NCT04511871进行中（未招募）1 期
A Phase I Trial to Assess Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) (CCT303-406) in Patients With Relapsed or Refractory HER2 Positive Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- MTD: to determine the maximum tolerated dose of CCT303-406
研究概览
简要总结
This clinical study is to investigate the safety and tolerability of CCT303-406 CAR modified autologous T cells (CCT303-406) in subjects with relapsed or refractory stage IV metastatic HER2-positive solid tumors.
详细描述
This is a single arm, open label, dose escalation clinical study to evaluate the safety and preliminary therapeutic efficacy of CCT303-406 cells in adult subjects with HER2 positive relapsed or refractory stage IV metastatic solid tumors.
Subjects that meet inclusion criteria with positive biopsy HER2 (IHC 3+ in ≥50% tumor cells) will receive CCT303-406 according to the 3+3 dose escalation design.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with willingness to be in the study and follow all study procedures, and capable of providing informed consent
- •Male or female aged 18-70 years
- •Patients with stage IV (according to the 8th edition of AJCC) advanced solid tumor malignancies that have failed standard treatment of relapsed or difficult-to-treat solid tumors confirmed by histology or cytology
- •At least one measurable lesion, i.e. the length of non-lymph node lesions examined according to CT cross-sectional scanning or magnetic resonance imaging (MRI), or the short diameter of the lymph node lesions is ≥15 mm according to RECIST 1.1
- •Tumors with HER2 IHC 3+ in≥50% of all tumor cells as determined by IHC according to the Breast Cancer HER2 Testing (2019 edition) and the Gastric Cancer HER2 Testing (2016 edition); For HER2 IHC 3+ tumors other than gastric and breast cancers, FISH is required to confirm HER2 expression; For relapsed patients after HER2-targeted therapies, biopsy and IHC are required to confirm HER2 expression per enrollment criteria.
- •ECOG Performance Status 0-1
- •Expected survival greater than 12 weeks
- •Adequate organ and hematopoietic system functions to meet the following requirements:
- •Hemoglobin (HGB) s 90 g/L, no blood transfusions within two weeks;
- •White blood cell (WBC) count≥2.5×109/L
- •Absolute Neutrophil Count (ANC) ≥1.5 x 109/L
- •Platelet (PLT) count ≥80-109/L
- •Total bilirubin (TBIL) ≤3.0ng/dL or ≤5 ULN
- •ALT and AST ≤5 ULN; for liver metastasis, ALT and AST ≤5 ULN
- •Creatinine (Cr) ≤1.5 x ULN; or creatinine removal rate (CrCl) ≥50 mL/min
- •Serum troponin T <0.03 ng/mL
- •PT: INR < 1.7 or extended PT to normal value < 4s
- •Normal language, recognition and consciousness assessed by investigator during screening phase
- •Capable of receiving treatment and follow-up, including treatment in the clinical center;
- •Female subjects of childbearing age must take acceptable measures to minimize the likelihood of pregnancy during the trial. The results of serum or urine pregnancy test must be negative
- •Female subjects must not be in the lactation period.
