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Evaluate TCRT-ESO-A2 Autologous T Cells Expressing TCR Specific for NY-ESO-1 in Subjects With Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04878484
Recruitment Status : Recruiting
First Posted : May 7, 2021
Last Update Posted : February 3, 2022
Sponsor:
Information provided by (Responsible Party):
Athenex, Inc.

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Biological: TCRT-ESO-A2 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: open-label, multi-site, "3+3" dose escalation study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-label Study to Evaluate the Safety, Tolerability, and Activity of TCRT-ESO-A2 Autologous T Cells Expressing TCR Specific for NY-ESO-1 in Subjects With Advanced Solid Tumors
Actual Study Start Date : August 11, 2021
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : December 2024

Arm Intervention/treatment
Experimental: Cohort 1: TCRT-ESO-A2: 0.3 × 1010 TCRT-ESO-A2 cells * ±30%
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.
Biological: TCRT-ESO-A2
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.

Experimental: Cohort 2: TCRT-ESO-A2: 1.0 × 1010 TCRT-ESO-A2 cells ±30%
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.
Biological: TCRT-ESO-A2
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.

Experimental: Cohort 3: TCRT-ESO-A2 : 3.0 × 1010 TCRT-ESO-A2 cells ±30%
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.
Biological: TCRT-ESO-A2
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.




Primary Outcome Measures :
  1. 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 [ Time Frame: Day 28 ]
    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


Secondary Outcome Measures :
  1. Dose Escalation: Abnormal Heart Rate Measurement Assessment [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate heart rate as assessed by clinically significant abnormal heart rate measurement changes from baseline

  2. Dose Escalation: Systolic Blood Pressure Measurement Assessment [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate systolic blood pressure measurement as assessed by clinically significant abnormal systolic blood pressure measurement changes from baseline

  3. Dose Escalation: Diastolic Blood Pressure Measurement Assessment [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate diastolic blood pressure pressure as assessed by the incidence of clinically significant abnormal diastolic blood pressure measurement changes from baseline

  4. Dose Escalation: Respiratory Rate Assessment [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate respiratory rate as assessed by by the incidence of clinically significant abnormal respiratory rate changes from baseline

  5. Dose Escalation: Oxygen Level Assessment [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate pulse oximetry reading as assessed by by the incidence of clinically significant abnormal oxygen level changes from baseline

  6. Dose Escalation: Body Temperature Assessment [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate Body Temperature as assessed by the incidence of clinically significant changes f≥38°C

  7. Dose Escalation: White Blood Cell Count Analysis [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate white blood cell count as assessed by the incidence of clinically significant abnormal white blood cell count changes from baseline

  8. Dose Escalation: Serum Absolute Neutrophil Count Analysis [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate serum absolute neutrophil as assessed by the incidence of clinically significant abnormal absolute neutrophil count changes from baseline

  9. Dose Escalation: Serum Absolute Lymphocyte Count Analysis [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate absolute lymphocyte as assessed by the incidence of clinically significant abnormal absolute lymphocyte count changes from baseline

  10. Dose Escalation: Serum Absolute Monocyte Count Analysis [ Time Frame: Baseline to disease progression, averaging one year ]
    Evaluate serum monocyte count as assessed by the incidence of clinically significant abnormal monocyte count changes from baseline

  11. Dose Escalation: Serum Absolute Eosinophil Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate absolute eosinophil count as assessed by the incidence of significant abnormal eosinophil count changes from baseline

  12. Dose Escalation: Red Blood Cell Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate red blood cell count as assessed by the incidence of clinically significant abnormal red blood cell count changes from baseline

  13. Dose Escalation: Blood Hemoglobin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate blood hemoglobin as assessed by the incidence of clinically significant abnormal hemoglobin changes from baseline

  14. Dose Escalation: Blood Platelet Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate blood platelet count as assessed by the incidence of clinically significant abnormal platelet count changes from baseline

  15. Dose Escalation: International Normalized Ratio Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate international normalized ratio as assessed by the incidence of clinically significant abnormal International Normalized Ratio changes from baseline

