Evaluating anti-HER2-CAR-T cell injections for patients with solid tumors

An Exploratory Clinical Study Evaluating the Safety and Efficacy of Anti-HER2-CAR-T Cells Injection in Patients With HER2+ Locally Advanced and/ or Metastatic Solid Tumors

This study is testing a new type of cell therapy for patients with certain advanced solid tumors to see if it can help them when other treatments haven't worked.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: China Medical University, China (Academic / other)
• Drugs / interventions: tocilizumab, CAR-T, cyclophosphamide, fludarabine, prednisone, CAR T
• Locations: 1 site (Shenyang, Liaoning)
• Trial ID: NCT06101082 on ClinicalTrials.gov

What this trial studies

This clinical study focuses on the safety and efficacy of anti-HER2-CAR-T cell therapy in patients with HER2-positive locally advanced and/or metastatic solid tumors. It involves a single-center, open-label design where eligible patients will receive an intravenous infusion of anti-HER2-CAR-T cells after undergoing a screening period and necessary pre-treatment. The study aims to assess the response to this innovative cell therapy in patients who have not responded to conventional treatments.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 70 with HER2-positive locally advanced or metastatic solid tumors who have not responded to conventional treatments.

Not a fit: Patients with solid tumors that do not express HER2 or those who are not eligible for CAR-T cell therapy due to other health conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with HER2-positive solid tumors that are resistant to standard therapies.

How similar studies have performed: Other studies using CAR-T cell therapy for solid tumors have shown promise, but this specific approach targeting HER2 is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Patients should understand and sign informed consent forms and voluntarily participate in clinical studies;
2. Age≥ 18, \< 70 years old, gender is not limited;
3. Locally advanced and/or metastatic solid tumors; HER2-positive expression in tumor tissues (staining 3+, or staining 2+ with HER2 gene amplification should be further performed by ISH and other methods) ;
4. Histology-confirmed solid tumors (breast cancer,gastric cancer, colorectal cancer, pancreas cancer, etc.), conventional treatment is ineffective or Intolerability conventional treatment or lack of effective treatment;
5. According to RECIST v 1.1, at least one measurable lesion with a maximum lesion diameter not exceeding 6 cm;
6. Expected survival≥ 12 weeks;
7. ECOG score≤ 2 ;
8. Adequate hematological function ; have no performed blood transfusion or received cell growth factor within 7 days before screening hematological evaluation:Neutrophil ≥ 1.0×10\^9/L;Hemoglobin≥ 80g/L;Platelet ≥ 75×10\^9/L;Lymphocytes ≥ 0.5×10\^9/L
9. Adequate liver function: serum total bilirubin ≤1.5× ULN (excluding Gilbert's syndrome); AST and ALT≤2.5×ULN( AST and ALT ≤5×ULN with liver metastasis);
10. Adequate renal function: creatinine ≤1.5× ULN or endogenous creatinine clearance ≥50 mL/min;
11. LVEF ≥ 50%;
12. There was no evidence that subjects had difficulty breathing at rest or pulse oximetry\>90% when breathing indoor air;
13. Sufficient intravenous access for apheresis; no other contraindications to blood cell separation;
14. The pregnancy test for women of childbearing age must be negative. All subjects must agree to take effective contraception from the signing of the informed consent to 6 months after the last dose of the study drug infusion.

Exclusion Criteria:

