Colorectal Cancer (CRC)Phase 1NCT07035002
Study on the Safety and Tolerability of PD-1 Knockout Tumor-infiltrating T Cells (TILs) in the Treatment of Advanced Colorectal Cancer
A Phase 1 study testing transfusion of 5×10^8 PD-1 knockout TILs per kg body weight, transfusion of 1×10^9 PD-1 edited TILs per kg body weight and transfusion of 2×10^9 PD-1 edited TILs per kg body weight in people with Colorectal Cancer (CRC) and Tumor Infiltrating Lymphocytes, run by Ruijin Hospital at 1 site in China.
Trial summary
TIL from tumor tissue of advanced colorectal cancer patients were cultured, modified and expanded in vitro, and then transfused back to the patients after quality control. The safety and efficacy of the treatment were investigated. The fundamental cause of oncogenesis lies in the accumulation of gene mutations. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer (CRC), Tumor Infiltrating Lymphocytes, PD-1
- What is being tested?
- transfusion of 5×10^8 PD-1 knockout TILs per kg body weight, transfusion of 1×10^9 PD-1 edited TILs per kg body weight and transfusion of 2×10^9 PD-1 edited TILs per kg body weight
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteChina
- Study dates
- 31 Dec 2024to Dec 2026
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage.
- Patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation.
- Aged ≥18 and ≤70 years old.
- At least one tumor lesion that could be evaluated according to RECIST, version 1.1.
- ECOG score was 0 or 1.
- Adequate bone marrow and organ function.
- The expected survival time of the enrolled patients was no less than 6 months.
Who cannot join
- Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, traditional Chinese medicine with anti-tumor indications and other anti-tumor treatments within 2 weeks before sampling, except the following:
- Nitrosourea or mitomycin C within 6 weeks before surgery;
- Oral fluorouracils and small molecule targeted drugs for 1 week before surgery.
- Received other unmarketed investigational drug or treatment within 4 weeks before sampling;
- Had undergone major organ surgery (excluding needle biopsy) within 4 weeks before sampling or had significant lesions Trauma, or the need for elective surgery during the trial;
- Received systemic glucocorticoid (prednisone >10mg/ day or equivalent dose) or other immunosuppressive therapy within 14 days before sampling; Treatment with topical, ocular, intra-articular, nasal, and inhaled glucocorticoids was excluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrast allergy)
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- Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferin, etc., within 14 days before sampling;
- Administration of live attenuated vaccine within 4 weeks before sampling;
- The toxicity of previous antineoplastic therapy has not recovered to CTCAE 5.0 grade ≤1 (except for alopecia and other researchers who judged that there was no safety risk);
- Patients with symptomatic central nervous system or leptomeningeal metastases or other evidence of uncontrolled central nervous system or leptomeningeal metastases as judged by the investigator to be ineligible for enrollment;
- Patients with active infection within 1 week before sampling and currently requiring systemic anti-infective treatment;
- A history of immunodeficiency, including positive HIV antibody test;
- Hepatitis B (HBsAg positive and/or hepatitis C (anti-HCV positive) and/or treponema pallidum antibody positive;
- Patients with current interstitial lung disease;
- Has a history of severe cardiovascular and cerebrovascular diseases, including but not limited to:
- severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia requiring clinical intervention, degree II-III atrioventricular block, etc.
- Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or higher cardiovascular and cerebrovascular events occurred within 6 months before the first dose of dose.
- New York Heart Association (NYHA) functional class ≥II or left ventricular ejection fraction (LVEF) <50%, or structural heart disease at high risk as judged by other investigators;
- clinically uncontrolled hypertension.