  16. Dose Escalation: Blood Prothrombin Time Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate blood prothrombin time as assessed by the incidence of clinically significant abnormal prothrombin time changes from baseline

  17. Dose Escalation: Blood Activated Partial Thromboplastin Time Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate activated partial thromboplastin time as assessed by the incidence of clinically significant abnormal activated partial thromboplastin time changes from baseline

  18. Dose Escalation: Blood Thrombin Time Analysis [ Time Frame: Up to Day 15 ]
    Evaluate blood thrombin time as assessed by the incidence of clinically significant abnormal thrombin time changes from baseline

  19. Dose Escalation: Serum Fibrinogen Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum fibrinogen as assessed by the incidence of clinically significant abnormal fibrinogen changes from baseline

  20. Dose Escalation: Serum Alanine Aminotransferase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum alanine aminotransferase as assessed by the incidence of clinically significant abnormal alanine aminotransferase changes from baseline

  21. Dose Escalation: Serum Alkaline Phosphatase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum alkaline phosphatase as assessed by the incidence of clinically significant abnormal alkaline phosphatase changes from baseline

  22. Dose Escalation: Serum Aspartate Aminotransferase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum aspartate aminotransferase as assessed the incidence of by clinically significant abnormal aspartate aminotransferase changes from baseline

  23. Dose Escalation: Total Blood Urea Nitrogen Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate total blood urea nitrogen as assessed by the incidence of clinically significant abnormal total blood urea nitrogen changes from baseline

  24. Dose Escalation: Serum Troponin Analysis [ Time Frame: Up to Day 15 ]
    Evaluate serum troponin analysis as assessed by the incidence of clinically significant abnormal troponin changes from baseline

  25. Dose Escalation: Serum Chloride Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum chloride as assessed by the incidence of clinically significant abnormal chloride changes from baseline

  26. Dose Escalation: Serum Potassium Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum potassium as assessed by the incidence of clinically significant abnormal potassium changes from baseline

  27. Dose Escalation: Serum Creatinine Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum creatinine as assessed by the incidence of clinically significant abnormal creatinine changes from baseline

  28. Dose Escalation: Serum Albumin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum albumin as assessed by the incidence of clinically significant abnormal albumin changes from baseline

  29. Dose Escalation: Serum Calcium Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum calcium as assessed by the incidence of clinically significant abnormal calcium changes from baseline

  30. Dose Escalation: Serum Magnesium Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum magnesium as assessed by the incidence of clinically significant abnormal magnesium changes from baseline

  31. Dose Escalation: Serum Phosphate Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum phosphate as assessed by the incidence of clinically significant abnormal phosphate changes from baseline

  32. Dose Escalation: Serum Cholesterol Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum cholesterol as assessed by the incidence of clinically significant abnormal cholesterol changes from baseline

  33. Dose Escalation: Serum Glucose Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum glucose as assessed by the incidence of clinically significant abnormal glucose changes from baseline

  34. Dose Escalation: Serum Bilirubin Lactate Dehydrogenase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum bilirubin as assessed by the incidence of clinically significant abnormal bilirubin lactate dehydrogenase changes from baseline

  35. Dose Escalation: Serum Total Protein Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum total protein as assessed by the incidence of clinically significant abnormal total protein changes from baseline

  36. Dose Escalation: Serum Triglycerides Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum triglycerides as assessed by the incidence of clinically significant abnormal triglyceride changes from baseline

  37. Dose Escalation: Serum Uric Acid Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum uric acid as assessed by the incidence of clinically significant abnormal uric acid changes from baseline

  38. Dose Escalation: Serum Direct Bilirubin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum direct bilirubin as assessed by the incidence of clinically significant abnormal direct bilirubin changes from baseline

  39. Dose Escalation: Serum Total Bilirubin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum total bilirubin as assessed by the incidence of clinically significant abnormal total bilirubin changes from baseline

  40. Dose Escalation: Urine Bilirubin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine bilirubin as assessed by the incidence of clinically significant abnormal urine bilirubin changes from baseline

  41. Dose Escalation: Urine Ketones Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine ketones as assessed by the incidence of clinically significant abnormal urine ketones changes from baseline

  42. Dose Escalation: Urine pH Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine pH as assessed by the incidence of clinically significant abnormal urine pH changes from baseline