1. Previously using any CAR-T cell products or other genetically modified T cell therapies;
2. Patients who are waiting for organ transplantation or with a history of allogeneic stem cell or solid organ transplantation;
3. Patients with acute or uncontrolled active infection, including but not limited to active tuberculosis;
4. Patients with Hepatitis B infection (HBV surface antigen positive and/or hepatitis B core antibody positive and hepatitis B DNA \>10\^3 copies /mL) ; hepatitis C infection(hepatitis C antibodies positive) ; Syphilis infection (antibody positive), HIV infection (antibody positive);
5. Patients with hyponatremia and/or hypokalemia, blood sodium \<125mmol/L and/or blood potassium\<3.5mmol/L (Sodium and/or potassium supplementation may be given before participating in the study to restore blood sodium and/or potassium above this level);
6. Imaging results the proportion of liver replaced by tumor ≥50%;
7. Patients who taken continuous systemic steroids within 14 days before apheresis or within 72 hours before cell therapy (prednisone\> 5 mg/day or equivalent dose of other hormones), excepting for those who use inhaled Steroid hormones;
8. Systemic sexualization is accepted 2 weeks before apheresis or 5 half-lives (whichever is shorter). Toxicity to previous antineoplastic therapy has not recovered (based on CTCAE version 5.0 assessment); excepting for alopecia, pigmentation and other tolerable events judged by the investigator or permitted laboratory 9.abnormalities according to the protocol;
9. Antibody therapy within 4 weeks before apheresis and preconditioning;
10. Anti-PD-1/PD-L1 monoclonal antibody therapy within 4 weeks before apheresis and preconditioning;
11. Immunostimulation or immunosuppressive therapy within 28 days prior to apheresis;
12. Radiotherapy within 28 days prior to apheresis, except limited local palliative radiotherapy;
13. Patients with other malignant tumors within the past 5 years or at the present (except for basal cell carcinoma of the skin, breast/cervix Carcinoma in situ and other malignant tumors that have not been treated in the past five years have been effectively controlled);
14. Patients with active ulcers or active gastrointestinal bleeding that are difficult to control;
15. Patients with previous medical history of central nervous system (CNS) primary or metastatic tumors including meningeal metastases, unless previously treated for brain metastases, who are currently asymptomatic, and do not need steroid or enzyme-inducing antiepileptic drug treatment within 14 days before screening;
16. Patients with other central nervous system diseases that may affect the safety of the subjects as judged by the researchers (such as epileptic seizures, cerebral hemorrhage, dementia, etc.);
17. Patients with uncontrolled hypertension, unstable angina, NYHA III or higher-grade congestive heart failure with an ejection fraction of the heart below 50%, or an ECG with significant abnormalities, serious arrhythmias requiring treatment and medical history of myocardial infarction within 6 months prior to initiation of study treatment;
18. Patients with severe respiratory diseases before apheresis, such as interstitial lung disease, active pulmonary tuberculosis;
19. Patients with active or past autoimmune diseases that may relapse (such as systemic lupus erythematosus, rheumatoid arthritis, etc.), except for the following diseases: type 1 diabetes, hypothyroidism that only needs hormone replacement therapy, skin diseases that do not require systemic therapy (such as vitiligo, psoriasis or hair loss);
20. Any serious or uncontrollable systemic disease, systemic Complications, other serious concurrent diseases (such as hemophagocytic syndrome, etc.), special cases of tumor conditions according to the investigator's judgment that may make patients unsuitable for entry into the study or affect compliance with the protocol, or significant interference with the correct assessment of drug safety, toxicity, and effectiveness;
21. Received any major surgery within 4 weeks before apheresis (except exploratory laparotomy or laparoscopy exploration) or severe trauma; Any major surgery during the DLT observation period, or has not yet completely recovered from any previous invasive procedure;
22. Patient allergic or intolerant to the preconditioning drugs that may be used in the research process or the drugs for symptomatic treatment of CRS , including but not limited to fludarabine and cyclophosphamide or tocilizumab;Known hypersensitivity to the components of anti-HER2-CAR-T; or have any history of severe allergies, for example, anaphylactic shock;
23. Patients who have participated in other interventional clinical trials within 1 month before administration;
24. Pregnant or lactating women;
25. Patients of childbearing age who are unwilling or unable to use reliable contraception during the study period;
26. Patients who are unable or unwilling to comply with clinical protocols as judged by the investigator;
27. Persons involved in the study plan and execution.

Where this trial is running

Shenyang, Liaoning

• Phase I Clinical Trials Center Of The First Hospital of China Medical University — Shenyang, Liaoning, China (Recruiting)

Study contacts

• Principal investigator: Zhenning Wang, doctor — The First Affiliated Hospital of China Medical Univeristy
• Study coordinator: Shuhui Song, bachelor

Conditions Solid Tumor; CAR-T; solid tumor; Cell therapy; HER2