Liver CancerPhase 1NCT04842812
Engineered TILs/CAR-TILs to Treat Advanced Solid Tumors
A Phase 1 study testing TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3 in people with Liver Cancer and Lung Cancer, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Liver Cancer, Lung Cancer, Breast Cancer
- What is being tested?
- TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2021to 1 Jan 2035
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with advanced cancers that failed to current available therapies;
- Life expectancy >12 weeks;
- Adequate heart, lung, liver, kidney functions;
- Available for tumor biopsy or cancerous effusions;
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
Who cannot join
- Had accepted gene therapy before;
- Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity;
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, 510260
Zhenfeng Zhang, MD, PhD, +862039195966, zhangzhf@gzhmu.edu.cn
Bingjia He, +862039195965, 464677938@qq.com
About this study
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
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.
Read the detailed description
- Choose appropriate patients with advanced lung or other cancers, with written consent for this study;
- Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;
- 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;
- 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;
- Evaluate the clinical results as needed.
- Conditions
- Liver Cancer, Lung Cancer, Breast Cancer, Colo-rectal Cancer, Brain Tumor, Solid Tumor, Adult
- Being tested
- TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3
- Keywords
- liver Cancer, Lung Cancer, Solid Tumor, TIL, CAR-TIL, PD1, CTLA4, GPC3, Mesothelin, B7-H3, CRISPRA-CAS9
- Medical subject headings
- Liver Neoplasms, Lung Neoplasms, Breast Neoplasms, Colonic Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3Biological
TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles.
| Study group | Role | What they receive |
|---|---|---|
| TILs/CAR-TILs treatment | Experimental | Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment. Receives: Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: up to 36 months
Secondary outcomes (1)
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.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Apr 2021
- Study start1 Jan 2021
- Primary completion31 Dec 2029 (estimated)
- Study completion1 Jan 2035 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- TILs treatment of solid cancers
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
- Responsible party
- Sponsor
- Investigators
- Zhenfeng Zhang, MD, PhD, Principal investigator, Second Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04842812
- Sponsor's protocol ID
- ZZTIL-012
- Status last verified
- Jun 2024
- First submitted
- 4 Apr 2021
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04842812
- Acronym / sponsor ID
- ZZTIL-012
- Conditions
- Liver Cancer, Lung Cancer, Breast Cancer, Colo-rectal Cancer, Brain Tumor, Solid Tumor, Adult
- Keywords
- liver Cancer, Lung Cancer, Solid Tumor, TIL, CAR-TIL, PD1, CTLA4, GPC3
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Collaborators
- Guangdong Zhaotai InVivo Biomedicine Co. Ltd.
- Study start
- 1 Jan 2021 (actual)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 1 Jan 2035 (estimated)
- First posted
- 13 Apr 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
- Choose appropriate patients with advanced lung or other cancers, with written consent for this study;
- Perform biopsy or collect cancerous effusion in thorax or abdomen to obtain TILs by standard protocol;
- 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;
- 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;
- Evaluate the clinical results as needed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- TILs treatment of solid cancers
| Arm | Type | Receives |
|---|---|---|
| TILs/CAR-TILs treatment | Experimental | Biological: TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3Obtain TILs/CAR-TILs from advanced solid tumor patients and infuse them back to evaluate safety and clinical efficacy of the treatment. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients with advanced cancers that failed to current available therapies;
- Life expectancy >12 weeks;
- Adequate heart, lung, liver, kidney functions;
- Available for tumor biopsy or cancerous effusions;
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
Key exclusion criteria (7 listed)
- Had accepted gene therapy before;
- Severe virus infection such as HBV, HCV, HIV, et al; Known HIV positivity;
- Active infectious disease related to bacteria, virus, fungi, et al;
- Other severe diseases that the investigators consider not appropriate;
- Pregnant or lactating women;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3TILs and CAR-TILs injection: 1-10×10e7/kg cells for each treatment; 3 or more cycles. | Biological | TILs/CAR-TILs treatment |
Primary outcome
Safety of TILs/CAR-TILs treatment in advanced solid cancers
Time frame: up to 36 months
Assessing Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.
1 secondary outcome
Primary clinical efficacy of the TILs/CAR-TILs treatment in advanced solid cancers
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
- Individual participant dataSharing planned: No
Related trials for Liver Cancer
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Not yet recruitingPhase 3
Personalized Adaptive Radiotherapy for Hepatocellular Carcinoma
Hepatocellular Carcinoma (HCC)
Not yet recruiting
Overcoming Immunotherapy Resistance in Hepatocellular Carcinoma
Hepatocellular Carcinoma Non-Resectable
RecruitingPhase 2
Cabozantinib Combined With Ipilimumab/Nivolumab and TACE in Patients With Hepatocellular Carcinoma
Hepatocellular Carcinoma, HCC
Active, not recruitingPhase 2
Testing the Combination of Pevonedistat With Chemotherapy for Bile Duct Cancer of the Liver
Metastatic Cholangiocarcinoma, Metastatic Hepatocellular Carcinoma
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zhenfeng Zhang, MD, PhD principal investigator
Second Affiliated Hospital of Guangzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing TILs and CAR-TILs targeting HER2, Mesothelin, PSCA, MUC1, Lewis-Y, GPC3, AXL, EGFR, Claudin18.2/6, ROR1, GD1, or B7-H3 in people with Liver Cancer and Lung Cancer, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhenfeng Zhang, MD, PhD (+862039195966, zhangzhf@gzhmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of TILs/CAR-TILs treatment in advanced solid cancers (time frame: up to 36 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.