A Phase I/II, Open-label, Multicenter Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Anti-GPRC5D CAR-T Cell Product (OriCAR-017) in Subjects With Relapsed/Refractory Multiple Myeloma.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Maximum tolerated dose (MTD) of OriCAR-017 US-P1
研究概览
简要总结
The is a first clinical study for Oricell Therapeutics Inc. in the United States to evaluate the safety, PK, PD and preliminary efficacy of our anti-GPRC5D cell product (OriCAR-017) in subjects with relapsed/refractory multiple myeloma.
RIGEL Study
详细描述
This is a Phase I/II, open-label multicenter study to evaluate the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of anti-GPRC5D CAR-T cell product (OriCAR-017) in subjects with relapsed/refractory multiple myeloma". The study will consist of a Phase I dose escalation stage involving three doses as a single IV infusion) with up to 18 evaluable subjects and a dose expansion stage with 10-15 evaluable subjects, followed by a Phase II stage with up to 48 evaluable subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Capable of giving signed informed consent
- •Subjects aged 18 to 75 years (inclusive) at Screening (signing the ICF).
- •Expected survival period is >12 weeks.
- •Diagnosis of MM according to the IMWG criteria (2016 version).
- •One of the following criteria must be met:
- •If immunoglobulin (Ig)G type MM, then serum M protein >10 g/L; if IgA, IgD, IgE or IgM type MM, then serum M protein >5 g/L
- •Urine M protein level >200 mg/24 hour
- •If light chain type MM, then serum free light chain (sFLC) >100 mg/L and K/λ FLC ratio is abnormal.
- •Extramedullary lesions (>1 cm for diameter of the short axis).
- •For Phase I (dose-escalation) - Subjects who had received at least 3 prior lines of therapy, had previous exposure to BCMA-Ag+ therapies, and were refractory to the last line of therapy.
- •For Phase I (dose-expansion) and Phase II: Subjects with previous exposure to BCMA directed therapies including BCMA bispecific antibody (e.g., teclistamab), BCMA antibody directed conjugate (such as BLENREP), and BCMA-CAR-T (such as CARVYKT1TM)
- •Subjects with adequate hematologic, renal, hepatic, pulmonary and cardiac function.
- •Subject and partners willing to take and or use effective contraceptive measures until 2 years post IMP infusion.
排除标准
- •Pregnant or breastfeeding.
- •Seropositive for history of human immunodeficiency virus Active Hepatitis B infection and or Hepatitis C infection
- •Known active or prior history of CNS involvement
- •History of autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) caused damage to terminal organs or required systemic application of immunosuppressive or other drugs in the past 2 years
- •Presence of uncontrolled active infection
- •Subjects who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks of Screening Visit or who plan to undergo ASCT during the study.
- •Subjects who received allogeneic stem cell therapy.
- •Any condition that in the opinion of the Investigator, would interfere with evaluation of the IMP.
- •Received Bendamustine treatment 1 year prior to Screening Visit.
研究组 & 干预措施
OriCAR-017
Single OriCAR-017 infusion
干预措施: OriCAR-017 (Drug)
结局指标
主要结局
Maximum tolerated dose (MTD) of OriCAR-017 US-P1
时间窗: Up to 28 days
The MTD is defined as the highest dose with an observed incidence of DLT in no more than one out of six patients treated at a particular dose level.
Dose-limiting toxicity (DLT)
时间窗: Up to 28 days
A DLT is defined as any of the treatment-emergent adverse events (TEAEs; a TEAE is defined as an adverse event \[AE\] that starts on or after the first administration of study medication) condition or concomitant medications.
次要结局
- Assessment of MRD negative Rate(Up to 2 years)
- Assessment of Overall Survival (OS) of treatment in patients with RR/MM(Up to 2 years)
- Assessment of Overall Response Rate (ORR)(Up to 2 years)
- Assessment of Clinical Benefit Rate (CBR)(Up to 2 years)
- Evaluate PK parameters of OriCAR-017 in subjects with relapsed/refractory MM(Up to 2 years)
- Evaluate PD parameters of OriCAR-017 in subjects with relapsed/refractory MM(Up to 2 years)
- Assessment of Duration of Response (DOR) of treatment in patients with RR/MM(Up to 2 years)
- Progress-Free Survival (PFS) of treatment in patients with RR/MM(Up to 2 years)
- Assessment of Disease Control Rate (DCR)(Up to 2 years)