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

Stage IV Ovarian Cancer Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05410717
• Other study ID #: ZCARNK-017
• Status: Recruiting
• Phase: Phase 1
• Start date: June 1, 2022
• Est. completion date: May 31, 2034

Study information

• Verified date: January 2024
• Source: Second Affiliated Hospital of Guangzhou Medical University
• Contact: Zhenfeng Zhang, MD, PHD
• Phone: +862039195966
• Email: zhangzhf[@]gzhmu.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: May 31, 2034
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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. -

Related Conditions & MeSH terms

• Endometrial Cancer Recurrent
• Endometrial Neoplasms
• Stage IV Ovarian Cancer
• Testicular Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Guangzhou Medical University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Guangzhou Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety by Common Terminology Criteria for Adverse Events (CTCAE) V5.0	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.	After CAR-NK cells infusion, up to 52 weeks.
Secondary	Objective Response Rate (ORR)	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.	After CAR-NK cells infusion, up to 52 weeks.
Secondary	Disease control rate (DCR)	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.	up to 52 weeks.
Secondary	Duration of response (DOR)	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.	up to 36 months