Pancreatic Cancer
Conditions
Keywords
TCR-T, T cells, RAS, TP53, Cell therapy
Brief summary
To investigate the safety, tolerability, efficacy and pharmacokinetics of TCR-T cells in the treatment of advanced pancreatic cancer
Detailed description
The aim of this clinical trial is to investigate the safety, tolerability, efficacy and pharmacokinetics of TCR-T cell therapy in patients with advanced pancreatic cancer by intravenous injection, in order to explore an effective cellular immunotherapy method for the treatment of advanced pancreatic cancer
Interventions
DRUGTCR-T Cells Injection（GB3010 Cells Injection）
The TCRT cells used in this clinical trial were derived from the patient's autologous peripheral-blood T cells and were genetically transduced to express a T-cell Receptor that recognizes the RAS/TP53.Patients were sequentially enrolled into 3 dose escalation groups(dose level 1-3) :5×10\^8±20%,5×10\^9±20%,5×10\^10±20%.
Sponsors
Shanghai Essight Bio Co.,Ltd
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Patients were sequentially enrolled into 3 dose escalation groups(dose level 1 to 3):5×10\^8±20%,5×10\^9±20%,5×10\^10±20%. Twenty-eight days after infusion of GB3010 cells was the observation period for DLT evaluation.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* To be eligible for the study, patients must meet all of the following criteria: 1. Male or female, aged 18-75 years; 2. Patients with advanced pancreatic cancer diagnosed by histology or cytology, patients who failed to respond to standard treatment, relapsed or voluntarily gave up; 3. Patients must have tumor tissue that expresses specific tumor antigens, such as mutations in RAS and/or TP53; 4. Patients must undergo HLA matching testing and meet the requirements of HLA matching. 5. At least one measurable or evaluable lesion ≥15 mm according to RECIST1.1 criteria; 6. Patients with ECOG \< 2 and life expectancy ≥3 months; 7. a) Liver function: ALT/AST \< 3 times the upper limit of normal value (ULN) and bilirubin ≤34.2μmol/L; b) renal function: creatinine \< 220μmol/L; c) terminal oxygen saturation ≥95% in room air; d) Cardiac function: left ventricular ejection fraction (LVEF) ≥60%; e) Blood routine: absolute neutrophil count ≥ 1×109/L; Platelet count ≥70×109/L; Absolute lymphocyte count ≥100 cells /μL; 8. The patients met the requirements of apheresis without any contraindications. 9. Women of childbearing age who have a negative urine pregnancy test at screening and before starting dosing and who have agreed to use highly effective contraception for at least 100 days after infusion; Female participants must agree not to donate eggs (oocytes, oocytes) for assisted reproductive purposes during the study and for 90 days after receiving the last study drug; 10. Male subjects with a fertile partner must consent to use an effective barrier method of contraception for at least 100 days after infusion; Must agree not to donate sperm for at least one year; 11. Sign an informed consent form.
Exclusion criteria
* Patients who met any of the following criteria were not eligible for inclusion in the study: 1. Persons with severe mental disorders; 2. A positive virological test for any of the following: HIV; HCV; HBsAg; HBcAb was positive, and HBV DNA copy number and TPPA were positive. 3. Patients with severe allergic history or allergic constitution; 4. Severe underlying medical conditions such as evidence of other serious active viral, bacterial or uncontrolled systemic fungal infection; Active autoimmune disease or a history of autoimmune disease within 3 years; 5. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus) leading to end-organ damage or requiring systemic immunosuppressive/systemic disease modulating drugs within the past 2 years; 6. Combined with organ dysfunction, such as renal insufficiency; 7. Had been enrolled in another clinical trial within 4 weeks before enrollment in the trial; 8. Those who were unable to comply with the study protocol and follow-up plan due to physiological, family, social, geographical and other factors; 9. Patients with contraindications to cyclophosphamide or fludarabine chemotherapy; 10. Subjects who required additional immunosuppressive drug therapy within 72 hours before TCR-T infusion, except for the treatment of adverse events during the trial; 11. Pregnant, lactating women, or men who plan to have children while participating in the study or within 100 days of receiving study treatment; 12. Any other condition considered by the investigator to be ineligible for enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Incidence of Treatment Related Adverse Events of TCRT cells in patients with advanced pancreatic cancer | 2years | collect adverse events (AE), serious adverse events (SAE), adverse events of special interest (AESI), and laboratory abnormalities (type, frequency, and severity) |
| Characterize the Peak of Peripheral Blood Concentration and Area under the Peripheral Blood concentration versus time curve of TCRT cells and observe their proliferation and persistence in body | 2years | After infusion of neoantigen-specific TCRT cells, collect peak (Cmax) of neoantigen-specific TCRT cells in blood and tumor tissue, time to peak (number of days to peakTCRT cells after infusion), Tmax) and AUC0-28 (area under the curve plotted against visit time by the number of neoantigen-specific TCRT cells in peripheral blood from day 0 to 28). If possible, AUC0-inf, terminal phase elimination rate constant (λz), elimination half-life (t1/2) will be evaluated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation of the pharmacokinetic profile of TCRT cells with the Incidence of CRS and ICANS events | 2years | collect changes in mutant cell concentration in peripheral blood and tumor tissue after TCRT cell reinfusion,observe correlation of these measures with CRS and ICANS events |
| Evaluate tumor size (mm) , tumor biomarker CA19-9 (U/ml), ORR/DCR/PFS and OS of patients with advanced pancreatic cancer | 2years | ORR at 2, 4, and 6 months after TCRT cell infusion (ORR=CR+PR). The primary efficacy outcome was the change in target tumor size (local control rate of target lesions). Secondary efficacy indicators: changes in tumor markers; Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) according to RECIST1.1 criteria |
Other
| Measure | Time frame | Description |
|---|---|---|
| To explore the correlation between the proliferation and persistence of TCRT cells in body and the efficacy | 2years | observe correlation of the PK parameters with response (CR, PR, relapse),PK parameters including peak (Cmax) of neoantigen-specific TCRT cells in blood and tumor tissue, time to peak (number of days to peakTCRT cells after infusion), Tmax) and AUC0-28 (area under the curve plotted against visit time by the number of neoantigen-specific TCRT cells in peripheral blood from day 0 to 28). |
Countries
China
Contacts
Primary ContactChenLeiWen
Backup ContactBoYongShen
Outcome results
None listed