- Patients with active or previous autoimmune diseases (such as systemic lupus erythematosus, rheumatoid arthritis, vasculitis, etc.), excluding patients with clinically stable autoimmune thyroid diseases and well-controlled type I diabetes;
- Received immunotherapy with grade ≥ 3 irAE;
- Clinically uncontrollable serous cavity effusion, which was judged by the investigator as not suitable for enrollment;
- Known alcohol or drug dependence;
- Persons with mental disorders or poor compliance;
- Pregnant or lactating women;
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
Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, None Selected, 200025
Ren Zhao, M.D., Ph.D., 86-021-64370045, rjzhaoren@139.com
About this study
TIL from tumor tissue of advanced colorectal cancer patients were cultured, modified and expanded in vitro, and then transfused back to the patients after quality control. The safety and efficacy of the treatment were investigated. The fundamental cause of oncogenesis lies in the accumulation of gene mutations. A large number of gene mutations in tumor cells lead to changes in the encoded amino acid sequence, resulting in the production of tumor-specific proteins. Human T cells recognize tumor-specific peptides (tumor neoantigens) that are presented on the MHC molecules on the surface of tumor cells, leading to T cell enrichment within the tumor. However, due to the immunosuppressive effect of tumors through various ways, the enriched T cells in tumors cannot effectively kill tumor cells. One of the most common examples is that tumors up-regulate the expression of immune checkpoint protein PD-L1, which binds to PD-1 on the surface of T cells and inhibits T cell function. Therefore, in this study, we will obtain tumor tissue via surgery resection or biopsy, and then isolate TIL cells in the tumor under GMP conditions, and further use gene editing technology to knockout PD-1, the obtained gene-edited T cells will have the characteristics of specific recognition of tumor cells, but not sensitive to the immunosuppressive function of tumor cells, so as to achieve the therapeutic effect on tumor patients.
Read the detailed description
Study name: Study on the safety and tolerability of PD-1 gene knockout tumor-infiltrating T cells (TIL) in the treatment of advanced colorectal cancer.
About the study: TIL from tumor tissue of advanced colorectal cancer patients were cultured, modified and expanded in vitro, and then transfused back to the patients after quality control. The safety and efficacy of the treatment were investigated. The fundamental cause of oncogenesis lies in the accumulation of gene mutations. A large number of gene mutations in tumor cells lead to changes in the encoded amino acid sequence, resulting in the production of tumor-specific proteins. Human T cells recognize tumor-specific peptides (tumor neoantigens) that are presented on the MHC molecules on the surface of tumor cells, leading to T cell enrichment within the tumor. However, due to the immunosuppressive effect of tumors through various ways, the enriched T cells in tumors cannot effectively kill tumor cells. One of the most common examples is that tumors up-regulate the expression of immune checkpoint protein PD-L1, which binds to PD-1 on the surface of T cells and inhibits T cell function. Therefore, in this study, we will obtain tumor tissue via surgery resection or biopsy, and then isolate TIL cells in the tumor under GMP conditions, and further use gene editing technology to knockout PD-1, the obtained gene-edited T cells will have the characteristics of specific recognition of tumor cells, but not sensitive to the immunosuppressive function of tumor cells, so as to achieve the therapeutic effect on tumor patients.
Objectives of the study:
Primary objective: To evaluate the safety and tolerability of PD-1 knockout TILs transfer treatment.
Secondary objectives: Objective response rate (ORR) and overall survival (OS) of PD-1 knockout TILs transfer treatment.
Subjects: The subjects were patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage. There were no restrictions on sex and region of origin, and patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation. Aged ≥18 and ≤70 years old. At least one tumor lesion that could be evaluated according to RECIST, version 1.1. ECOG score was 0 or 1. Adequate bone marrow and organ function. A total of 20 patients were enrolled. The expected survival time of the enrolled patients was no less than 6 months.
Research setting/location: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Study intervention: TILs were isolated from tumor tissue and infused back into patients after PD-1 knockout and expanded culturing. The patients were treated with cyclophosphamide and fludarabine before TILs transfusion.
The evaluation of efficacy included: the concentration of cytokines in blood, the number and duration of TILs in blood, adverse complications, evaluations of tumor size based on RESIST v1.1(by B-ultrasound, CT or MRI), tumor biomarkers, tumor related ctDNA.
