Advanced Solid TumorPhase 1NCT06170294
MAGE-A4-directed TCR-T in the Treatment Amongst Subjects With Advanced Solid Tumors
A Phase 1 study testing TCR-MAGE-A4 T-Cells in people with Advanced Solid Tumor, run by Peking University at 1 site in China.
Trial summary
A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- TCR-MAGE-A4 T-Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2024to 31 Dec 2028
- 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
- 18-75 year-old, male or female
- Voluntarily willing to participate in the study and sign the written informed consent form
- Life expectation ≥12 weeks
- European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion
- Histologically-confirmed recurrent/metastatic advanced solid tumors
- Radiologically-confirmed progression disease after at least one prior line of systematic treatment and no available standard of care at screening, judged by investigators
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- Fresh or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained MAGE-A4 positive
- Human leukocyte antigen (HLA)-A*02 allele matched
- Per response evaluation criteria in solid tumors (RECIST) version 1.1, at least one measurable lesion
- Adequate organ functions
- Adequate venous access for APH
- Non-hematological adverse events induced by previous treatment must have recovered to Grade ≤1 according to Common Terminology Criteria for Adverse Events (CTCAE), 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 1 year post infusion, and sperm donation is prohibited during the study
- Women of childbearing potential must have negative serum human chorionic gonadotropin β (β-hCG) test result at screening and 48 hours prior to lymphodepletion
Who cannot join
- Pregnant or lactating women
- Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19)
- Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH
- Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
- Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators
- Systematic autoimmune disorders requiring long-term systematic treatment
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- Previously treated with any genetically engineered modified T cell therapy or other cell and gene therapy (CGT)
- History of organ transplant
- Uncontrolled or active infection within 72 hours prior to screening, APH, LD, or within 5 days prior to infusion
- Subjects with other serious diseases that may restrict them from participating in this study
- Clinically significant CNS disorders, such as epilepsy, stroke, Parkinson disease, etc
- Grade ≥ 2 hemorrhage within 30 days prior to screening, or in need of longterm anticoagulants
- Active digestive ulcer or gastrointestinal (GI) bleeding within 3 months prior to screening
- Not satisfying wash-out period for APH
- Previously allergic or intolerable to JWTCR001 or its components
- Unable or unwilling to comply with the study protocol, judged by the investigators
- Other situations implying that the subject might not be appropriate to participate in the study
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
Department of GI Oncology,Peking University Cancer Hospital
Beijing, Beijing Municipality, 100142
Lin Shen, MD,phD
Changsong Qi, MD,phD
About this study
Official title: A Single-arm, Open-label, Dose Exploratory Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous Humanized MAGE-A4-directed T Cell Receptor Engineered T Cell (JWTCR001) in Patients With Advanced Solid Tumors
A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.
Read the detailed description
This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic treatments.
- Conditions
- Advanced Solid Tumor
- Being tested
- TCR-MAGE-A4 T-Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TCR-MAGE-A4 T-CellsDrug
Also called MAGE-A4-directed T cell receptor-engineered T Cells
- Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses
- MAGE-A4-directed T cell receptor-engineered T Cells
| Study group | Role | What they receive |
|---|---|---|
| TCR-MAGE-A4 T-Cells | Experimental | The subjects enrolled will be sequentially assigned to the corresponding dose level. Receives: Drug: TCR-MAGE-A4 T-Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of dose-limiting toxicities (DLTs)
Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWTCR001 infusion that met any of the following criteria. Any Grade ≥3 non-hematologic toxicity associated with JWTCR001 that has not resolved to Grade ≤2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators. Grade ≥3 hematological toxicities. 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 TCR-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
Rate and severity of adverse events (AEs) and severe adverse events (SAEs)
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
Rate and severity of clinically-significant abnormalities in laboratory testings
Clinically-significant abnormalities in laboratory testings.
Measured: 2 years
Secondary outcomes (8)
Copy number of the vector transgene of JWTCR001 in peripheral blood
The pharmacokinetic parameters of JWTCR001 will be evaluated by quantitative polymerase chain reaction (qPCR) for the copy number of the vector transgene of JWTCR001 in peripheral blood to evaluate T-cell expansion and persistence.
