Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors

Breast Cancer Clinical Trial

Official title:

Engineered TILs/CAR-TILs With PD1 Knockout and Anti-PD1/CTLA4-scFv Secreting or CARs Against Various Antigens to Treat Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04842812
• Other study ID #: ZZTIL-012
• Status: Recruiting
• Phase: Phase 1
• Start date: January 1, 2021
• Est. completion date: January 1, 2035

Study information

• Verified date: February 2023
• 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

Tumor infiltration lymphocytes (TILs) have been harvested from advanced cancer patients and constructed to knockout PD1 gene and express scFvs against both PD1 and CTALA4 and CARs against various antigens, followed by transfusion into the patients. The safety, tolerance, and preliminary clinical efficacy of the TILs will be evaluated.

Description:

1. Choose appropriate patients with advanced lung or other cancers, with written consent for this study;

2. Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;

3. Grow TILs and engineered the tumor-effective TILs with CRISPRA-CAS9 technique to knockdown PD1 and electronic-transfection strategy to express scFvs that target PD1 and CTLA4; amplify the engineered T cells as needed, test the quality and killing activity of the TILs and then transfuse them back the patients via systemic or local injections via standard protocol, and follow up closely to collect related parameters as needed;

4. To enhance the killing capability, tumor-noneffective TILs have also been genetically engineered to express various CARs targeting HER2/Mesothelin/Lewis-Y/PSCA/MUC1/ GPC3/AXL/EGFR/Claudin18.2/B7-H3/ROR1/GD2/AXL/Claudin6-DAP10 with knockdown of PD1/HPK1 as appropriate;

5. Evaluate the clinical results as needed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 1, 2035
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Patients with advanced cancers that failed to current available therapies;

2. Life expectancy >12 weeks;

3. Adequate heart, lung, liver, kidney functions;

4. Available for tumor biopsy or cancerous effusions;

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. Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity;

3. Active infectious disease related to bacteria, virus, fungi, et al;

4. Other severe diseases that the investigators consider not appropriate;

5. Pregnant or lactating women;

6. Systemic steroid treatment (greater than or equal to 0.5 mg prednisone equivalent/kg/day);

7. Other conditions that the investigators consider not appropriate.

Related Conditions & MeSH terms

• Brain Tumor
• Breast Cancer
• Colo-rectal Cancer
• CTLA4
• Liver Cancer
• Liver Neoplasms
• Lung Cancer
• Neoplasms
• PD1
• Solid Tumor, Adult

Intervention

Biological:
• TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Second Affiliated Hospital of Guangzhou Medical University	Guangdong Zhaotai InVivo Biomedicine Co. Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of TILs/CAR-TILs treatment in advanced solid cancers	Assessing Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.	up to 36 months
Secondary	Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers	Assessing various clinical response rates including complete response, partial response, stable disease, and progress disease during and after TILs/CAR-TILs treatment in advanced solid cancers.	15 years