Study Duration: The overall study duration was 24 months, including the time from the recruitment of the first patient to the completion of the data analysis of the last patient.
Duration of subject participation: Each enrolled patient was followed up for 12 months after completion of the TILs transfusion.
- Being tested
- transfusion of 5×10^8 PD-1 knockout TILs per kg body weight, transfusion of 1×10^9 PD-1 edited TILs per kg body weight, transfusion of 2×10^9 PD-1 edited TILs per kg body weight, transfusion of maximum dose without side effects among group A, B and C
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
transfusion of 5×10^8 PD-1 knockout TILs per kg body weightBiological
Obtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient.
transfusion of 1×10^9 PD-1 edited TILs per kg body weightBiological
Obtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient.
transfusion of 2×10^9 PD-1 edited TILs per kg body weightBiological
Obtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient.
transfusion of maximum dose without side effects among group A, B and CBiological
Obtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient.
| Study group | Role | What they receive |
|---|---|---|
| Group A: Low dose | Experimental | The dose of 5×10^8 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded and the dose would be escalated for group B. If one patient developed dose-limiting toxicity (DLT), another 3 patients with the same dose of group A would be added for expanded investigation. If there was lower than 1/6 of the patients in group A developed DLT, the study would be proceeded and the dose would be escalated for group B. Receives: Biological: transfusion of 5×10^8 PD-1 knockout TILs per kg body weight |
| Group B: Middle dose | Experimental | The dose of 1×10^9 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded and the dose would be escalated for group C. If one patient developed DLT, another 3 patients with the same dose of group B would be added for expanded investigation. If there was lower than 1/6 of the patients in group B developed DLT, the study would be proceeded and the dose would be escalated for group C. If there was more than 2/6 of the patients in group B developed DLT, the study would be proceeded with the dose would be dropped for group A. Receives: Biological: transfusion of 1×10^9 PD-1 edited TILs per kg body weight |
| Group C: High dose | Experimental | The dose of 2×10^9 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded for group D. If one patient developed DLT, another 3 patients with the same dose of group C would be added for expanded investigation. If there was more than 2/6 of the patients in group B developed DLT, the study would be proceeded with the dose would be dropped for group B. Receives: Biological: transfusion of 2×10^9 PD-1 edited TILs per kg body weight |
| Group D: Expanded investigation | Experimental | The highest dose of TILs without side effects in groups A, B and C would be transfused. In the case that there were no DLT in group A, B and C, there were total 11 cases in group D. Receives: Biological: transfusion of maximum dose without side effects among group A, B and C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tolerance as the highest dose without side effects
Without the following side effects from each drug:
- Cyclophosphamide: suppression of bone marrow, nausea, mucositis, rash, hemorrhagic cystitis, myocardial injury, alopecia, infertility, nausea and vomiting, syndrome of abnormal secretion of antidiuretic hormone (SIADH).
- Fludarabine: myelosuppression, fever, chills, nausea and vomiting, malaism, fatigue, anorexia, weakness, neurotoxicity and interstitial pneumonia.
- General antibiotics: anaphylaxis, renal insufficiency, nausea, vomiting, liver damage, myelosuppression, photosensitivity.
- High-dose IL-2: High-dose IL-2 has a variety of side effects. Since the most common side effects are due to the adjuvant drugs used in the treatment, the main interventions we will take to reduce the occurrence of serious side effects include: timely monitoring of patients after drug administration and cell infusion, providing adequate clinical support measures and complete first aid protocols, and adjusting according to patients' response.
Measured: From enrollment to the end of follow up at 12 months
Safety as severe treatment related complications
The rates of complications occurred, including :
- Cyclophosphamide: suppression of bone marrow, nausea, mucositis, rash, hemorrhagic cystitis, myocardial injury, alopecia, infertility, nausea and vomiting, syndrome of abnormal SIADH.
- Fludarabine: myelosuppression, fever, chills, nausea and vomiting, malaism, fatigue, anorexia, weakness, neurotoxicity and interstitial pneumonia.
