Stage IV Ovarian CancerPhase 1NCT05410717
CLDN6/GPC3/Mesothelin/AXL-CAR-NK Cell Therapy for Advanced Solid Tumors
A Phase 1 study testing Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in people with Stage IV Ovarian Cancer and Testis Cancer, Refractory, run by Second Affiliated Hospital of Guangzhou Medical University at 1 site in China.
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) Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Stage IV Ovarian Cancer, Testis Cancer, Refractory, Endometrial Cancer Recurrent
- What is being tested?
- Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Jun 2022to 31 May 2036
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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. -
Who cannot join
- 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
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- 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
The Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong
Zhenfeng Zhang, MD, PHD
About this study
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
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)
Read the detailed description
- Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study;
- 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;
- 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);
- Evaluate the clinical results as needed.
- Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.
- Being tested
- Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells
- Keywords
- Solid tumor, Claudin6, CAR NK, GPC3, Mesothelin, AXL, Cannabidiol, Nicotinamide adenine dinucleotide, IL7, CCL19, PD1 antibody, PDL1 antibody, CTLA1 antibody
- Medical subject headings
- Ovarian Neoplasms, Testicular Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| CAR-NK cell therapy group | Experimental | 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. Receives: Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells |
| IL7/CCL19 secreting CAR-NK cell therapy group | Experimental | 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. Receives: Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells |
| PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group | Experimental | 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. Receives: Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells |
| CAR-NK cell plus CBD therapy group | Experimental | 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. Receives: Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells |
| CAR-NK cell plus NAD therapy group | Experimental | 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. Receives: Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After CAR-NK cells infusion, up to 52 weeks.
Secondary outcomes (3)
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.
Measured: After CAR-NK cells infusion, up to 52 weeks.
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.
Measured: up to 52 weeks.
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.
Measured: up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2022
- Study start1 Jun 2022
- Primary completion1 Jun 2030 (estimated)
- Study completion31 May 2036 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Stage IV Ovarian 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Zhenfeng Zhang, MD, PHD, Principal investigator, Second Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05410717
- Sponsor's protocol ID
- ZZCARNK-017
- Status last verified
- Jun 2024
- First submitted
- 5 Jun 2022
- Last updated
- 25 Jun 2024
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 38481806
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
- 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
- ClinicalTrials.gov ID
- NCT05410717
- Acronym / sponsor ID
- ZZCARNK-017
- Keywords
- Solid tumor, Claudin6, CAR NK, GPC3, Mesothelin, AXL, Cannabidiol, Nicotinamide adenine dinucleotide
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Study start
- 1 Jun 2022 (actual)
- Primary completion
- 1 Jun 2030 (estimated)
- Study completion
- 31 May 2036 (estimated)
- First posted
- 8 Jun 2022 (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.
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
- Choose appropriate advanced cancer patients with Claudin6, GPC3, Mesothelin, or AXL expression, with written consent for the study;
- 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;
- 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);
- Evaluate the clinical results as needed.
- Will also perform the similar clinical trial on different cancer types with Claudin6, GPC3, Mesothelin, or AXL expression.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| CAR-NK cell therapy group | Experimental | Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsAppropriate 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. |
| IL7/CCL19 secreting CAR-NK cell therapy group | Experimental | Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsAppropriate 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. |
| PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group | Experimental | Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsAppropriate 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. |
| CAR-NK cell plus CBD therapy group | Experimental | Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsAppropriate 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. |
| CAR-NK cell plus NAD therapy group | Experimental | Biological: Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsAppropriate 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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. -
Key exclusion criteria (10 listed)
- 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
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 |
|---|---|---|
| Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cellsEngineering 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. | Biological | CAR-NK cell plus CBD therapy group, CAR-NK cell plus NAD therapy group, CAR-NK cell therapy group, IL7/CCL19 secreting CAR-NK cell therapy group, PD1/PDL1/CTLA4-scfv secreting CAR-NK cell therapy group |
Primary outcome
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.
3 secondary outcomes
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
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.
- Derived from this study: PubMed 38481806Li 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.
- Individual participant dataSharing planned: No
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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 Claudin6, GPC3, Mesothelin, or AXL targeting CAR-NK cells in people with Stage IV Ovarian Cancer and Testis Cancer, Refractory, 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 10 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 by Common Terminology Criteria for Adverse Events (CTCAE) V5.0 (time frame: After CAR-NK cells infusion, up to 52 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05410717, which also lists 1 linked publication.
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.