  43. Dose Escalation: Urine Glucose Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine glucose as assessed by the incidence of clinically significant abnormal urine glucose changes from baseline

  44. Dose Escalation: Urine Occult Blood Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine occult blood as assessed by the incidence of clinically significant abnormal urine occult blood changes from baseline

  45. Dose Escalation: Urine Nitrite Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine nitrite as assessed by clinically significant abnormal urine nitrite changes from baseline

  46. Dose Escalation: Urine Leukocyte Esterase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine leukocyte esterase as assessed by the incidence of clinically significant abnormal urine leukocyte esterase changes from baseline

  47. Dose Escalation: Incidence of Urine Protein Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate the incidence of urine protein as assessed by the incidence of clinically significant abnormal urine protein changes from baseline

  48. Dose Escalation: Incidence of Urine Specific Gravity Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine specific gravity as assessed by the incidence of clinically significant abnormal urine specific gravity changes from baseline

  49. Dose Escalation: Incidence of Urine Urobilinogen Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine urobilinogen as assessed by the incidence of clinically significant abnormal urine urobilinogen changes from baseline

  50. Dose Expansion: Incidence of Abnormal Cardiac Rhythm Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate cardiac rhythm as assessed by the incidence of clinically significant abnormal cardiac rhythm changes from electrocardiogram baseline.

  51. Dose Escalation: Incidence of Abnormal Heart Rate Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate heart rate as assessed by the incidence of clinically significant abnormal heart rate changes from electrocardiogram baseline.

  52. Dose Escalation: Incidence of Abnormal RR Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate RR as assessed by the incidence of clinically significant abnormal RR interval changes from electrocardiogram baseline.

  53. Dose Escalation: Incidence of Abnormal PR Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate PR interval as assessed by the incidence of clinically significant abnormal PR interval changes from electrogram baseline.

  54. Dose Escalation: Incidence of Abnormal QRS Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QRS interval as assessed by the incidence of clinically significant abnormal QRS changes from electrocardiogram baseline

  55. Dose Escalation: Incidence of Abnormal QT Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QT interval as assessed by the incidence of clinically significant abnormal QT interval changes from electrocardiogram baseline

  56. Dose Escalation: Incidence of Abnormal QTcB Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QTcB as assessed by the incidence of clinically significant abnormal QTc changes from electrocardiogram baseline electrocardiogram baseline

  57. Dose Escalation: Incidence of Abnormal QTcF Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QTcF as assessed by the incidence of clinically significant electrocardiogram QTcF interval changes from electrocardiogram baseline

  58. Dose Escalation: Eastern Cooperative Oncology Group Performance Assessment Scale a Standardized Assessment Tool With the Highest Score of 0 is Fully Fully Active and Lowest Score is 4 Dead. [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate performance as assessed by the incidence of clinically significant abnormal changes from Eastern Cooperative Oncology Group performance scale baseline.

  59. Dose Escalation: : Incidence of Abnormal General Appearance Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate general appearance as assessed by the incidence of clinically significant abnormal general appearance changes from physical examination baseline

  60. Dose Escalation: Incidence of Abnormal Head Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate abnormal head as assessed by the incidence of clinically significant abnormal head changes from physical examination baseline

  61. Dose Escalation: Incidence of Abnormal Ear Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate Ear as assessed by the incidence of clinically significant abnormal ear changes from physical examination baseline

  62. Dose Escalation: Incidence of Abnormal Eye Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate Eye as assessed by the incidence of clinically significant abnormal eye changes from physical examination baseline

  63. Dose Escalation: Incidence of Abnormal Nose Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate nose as assessed by the incidence of clinically significant abnormal nose changes from physical examination baseline

  64. Dose Escalation: Incidence of Abnormal Physical Examination Throat [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate throat as assessed by the incidence of clinically significant abnormal throat changes from physical examination baseline

  65. Dose Escalation: Incidence of Abnormal Thorax (Cardiovascular) Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate thorax (cardiovascular) as assessed by the incidence of clinically significant abnormal thorax (cardiovascular) changes from physical examination baseline

