Solid Tumor, AdultEarly Phase 1NCT06619886
TP53 R248Q TCR-T Cell Therapy for Advanced Solid Tumor
A Early Phase 1 study testing Autologous, engineered T Cells targeting TP53 R248Q in people with Solid Tumor, Adult and Lung Adenocarcinoma, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine at 1 site in China.
Trial summary
To evaluate the safety and efficacy of T cell therapy with mutated TP53 R248Q specific TCR transduction in patients with advanced solid tumor expressing the TP53 R248Q mutation and the HLA-A*11:01 allele. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Tumor, Adult, Lung Adenocarcinoma, Pancreas Cancer
- What is being tested?
- Autologous, engineered T Cells targeting TP53 R248Q
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteChina
- Study dates
- 24 Sep 2024to 31 Oct 2027
- Phase
- Early 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
- signed a written informed consent form (ICF), and can comply with protocol-specified visits and related procedures;
- aged ≥ 18 years, and ≤ 75 years, male or female;
- Subject must be pathologically confirmed with one of the histology below:
- Lung carcinoma Colorectal adenocarcinoma Pancreatic adenocarcinoma Any other solid tumor (progression after receiving standard treatment);
- subjects with TP53R248Q mutation in genetic testing, as determined by DNA or RNA sequencing methods;
- if patients with brain metastases are asymptomatic and less than 3 brain lesions less than 3 cm in diameter, they may be eligible;
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- ECOG score 0-1;
- Expected survival of no less than 12 weeks;
- According to RECISTv1.1 and mRECIST, subjects have at least 1 measurable lesion (lesions that have received local therapy such as radiotherapy and interventional therapy cannot be used as measurable lesions unless imaging evidence confirms that the lesion has clearly progressed), RECISTv1.1 is non-lymph node lesions with the longest diameter ≥ 10 mm on CT or MRI, and/or lymph node lesions with the short diameter ≥ 15 mm; mRECIST is non-lymph node measurable lesion criteria that meet RECISTv1.1 criteria, and showed intratumoral arterial enhancement in enhanced CT or MRI;
- subjects should provide fresh tumor tissue samples that meet the requirements or within 2 years before signing the ICF;
- Adequate organ and bone marrow function as defined by the following laboratory criteria: (1) bone marrow function: absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet (PLT) ≥ 75 × 109/L (transfusion or hematopoietic stimulating factor not acceptable within 14 days prior to Screening); (2) hemoglobin ≥ 90 g/L; (3) liver function: total bilirubin ≤ 2.5 × ULN; alanine aminotransferase ≤ 5 × ULN; aspartate aminotransferase ≤ 5 × ULN; (4) renal function: serum creatinine ≤ 1.5 × ULN, or creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); (5) coagulation function: international normalized ratio (INR) ≤ 1.5 × ULN, activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (INR between 2.0 and 3.0 is required for subjects receiving prophylactic anticoagulant therapy);
- Males of childbearing potential and females of childbearing potential must agree to use effective contraception from signing the ICF until one year after the last cell infusion and females of childbearing potential must have a negative blood pregnancy test at screening.
