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TCRT-ESO-A2 is an autologous cell therapy comprised of a subject's T cells stimulated ex vivo and transduced with a lentiviral vector encoding an affinity enhanced TCR targeting tumor-associated antigen NY-ESO-1.
This study will investigate the safety, tolerability, activity, and pharmacokinetics/ pharmacodynamics of TCRT-ESO-A2 infusion. A maximum tolerated dose study of TCRT-ESO-A2 in subjects with advanced malignancies expressing NY-ESO-1 is considered to be an acceptable risk. Once safety, tolerability, and pharmacokinetic/pharmacodynamic data are available, the activity of TCRT-ESO-A2 in NY-ESO-1-positive tumors may be explored further.
This is a Phase 1 open-label, multi-site, "3+3" dose escalation, study to evaluate the maximum tolerated dose, safety and tolerability, of TCRT-ESO-A2 suspension for IV infusion. Approximately 24 HLA-A*0201-positive subjects with head and neck cancer, hepatocellular carcinoma, lung squamous cell carcinoma, synovial sarcoma, and triple-negative breast cancer expressing NY-ESO-1 who have received at least first-line therapy for their cancer, or which there is no accepted therapy will be enrolled. Tumor tissue samples will be evaluated and scored using the NY-ESO-1 IHC assay developed specifically to support this study.
Following screening and enrollment (approximately Days -63 to -36) subjects will undergo leukapheresis for T cell collection at approximately Day -35 (Figure 3). Harvested cells will be fractionated, genetically engineered, and expanded ex vivo to produce autologous TCRT-ESO-A2 TCR-T. Following TCRT-ESO-A2 product release, subjects will receive a 3-day, non-myeloablative lymphodepletion regimen of fludarabine/cyclophosphamide from approximately Days -5 to -3 (recommend Wednesday to Friday) to prime the subject for immune re-population. Subjects will receive their TCRT-ESO-A2 cell product on Day 1 (recommend Monday) as an IV infusion over approximately 30 minutes. Within 30 minutes after completion of TCRT-ESO-A2 infusion, low dose subcutaneous aldesleukin (rhIL-2) will be administered at 500,000 IU BID daily for 14 days.
Dose escalation will be divided into three dose groups of three subjects each, with doses calculated as the number of TCR Vβ8-positive cells (total TCRT-ESO-A2 dose), with an allowable variance in cell count of ±30%. Escalation to higher doses will be based on the safety and tolerability of the previous cohort evaluated. If dose-limiting toxicity is observed in one subject at a dose level, up to an additional three dose limiting toxicity-evaluable subjects will be enrolled at that dose level. Subjects will be evaluated for dose limiting toxicity up to 28 days post-TCRT-ESO-A2 infusion. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to 28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity.
Three dose groups of subjects will be enrolled:
Cohort 1: 0.3 × 1010 TCRT-ESO-A2 cells* Cohort 2: 1.0 × 1010 TCRT-ESO-A2 cells* Cohort 3: 3.0 × 1010 TCRT-ESO-A2 cells*
* ±30% Subjects will be monitored daily during in-patient hospitalization for 5 days post dose. Subjects will then visit an out-patient clinic weekly during the Dose Limiting Toxicity Evaluation Period of 4 weeks and followed at approximately Days 60, 90, and every 3 months until confirmation of disease progression. Disease monitoring will be conducted by Magnetic Resonance Imaging or Computed Tomography scan (as appropriate for disease), during screening (if recent scans are not available), during lead-in approximately 7 days prior to TCRT-ESO-A2 infusion, at approximately Days 28, 60, 90, and every 3 months until confirmation of disease progression. If subjects remain clinically stable, confirmation of progression may be assessed 4- to 8-weeks later. Positron emission tomography scanning may be used as appropriate as an adjunct. Tumor biopsies will be taken from non-target lesions, if accessible, at baseline, approximately Days 28, 90, 180, and upon progression. Ascites/pleural fluid may be collected in addition to biopsies for correlative research studies if the subject requires paracentesis or pleuracentesis. At progression, long term follow-up will commence. During long term follow-up, subjects will be followed twice yearly for up to 5 years post-infusion and then annually for up to 15 years.
