Clinical trial NCT05745454: A Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T-cell (CART) in the Treatment of Solid Tumors
Official title: A Phase I Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor T-cell (CART) in the Treatment of Human Epidermalgrowth Factor Receptor-2 (HER2) Positive and Refractory Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Solid Tumor
Lead sponsor: Tang-Du Hospital
Sponsor class: OTHER
First posted: 2023-02-27
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Occurence of Adverse event rate
timeFrame: Adverse events will be collected from the beginning to the end of the study, up to 2 years after the last cell transfusion
Secondary outcomes:
measure: Time to peak of serum cytokine Interleukin-2
timeFrame: 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.
measure: Time to peak of serum cytokine Interleukin-6
timeFrame: 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.
measure: Time to peak of serum cytokine Interleukin-10
timeFrame: 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.
measure: Time to peak of serum cytokine Tumor Necrosis Factor-α
timeFrame: 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.
measure: Time to peak of serum cytokine Tumor Necrosis Factor-γ
timeFrame: 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.
measure: Overall survival (OS)
timeFrame: Baseline up to death event.
measure: Objective Response Rate (ORR)
timeFrame: Baseline up to 144 weeks
measure: Disease Control Rate (DCR)
timeFrame: Baseline up to 144 weeks
measure: Duration of Response (DOR)
timeFrame: Baseline up to 144 weeks
measure: Progression Free Survival (PFS)
timeFrame: Baseline up to 144 weeks
measure: Effects on subjects' health-related quality of life
timeFrame: Baseline up to 144 weeks
measure: Peak concentration (Cmax)
timeFrame: 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.
measure: Area Under The Curve（AUC）
timeFrame: 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.
measure: Time to Maximum Plasma Concentration（Tmax）
timeFrame: 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.
measure: Elimination half-life (t1/2)-Single dose
timeFrame: 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.
Other outcomes:
Locations:
Study officials:
affiliation: The Second Affiliated Hospital of PLA Air Force Medical University
name: Haichuan Su, Doctor
role: PRINCIPAL_INVESTIGATOR
References: