CDH17-positive Advanced Solid Tumors
Conditions
Keywords
CDH17 CAR-T
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALAnti-CDH17 CAR-T cells infusion
Subiects who meet the enrollment conditions will receive intravenous infusion of anti-CDH17 CAR-T Cells after lymphodepleting therapy.
Sponsors
Guangzhou Bio-gene Technology Co., Ltd
920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. 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; 2. Age 18-75 years old, gender unlimited; 3. 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; 4. Have at least one extracranial measurable lesion according to RECIST 1.1 criteria; 5. Estimated survival ≥ 12 weeks; 6. Baseline ECOG (Eastern Cooperative Oncology Group) score ≤ 1 point; 7. 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); 8. Venous access could be established; without contraindications of apheresis.
Exclusion criteria
1. Patients with prior or current other malignancies; 2. Presence of brain metastases and clinically significant central nervous system disease; 3. 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; 4. 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 5. Those who have a positive sputum smear and T-cell test for tuberculosis infection; 6. 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; 7. Patients have a severe allergic history; 8. Patients with severe heart disease or uncontrollable refractory hypertension; 9. Patients with severe liver and kidney dysfunction or consciousness disorders; 10. Active autoimmune or inflammatory diseases of the nervous system; 11. Uncontrolled infections that need antibiotics treatment; 12. Live attenuated vaccine within 4 weeks before screening; 13. Alcoholics or persons with a history of drug abuse; 14. Pregnant or Lactating Women; Patients and his or her spouse have a fertility plan within two years after CAR-T cell infusion; 15. Any unsuitable to participate in this trial judged by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events(AE) after infusion | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | within 52 weeks post-infusion | The Objective Response Rate (ORR) is the percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1. |
| 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 | Concentration of CAR-T cells measured by Flow cytometry after CAR-T infusion |
| Progression-free survival(PFS) | within 52 weeks post-infusion | Progression-free survival(PFS) refers to the time from cell reinfusion to the first assessment of tumor progression or death from any cause. |
| Overall survival(OS) | within 52 weeks post-infusion | Overall survival (OS) refers to the time from the time the patient received an infusion of CAR-T cells until death (from any cause). |
Countries
China
Contacts
Primary ContactSanbin Wang, MD
Outcome results
None listed