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Recruiting NCT05410717

CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors

Phase I Interventional Stage IV Ovarian Cancer Testis Cancer, Refractory Endometrial Cancer Recurrent CAR NK

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells.
Who it may be relevant to
Registry conditions: Stage IV Ovarian Cancer, Testis Cancer, Refractory, Endometrial Cancer Recurrent, CAR NK. Basic parameters: 18 years — 75 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
China
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

Phase I Trial to Evaluate Safety and Preliminary Efficacy of CLDN6/GPC3/Mesothelin/AXL-CAR-NK in Patients With CLDN6/GPC3/Mesothelin/AXL-positive Advanced Solid Tumors

Overview

This study is an open, exploratory clinical study to evaluate the safety and preliminary efficacy of Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in patients with Claudin6, GPC3, Mesothelin, or AXL-positive advanced solid tumors (ovarian cancer and others)

Detailed description

1. Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study; 2. Perform PBMCs apheresis from the patient and isolate NK cells, transfect the NK cells with Claudin6, GPC3, Mesothelin, or AXL targeting CAR, amplify the number of transfected NK cells as needed, test the quality and killing activity of the Claudin6, GPC3, Mesothelin, or AXL-CAR-NK cells and then transplant back the patients via systemic or local infusions (via artery or intra-tumor), and follow up closely to collect related results as needed; 3. To enhance the killing capability, some CAR-NK cells are genetically engineered to express and secret IL7/CCL19 and/or SCFVs against PD1/CTLA4/Lag3; some CAR-NK cells are combined with Cannabidiol(CBD) or Nicotinamide adenine dinucleotide (NAD); 4. Evaluate the clinical results as needed. 5. Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.

Interventions

  • Biological Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells
    Engineering Claudin6, GPC3, Mesothelin, or AXL targeting CAR combined with/or without IL7/CCL19 and/or scfv against PD1/CTLA4/Lag3 secreting vector into NK cells, which are isolated from patients with advanced ovarian cancer or other cancers with expression of Claudin6, GPC3, Mesothelin, or AXL, and then transfusing them back the patients. In some cases, the CAR-NK cells will be combined with CBD or NAD to enhance the therapeutic efficacy.

Primary outcome measures

  • Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 [Time frame: After CAR-NK cells infusion, up to 52 weeks.]
Secondary outcome measures (3)
  • Objective Response Rate (ORR) [Time frame: After CAR-NK cells infusion, up to 52 weeks.]
  • Disease control rate (DCR) [Time frame: up to 52 weeks.]
  • Duration of response (DOR) [Time frame: up to 36 months]

Eligibility criteria

Inclusion criteria

  • patients with advanced ovarian cancer or other cancers with expression of claudin6.
  • Life expectancy >12 weeks
  • Adequate heart,lung,liver,kidney function
  • Available autologous transduced NK cells with greater than or equal to 20% expression of Claudin6, GPC3, Mesothelin, or AXL-CAR determined by flow-cytometry and killing of claudin6-positive targets greater than or equal to 20% in cytotoxicity assay
  • Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion criteria

  • Had accepted gene therapy before;
  • Tumor size more than 25cm;
  • Severe virus infection such as HBV,HCV,HIV,et al
  • Known HIV positivity
  • History of liver/renal transplantation
  • Active infectious disease related to bacteria, virus,fungi,et al
  • Other severe diseases that the investigators consider not appropriate;
  • Pregnant or lactating women
  • Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
  • Other conditions that the investigators consider not appropriate. -

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Randomized
Model
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

China · 1 center
  • The Second Affiliated Hospital of Guangzhou Medical University — Guangzhou

Publications

  • Li J, Hu H, Lian H, Yang S, Liu M, He J, Cao B, Chen D, Hu Y, Zhi C, Shen Y, Ye X, He B, Zhao M, Fan W, Xu L, Leidner R, Wu Q, Yang L, Zhang Z. NK-92MI Cells Engineered with Anti-claudin-6 Chimeric Antigen Receptors in Immunotherapy for Ovarian Cancer. Int J Biol Sci. 2024 Feb 11;20(5):1578-1601. doi: 10.7150/ijbs.88539. eCollection 2024. PMID 38481806

Identifiers

NCT: NCT05410717 · ZZCARNK-017

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