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

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ClinicalTrials.gov Identifier: NCT05410717
Recruitment Status : Recruiting
First Posted : June 8, 2022
Last Update Posted : January 9, 2024
Sponsor:
Information provided by (Responsible Party):
Second Affiliated Hospital of Guangzhou Medical University

Study Description
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Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Stage IV Ovarian Cancer Testis Cancer, Refractory Endometrial Cancer Recurrent CAR NK Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells Phase 1

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : June 1, 2022
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : May 31, 2034

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: CAR-NK cell therapy group
Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell therapy group.
 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.
Experimental: IL7/CCL19 secreting CAR-NK cell therapy group
Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the IL7/CCL19 secreting CAR-NK cell therapy group.
 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.
Experimental: PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group
Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group.
 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.
Experimental: CAR-NK cell plus CBD therapy group
Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus CBD therapy group.
 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.
Experimental: CAR-NK cell plus NAD therapy group
Appropriate patients who could benefit from the Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cell therapy against solid cancers are chosen to be the CAR-NK cell plus NAD therapy group.
 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.


Outcome Measures
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Primary Outcome Measures :
  1. Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 [ Time Frame: After CAR-NK cells infusion, up to 52 weeks. ]
    The type, frequency, severity, and duration of adverse events as a result of Claudin6, GPC3, Mesothelin, or AXL- CAR-NK cells infusion will be summarized.


Secondary Outcome Measures :
  1. Objective Response Rate (ORR) [ Time Frame: After CAR-NK cells infusion, up to 52 weeks. ]
    Per Response Evaluation Criteria in Solid Tumours (RECIST 1.1) assessed by MRI or CT. ORR defined as the proportion of patients in whom a complete response (CR) or partial response (PR) is observed as best overall response, prior to progression or further anti-cancer therapy.

  2. Disease control rate (DCR) [ Time Frame: up to 52 weeks. ]
    Disease control rate (DCR) defined as the proportion of patients in whom a CR or PR or stable disease (SD) (per RECIST 1.1, SD assessed at least 6 weeks after the first dose) is observed as best overall response.

  3. Duration of response (DOR) [ Time Frame: up to 36 months ]
    Duration of response (DOR) defined as the time from first objective response (CR or PR per RECIST 1.1) to first occurrence of objective tumor progression (Progressive disease (PD) per RECIST 1.1/recurrence) or death from any cause, whichever occurs first.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. patients with advanced ovarian cancer or other cancers with expression of claudin6.
  2. Life expectancy >12 weeks
  3. Adequate heart,lung,liver,kidney function
  4. 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
  5. Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent. -

Exclusion Criteria:

  1. Had accepted gene therapy before;
  2. Tumor size more than 25cm;
  3. Severe virus infection such as HBV,HCV,HIV,et al
  4. Known HIV positivity
  5. History of liver/renal transplantation
  6. Active infectious disease related to bacteria, virus,fungi,et al
  7. Other severe diseases that the investigators consider not appropriate;
  8. Pregnant or lactating women
  9. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day)
  10. Other conditions that the investigators consider not appropriate. -
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05410717


Contacts
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Contact: Zhenfeng Zhang, MD, PHD +862039195966 zhangzhf@gzhmu.edu.cn
Contact: Bingjia He, MD +862039195965 464677938@qq.com

Locations
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China, Guangdong
The Second Affiliated Hospital of Guangzhou Medical University Recruiting
Guangzhou, Guangdong, China
Contact: Zhenfeng Zhang, MD, PHD         
Sponsors and Collaborators
Second Affiliated Hospital of Guangzhou Medical University
Investigators
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Principal Investigator: Zhenfeng Zhang, MD, PHD Second Affiliated Hospital of Guangzhou Medical University
More Information
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Responsible Party: Second Affiliated Hospital of Guangzhou Medical University
ClinicalTrials.gov Identifier: NCT05410717    
Other Study ID Numbers: ZCARNK-017
First Posted: June 8, 2022    Key Record Dates
Last Update Posted: January 9, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Second Affiliated Hospital of Guangzhou Medical University:
Solid tumor
Claudin6
CAR NK
GPC3
Mesothelin
AXL
Cannabidiol
 Nicotinamide adenine dinucleotide
IL7
CCL19
PD1 antibody
PDL1 antibody
CTLA1 antibody
Additional relevant MeSH terms:
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Endometrial Neoplasms
Testicular Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Female
Female Urogenital Diseases
Female Urogenital Diseases and Pregnancy Complications
Urogenital Diseases
Genital Neoplasms, Female
 Urogenital Neoplasms
Genital Diseases
Endocrine System Diseases
Gonadal Disorders
Uterine Neoplasms
Uterine Diseases
Genital Neoplasms, Male
Genital Diseases, Male
Male Urogenital Diseases
Testicular Diseases