A Phase I Clinical Study to Assess the Safety and Efficacy of CD70-targeted CAR-T in the Treatment of CD70-positive Refractory or Relapsed Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 18
- 主要终点
- Incidence of Adverse events after CD70 UCAR-T cells infusion (Safety and Tolerability)
研究概览
简要总结
This is a single-center, single-arm ，open-label ，dose escalation and dose extension study. In this study we plan to evaluate the safety and efficacy of CD70-targeting UCAR-T cells in the treatment of CD70-positive refractory or relapsed solid tumors, and obtain recommended doses and infusion patterns.
详细描述
In the discovery phase, accelerated titration combined with the "3+3" dose escalation principle was adopted, starting from the initial dose of 3×106/kg. If a grade ≥3 AE occurs during DLT observation, the accelerated titration mode will switch to "3+3" dose escalation, at least 12 eligible patients will be enrolled and receive 4 doses of CD70 UCAR-T cell therapy (3 × 10^6 cells/kg, 6 × 10^6 cells/kg, 8× 10^6 cells/kg, 1 × 10^7 cells/kg).
In the dose expansion phase, each group will choose one or two dose groups to verify the safety and efficacy, and plan to recruit about 6 subjects in each dose group.
During the clinical study, after the completion of each dose group, the Safety Monitoring Committee (SMC) will determine whether it is possible to continue to increase to the next higher dose group, or add more subjects to the current dose group, or reduce to a lower dose group to continue to explore, or climb to a higher dose after reaching the highest dose (1 × 10^7 cells/kg).
Conditions Relapsed Tumor, Refractory Solid Tumor, Renal Cell Carcinoma, Head and Neck Squamous Cell Carcinoma, Nasopharyngeal carcinoma, Ovarian Cancer, Cervix Cancer etal
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
- •Ability to understand and sign a written informed consent documen；
- •Age ≥18 years old, male or female；
- •Histopathological confirmed advanced or metastatic solid tumors failed to at least second-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy；
- •Histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) diagnosed as advanced/metastatic solid tumor (positive tumor CD70 expression (tumor CD70 positive (IHC 2+) confirmed by histology or pathology));
- •At least one measurable lesion at baseline per RECIST version 1.1；
- •The expected survival time is more than 12 weeks;
- •ECOG 0-1 points;
- •The function of important organs is basically normal:Hematopoietic function:
- •Hematopoietic function: neutrophils ≥ 1.5×109/L, platelets ≥ 90×109/L, hemoglobin ≥ 90g/dL;
- •Renal function: serum creatinine≤1.5×ULN;
- •WBC≥3.0×109/L,
- •Liver function: Total bilirubin ≤ 1.5×ULN(Except Gilbert syndrome), extrahepatic metastasis：ALT and AST ≤ 3.0×ULN (Nonhepatic metastasis：it can be relaxed to ≤ 5.0×ULN);
- •coagulation function：INR≤1.5×ULN，APTT≤1.5×ULN
- •Subjects agree to use reliable and effective contraceptive methods for contraception within 6 months after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);
排除标准
- •Received anti-CD70 drug treatment before screening;
- •Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is longer) before Received;
- •Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to Received；
- •Pregnant, lactating, or breastfeeding females;
- •Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV) RNA titer test is greater than the normal range; human immunodeficiency virus (HIV) antibody positive; syphilis test positive; cytomegalovirus (CMV) DNA test positive;
- •Have any of the following heart conditions:
- •New York Heart Association (NYHA) stage III or IV congestive heart failure; Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment; Clinically significant ventricular arrhythmia, echocardiography showed cardiac ejection fraction<50%,
- •Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;
- •Prior organ allograft transplantations or allogeneic hematopoietic stem cell transplantation;
- •Vaccination within 14 days of study enrollment;
- •Received live attenuated vaccine within 4 weeks before screening;
- •Malignant tumors other than the target tumor within 3 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 3 years prior to enrollment;
- •Other investigators deem it inappropriate to participate in the study.
- •Serious or uncontrollable systemic disease or any unstable systemic disease, including but not limited to uncontrolled hypertension, uncontrolled hyperglycemia, liver and kidney insufficiency or metabolic disease, central nervous system disease, etc
研究组 & 干预措施
Anti-CD70 UCAR-T Cell Injection
In the discovery phase, accelerated titration combined with the "3+3" dose escalation principle was adopted, starting from the initial dose of 3×106/kg. If a grade ≥3 AE occurs during DLT observation, the accelerated titration mode will switch to "3+3" dose escalation, at least 12 eligible patients will be enrolled and receive 4 doses of CD70 UCAR-T cell therapy (3 × 10^6 cells/kg, 6 × 10^6 cells/kg, 8× 10^6 cells/kg, 1 × 10^7 cells/kg).
In the dose expansion phase, each group will choose one or two dose groups to verify the safety and efficacy, and plan to recruit about 6 subjects in each dose group.
干预措施: CHT101 (Drug)
结局指标
主要结局
Incidence of Adverse events after CD70 UCAR-T cells infusion (Safety and Tolerability)
时间窗: 28 days
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
次要结局
- Disease control rate (DCR)(42 days)
- Objective response rate (ORR)(42 days)
研究者
Weijia Fang, MD
Professor
Zhejiang University