Exploratory Study on the Treatment of Recurrent and Refractory Hematological Malignancies With WGb-0302 Injection

Обзор

At present, the treatment of multiple myeloma (MM) has evolved from traditional chemotherapy to a comprehensive model that includes targeted drugs, immunotherapy, etc. However, the prognosis of recurrent/refractory MM patients remains severe. For patients who are already resistant to multiple major drugs such as proteasome inhibitors, immunomodulators, and CD38 monoclonal antibodies, the prognosis is particularly poor. B-cell maturation antigen (BCMA) plays a crucial role in regulating B cell proliferation and survival. BCMA is expressed in various hematological malignancies such as multiple myeloma and has become an important biomarker, promising therapeutic target, and research direction for these diseases. The advent of COVID-19 vaccine has brought LNP mRNA technology into the public's view. After years of development, it not only shines brilliantly in COVID-19 vaccine, but also is widely used in the treatment and exploration of cancer, rare diseases and other fields. The core of LNP mRNA technology targeting BCMA is to encapsulate the mRNA encoding specific proteins (such as anti BCMA related proteins) in lipid nanoparticles and deliver them to the body through intravenous or intramuscular injection. The experimental drug WGb 0302 injection is a BCMA based messenger RNA (mRNA) therapeutic drug, formed by loading mRNA encoding BCMA receptor related proteins onto lipid nanoparticles (LNP).

Вмешательства

• Препарат WGb-0302 injection
  WGb-0303 injection

Первичные конечные точки

• The incidence of dose limiting toxicity (DLT) [Срок оценки: Within 90 days after the initial treatment]
• Maximum tolerated dose (MTD)or optimal biological dose (OBD) [Срок оценки: Through study completion, an average of 2 years]

Вторичные конечные точки (2)

• Objective response rate (ORR) [Срок оценки: Through study completion, an average of 2 years]
• Progression free survival (PFS) [Срок оценки: From date of initial treatment until the date of first comfired progression or date of death from any cause, whichever came first, assessed up to 24 months]

Критерии участия

Критерии включения

• 1\. Age range: 18-75 years old, gender not limited;
• 2\. Expected survival time exceeds 12 weeks;
• 3\. According to the diagnostic criteria of the International Myeloma Working Group (IMWG) for multiple myeloma, the diagnosis is multiple myeloma (MM), and the expression of BCMA target antigen is confirmed by flow cytometry, bone marrow pathology, and immunohistochemistry.
• 4\. Having measurable multiple myeloma lesions:
• 5\. The physical fitness status score of the Eastern Cancer Collaboration Group (ECOG) is 0 or 1 point;
• 6\. Before screening (at baseline), corresponding conditions should be met;
• 7\. Male and female patients of appropriate age must use reliable methods of contraception before entering the trial, during the research process until 30 days after discontinuation of medication; Reliable contraceptive methods will be determined by the primary researchers or designated personnel;
• 8\. Those who can understand this experiment and have signed the informed consent form.

Критерии исключения

• 1\. Accompanied by other uncontrolled malignant tumors;
• 2\. Previously received chimeric antigen receptor therapy or other transgenic T cell therapy less than 6 months after the first administration;
• 3\. Have received any anti myeloma treatment (including but not limited to chemotherapy, targeted therapy, immunotherapy, radiation therapy \[excluding local radiotherapy for pain control\], etc.) within 14 days prior to the first use of medication;
• 4\. Known history of HIV or hepatitis B (HBsAg positive and HBV DNA reaching the detection limit) or hepatitis C virus (anti HCV positive) infection;
• 5\. Participants with a history of CNS lymphoma, malignant cells in cerebrospinal fluid, or brain metastases;
• 6\. Within 14 days prior to enrollment, there is an uncontrolled active infection. Note: If there is no evidence of active infection within 72 hours before enrollment, subjects who continue to use prophylactic antibiotics, antifungal drugs, or antiviral drugs are allowed;
• 7\. Emergency treatment is required due to the impact of tumor masses, such as intestinal obstruction or vascular compression;
• 8\. Suffering from serious diseases such as coronary heart disease, angina pectoris, myocardial infarction, arrhythmia, cerebral thrombosis, cerebral hemorrhage, poorly controlled hypertension, or other uncontrolled active diseases that hinder participation in the trial;
• 9\. Unstable pulmonary embolism, deep vein thrombosis, or other significant arterial/venous thromboembolism events occurred within 30 days prior to enrollment. If receiving anticoagulant therapy, the treatment dose of participants must reach a stable level before enrollment;
• 10\. Long term use of immunosuppressants due to autoimmune diseases or organ transplantation, except for recent or current inhaled corticosteroid therapy;
• 11\. Any pregnant or breastfeeding woman, or participant who plans to conceive during or within 18 months after treatment;
• 12\. The researcher believes that there are any other factors that are not suitable for the study participants to enter this trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07362732 · LNP-mRNA for BCMA

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