OriCAR-017 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of R/RMM

Официальное название

An Open Label,Multi-center Study to Evaluate the Safety, Pharmacokinetics and Efficacy of Autologous T Cell Injection Targeting GPRC5D OriCAR-017 in Patients With Relapsed and/or Refractory Multiplemyeloma

Обзор

An open label, dose exploratory clinical study to evaluate the safety, efficacy, and pharmacokinetics of OriCAR-017 in R/RMM

Подробное описание

This is a Phase I and Phase II, open-label, multi-center study to assess the safety, pharmacokinetics, and efficacy of GPRC5D directed chimeric antigen receptor modified T cells injection (OriCAR-017) in n patients with relapsed and/or refractory multiplemyeloma (R/RMM).

Вмешательства

• Биопрепарат OriCAR-017
  GPCRC5D-directed chimeric antigen receptor modified T cells

Первичные конечные точки

• Maximum tolerated dose of OriCAR-017-P1 [Срок оценки: Up to 28 days]
• Dose-limiting toxicity (DLT) [Срок оценки: Up to 28 days]

Вторичные конечные точки (5)

• Objective Response Rate [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause or withdraw, whichever came first, assessed up to 2 Years]
• Pharmacokinetics (the number of cell copies and cell persistence duration in peripheral blood) [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause or withdraw, whichever came first, assessed up to 2 years]
• Antitumor efficacy-Progression-free survival (PFS) [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years]
• Antitumor efficacy-Duration of response (DOR) [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 2 years]
• Long term survival follow up [Срок оценки: From date of randomization until the date of first documented date of death from any cause, assessed up to 15 years]

Критерии участия

Main Inclusion Criteria:

• Diagnosis of R/RMM according to the IMWG criteria;
• Expected survival period is >12 weeks;
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 or 2 at the time of ICF signature;
• The expression of GPRC5D in bone marrow plasma cells membrane is more than 20% by flow cytometry and/or immunohistochemistry, multiple myeloma with measurable lesions, and at least one of the following criteria must be met:

• Serum M protein >5 g/L;
• Urine M protein level >200 mg/24 hour;
• Serum free light chain (sFLC) >100 mg/L and K/λ FLC ratio is abnormal;
• Primitive immature or monoclonal plasma cells >5% by bone marrow cytology or flow cytometry.
• Subjects who had received at least 3 prior lines of therapy including (but not limited to) immunomodulatory drugs (IMiDs), proteasome inhibitors, anti-CD38 monoclonal antibodies, etc., but have failed treatment, including those who have experienced relapse (within 12 months), refractory or intolerant to the last line treatment regimen.

Main Exclusion Criteria:

• Smoldering myeloma (asymptomatic)
• Multiple myeloma with only extramedullary lesions;
• Plasma cell leukemia;
• Concurrent amyloidosis;
• Central nervous system metastasis, leptomeningeal disease or metastatic central compression;
• HBsAg or HbcAb is positive, and the quantitative detection of hepatitis B virus (HBV) DNA in peripheral blood is more than 100 copies/L; hepatitis C virus (HCV) antibody and HCV RNA in peripheral blood is positive; human immunodeficiency virus (HIV) antibody positive; syphilis antibody is positive at Screening; Cytomegalovirus DNA test is positive;
• Had hypersensitivity or intolerance to any drug/excipient (including conditioning chemotherapy) used in this study;
• Previously received treatment targeting GPRC5D, including but not limited to antibodies, ADC, or CAR-T;
• Subjects who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks of Screening Visit or who plan to undergo ASCT during the study;
• Any uncontrolled active infection within 4 weeks prior to ICF signing or leukapheresis requires parenteral antibiotic, antiviral, or antifungal treatment
• Major surgery within 28 days prior to Screening Visit with the exception of a biopsy and an insertion of a central venous catheter or during the study;
• Subjects who received allogeneic stem cell therapy;
• Subjects complications or other conditions evaluated by investigators may affect compliance with the protocol or make them unsuitable to participate in this study;
• Pregnant or breastfeeding.

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 · 5 центров

• The First Affiliated Hospital College of Medicine Zhejiang University — Ханчжоу
• Beijing GoBroad Hospital — Пекин
• The First Affiliated Hospital with Nanjing Medical University — Нанкин
• Tongji Hospital of Tongji University — Шанхай
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Ухань

Идентификаторы

NCT: NCT06182696 · OriCAR-017-P1

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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