排除标准
- •Females with pregnancy or in lactation period
- •Patients with active hepatitis B, or active hepatitis C
- •HIV positive
- •Other active infections of clinical significance
- •Patients receiving in situ surgery within 3 months
- •Patients with the following previous or accompanying diseases:
- •Patients diagnosed as severe autoimmune diseases that require long term (more than 2 months) treatment with systemic immunosuppressants (steroids), or diseases with immune-mediated symptoms, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), and autoimmune vasculitis
- •Patients with ≥Grade 2 peripheral neuronal diseases (according to NCI-CTCAE v5.0)
- •Patients with any mental illness, including dementia, mental changes, which may cause difficulties understanding the informed consent and related questionnaires
- •Patients with serious uncontrollable diseases, which may interfere with the therapies in this study
- •Patients with other active malignancies in the past 5 years excluding those with completely cured basal or squamous skin cancers, superficial bladder cancers or primary breast cancers without need of follow-up treatment
- •Patients receiving systemic steroids or steroid inhalants
- •Patients who have received tumor immunotherapy (including monoclonal antibody or cell therapy) in the past 4 weeks
- •Patients allergic to immunotherapies or related drugs
- •Patients with metastatic lesions in meninges or central nervous system, or clear evidence of central nervous system diseases with continous significant symptoms in the last 6 months
- •Patients with NYHA class II heart failure, or hypertension incontrollable by standard care, or medical history of myocarditis, or heart attack within a year
- •Patients who have received or are going to receive organ transplantation
- •Patients with active bleeding
- •Patients with incontrollable pleural or abdominal fluid that needs clinical treatment or intervention
- •Patients having undergone major surgery within 4 weeks or have not fully recovered from prior surgery
- •Patients that have received radiotherapy within 4 weeks, excluding those who received local irradiation for the peripheral bone metastatic lesions for more than 2 weeks, and recovered from all acute toxicities of radiotherapy
- •Patients that have received anthracyclines within 8 weeks
- •Patients as determined by the investigators to be inappropriate for the study
研究组 & 干预措施
CCT303-406
Experimental
To determine the safety, tolerability, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of CCT303-406 cell therapy in patients with HER2-positive (IHC 3+ in ≥50% tumor cells) relapsed or refractory solid tumors.
Dose cohorts:
- Dose 1: 3x10^5 CCT303-406 CAR-positive T cells/kg body weight, intravenous infusion
- Dose 2: 1x10^6 CCT303-406 CAR-positive T cells/kg body weight, intravenous infusion
- Dose 3: 1x10^7 CCT303-406 CAR-positive T cells/kg body weight, intravenous infusion
干预措施: CCT303-406 (Biological)
结局指标
主要结局
MTD: to determine the maximum tolerated dose of CCT303-406
时间窗: 28 days following infusion
To assess the DLT (dose limiting toxicities) attributed to CCT303-406 per cohort and determine the RP2D (recommended phase 2 dose).
次要结局
- AE: Adverse Events(Up to 52 weeks)
- The persistence over time of genetically modified CCT303-406 cells in the peripheral blood as determined by Flow Cytometry (% CAR + cells)(Up to 52 weeks)
- ORR (overall response rate): Proportion of subjects with the best overall response (BOR)(Up to 52 weeks)
- DCR: Disease control rate(Up to 52 weeks)
- The expansion over time of genetically modified CCT303-406 cells in the peripheral blood as determined by QPCR (copies/ug gDNA)(Up to 52 weeks)
- PFS: Progression free survival(Up to 52 weeks)
- 12 month survival rate(Up to 52 weeks)
- DOR: Duration of reponse(Up to 52 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
终止
1 期
CCT301-38 CAR-T in Patients With Relapsed or Refractory AXL Positive SarcomasSARNCT05128786Shanghai PerHum Therapeutics Co., Ltd.9
招募中
1 期
Clinical Study of CEA-targeted CAR-T Therapy for CEA-positive Advanced/Metastatic Malignant Solid TumorsPancreas CancerGastric CancerColon CancerEsophagus CancerLung CancerBreast CancerCholangiocarcinomaNCT06010862Chongqing Precision Biotech Co., Ltd36
招募中
1 期
Clinical Study of Chimeric Antigen Receptor T Lymphocytes (CAR-T) in the Treatment of Relapsed/Refractory Non-Hodgkin LymphomaRelapsed Non-Hodgkin LymphomaRefractory Non-Hodgkin LymphomaNon Hodgkin LymphomaNCT05420493Chongqing Precision Biotech Co., Ltd54
已完成
1 期
Phase 1 Study of ART5803 Safety and PK After IVIG in Healthy ParticipantsAutoimmune EncephalitisAutoimmune Encephalitis Caused by N-Methyl D-Aspartate Receptor AntibodyAutoimmune Encephalitis Caused by N-Methyl D-Aspartate Receptor Antibody (Disorder)NCT06753955Arialys Therapeutics7
终止
1 期
GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular CarcinomaAdvanced Hepatocellular CarcinomaNCT05352542jianming xu10