- General antibiotics: anaphylaxis, renal insufficiency, nausea, vomiting, liver damage, myelosuppression, photosensitivity.
- High-dose IL-2: High-dose IL-2 has a variety of side effects. Since the most common side effects are due to the adjuvant drugs used in the treatment, the main interventions we will take to reduce the occurrence of serious side effects include: timely monitoring of patients after drug administration and cell infusion, providing adequate clinical support measures and complete first aid protocols, and adjusting in real time according to patients' response.
Measured: From enrollment to the end of follow up at 12 months
Secondary outcomes (2)
Objective response rate
Measured: From enrollment to the end of follow up at 12 months
Overall survival
Measured: From enrollment to the end of follow up at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2025
- Study start31 Dec 2024
- Primary completionDec 2025 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer (CRC)Studies of the same condition, open and under way.
- More trials run by Ruijin 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Zhao Ren, Ruijin Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07035002
- Sponsor's protocol ID
- 2024-570
- Status last verified
- Jun 2025
- First submitted
- 7 Jun 2025
- Last updated
- 24 Jun 2025
- 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 24 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Safety and Tolerability of PD-1 Knockout Tumor-infiltrating T Cells (TILs) in the Treatment of Advanced Colorectal Cancer
- ClinicalTrials.gov ID
- NCT07035002
- Acronym / sponsor ID
- 2024-570
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Study start
- 31 Dec 2024 (actual)
- Primary completion
- Dec 2025 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 24 Jun 2025 (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.
TIL from tumor tissue of advanced colorectal cancer patients were cultured, modified and expanded in vitro, and then transfused back to the patients after quality control. The safety and efficacy of the treatment were investigated. The fundamental cause of oncogenesis lies in the accumulation of gene mutations. A large number of gene mutations in tumor cells lead to changes in the encoded amino acid sequence, resulting in the production of tumor-specific proteins. Human T cells recognize tumor-specific peptides (tumor neoantigens) that are presented on the MHC molecules on the surface of tumor cells, leading to T cell enrichment within the tumor. However, due to the immunosuppressive effect of tumors through various ways, the enriched T cells in tumors cannot effectively kill tumor cells. One of the most common examples is that tumors up-regulate the expression of immune checkpoint protein PD-L1, which binds to PD-1 on the surface of T cells and inhibits T cell function. Therefore, in this study, we will obtain tumor tissue via surgery resection or biopsy, and then isolate TIL cells in the tumor under GMP conditions, and further use gene editing technology to knockout PD-1, the obtained gene-edited T cells will have the characteristics of specific recognition of tumor cells, but not sensitive to the immunosuppressive function of tumor cells, so as to achieve the therapeutic effect on tumor patients.
Detailed description
Study name: Study on the safety and tolerability of PD-1 gene knockout tumor-infiltrating T cells (TIL) in the treatment of advanced colorectal cancer.
About the study: TIL from tumor tissue of advanced colorectal cancer patients were cultured, modified and expanded in vitro, and then transfused back to the patients after quality control. The safety and efficacy of the treatment were investigated. The fundamental cause of oncogenesis lies in the accumulation of gene mutations. A large number of gene mutations in tumor cells lead to changes in the encoded amino acid sequence, resulting in the production of tumor-specific proteins. Human T cells recognize tumor-specific peptides (tumor neoantigens) that are presented on the MHC molecules on the surface of tumor cells, leading to T cell enrichment within the tumor. However, due to the immunosuppressive effect of tumors through various ways, the enriched T cells in tumors cannot effectively kill tumor cells. One of the most common examples is that tumors up-regulate the expression of immune checkpoint protein PD-L1, which binds to PD-1 on the surface of T cells and inhibits T cell function. Therefore, in this study, we will obtain tumor tissue via surgery resection or biopsy, and then isolate TIL cells in the tumor under GMP conditions, and further use gene editing technology to knockout PD-1, the obtained gene-edited T cells will have the characteristics of specific recognition of tumor cells, but not sensitive to the immunosuppressive function of tumor cells, so as to achieve the therapeutic effect on tumor patients.
