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TCR-T Cells in the Treatment of Advanced Pancreatic Cancer (GB3010-02)

Primary Purpose

Pancreatic Cancer

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
TCR-T Cells Injection(GB3010 Cells Injection)
Sponsored by
Ruijin Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pancreatic Cancer focused on measuring TCR-T, T cells, RAS, TP53, Cell therapy

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: To be eligible for the study, patients must meet all of the following criteria: Male or female, aged 18-75 years; Patients with advanced pancreatic cancer diagnosed by histology or cytology, patients who failed to respond to standard treatment, relapsed or voluntarily gave up; Patients must have tumor tissue that expresses specific tumor antigens, such as mutations in RAS and/or TP53; Patients must undergo HLA matching testing and meet the requirements of HLA matching. At least one measurable or evaluable lesion ≥15 mm according to RECIST1.1 criteria; Patients with ECOG < 2 and life expectancy ≥3 months; 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; The patients met the requirements of apheresis without any contraindications. 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; 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; Sign an informed consent form. Exclusion Criteria: Patients who met any of the following criteria were not eligible for inclusion in the study: Persons with severe mental disorders; A positive virological test for any of the following: HIV; HCV; HBsAg; HBcAb was positive, and HBV DNA copy number and TPPA were positive. Patients with severe allergic history or allergic constitution; 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; 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; Combined with organ dysfunction, such as renal insufficiency; Had been enrolled in another clinical trial within 4 weeks before enrollment in the trial; Those who were unable to comply with the study protocol and follow-up plan due to physiological, family, social, geographical and other factors; Patients with contraindications to cyclophosphamide or fludarabine chemotherapy; Subjects who required additional immunosuppressive drug therapy within 72 hours before TCR-T infusion, except for the treatment of adverse events during the trial; Pregnant, lactating women, or men who plan to have children while participating in the study or within 100 days of receiving study treatment; Any other condition considered by the investigator to be ineligible for enrollment.

Sites / Locations

  • Ruijin Hospital Affiliated to Shanghai Jiaotong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

TCR-T Cells Injection(GB3010 Cells Injection)

Arm Description

This study was designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of TCRT cell injection (GB3010) in patients with advanced pancreatic cancer by intravenous injection. The target population is patients with advanced pancreatic cancer who lack effective treatment methods, so that the benefits of patients participating in clinical trials will outweigh the risks.

Outcomes

Primary Outcome Measures

Evaluate the Incidence of Treatment Related Adverse Events of TCRT cells in patients with advanced pancreatic cancer
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
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 Outcome Measures

Correlation of the pharmacokinetic profile of TCRT cells with the Incidence of CRS and ICANS events
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
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

Full Information

First Posted
March 31, 2023
Last Updated
October 11, 2023
Sponsor
Ruijin Hospital
Collaborators
Shanghai Essight Bio Co.,Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT06054984
Brief Title
TCR-T Cells in the Treatment of Advanced Pancreatic Cancer
Acronym
GB3010-02
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

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 7, 2021 (Actual)
Primary Completion Date
June 7, 2024 (Anticipated)
Study Completion Date
September 7, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ruijin Hospital
Collaborators
Shanghai Essight Bio Co.,Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pancreatic Cancer
Keywords
TCR-T, T cells, RAS, TP53, Cell therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
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.
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TCR-T Cells Injection(GB3010 Cells Injection)
Arm Type
Experimental
Arm Description
This study was designed to evaluate the safety, tolerability, efficacy, and pharmacokinetics of TCRT cell injection (GB3010) in patients with advanced pancreatic cancer by intravenous injection. The target population is patients with advanced pancreatic cancer who lack effective treatment methods, so that the benefits of patients participating in clinical trials will outweigh the risks.
Intervention Type
Drug
Intervention Name(s)
TCR-T Cells Injection(GB3010 Cells Injection)
Intervention Description
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%.
Primary Outcome Measure Information:
Title
Evaluate the Incidence of Treatment Related Adverse Events of TCRT cells in patients with advanced pancreatic cancer
Description
collect adverse events (AE), serious adverse events (SAE), adverse events of special interest (AESI), and laboratory abnormalities (type, frequency, and severity)
Time Frame
2years
Title
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
Description
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."
Time Frame
2years
Secondary Outcome Measure Information:
Title
Correlation of the pharmacokinetic profile of TCRT cells with the Incidence of CRS and ICANS events
Description
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
Time Frame
2years
Title
Evaluate tumor size (mm) , tumor biomarker CA19-9 (U/ml), ORR/DCR/PFS and OS of patients with advanced pancreatic cancer
Description
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
Time Frame
2years
Other Pre-specified Outcome Measures:
Title
To explore the correlation between the proliferation and persistence of TCRT cells in body and the efficacy
Description
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).
Time Frame
2years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: To be eligible for the study, patients must meet all of the following criteria: Male or female, aged 18-75 years; Patients with advanced pancreatic cancer diagnosed by histology or cytology, patients who failed to respond to standard treatment, relapsed or voluntarily gave up; Patients must have tumor tissue that expresses specific tumor antigens, such as mutations in RAS and/or TP53; Patients must undergo HLA matching testing and meet the requirements of HLA matching. At least one measurable or evaluable lesion ≥15 mm according to RECIST1.1 criteria; Patients with ECOG < 2 and life expectancy ≥3 months; 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; The patients met the requirements of apheresis without any contraindications. 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; 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; Sign an informed consent form. Exclusion Criteria: Patients who met any of the following criteria were not eligible for inclusion in the study: Persons with severe mental disorders; A positive virological test for any of the following: HIV; HCV; HBsAg; HBcAb was positive, and HBV DNA copy number and TPPA were positive. Patients with severe allergic history or allergic constitution; 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; 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; Combined with organ dysfunction, such as renal insufficiency; Had been enrolled in another clinical trial within 4 weeks before enrollment in the trial; Those who were unable to comply with the study protocol and follow-up plan due to physiological, family, social, geographical and other factors; Patients with contraindications to cyclophosphamide or fludarabine chemotherapy; Subjects who required additional immunosuppressive drug therapy within 72 hours before TCR-T infusion, except for the treatment of adverse events during the trial; Pregnant, lactating women, or men who plan to have children while participating in the study or within 100 days of receiving study treatment; Any other condition considered by the investigator to be ineligible for enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
ChenLeiWen
Phone
13761638756
Email
wcl12161@rjh.com.cn
First Name & Middle Initial & Last Name or Official Title & Degree
BoYongShen
Phone
13901943778
Email
shenby@shsmu.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
BoYongShen
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine
City
ShangHai
State/Province
Shanghai
ZIP/Postal Code
200025
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
ChenLeiWen
Phone
13761638756
Email
wcl12161@rjh.com.cn
First Name & Middle Initial & Last Name & Degree
BoYongShen
Phone
13901943778
Email
shenby@shsmu.edu.cn

12. IPD Sharing Statement

Learn more about this trial

TCR-T Cells in the Treatment of Advanced Pancreatic Cancer

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