Timing of tumor and liquid biopsies may be adjusted as may the timing of other procedures or safety studies. In addition, up to 150 additional mL of blood may be collected over a three-month period without amendment of the protocol. Additional safety measures may be included, and tests may be done at any time if clinically indicated. In addition, if objective responses are observed in tumors after the safety of each cohort has been evaluated, up to 12 additional subjects with that tumor type (up to 2 tumor types) may be enrolled to further explore the tumor response rate in that tumor type.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1: TCRT-ESO-A2: 0.3 × 1010 TCRT-ESO-A2 cells * ±30% | Experimental | Subjects will be evaluated for DLTs up to 28 days post-TCRT-ESO-A2 infusion. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort. |
|
| Cohort 2: TCRT-ESO-A2: 1.0 × 1010 TCRT-ESO-A2 cells ±30% | Experimental | Subjects will be evaluated for DLTs up to 28 days post-TCRT-ESO-A2 infusion. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. |
|
| Cohort 3: TCRT-ESO-A2 : 3.0 × 1010 TCRT-ESO-A2 cells ±30% | Experimental | Subjects will be evaluated for DLTs up to 28 days post-TCRT-ESO-A2 infusion. Enrollment into a dose level will be suspended if two of no more than six subjects at a dose level experience dose-limiting toxicity. Prior to increasing the dose, a cohort management meeting will be held after the final enrolled subject has been followed for up to28 days. The decision to increase to the next dose level will be a joint decision of the clinical site Investigators and Sponsor. At each cohort, there will be at least 7 days between infusion of each subject in the cohort. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| TCRT-ESO-A2 | Biological | TCRT-ESO-A2 is an autologous cell therapy comprised of a subject's T cells stimulated ex vivo and transduced with a lentiviral vector encoding an affinity enhanced TCR targeting tumor-associated antigen NY-ESO-1. |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation: Evaluate up to Eighteen Subjects With Tumors Expressing TCRT-ESO-A1 and Having Dose Limiting Toxicity Adverse Events as Assessed by CTCAE-Version 5 | TCRT-ESO-A2 maximum tolerated dose as assessed by the occurrence of dose-limiting toxicity adverse events at least possibility related to TCRT-ESO - A2 in two of six subjects who received TCRT-ESO-A2 | Day 28 |
| Measure | Description | Time Frame |
|---|---|---|
| Dose Escalation: Tumor Response for Partial Response as Assessed by RECIST 1.1. | Evaluate tumor response for partial response response as assessed by RECIST 1.1, standardized assessment with complete response being the highest and disease progression being the lowest outcome. | Day 28 and every 3 months until disease progression averaging one year |
| Measure | Description | Time Frame |
|---|---|---|
| Explore Persistence of Genetically Modified T cells in vivo. | Characteristics of Persistence of Genetically Modified T cells in vivo will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Phenotype of Genetically Modified T cells in vivo. |
Inclusion Criteria:
Able to understand and voluntarily sign an informed consent form (ICF).
Age ≥18 years of age at the time of informed consent.
HLA-A*0201 positive by high resolution testing.
Any of the following solid tumors with positive NY-ESO-1 expression characterized by IHC:
Received standard curative or palliative therapy including any targeted therapy based on mutation status for their cancer, or advanced solid tumors for which there is no accepted therapy, standard therapies are no longer effective, or the subject refuses additional standard therapy.
Measurable disease as defined per RECIST 1.1 (Eisenhauer 2009).
Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
Life expectancy of >4 months.
Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain:
Adequate liver function as demonstrated by:
Creatinine clearance ≥50 mL/min. Creatinine clearance of subjects <65 years of age may be estimated by the Cockcroft-Gault formula. Subjects ≥65 years of age must have renal function measured either by 24-hour urine creatinine collection or by nuclear medicine glomerular filtration rate.
Prior therapies:
Recovered from previous surgery or treatment-related adverse reactions to \
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| Name | Affiliation | Role |
|---|---|---|
| Carlos Becerra, MD | Baylor University Medical Cancer Hospital | Principal Investigator |
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No patients enrolled therefore no data available to share.