Who cannot join
- previous bone marrow or organ transplantation (including but not limited to liver transplantation) or waiting for transplantation;
- previous or concurrent history of other malignancies (cured and at least 2 years before screening without recurrence of cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer or radical treatment of local prostate cancer, radical resection of ductal carcinoma in situ can be enrolled in the study);
- hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and HBV DNA \> 500 IU/mL (lower limit of detection \< HBV DNA ≤ 500 IU/mL, clear lymphocyte conditioning medication before the need for at least 14 days of antiviral therapy and continuous antiviral therapy during the study can be enrolled); hepatitis C virus (HCV) antibody positive and HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis antibody positive;
- HLA antibody positive subjects, including weak positive, positive and strong positive (those with different HLA typing sites from TP53R248QTCR-T cell injection can be enrolled in the study);
- previous treatment with other cell products or TP53 targeted drugs;
- treatment with any fluorouracil chemotherapeutic drugs or small molecule targeted drugs within 14 days or 5 half-lives (whichever is shorter) before screening, and any antineoplastic biological agents or non-fluorouracil chemotherapeutic agents; radical radiotherapy or extensive radiotherapy within 28 days before screening (except palliative radiotherapy for non-target lesions performed locally to relieve symptoms); traditional Chinese medicine/Chinese herbal medicine and local interventional therapy with antineoplastic indications within 14 days before screening;
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- adverse events caused by previous antineoplastic therapy have not yet recovered to grade 1 or baseline levels, except for alopecia, grade 2 peripheral neurotoxicity, and hypothyroidism stabilized by hormone replacement therapy;
- live attenuated vaccination within 28 days before screening, or live attenuated vaccination during the study;
- major surgical treatment (except liver mass biopsy) within 28 days before screening, or major surgical treatment during the study;
- Requirement for chronic systemic corticosteroids (at doses ≥ 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first study drug infusion or during the study, with the exception of inhaled or topical use;
- Subjects with fungal, bacterial, viral, tuberculosis or other infection requiring systemic anti-infective therapy within 14 days prior to screening;
- Patients with active or previous autoimmune diseases that may relapse, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vasculitis, psoriasis, etc.;
- Previous or current interstitial lung disease, dust disease, radiation pneumonitis, severely impaired pulmonary function and other conditions;
- Third space effusion that is not clinically well controlled before screening, such as pleural effusion and ascites that cannot be controlled by drainage or other methods;
- History of serious cardiovascular and cerebrovascular diseases, including but not limited to:
- severe heart rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, grade II-III atrioventricular block, etc.;
- prolonged QT interval corrected by Fridericia formula (QTcF), \> 450 ms in men and \> 470 ms in women;
- acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other ≥ Grade 3 cardiovascular and cerebrovascular events within 6 months before screening;
- presence of heart failure with New York Heart Association (NYHA) functional class ≥ II or left ventricular ejection fraction (LVEF) \< 50%;
- clinically uncontrolled hypertension, systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg.
- Patients with a history of pulmonary embolism or severe lower extremity deep venous thrombosis, need to undergo inferior vena cava filter placement and other interventional therapy or need to use therapeutic doses of anticoagulants during screening;
- Subjects are participating in other interventional clinical studies;
- Pregnant or lactating women;
- Researchers believe that subjects have other conditions that may affect compliance or are not suitable for participating in this 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
Department of Oncology, Shanghai General Hospital
Shanghai, Shanghai Municipality, 200080
Haiyan Zhang, Dr., 18930220751, 13611956117@163.com
About this study
Official title: Early Clinical Study to Evaluate the Safety and Efficacy of TP53 R248Q Mutation-specific TCR-T Cell Therapy for Advanced Solid Tumor
To evaluate the safety and efficacy of T cell therapy with mutated TP53 R248Q specific TCR transduction in patients with advanced solid tumor expressing the TP53 R248Q mutation and the HLA-A*11:01 allele.
Read the detailed description
Malignant tumors are a major disease threatening the health of the Chinese people, with about 4.6 million new cancer patients and 2 million deaths each year in China. P53 gene mutation is an important driver gene in the pathogenesis of malignant tumors. P53 gene mutation is present in about half of cancer patients. Tumors carrying P53 gene mutation are insensitive to treatment, have poor response, are easy to be resistant, are easy to relapse, and have a high mortality rate. At present, there is no drug that directly targets P53 gene mutation. Our laboratory has previously built a TCR-T cell R \& D platform. Using this platform, we have successfully developed a TCR-T cell specific killing function for tumor cells targeting the R248Q mutation of the most common TP53 protein in hematological tumors and targeting the most high-frequency HLA-A11:01 subtype of TCR-T cells in the Chinese population using in vitro and in vivo animal models, and applied for a Chinese invention patent and PCT invention patent. The findings provide new ideas and treatment methods for immune cell therapy of malignant tumors. At present, we cooperate with the hematology clinical team of Shanghai First People's Hospital and Shanghai Pharmaceutical Group Biotherapy Technology Co., Ltd. to prepare to carry out investigator-initiated clinical trials.
- Conditions
- Solid Tumor, Adult, Lung Adenocarcinoma, Pancreas Cancer, Colorectal Cancer, Other Solid Tumor
- Being tested
- Autologous, engineered T Cells targeting TP53 R248Q
- Keywords
- TP53-R248Q, TCR-T, advanced solid tumor
- Medical subject headings
- Adenocarcinoma of Lung, Pancreatic Neoplasms, Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous, engineered T Cells targeting TP53 R248QBiological
TP53-R248Q mutant TCR-T Cells Injection, 28 days as a treatment cycle (cycle number N≤3), each cycle was divided into three D0, D7, D14 infusion, a total of 3 dose groups were set up, the single infusion of cells within the range of ±20% all meet the requirements
| Study group | Role | What they receive |
|---|---|---|
| TP53 R248Q specific TCR transduction T cell therapy | Experimental | Dose Escalation of TCR T cell product Receives: Biological: Autologous, engineered T Cells targeting TP53 R248Q |
What is being measured
The primary outcome is the main question the study is designed to answer.
Short term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors
Incidence of dose-limiting toxicities (DLTs) after the infusion of TP53-R248Q TCR-T cell injection;
Measured: 28 days after infusion
Long term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors
Incidence of adverse events and serious adverse events; Treatment-emergent adverse events, and serious adverse events
Measured: 28 days after infusion and up to 24 months after infusion
Secondary outcomes (1)
Preliminary anti-tumor activity of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors
Objective Response Rate (ORR) per RECIST V1.1 determined by Investigator assessment.
Measured: Up to 24 months after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start24 Sep 2024 (estimated)
- Primary completion31 Oct 2026 (estimated)
- Study completion31 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Qi Li, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
- Investigators
- Qi Li, Prof., Principal investigator, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06619886
- Sponsor's protocol ID
- TP53-R248Q-PC
- Status last verified
- Sep 2024
- First submitted
- 23 Sep 2024
- Last updated
- 1 Oct 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 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Clinical Study to Evaluate the Safety and Efficacy of TP53 R248Q Mutation-specific TCR-T Cell Therapy for Advanced Solid Tumor
- ClinicalTrials.gov ID
- NCT06619886
- Acronym / sponsor ID
- TP53-R248Q-PC
- Conditions
- Solid Tumor, Adult, Lung Adenocarcinoma, Pancreas Cancer, Colorectal Cancer, Other Solid Tumor
- Keywords
- TP53-R248Q, TCR-T, advanced solid tumor
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Shanghai General Hospital, Shanghai Jiao Tong University School of MedicineUniversity, hospital or other
- Study start
- 24 Sep 2024 (estimated)
- Primary completion
- 31 Oct 2026 (estimated)
- Study completion
- 31 Oct 2027 (estimated)
- First posted
- 1 Oct 2024 (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.
To evaluate the safety and efficacy of T cell therapy with mutated TP53 R248Q specific TCR transduction in patients with advanced solid tumor expressing the TP53 R248Q mutation and the HLA-A*11:01 allele.
