Hepatocellular CarcinomaNCT05926726
GPC3-directed CAR-T in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma
A study testing CAR-GPC3 T cells in people with Hepatocellular Carcinoma, run by RenJi Hospital at 1 site in China.
Trial summary
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous armored GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- CAR-GPC3 T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2023to 31 Dec 2026
- Phase
- Interventional
- 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
- 18-75 years-old, male or female
- Voluntarily willing to participate in the study and sign the written informed consent form
- Life expectation ≥12 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1
- Histologically-confirmed hepatocellular carcinoma (HCC)
- No benefits from curative surgery or other local therapies are expected at screening, judged by investigators
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- Radiologically-confirmed progression disease after at least one prior line of systematic treatment and limited benefits from current guideline or consensus for hepatocellular carcinoma are expected at screening, judged by investigators
- Fresh samples or FFPE, immunohistochemistry (IHC)-stained GPC-3 positive with intensity ++ or +++
- Per RECIST v1.1, at least one measurable lesion
- Manageable lung metastasis
- Barcelona Clinic Liver Cancer (BCLC) stage C or B and Child-Pugh ≤7
- No active HBV infections
- Adequate organ functions
- Adequate venous access for APH
- Non-hematological AEs induced by previous treatment must have recovered to CTCAE ≤1, except for alopecia and peripheral neuropathy
- Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1year post infusion, and sperm donation is prohibited during the study
- Women of childbearing potential must have negative serum β-hCG test result at screening and 48 hours prior to lymphodepletion
Who cannot join
- Cholangiocarcinoma or histological-mixed hepatocellular cholangiocarcinoma
- Active brain metastasis
- Primary lesion or infused lesions with the longest diameter ≥15cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator
- Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
- Systematic autoimmune disorders requiring long-term systematic immunosuppression
- Previously treated with any genetically engineered modified T cell therapy (TCR-T/CAR-T) or other CGT
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- Active HCV, HIV, or syphilis
- History of organ transplant
- Uncontrolled or active infection at screening, prior to APH, 72 hours prior to lymphodepletion or 5 days prior to JWATM214 infusion
- With severe cardiovascular disease
- History or presence of clinically-relevant CNS disorders
- Current presence of hepatic encephalopathy
- ≥G2 hemorrhage within 30 days prior to screening, or in need of long-term anticoagulants
- Active digestive ulcer or gastrointestinal bleeding within 3 months prior to screening
- Pregnant or lactating women
- Not satisfying wash-out period for APH
- Unable or unwilling to comply with the study protocol, judged by the investigator
- Other situations implying that the subject might not be appropriate to participate in the study
- Previously allergic or intolerable to JWATM214 or its components
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
Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University
Shanghai, 200127
Hao Feng, MD, PhD, surgeonfeng@live.com
About this study
Official title: JWATM214，an Armored GPC3-directed CAR-T ，in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma ：a Single-arm, Open-label，Dose-escalation Study
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous armored GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- CAR-GPC3 T cells
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-GPC3 T cellsBiological
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWATM214 . During JWATM214 production, subjects will receive a preconditioning chemotherapy regimen of cyclophosphamide and fludarabine to deplete the lymphocytes. After lymphodepletion, subjects will receive single-dose treatment with JWATM214 by intravenous (IV) injection.
| Study group | Role | What they receive |
|---|---|---|
| CAR-GPC3 T cells | Experimental | The safety and efficacy of JWATM214 will be evaluated in a 'BOIN'-designed dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10^8, 3×10^8, and 10×10^8, whereas the dosage 0.5×10^8 and 30×10^8 CAR-T cells will be selected as optional back-up doses for potential escalation or de-escalation. Receives: Biological: CAR-GPC3 T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment-related adverse events (AEs)
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Measured: 2 years
Dose-limiting toxicities
DLT (Dose-limiting toxicity) was an adverse event that occurred within 28 days after JWATM214 infusion that met any of the following criteria.
- Any grade ≥3 nonhematologic toxicity associated with JWATM214 that has not resolved to ≤ grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators
- Hematologic toxicity
- Grade ≥3 anaphylaxis
- Grade ≥3 infection did not resolve to grade ≤2 within 7 days after anti-infective treatment.
- ≥ grade 3 autoimmune toxicity during treatment
- Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to grade ≤2 within 72 hours.
- Grade ≥3 CAR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to grade ≤2 within 72 hours.
- Grade 5 events of any nonmalignant cause.
Measured: 28 days
RP2D of JWATM214 in HCC patients
Recommended phase 2 dose of JWATM214
Measured: 2 years
Secondary outcomes (5)
PK of JWATM214 in the peripheral blood (qPCR)
The pharmacokinetic parameters of JWATM214 will be evaluated by qPCR for the copy number of the vector transgene of JWATM214 in peripheral blood to evaluate T-cell expansion and persistence.
