Clinical trial NCT06054984: TCR-T Cells in the Treatment of Advanced Pancreatic Cancer
Official title: To Investigate the Safety, Tolerability, Efficacy and Pharmacokinetics of T Cell Receptor T Cell Therapy in the Treatment of Advanced Pancreatic Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Pancreatic Cancer
Keywords: TCR-T
T cells
RAS
TP53
Cell therapy
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: Shanghai Essight Bio Co.,Ltd
First posted: 2023-09-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
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.
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Evaluate the Incidence of Treatment Related Adverse Events of TCRT cells in patients with advanced pancreatic cancer
timeFrame: 2years
measure: 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
timeFrame: 2years
Secondary outcomes:
measure: Correlation of the pharmacokinetic profile of TCRT cells with the Incidence of CRS and ICANS events
timeFrame: 2years
measure: Evaluate tumor size (mm) , tumor biomarker CA19-9 (U/ml), ORR/DCR/PFS and OS of patients with advanced pancreatic cancer
timeFrame: 2years
Other outcomes:
measure: To explore the correlation between the proliferation and persistence of TCRT cells in body and the efficacy
timeFrame: 2years
Locations:
city: ShangHai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: BoYongShen
role: STUDY_DIRECTOR
References: