A Phase I Clinical Study to Evaluate the Safety and Preliminary Efficacy of CDH17 CAR-T in Patients with CDH17-positive Advanced Solid Tumors
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of adverse events(AE) after infusion
研究概览
简要总结
This is a single-center, open-label, single-arm study to evaluate the safety and preliminary efficacy of anti-CDH17 CAR-T cells in patients with CDH17-positive advanced solid tumors.
详细描述
This is a single-center, open-label, single-arm study to evaluate the safety and preliminary efficacy of anti-CDH17 CAR-T cells in patients with CDH17-positive advanced solid tumors.A leukapheresis procedure will be performed to manufacture Anti-CDH17 chimeric antigen receptor (CAR) modified T cells. Prior to Anti-CDH17 CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.
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
- •The patient understands and voluntarily signs the informed consent form, and is expected to complete the follow-up examination and treatment of the study procedures;
- •Age 18-75 years old, gender unlimited;
- •Tumor patients who have positive expression of CDH17 target in tumor tissues measured by immunohistochemistry (IHC) in a laboratory approved by the partner, and have no standard therapy or are ineffective or not suitable for standard treatment;
- •Have at least one extracranial measurable lesion according to RECIST 1.1 criteria;
- •Estimated survival ≥ 12 weeks;
- •Baseline ECOG (Eastern Cooperative Oncology Group) score ≤ 1 point;
- •The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade < 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy);
- •Venous access could be established; without contraindications of apheresis.
排除标准
- •Patients with prior or current other malignancies;
- •Presence of brain metastases and clinically significant central nervous system disease;
- •Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter;
- •Subjects with positive HBsAg or HBcAb positive and peripheral blood HBV DNA titer is higher than the lower limit of detection of the research institution; HCV antibody positive; HIV antibody positive; CMV DNA titer is higher than the lower limit of detection of the research institution; EBV DNA titer is higher than the lower limit of detection of the research institution
- •Those who have a positive sputum smear and T-cell test for tuberculosis infection;
- •Patients with objective evidence of a history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, and severe impairment of lung function, both past and present;
- •Patients have a severe allergic history;
- •Patients with severe heart disease or uncontrollable refractory hypertension;
- •Patients with severe liver and kidney dysfunction or consciousness disorders;
- •Active autoimmune or inflammatory diseases of the nervous system;
- •Uncontrolled infections that need antibiotics treatment;
- •Live attenuated vaccine within 4 weeks before screening;
- •Alcoholics or persons with a history of drug abuse;
- •Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion;
- •Any unsuitable to participate in this trial judged by the investigator.
研究组 & 干预措施
Anti-CDH17 CAR-T cells
CDH17 CAR-T is a novel CAR cell therapy for the treatment of advanced solid tumors.
干预措施: Anti-CDH17 CAR-T cells infusion (Biological)
结局指标
主要结局
Incidence of adverse events(AE) after infusion
时间窗: within 52 weeks post-infusion
The frequency, severity, and laboratory findings of all adverse events/serious adverse events are included.Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome are graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
次要结局
- Progression-free survival(PFS)(within 52 weeks post-infusion)
- Overall survival(OS)(within 52 weeks post-infusion)
- Objective Response Rate (ORR)(within 52 weeks post-infusion)
- Concentration of CAR-T cells(Days 2, 5, 8, 11, 14, 21, 28, 35 and weeks 6, 12, 18, 26, 34, 42, 52 after infusion)