Detailed description
Malignant tumors are a major disease threatening the health of the Chinese people, with about 4.6 million new cancer patients and 2 million deaths each year in China. P53 gene mutation is an important driver gene in the pathogenesis of malignant tumors. P53 gene mutation is present in about half of cancer patients. Tumors carrying P53 gene mutation are insensitive to treatment, have poor response, are easy to be resistant, are easy to relapse, and have a high mortality rate. At present, there is no drug that directly targets P53 gene mutation. Our laboratory has previously built a TCR-T cell R \& D platform. Using this platform, we have successfully developed a TCR-T cell specific killing function for tumor cells targeting the R248Q mutation of the most common TP53 protein in hematological tumors and targeting the most high-frequency HLA-A11:01 subtype of TCR-T cells in the Chinese population using in vitro and in vivo animal models, and applied for a Chinese invention patent and PCT invention patent. The findings provide new ideas and treatment methods for immune cell therapy of malignant tumors. At present, we cooperate with the hematology clinical team of Shanghai First People's Hospital and Shanghai Pharmaceutical Group Biotherapy Technology Co., Ltd. to prepare to carry out investigator-initiated clinical trials.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TP53 R248Q specific TCR transduction T cell therapy | Experimental | Biological: Autologous, engineered T Cells targeting TP53 R248QDose Escalation of TCR T cell product |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- signed a written informed consent form (ICF), and can comply with protocol-specified visits and related procedures;
- aged ≥ 18 years, and ≤ 75 years, male or female;
- Subject must be pathologically confirmed with one of the histology below:
- Lung carcinoma Colorectal adenocarcinoma Pancreatic adenocarcinoma Any other solid tumor (progression after receiving standard treatment);
- subjects with TP53R248Q mutation in genetic testing, as determined by DNA or RNA sequencing methods;
Key exclusion criteria (24 listed)
- previous bone marrow or organ transplantation (including but not limited to liver transplantation) or waiting for transplantation;
- previous or concurrent history of other malignancies (cured and at least 2 years before screening without recurrence of cervical carcinoma in situ, non-invasive basal cell or squamous cell skin cancer or radical treatment of local prostate cancer, radical resection of ductal carcinoma in situ can be enrolled in the study);
- hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and HBV DNA \> 500 IU/mL (lower limit of detection \< HBV DNA ≤ 500 IU/mL, clear lymphocyte conditioning medication before the need for at least 14 days of antiviral therapy and continuous antiviral therapy during the study can be enrolled); hepatitis C virus (HCV) antibody positive and HCV RNA positive; human immunodeficiency virus (HIV) antibody positive; syphilis antibody positive;
- HLA antibody positive subjects, including weak positive, positive and strong positive (those with different HLA typing sites from TP53R248QTCR-T cell injection can be enrolled in the study);
- previous treatment with other cell products or TP53 targeted drugs;
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 |
|---|---|---|
| Autologous, engineered T Cells targeting TP53 R248QTP53-R248Q mutant TCR-T Cells Injection, 28 days as a treatment cycle (cycle number N≤3), each cycle was divided into three D0, D7, D14 infusion, a total of 3 dose groups were set up, the single infusion of cells within the range of ±20% all meet the requirements | Biological | TP53 R248Q specific TCR transduction T cell therapy |
Primary outcome
Short term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors
Time frame: 28 days after infusion
Incidence of dose-limiting toxicities (DLTs) after the infusion of TP53-R248Q TCR-T cell injection;
Long term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors
Time frame: 28 days after infusion and up to 24 months after infusion
Incidence of adverse events and serious adverse events; Treatment-emergent adverse events, and serious adverse events
1 secondary outcome
Preliminary anti-tumor activity of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors
Time frame: Up to 24 months after infusion
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 1 Oct 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.
Qi Li, Prof. principal investigator
Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Autologous, engineered T Cells targeting TP53 R248Q in people with Solid Tumor, Adult and Lung Adenocarcinoma, run by Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine 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 12 inclusion and 24 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: opening soon, as of the sponsor's last update on 1 Oct 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Jingyi Zhou, Dr. (15618122509, jingyi_zhou9468@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Short term Safety of TP53-R248Q TCR-T cell injection in subjects with unresectable, advanced, and/or metastatic solid tumors (time frame: 28 days after infusion). The study lists 2 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 1 Oct 2024; AzTrials last refreshed its copy on 26 Oct 2026.