  66. Dose Escalation: Incidence of Abnormal Thorax (Lung) Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate thorax (lung) as assessed by the incidence of clinically significant abnormal thorax (Lungs) changes from physical examination baseline

  67. Dose Escalation: Incidence of Abnormal Abdomen Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate abdomen as assessed by the incidence of clinically significant abnormal abdomen changes from physical examination baseline

  68. Dose Escalation: Incidence of Abnormal Skin Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate skin as assessed by the incidence of clinically significant abnormal skin changes from physical examination baseline

  69. Dose Escalation: Incidence of Abnormal Musculoskeletal Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate musculoskeletal as assessed by the incidence of clinically significant abnormal musculoskeletal changes from physical examination baseline

  70. Dose Expansion: Incidence of Abnormal Extremities Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate extremities as assessed by the incidence of clinically significant abnormal extremity changes from physical examination baseline

  71. Dose Escalation: Incidence of Abnormal Neurological Status Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate neurological status as assessed by the incidence of clinically significant abnormal neurological changes from physical examination baseline

  72. Dose Escalation : Incidence of Abnormal Cognitive Orientation [ Time Frame: Up to Day 60 ]
    Evaluate cognitive orientations as assessed by the incidence of Mini Mental State Examination cognitive orientation score for clinically significant changes from mini mental state examination baseline

  73. Dose Escalation : Incidence of Abnormal Cognitive Attention [ Time Frame: Up to Day 60 ]
    Evaluate cognitive attention as assessed by the incidence of clinically significant abnormal significant changes from mini mental state examination cognitive attention baseline

  74. Dose Escalation : Incidence of Abnormal Cognitive Short-Term Recall [ Time Frame: Up to Day 60 ]
    Evaluate cognitive short-term recall as assessed by the incidence of clinically significant abnormal changes for Mini Mental State Examination cognitive short-term recall baseline

  75. Dose Escalation: Incidence of Abnormal Cognitive Immediate Recall [ Time Frame: Up to Day 60 ]
    Evaluate cognitive immediate recall as assessed by the incidence of clinically significant abnormal changes from Mini Mental State Examination cognitive immediate recall baseline

  76. Dose Escalation :Incidence of Abnormal Cognitive Language [ Time Frame: Up to Day 60 ]
    Evaluate cognitive language as assessed by the incidence of clinically significant abnormal changes from Mini Mental State Examination cognitive language baseline

  77. Dose Escalation : Incidence of Abnormal Cognitive Ability to Follow Simple Verbal Commands . [ Time Frame: Up to Day 60 ]
    Evaluate ability to follow simple verbal commands as assessed by the incidence of clinically significant abnormal changes from Mini Mental State Examination cognitive ability to follow simple verbal commands baseline

  78. Dose Escalation : Incidence of Abnormal Cognitive Ability to Follow Simple Written Commands . [ Time Frame: Up to Day 60 ]
    Evaluate cognitive ability to follow simple written commands as assessed by the incidence of clinically significant abnormal changes from Mini Mental State Examination ability to follow simple written commands baseline

  79. Dose Escalation: TCRT-ESO-A2 Maximum Concentration pharmacokinetic characteristics [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 maximum concentration pharmacokinetic characteristics as assessed by CD3-Positive/Tetramer-Positive T Cells Maximum Concentration

  80. Dose Escalation: TCRT-ESO-A2 Area Under the Plasma Concentration-Time Curve (AUC0-t) pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 area under the curve area under the curve-time plasma concentration -time curve as assessed by CD3-positive/tetramer-positive T Cells Area Under the Plasma Concentration-Time Curve

  81. Dose Escalation: TCRT-ESO-A2 Area Under the Concentration Curve Zero to Infinity (AUC0-∞) pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCR-ESO-A2 area under the concentration curve zero to infinity as assessed by CD3-positive/tetramer-positive T Cells Area Under the Concentration Curve Zero to Infinity

  82. Dose Escalation: Assess TCRT-ESO-A2 Half-Life pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 half-life(t1/2) as assessed by CD3-positive/tetramer-positive T Cells Half-Life

  83. Dose Escalation: TCRT-ESO-A2 time last pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells time last

  84. Dose Escalation: Tumor Response for Complete Response as Assessed by RECIST 1.1. [ Time Frame: Day 28 and every 3 months until disease progression averaging one year ]
    Evaluate tumor response for complete response as assessed by RECIST 1.1, a standardized assessment with complete response being the highest and disease progression being the lowest outcome.