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open-label, multi-site, "3+3" dose escalation study
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| Dose Escalation: Tumor Response Stable Disease as Assessed by RECIST 1.1. | Evaluate tumor response for stable disease response response as assessed by RECIST 1.1, a standardized assessment with complete response being the highest and disease progression being the lowest outcome. | Day 28 and every 3 months until disease progression averaging one year |
| Dose Escalation: Tumor Response Disease Progression as Assessed by RECIST 1.1. | Evaluate tumor response for disease progression response as assessed by RECIST 1.1, a standardized assessment with complete response being the highest and disease progression being the lowest outcome. | Day 28 and every 3 months until disease progression averaging one year |
| Dose Escalation: Tumor Response Overall Survival as Assessed by RECIST 1.1. | Evaluate tumor response for overall survival as assessed by RECIST 1.1, a standardized assessment with complete response being the highest and disease progression being the lowest outcome. | Day 28 and every 3 months until disease progression averaging one year |
| Dose Escalation: Tumor Response Progression-Free Survival as Assessed by RECIST 1.1. | Evaluate tumor response for disease progression-free survival as assessed by RECIST 1.1, a standardized assessment with complete response being the highest and disease progression being the lowest outcome. | Day 28 and every 3 months until disease progression averaging one year |
| Dose Escalation: Persistence of Genetically Modified T Cells in Vivo and T Cell Subpopulations | Evaluate the persistence of genetically modified T cells in vivo as assessed by evidence of an abundance of T cell subpopulations in circulation | Day 28 to disease progression averaging one year |
| Dose Escalation: Persistence of Genetically Modified T Cells in Vivo and Antigen Specific CD8 + Cytotoxic T lymphocytes | Evaluate persistence of genetically modified T cells in vivo and antigen specific CD8 + cytotoxic T lymphocytes in circulation | Day 28 to disease progression averaging one year |
| Dose Escalation: Phenotype of Genetically Modified T Cells in Vivo and Functional Characteristics | Evaluate the phenotype of genetically modified T cells in vivo as assessed by functional characteristics | Day 28 to disease progression averaging one year |
| Dose Escalation: Monitor Presence of Potentially Replication-Competent Lentivirus before TCRT ESO A2 Infusion | Monitor presence of potentially Replication-Competent Lentivirus before TCRT 001 ESO A2 infusion as assessed by qualitative PCR assay to detect and measure gene coding copies for the VSV- G Envelope Protein | Days - 7 |
| Dose Escalation: Monitor Presence of Potentially Replication-Competent Lentivirus After TCRT ESO A2 Infusion | Monitor presence of potentially Replication-Competent Lentivirus after TCRT 001 ESO A2 infusion as assessed by qualitative PCR assay to detect and measure gene coding copies for the VSV- G Envelope Protein | Days 90 and 270 |
| Maximum Tolerated Dose Expansion: Overall Survival Assessment | Evaluate overall survival as assessed by RECIST 1.1 | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Objective Response Rate Assessment | Evaluate objective response rate as assessed by RECIST 1.1 | 3 months |
| Maximum Tolerated Dose Expansion: Progression-free Survival Assessment | Evaluate progression-free survival 3-months as assessed by RECIST 1.1 every 3 months | 3 months |
| Maximum Tolerated Dose Expansion: Disease Control Rate Assessment | Evaluate disease control rate at 3-months as assessed by RECIST 1.1 | 3 months |
| Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Maximum Concentration Pharmacokinetic Characteristics | Evaluate TCRT-ESO-A2 as assessed by CD3-Positive/Tetramer-Positive T Cells maximum concentration | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year |
| Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Maximum Concentration pharmacokinetic characteristics | Evaluate TCRT-ESO-A2 as assessed by CD3-Positive/Tetramer-Positive T Cells Time to maximum concentration | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year |
| Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Half-Life pharmacokinetic characteristic | Evaluate TCRT-ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells Half-Life | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year |
| Maximum Tolerated Dose Expansion: TCRT-ESO-A2 time last pharmacokinetic characteristic | Evaluate TCRT-ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Evaluate Tumor for Complete Response as Assessed by RECIST 1.1. | Evaluate tumor for complete response as assessed by RECIST 1.1, a standardized assessment with complete response the highest and disease progression the lowest outcome assessment | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Evaluate Tumor for Partial Response as Assessed by RECIST 1.1. | Evaluate tumor for partial response as assessed by RECIST 1.1, a standardized assessment with complete response the highest and disease progression the lowest outcome assessment | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Evaluate Tumor for Stable Disease as Assessed by RECIST 1.1. | Evaluate tumor for stable disease response as assessed by RECIST 1.1, a standardized assessment with complete response the highest