CD70-targeted CAR-NKT cell therapy for advanced renal cell carcinoma

A Phase I Clinical Study to Assess the Safety and Efficacy of CD70-targeted CAR-NKT in the Treatment of Relapsed or Metastatic Advanced Renal Cell Carcinoma.

This study is testing a new type of cell therapy for patients with advanced kidney cancer to see if it is safe and effective.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Fudan University (Academic / other)
• Drugs / interventions: chemotherapy, Immunotherapy
• Locations: 1 site (Shanghai)
• Trial ID: NCT06182735 on ClinicalTrials.gov

What this trial studies

This phase I, open-label, single-arm study aims to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of CGC729, a CD70-targeted CAR-NKT cell therapy, in patients with relapsed or metastatic advanced renal cell carcinoma. The study employs a dose-escalation design to determine the maximum tolerated dose (MTD) while monitoring for dose-limiting toxicities (DLTs). Patients will receive a combination of cyclophosphamide, fludarabine, and CAR-NKT cell infusion, with safety assessments conducted at various dose levels. The trial will help identify a safe and effective dose for further evaluation in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced clear cell renal cell carcinoma that is recurrent or metastatic after at least second-line treatment.

Not a fit: Patients with non-clear cell renal cell carcinoma or those who have not undergone at least second-line treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could provide a novel treatment option for patients with advanced renal cell carcinoma who have limited treatment alternatives.

How similar studies have performed: While this approach is novel in targeting CD70 with CAR-NKT cells, similar CAR-T cell therapies have shown success in other cancers, suggesting potential for efficacy.

Eligibility criteria

Inclusion Criteria:

1. 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.
2. Age 18 to 75 years.
3. Patients with advanced clear cell renal cell carcinoma confirmed by histology or cytology to be recurrent or metastatic after at least second-line treatment.
4. Archival and/or fresh tumor tissue samples are required.
5. At least one measurable lesion at baseline per RECIST version 1.1.
6. ECOG 0-1 points.
7. The expected survival time is more than 12 weeks.
8. The functions of important organs are basically normal: Hematopoietic function: neutrophils 1.5×109/L, platelets 75×109/L, hemoglobin 80g/L; Renal function: creatinine clearance of ≥60 mL/min.; Liver function: ALT and AST≤2.5×ULN (≤5 × ULN for patients with liver metastases); Total bilirubin≤1.5×ULN. Coagulation INR \< 1.7.
9. Pregnancy tests for women of childbearing age shall be negative, Both men and women agreed to use effective contraception.

Exclusion Criteria:

1. Pregnant or lactating female subjects.
2. Pregnant or lactating female subjects.
3. Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS).
4. Active infection or uncontrollable infection.
5. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, etc. .
6. Having a history of any mental illness, including dementia, altered mental status, which may affect informed consent and the understanding of the subject by the relevant questionnaire.
7. Have a serious uncontrollable illness that may affect the subject receiving treatment for this study.
8. Subjects with other malignant tumors within the past 2 years, except basal or squamous skin cancer, superficial bladder cancer, and breast cancer in situ, have been completely cured and do not need follow-up treatment.
9. Subjects who are using systemic steroids or steroid inhalers for treatment.
10. Use of anti-CD70 therapy or cell therapy within the previous 3 months.
11. Immunotherapy, targeted drug therapy or chemotherapy within 5 drug half-lives within 2 weeks before cell infusion.
12. Subjects allergic to immunotherapy or related drugs.
13. Patients with leptomeningeal metastasis or central nervous system metastasis, and definite central nervous system underlying diseases with significant symptoms in the past 6 months.
14. Subjects with NYHA heart failure class ≥2 or hypertension uncontrolled by standard therapy requiring special treatment, previous history of myocarditis, or myocardial infarction within 6 months.
15. Earnestly received or organ transplantation or preparing to receive organ transplants.
16. Other investigators deem it unsuitable to participate in the study.

Where this trial is running

Shanghai

• Jian Zhang — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Jian Zhang — Fudan University
• Study coordinator: Jian Zhang

Conditions Renal Cell Carcinoma