Solid Tumor
Conditions
Brief summary
This is a single-arm, investigator-initiated exploratory study.The study is designed to evaluate the safety and the tolerability of HER2-E-CART cells for the treatment of patients with HER2-positive, refractory advanced solid tumors in three dose groups: low, medium and high.
Detailed description
This study was a one-arm,investigator-initiated exploratory study. According to the 3+3 principle, three dose groups with increasing dose were set up, namely low, medium and high dose groups, with separate cell counts. A total of 9-12 subjects were enrolled in the group and given intravenous infusion. Dose-limited toxicity was observed from the beginning of preconditioning to 28 days after CAR T infusion.
Interventions
BIOLOGICALHER2-E-CART cells
E-CAR-T is a novel second-generation CAR-T product targeting HER2 protein
Sponsors
su haichuan
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Voluntarily signed an informed consent form and were able to complete the study procedures and follow-up examinations and treatment 2. Age ≥ 18 years and ≤ 70 years, regardless of gender 3. Weight \> 40 kg 4. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 to 1 5. Patients with refractory advanced solid tumors who have failed or are intolerant of existing standard regimens or whose patients have refused standard regimens 6. The presence of at least one measurable lesion according to Response Evaluation Criteria In Solid Tumors 1.1 criteria 7. With good organ function 8. Positive HER2 cell membrane expression 9. Women of childbearing potential must have a pregnancy test with negative results within 7 days prior to initiation of treatment
Exclusion criteria
1. Any systemic antitumor therapy within 2 weeks prior to the single blood collection 2. History of organ transplantation 3. Pregnant or lactating women 4. Uncontrolled infectious disease, such as baseline Hepatitis B Virus DNA ≥ 1000 IU/ml, anti-HIV positive, Hepatitis C Virus-RNA positive 5. Other clinically significant active infections 6. Other active malignancies within the previous 5 years, such as basal or squamous skin cancer, superficial bladder cancer, or in situ breast cancer that has been completely cured and does not require follow-up treatment subjects are not included 7. Patients with severe autoimmune or immunodeficiency diseases, such as subjects with a confirmed diagnosis of a severe autoimmune disease requiring systemic immunosuppressive (steroid) therapy for a prolonged period of time (more than 2 months) or with immune-mediated symptomatic diseases, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), autoimmune vasculitis (e.g., Wegener's granulomatosis), etc 8. Subjects with known severe allergic reactions to pretreatment drugs such as injectable cyclophosphamide, injectable paclitaxel (albumin-bound), or CAR-T cell preparations including adjuvants, dimethylsulfoxide 9. Any unstable systemic disease: including but not limited to unstable angina pectoris, cerebrovascular accident or transient ischemia (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), New York Heart Association (NYHA) classification ≥ Class III congestive heart failure, severe arrhythmias poorly controlled by medications, liver, kidney or metabolic disease, and hypertension uncontrolled by standard therapy 10 10. Those with active bleeding, thrombotic disorders requiring treatment 11. Patients with pericardial, thoracic, or abdominal effusions requiring clinical management or intervention 12. The presence of known or suspected brain metastases, including central nervous system and spinal cord compressions or meningeal metastases 13. Subjects undergoing treatment with systemic steroids or steroid inhalers 14. Subjects with any psychiatric disorder, including dementia, altered mental status, that may interfere with informed consent and understanding of relevant questionnaires 15. Having participated in another clinical trial within the previous 30 days 16. Have received a live or attenuated vaccine within 4 weeks prior to pretreatment 17. Those who have been judged by the investigator to have a serious uncontrollable disease or have other conditions that may interfere with receiving treatment in this study and are considered unsuitable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurence of Adverse event rate | Adverse events will be collected from the beginning to the end of the study, up to 2 years after the last cell transfusion | The occurrence of all adverse events (AEs), serious adverse events (SAEs) and treatment-related adverse events (TEAEs). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to peak of serum cytokine Tumor Necrosis Factor-γ | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Time to peak of serum cytokine Tumor Necrosis Factor-γ |
| Overall survival (OS) | Baseline up to death event. | From randomization to the time of death from any cause |
| Objective Response Rate (ORR) | Baseline up to 144 weeks | The proportion of patients with tumor size reduction of a predefined amount and for a minimum time period |
| Time to peak of serum cytokine Interleukin-2 | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Time to peak of serum cytokine Interleukin-2 |
| Time to peak of serum cytokine Interleukin-6 | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Time to peak of serum cytokine Interleukin-6 |
| Time to peak of serum cytokine Interleukin-10 | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Time to peak of serum cytokine Interleukin-10 |
| Disease Control Rate (DCR) | Baseline up to 144 weeks | The percentage of patients with advanced or metastatic cancer who have achieved complete response (CR), partial response (PR) and stable disease (SD) to a cancer treatment in clinical trials |
| Time to peak of serum cytokine Tumor Necrosis Factor-α | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Time to peak of serum cytokine Tumor Necrosis Factor-α |
| Progression Free Survival (PFS) | Baseline up to 144 weeks | The time from the first dose to the first documentation of progressive disease (PD) or death from any cause,whichever occurs first |
| Effects on subjects' health-related quality of life | Baseline up to 144 weeks | Quality of life related scale ，for questions 1 to 28, choose a number from 1 to 4, 1 means none and 4 means very good. For questions 29 and 30, choose a number from 1 to 7, with 1 being very poor and 7 being very good. |
| Peak concentration (Cmax) | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Maximum plasma drug concentration |
| Area Under The Curve（AUC） | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | Area under the plasma concentration-time curve Single dose |
| Time to Maximum Plasma Concentration（Tmax） | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | The time required to reach peak concentration after administration |
| Elimination half-life (t1/2)-Single dose | Within 72 hours before lymphodepletion pretreatment, within 24 hours before and 1 hour after reinfusion, 24 hours, Day 4, Day 7, Day 10, Day 14, Day 28, Day 60, Day 90, Day 180, Day 270, Day 360. | t1/2 is time it takes for the blood concentration of HER2-E-CART cells or metabolite(s) to drop by half |
| Duration of Response (DOR) | Baseline up to 144 weeks | The time from the date of first documentation of a CR or PR or PD to the date of first documentation of tumor progression. |
Contacts
Primary ContactHaichuan Su, Doctor
Backup ContactSong Yang, Doctor
Outcome results
None listed