and disease progression the lowest outcome assessment | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Evaluate Tumor for Disease Progression as Assessed by RECIST 1.1. | Evaluate tumor for disease progression as assessed by RECIST 1.1, a standardized assessment with complete response the highest and disease progression the lowest outcome assessment | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Evaluate Tumor for Progression-Free Survival as Assessed by RECIST 1.1. | Evaluate tumor for progression-free survival as assessed by RECIST 1.1, a standardized assessment with complete response the highest and disease progression the lowest outcome assessment | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Evaluate Tumor for Overall Survival as Assessed by RECIST 1.1. | Evaluate tumor for overall survival as assessed by RECIST 1.1, a standardized assessment with complete response the highest and disease progression the lowest outcome assessment | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Persistence of Genetically Modified T Cells in Vivo as Assessed by Functional Characteristics and Persistence in the Circulation | Evidence of abundance of T cell subpopulations, antigen specific CD8+ cytotoxic T lymphocytes , functional characteristics and persistence in the circulation | Baseline to disease progression averaging one year |
| Maximum Tolerated Dose Expansion: Monitor Presence of Potentially Replication-Competent Lentivirus (RCL) before TCRT ESO A2 Infusion | Monitor presence of potentially Replication-Competent Lentivirus before TCRT 001 ESO A2 infusion as assessed by qualitative PCR assay to detect and measure gene coding copies for the VSV- G Envelope Protein | Day -7 |
| Maximum Tolerated Dose Expansion: Monitor Presence of Potentially Replication-Competent Lentivirus (RCL) after TCRT ESO A2 Infusion | Monitor presence of potentially Replication-Competent Lentivirus after TCRT 001 ESO A2 infusion as assessed by qualitative PCR assay to detect and measure gene coding copies for the VSV- G Envelope Protein | Days 90, 270 |
| Long Term Follow Up Period: Monitor VSV-G DNA qualitative PCR | Monitor presence of potentially Replication-Competent Lentivirus as assessed by qualitative PCR assay to detect and measure gene coding copies for the VSV- G Envelope Protein | Progression of disease up to 15 years |
| Long Term Follow Up Period: Monitor New Incidence of Potentially Product-Related Infection | Monitor new incidence of potentially product-related infection as assessed by annual or biannual long term follow-up interview | Progression of disease up to 15 years |
| Long Term Follow Up Period: Monitor New Incidence of malignancy | Monitor incidence of new malignancy(ies) as reported in annual or biannual long term follow-up interview | Progression of disease up to 15 years |
Characteristics of phenotype of genetically modified T cells in vivo will be assessed by multiple linear regression. |
| Baseline to disease progression averaging one year |
| Explore Presence of CA-125 Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion | The presence of CA-125 tumor biomarker before TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of CA-125 Tumor Immune Biomarker after TCRT-ESO-A2 Infusion | The presence of CA-125 Tumor Biomarker After TCRT-ESO-A2 Infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of CEA Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion | The presence of CEA tumor immune biomarker before TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of CEA Tumor Immune Biomarker After TCRT-ESO-A2 infusion | The presence of CEA tumor immune biomarker after TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of PSA Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion | The presence of PSA tumor biomarker before TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of PSA Tumor Immune Biomarker After TCRT-ESO-A2 Infusion | The presence of PSA tumor biomarker after TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Distribution of PSA Tumor immune Biomarker After TCRT-ESO-A2 Infusion | The distribution of PSA tumor biomarker after TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Cytokine IFN-γ Presence Before TCRT-ESO-A2 Infusion | The presence of systemic cytokine IFN-γ before TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Cytokine IFN-γ Presence After TCRT-ESO-A2 Infusion | The presence of systemic cytokine IFN-γ after TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of Targeted Antigen NY-ESO-1, Before TCRT-ESO-A2 Infusion | The presence of targeted antigen NY-ESO-1 before TCRT-ESO-A2 infusion Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of Targeted Antigen NY-ESO-1 After TCRT-ESO-A2 Infusion | Evaluate the presence and distribution of and targeted antigen NY-ESO-1 after TCRT-ESO-A2 infusion | Baseline to disease progression averaging one year |
| Explore Distribution of Targeted Antigen NY-ESO-1 After TCRT-ESO-A2 Infusion | Evaluate the distribution of targeted antigen NY-ESO-1 after before TCRT-ESO-A2 infusion will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of PSA Tumor Immune Biomarker | The presence of PSA tumor biomarker will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Presence of CEA Tumor Immune Biomarker | The presence of CEA tumor biomarker will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| :Explore Persistence of Genetically Modified T cells in vivo. | Characteristics of persistence of genetically modified T cells in vivo will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Evaluate Presence of Cytokine IFN-γ MTD Expansion: Evaluate cytokine IFN-γ before and after TCRT-ESO-A2 infusion | The presence of systemic cytokine IFN-y will be assessed by multiple linear regression | Baseline to disease progression averaging one year |