Objectives of the study:
Primary objective: To evaluate the safety and tolerability of PD-1 knockout TILs transfer treatment.
Secondary objectives: Objective response rate (ORR) and overall survival (OS) of PD-1 knockout TILs transfer treatment.
Subjects: The subjects were patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage. There were no restrictions on sex and region of origin, and patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation. Aged ≥18 and ≤70 years old. At least one tumor lesion that could be evaluated according to RECIST, version 1.1. ECOG score was 0 or 1. Adequate bone marrow and organ function. A total of 20 patients were enrolled. The expected survival time of the enrolled patients was no less than 6 months.
Research setting/location: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine Study intervention: TILs were isolated from tumor tissue and infused back into patients after PD-1 knockout and expanded culturing. The patients were treated with cyclophosphamide and fludarabine before TILs transfusion.
The evaluation of efficacy included: the concentration of cytokines in blood, the number and duration of TILs in blood, adverse complications, evaluations of tumor size based on RESIST v1.1(by B-ultrasound, CT or MRI), tumor biomarkers, tumor related ctDNA.
Study Duration: The overall study duration was 24 months, including the time from the recruitment of the first patient to the completion of the data analysis of the last patient.
Duration of subject participation: Each enrolled patient was followed up for 12 months after completion of the TILs transfusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group A: Low dose | Experimental | Biological: transfusion of 5×10^8 PD-1 knockout TILs per kg body weightThe dose of 5×10^8 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded and the dose would be escalated for group B. If one patient developed dose-limiting toxicity (DLT), another 3 patients with the same dose of group A would be added for expanded investigation. If there was lower than 1/6 of the patients in group A developed DLT, the study would be proceeded and the dose would be escalated for group B. |
| Group B: Middle dose | Experimental | Biological: transfusion of 1×10^9 PD-1 edited TILs per kg body weightThe dose of 1×10^9 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded and the dose would be escalated for group C. If one patient developed DLT, another 3 patients with the same dose of group B would be added for expanded investigation. If there was lower than 1/6 of the patients in group B developed DLT, the study would be proceeded and the dose would be escalated for group C. If there was more than 2/6 of the patients in group B developed DLT, the study would be proceeded with the dose would be dropped for group A. |
| Group C: High dose | Experimental | Biological: transfusion of 2×10^9 PD-1 edited TILs per kg body weightThe dose of 2×10^9 PD-1 edited TILs per kg body weight will be transfused to 3 enrolled cases. If none of the 3 patients showed dose-limiting toxicity, the study would be proceeded for group D. If one patient developed DLT, another 3 patients with the same dose of group C would be added for expanded investigation. If there was more than 2/6 of the patients in group B developed DLT, the study would be proceeded with the dose would be dropped for group B. |
| Group D: Expanded investigation | Experimental | Biological: transfusion of maximum dose without side effects among group A, B and CThe highest dose of TILs without side effects in groups A, B and C would be transfused. In the case that there were no DLT in group A, B and C, there were total 11 cases in group D. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with advanced colorectal cancer confirmed by histology or cytology, who were not eligible to standard treatment at this stage.
- Patients volunteered to receive surgery or biopsy to obtain tumor tissue for TILs preparation.
- Aged ≥18 and ≤70 years old.
- At least one tumor lesion that could be evaluated according to RECIST, version 1.1.
- ECOG score was 0 or 1.
