CD70-targeted CAR-T treatment for advanced solid tumors

A Phase I Clinical Study of CD70-targeting CAR-T Therapy in the Treatment of CD70-positive Advanced/Metastatic Solid Tumors

This study is testing a new CAR-T therapy aimed at treating advanced solid tumors that have a specific marker called CD70 to see how safe it is for patients.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 36 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Chongqing Precision Biotech Co., Ltd (industry)
• Drugs / interventions: CAR-T, chemotherapy, prednisone
• Locations: 1 site (Jinan, Shandong)
• Trial ID: NCT05420545 on ClinicalTrials.gov

What this trial studies

This phase I clinical study evaluates the safety and tolerability of CD70-targeted CAR-T therapy in patients with CD70-positive advanced or metastatic solid tumors. The study is designed as a single-center, double-arm, open-label trial, with two groups receiving intravenous infusion and intraperitoneal injection of CAR-T cells, respectively. Each group will follow a dose-escalating 3+3 design, aiming to determine the maximum tolerated dose and the recommended dose for phase II. Approximately 24 subjects with confirmed CD70-positive tumors will be recruited for this trial.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with CD70-positive advanced or metastatic solid tumors who have failed or are intolerant to standard treatments.

Not a fit: Patients with tumors that do not express CD70 or those who have not progressed after standard treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that express CD70.

How similar studies have performed: While CAR-T therapies have shown promise in hematological malignancies, this specific approach targeting CD70 in solid tumors is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age ≥18 years old, male or female;
2. Histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) diagnosed as advanced/metastatic solid tumor (positive tumor CD70 expression (tumor CD70 positive (IHC 3+) confirmed by histology or pathology));
3. Failure or intolerance after standard treatment (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), and there is currently no effective treatment;
4. According to the RECIST version 1.1 standard, at least one target lesion with measurable diameter and evaluable, measurable lesions are defined as: extranodal CT scan long diameter ≥ 10mm, lymph node lesions CT scan short diameter ≥ 15mm, scan slice thickness Not larger than 5mm, and has not received local treatment;
5. ECOG 0-2 points;
6. The expected survival time is more than 12 weeks;
7. No serious mental disorder;
8. The function of important organs is basically normal:

   1. Hematopoietic function: neutrophils\>1.0×109/L, platelets\>75×109/L, hemoglobin\>80g/L;
   2. Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
   3. Renal function: serum creatinine≤2.0×ULN;
   4. Liver function: ALT and AST ≤2.0×ULN (for patients with liver tumor infiltration, it can be relaxed to ≤3.0×ULN);
   5. Total bilirubin ≤2.0×ULN (Gilbert syndrome or combined liver tumor infiltration can be relaxed to ≤3.0×ULN);
   6. Oxygen saturation \> 92% in non-oxygen state.
9. Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;
10. Subjects agree to use reliable and effective contraceptive methods for contraception (excluding safe period contraception) within 1 year after signing the informed consent form to receiving CAR-T cell infusion;
11. Subjects or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.

Exclusion Criteria:

1. Received CAR-T therapy or other gene-modified cell therapy prior to screening;
2. Received anti-CD70 drug treatment before screening;
3. Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging-proven progression ≥4 weeks after the end of treatment before they can be enrolled;
4. Received any of the following treatments prior to screening:

   1. Participated in other interventional clinical studies before screening, including: the last use of unmarketed new drugs is less than 3 months before cell reinfusion, or the last use of marketed drugs is less than 5 half-lives from cell reinfusion;
   2. Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is shorter) before apheresis;
   3. Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to apheresis (inhalation or topical is allowed in the absence of active autoimmune disease Use steroids and adrenal corticosteroid replacement at doses greater than 10 mg/day of prednisone);
   4. Received live attenuated vaccine within 4 weeks before screening;
5. Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;
6. Malignant tumors other than the target tumor within 3 years prior to screening, except for the following: malignant tumors that have received radical treatment and no known active disease within ≥ 3 years prior to enrollment; or adequately treated of non-melanoma skin cancers with no evidence of disease;
7. Have any of the following heart conditions:

   1. New York Heart Association (NYHA) stage III or IV congestive heart failure;
   2. Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
   3. Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
   4. History of severe nonischemic cardiomyopathy.
8. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.;
9. Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C Virus (HCV) RNA titer test is greater than the normal range; human immunodeficiency virus (HIV) antibody positive; syphilis test positive; cytomegalovirus (CMV) DNA test positive;
10. The subject has experienced venous thromboembolic events (eg: pulmonary embolism) and still needs anticoagulation therapy, or meets the following conditions: a. Bleeding with grades 3 to 4 for more than 30 days; b. venous thrombosis Sequelae (such as persistent dyspnea and hypoxia); (Note: although subjects with venous thrombosis but not meeting the above conditions can participate in the trial);
11. Poorly controlled hypertension, defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 90 mmHg (blood pressure values measured based on the average of 3 readings at least 2 minutes apart, blood pressure ≥ 150/90 mmHg at initial screening is acceptable Antihypertensive treatment, screening can be performed if the blood pressure is less than 150/90mmHg and well controlled after treatment);
12. Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving CAR-T cell reinfusion;
13. Other investigators deem it inappropriate to participate in the study.

Where this trial is running

Jinan, Shandong

• The Second People's Hospital of Shandong Province — Jinan, Shandong, China (RECRUITING)

Study contacts

• Principal investigator: Jianfeng Bi, M.D — The Second People's Hospital of Shandong Province
• Study coordinator: Jingwang Bi, M.D

Conditions: Metastatic Tumor, Advanced Solid Tumor, Renal Cell Carcinoma, Ovarian Cancer, Cervix Cancer, CAR-T, CD70, CD70-positive advanced/metastatic solid tumors