| Explore Evaluate Cytokine IFN-γ Before TCRT-ESO-A2 Infusion MTD Expansion: Evaluate cytokine IFN-γ before and after TCRT-ESO-A2 infusion | Evaluate the presence of systemic cytokine IFN-y before TCRT-ESO-A2 infusion will be assessed by multiple linear regression | Baseline to disease progression averaging one year |
| Explore Presence of Targeted Antigen NY-ESO-1 Before TCRT-ESO-A2 Infusion | Evaluate the presence of targeted antigen NY-ESO-1, before TCRT-ESO-A2 infusion will be assessed by multiple linear regression | Baseline to disease progression averaging one year |
| Explore Perform NY-ESO-1 Immunohistochemistry Assay Using a Four-point Semi-quantitative Scale (low to high): 0, 1+, 2+, 3+ With High Inferring a Better Outcome | Evaluate the subject tumor to determine cut-off high and low NY ESO - 1 expression. | Baseline to disease progression averaging one year |
| Explore Association Between Maximum TCRT ESO A2 Concentration time and Systemic Cytokine IFN-γ Level | The association between maximum TCRT ESO A2 concentration time and systemic cytokine IFN-γ level will be assessed by multiple linear regression. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Association Between Maximum TCRT ESO A2 Concentration time and Systemic Cytokine IL-6 Level | The association between maximum TCRT ESO A2 concentration time and systemic cytokine IL-6 level will be assessed by multiple linear regression. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Association Between Maximum TCRT ESO A2 Concentration time and Systemic Cytokine TNFα Level | The association between maximum TCRT ESO A2 concentration time and systemic cytokine IFN-γ level will be assessed by multiple linear regression. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Association Between Maximum Dose Concentration Time and Disease Appropriate Circulating Tumor Marker CA-125 | The association between pharmacokinetic maximum dose concentration time and pharmacodynamic disease appropriate circulating tumor marker CA-125 will be assessed by multiple linear regression. | Day 28 |
| Explore Association Between Pharmacokinetic Maximum Dose Concentration Time and Disease Appropriate Circulating Tumor Marker CEA | The association between pharmacokinetic maximum dose concentration time and pharmacodynamic disease appropriate circulating tumor marker CEA will be assessed by multiple linear regression. | Day 28 |
| Explore Association Between Pharmacokinetic Maximum Dose Concentration and disease Appropriate Circulating Tumor Marker PSA | The association between pharmacokinetic maximum dose concentration time and pharmacodynamic circulating tumor marker PSA will be assessed by multiple linear regression. | Day 28 |
| Explore Association Between Pharmacokinetic Maximum TCRT ESO A2 Dose Concentration Time and Pharmacodynamic Adverse Events as Identified by CTCAE Version 5. | The association between pharmacokinetic parameters and pharmacodynamic adverse event incidence will be assessed by rank correlation. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Association Between Pharmacokinetic Maximum Dose Concentration time and Pharmacodynamic Adverse Event Incidence. | Explore association between pharmacokinetic maximum dose concentration time and pharmacodynamic adverse event incidence. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Association Between Pharmacokinetic Maximum Dose Concentration and Area Under the Curve zero to infinity | The association between maximum tolerated dose and area under the curve zero to infinity will be assessed by multiple linear regression. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Pharmacokinetic Relationship with Tlast of CD3-positive/tetramer-positive T cells | The association between pharmacokinetic parameters and [variable] will be assessed by multiple linear regression. | Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. |
| Explore Pharmacokinetic Relationship with Phenotype of Genetically Modified T cells in vivo | The association between pharmacokinetic parameters and phenotype of genetically modified T cells in vivo will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |
| Explore Pharmacokinetic Relationship with Tumor Objective Response Rate by RECIST 1.1 | The association between pharmacokinetic parameters and objective response rate will be assessed by multiple linear regression. | 3 months |
| Explore Pharmacokinetic Relationship with Progression-Free Survival by RECIST 1.1 | The association between pharmacokinetic parameters and progression-free survival will be assessed by multiple linear regression. | 3 months |
| Explore Pharmacokinetic Relationship With Disease Control Rate RECIST 1.1 | The association between pharmacokinetic parameters and disease control rate will be assessed by multiple linear regression | 3-months |
| Explore Pharmacokinetic Relationship With Overall Survival RECIST 1.1 | The association between pharmacokinetic parameters and overall survival will be assessed by multiple linear regression. | Baseline to disease progression averaging one year |