Measured: 1 years
Objective response rate (ORR).
Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients.
Measured: 1 years
Disease Control Rate
the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention in clinical trials of anticancer agents.
Measured: 2 years
progression-free survival (PFS)
Defined as time from randomisation to first progression by investigator assessment using modified RECIST 1.1 or death (by any cause in the absence of progression)
Measured: 2 years
overall survival (OS)
Defined as the time from randomisation to death due to any cause
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2023
- Study start1 Jan 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Qiang Xia, Prof. MD, Study chair, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTUHao Feng, MD.,Ph.D., Principal investigator, Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05926726
- Sponsor's protocol ID
- JWATM214001
- Status last verified
- May 2023
- First submitted
- 4 Apr 2023
- Last updated
- 3 Jul 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 3 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- JWATM214，an Armored GPC3-directed CAR-T ，in the Treatment Amongst Subjects With Advanced Hepatocellular Carcinoma ：a Single-arm, Open-label，Dose-escalation Study
- ClinicalTrials.gov ID
- NCT05926726
- Acronym / sponsor ID
- JWATM214001
- Conditions
- Hepatocellular Carcinoma
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 1 Jan 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 3 Jul 2023 (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 is a single arm, open-label, dose escalation clinical study to evaluate the safety and efficacy of infused autologous armored GPC3-directed CAR-T in patients with advanced hepatocellular carcinoma refractory to prior systematic treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR-GPC3 T cells | Experimental | Biological: CAR-GPC3 T cellsThe safety and efficacy of JWATM214 will be evaluated in a 'BOIN'-designed dose escalation approach. 3 CAR-T dose levels will be tested in this study: 1×10^8, 3×10^8, and 10×10^8, whereas the dosage 0.5×10^8 and 30×10^8 CAR-T cells will be selected as optional back-up doses for potential escalation or de-escalation. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- 18-75 years-old, male or female
- Voluntarily willing to participate in the study and sign the written informed consent form
- Life expectation ≥12 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status scale ≤1
- Histologically-confirmed hepatocellular carcinoma (HCC)
Key exclusion criteria (19 listed)
- Cholangiocarcinoma or histological-mixed hepatocellular cholangiocarcinoma
- Active brain metastasis
- Primary lesion or infused lesions with the longest diameter ≥15cm, or other potential risk which might not be appropriate for further study treatment judged by the investigator
- Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
- Systematic autoimmune disorders requiring long-term systematic immunosuppression
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 |
|---|---|---|
| CAR-GPC3 T cellsSubjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JWATM214 . During JWATM214 production, subjects will receive a preconditioning chemotherapy regimen of cyclophosphamide and fludarabine to deplete the lymphocytes. After lymphodepletion, subjects will receive single-dose treatment with JWATM214 by intravenous (IV) injection. | Biological | CAR-GPC3 T cells |
Primary outcome
Treatment-related adverse events (AEs)
Time frame: 2 years
An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
Dose-limiting toxicities
Time frame: 28 days
DLT (Dose-limiting toxicity) was an adverse event that occurred within 28 days after JWATM214 infusion that met any of the following criteria. 1. Any grade ≥3 nonhematologic toxicity associated with JWATM214 that has not resolved to ≤ grade 2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators 2. Hematologic toxicity 3. Grade ≥3 anaphylaxis 4. Grade ≥3 infection did not resolve to grade ≤2 within 7 days after anti-infective treatment. 5. ≥ grade 3 autoimmune toxicity during treatment 6. Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to grade ≤2 within 72 hours. 7. Grade ≥3 CAR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to grade ≤2 within 72 hours. 8. Grade 5 events of any nonmalignant cause.
RP2D of JWATM214 in HCC patients
Time frame: 2 years
Recommended phase 2 dose of JWATM214
5 secondary outcomes
PK of JWATM214 in the peripheral blood (qPCR)
Time frame: 1 years
Objective response rate (ORR).
Time frame: 1 years
Disease Control Rate
Time frame: 2 years
progression-free survival (PFS)
Time frame: 2 years
overall survival (OS)
Time frame: 2 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 3 Jul 2023.
- Individual participant dataSharing planned: Undecided
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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.
Qiang Xia, Prof. MD study chair
Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU
Hao Feng, MD.,Ph.D. principal investigator
Dept. Liver Surgery, Renji Hospital, School of Medicine, SJTU
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CAR-GPC3 T cells in people with Hepatocellular Carcinoma, run by RenJi Hospital 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 17 inclusion and 19 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 3 Jul 2023. 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.
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 Hao Feng, MD.,Ph.D (008615000901110, surgeonfeng@live.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment-related adverse events (AEs) (time frame: 2 years). The study lists 3 primary outcomes in all. 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 3 Jul 2023.