Measured: 2 years
MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood
The pharmacokinetic parameters of JWTCR001 will be evaluated by flow cytometry for the MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood to evaluate T cell expansion and persistence.
Measured: 2 years
Antitumor efficacy-Progression-free survival (PFS)
The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.
Measured: 2 years
Antitumor efficacy-Duration of response (DOR)
The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).
Measured: 2 years
Antitumor efficacy-Time to response (TTR)
The time from the first infusion to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR.
Measured: 2 years
Antitumor efficacy-Overall survival (OS)
The period from the first infusion to any cause of death.
Measured: 2 years
Antitumor efficacy-Objective response rate (ORR)
The number of cases in which tumor size is reduced to complete response (CR) or partial response (PR) / the total number of evaluable cases (%). In the event of CR or PR, the subjects should confirm it no less than 4 weeks after the first evaluation.
Measured: 2 years
Antitumor efficacy-Disease control rate (DCR)
The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).
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 posted14 Dec 2023
- Study start1 Jan 2024 (estimated)
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Ming Ju Biotechnology Co., Ltd.
- Responsible party
- Principal investigator, Shen Lin, Peking University
- Investigators
- Lin Shen, Principal investigator, Peking University Cancer Hospital & Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06170294
- Sponsor's protocol ID
- JWTCR001001
- Status last verified
- Dec 2023
- First submitted
- 6 Dec 2023
- Last updated
- 14 Dec 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm, Open-label, Dose Exploratory Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous Humanized MAGE-A4-directed T Cell Receptor Engineered T Cell (JWTCR001) in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT06170294
- Acronym / sponsor ID
- JWTCR001001
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Collaborators
- Shanghai Ming Ju Biotechnology Co., Ltd.
- Study start
- 1 Jan 2024 (estimated)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 14 Dec 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.
A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.
Detailed description
This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic treatments.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TCR-MAGE-A4 T-Cells | Experimental | Drug: TCR-MAGE-A4 T-CellsThe subjects enrolled will be sequentially assigned to the corresponding dose level. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 18-75 year-old, male or female
- Voluntarily willing to participate in the study and sign the written informed consent form
- Life expectation ≥12 weeks
- European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion
- Histologically-confirmed recurrent/metastatic advanced solid tumors
Key exclusion criteria (17 listed)
- Pregnant or lactating women
- Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19)
- Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH
- Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
- Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators
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 |
|---|---|---|
| TCR-MAGE-A4 T-CellsAlso: MAGE-A4-directed T cell receptor-engineered T Cells* Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses * MAGE-A4-directed T cell receptor-engineered T Cells | Drug | TCR-MAGE-A4 T-Cells |
Primary outcome
Rate of dose-limiting toxicities (DLTs)
Time frame: 28 days
Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWTCR001 infusion that met any of the following criteria. Any Grade ≥3 non-hematologic toxicity associated with JWTCR001 that has not resolved to Grade ≤2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators. Grade ≥3 hematological toxicities. 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 TCR-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.
Rate and severity of adverse events (AEs) and severe adverse events (SAEs)
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.
Rate and severity of clinically-significant abnormalities in laboratory testings
Time frame: 2 years
Clinically-significant abnormalities in laboratory testings.
8 secondary outcomes
Copy number of the vector transgene of JWTCR001 in peripheral blood
Time frame: 2 years
MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood
Time frame: 2 years
Antitumor efficacy-Progression-free survival (PFS)
Time frame: 2 years
Antitumor efficacy-Duration of response (DOR)
Time frame: 2 years
Antitumor efficacy-Time to response (TTR)
Time frame: 2 years
Antitumor efficacy-Overall survival (OS)
Time frame: 2 years
Antitumor efficacy-Objective response rate (ORR)
Time frame: 2 years
Antitumor efficacy-Disease control rate (DCR)
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 14 Dec 2023.
- Individual participant dataSharing planned: Yes
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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.
Lin Shen principal investigator
Peking University Cancer Hospital & Institute
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 TCR-MAGE-A4 T-Cells in people with Advanced Solid Tumor, run by Peking 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 14 inclusion and 17 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 14 Dec 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.
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 Lin Shen (861088196561, linshenpku@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of dose-limiting toxicities (DLTs) (time frame: 28 days). 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 14 Dec 2023.