Key exclusion criteria (25 listed)
- Received chemotherapy, radiotherapy, biological therapy, endocrine therapy, immunotherapy, traditional Chinese medicine with anti-tumor indications and other anti-tumor treatments within 2 weeks before sampling, except the following:
- Received other unmarketed investigational drug or treatment within 4 weeks before sampling;
- Had undergone major organ surgery (excluding needle biopsy) within 4 weeks before sampling or had significant lesions Trauma, or the need for elective surgery during the trial;
- Received systemic glucocorticoid (prednisone >10mg/ day or equivalent dose) or other immunosuppressive therapy within 14 days before sampling; Treatment with topical, ocular, intra-articular, nasal, and inhaled glucocorticoids was excluded. Short-term prophylaxis with glucocorticoids (e.g., to prevent contrast allergy)
- Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferin, etc., within 14 days before sampling;
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 |
|---|---|---|
| transfusion of 5×10^8 PD-1 knockout TILs per kg body weightObtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient. | Biological | Group A: Low dose |
| transfusion of 1×10^9 PD-1 edited TILs per kg body weightObtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient. | Biological | Group B: Middle dose |
| transfusion of 2×10^9 PD-1 edited TILs per kg body weightObtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient. | Biological | Group C: High dose |
| transfusion of maximum dose without side effects among group A, B and CObtaining individual tumor tissue via surgery resection or biopsy, and then isolating TILs in the tumor under GMP conditions, and further using gene editing technology to knockout PD-1 to finally obtain gene-edited TILs-T cells, and transfusing them back to the patient. | Biological | Group D: Expanded investigation |
Primary outcome
Tolerance as the highest dose without side effects
Time frame: From enrollment to the end of follow up at 12 months
Without the following side effects from each drug: 1. Cyclophosphamide: suppression of bone marrow, nausea, mucositis, rash, hemorrhagic cystitis, myocardial injury, alopecia, infertility, nausea and vomiting, syndrome of abnormal secretion of antidiuretic hormone (SIADH). 2. Fludarabine: myelosuppression, fever, chills, nausea and vomiting, malaism, fatigue, anorexia, weakness, neurotoxicity and interstitial pneumonia. 3. General antibiotics: anaphylaxis, renal insufficiency, nausea, vomiting, liver damage, myelosuppression, photosensitivity. 4. High-dose IL-2: High-dose IL-2 has a variety of side effects. Since the most common side effects are due to the adjuvant drugs used in the treatment, the main interventions we will take to reduce the occurrence of serious side effects include: timely monitoring of patients after drug administration and cell infusion, providing adequate clinical support measures and complete first aid protocols, and adjusting according to patients' response.
Safety as severe treatment related complications
Time frame: From enrollment to the end of follow up at 12 months
The rates of complications occurred, including : 1. Cyclophosphamide: suppression of bone marrow, nausea, mucositis, rash, hemorrhagic cystitis, myocardial injury, alopecia, infertility, nausea and vomiting, syndrome of abnormal SIADH. 2. Fludarabine: myelosuppression, fever, chills, nausea and vomiting, malaism, fatigue, anorexia, weakness, neurotoxicity and interstitial pneumonia. 3. General antibiotics: anaphylaxis, renal insufficiency, nausea, vomiting, liver damage, myelosuppression, photosensitivity. 4. High-dose IL-2: High-dose IL-2 has a variety of side effects. Since the most common side effects are due to the adjuvant drugs used in the treatment, the main interventions we will take to reduce the occurrence of serious side effects include: timely monitoring of patients after drug administration and cell infusion, providing adequate clinical support measures and complete first aid protocols, and adjusting in real time according to patients' response.
2 secondary outcomes
Objective response rate
Time frame: From enrollment to the end of follow up at 12 months
Overall survival
Time frame: From enrollment to the end of follow up at 12 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 24 Jun 2025.
- 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.
Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine
Shanghai, China
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 transfusion of 5×10^8 PD-1 knockout TILs per kg body weight, transfusion of 1×10^9 PD-1 edited TILs per kg body weight and transfusion of 2×10^9 PD-1 edited TILs per kg body weight in people with Colorectal Cancer (CRC) and Tumor Infiltrating Lymphocytes, run by Ruijin 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 7 inclusion and 25 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 24 Jun 2025. 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?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerance as the highest dose without side effects (time frame: From enrollment to the end of follow up at 12 months). 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 24 Jun 2025.