 (approximately 2 months after first dose) and End of Cycle 4 (approximately 4 months after first dose)
Treatment response will be evaluated according to the International Myeloma Working Group (IMWG) consensus criteria, categorizing disease status as stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), or progressive disease (PD). Results will be used to assess preliminary antitumor efficacy.
Contact information is provided by the study sponsor or research team.
Lei Kang, MD
CONTACT
TIANYAO Wang, PhD
CONTACT
Peking University First Hospital
Other
Clinical PET Imaging Evaluation of 68Ga-NB381 Probe in Multiple Myeloma
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