  85. Dose Escalation: Tumor Response for Partial Response as Assessed by RECIST 1.1. [ Time Frame: Day 28 and every 3 months until disease progression averaging one year ]
    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.

  86. Dose Escalation: Tumor Response Stable Disease as Assessed by RECIST 1.1. [ Time Frame: Day 28 and every 3 months until disease progression averaging one year ]
    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.

  87. Dose Escalation: Tumor Response Disease Progression as Assessed by RECIST 1.1. [ Time Frame: Day 28 and every 3 months until disease progression averaging one year ]
    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.

  88. Dose Escalation: Tumor Response Overall Survival as Assessed by RECIST 1.1. [ Time Frame: Day 28 and every 3 months until disease progression averaging one year ]
    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.

  89. Dose Escalation: Tumor Response Progression-Free Survival as Assessed by RECIST 1.1. [ Time Frame: Day 28 and every 3 months until disease progression averaging one year ]
    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.

  90. Dose Escalation: Persistence of Genetically Modified T Cells in Vivo and T Cell Subpopulations [ Time Frame: Day 28 to disease progression averaging one year ]
    Evaluate the persistence of genetically modified T cells in vivo as assessed by evidence of an abundance of T cell subpopulations in circulation

  91. Dose Escalation: Persistence of Genetically Modified T Cells in Vivo and Antigen Specific CD8 + Cytotoxic T lymphocytes [ Time Frame: Day 28 to disease progression averaging one year ]
    Evaluate persistence of genetically modified T cells in vivo and antigen specific CD8 + cytotoxic T lymphocytes in circulation

  92. Dose Escalation: Phenotype of Genetically Modified T Cells in Vivo and Functional Characteristics [ Time Frame: Day 28 to disease progression averaging one year ]
    Evaluate the phenotype of genetically modified T cells in vivo as assessed by functional characteristics

  93. Dose Escalation: Monitor Presence of Potentially Replication-Competent Lentivirus before TCRT ESO A2 Infusion [ Time Frame: Days - 7 ]
    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

  94. Dose Escalation: Monitor Presence of Potentially Replication-Competent Lentivirus After TCRT ESO A2 Infusion [ Time Frame: Days 90 and 270 ]
    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

  95. Maximum Tolerated Dose Expansion: Heart Rate Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate heart rate as assessed by the incidence of clinically significant changes from baseline

  96. Maximum Tolerated Dose Expansion: Systolic Blood Pressure Measurement Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate systolic blood pressure as assessed by the incidence of systolic blood pressure for clinically significant changes from baseline

  97. Maximum Tolerated Dose Expansion: Diastolic Blood Pressure Measurement Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate diastolic blood pressure as assessed by the incidence off clinically significant changes from baseline

  98. Maximum Tolerated Dose Expansion: Respiratory Rate Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate respiratory rate as assessed by the incidence of clinically significant changes from baseline

  99. Maximum Tolerated Dose Expansion: Oxygen Level Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate pulse oximetry reading as assessed by the incidence of clinically significant oxygen level changes from baseline

  100. Maximum Tolerated Dose Expansion: Body Temperature Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate Body Temperature for clinically significant change ≥38°Centergrade from baseline

  101. Maximum Tolerated Dose Expansion: White Blood Cell Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate white blood cell count as assessed by the incidence of clinically significant abnormal white blood cell count changes from baseline

  102. Maximum Tolerated Dose Expansion: Serum Absolute Neutrophil Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum absolute neutrophil count as assessed by the incidence of clinically significant abnormal absolute neutrophil count changes from baseline

  103. Maximum Tolerated Dose Expansion: Serum Absolute Eosinophil Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum absolute eosinophil count as assessed by the incidence of clinically significant abnormal absolute eosinophil count changes from baseline

  104. Maximum Tolerated Dose Expansion: Serum Absolute Monocyte Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum absolute monocyte count as assessed by the incidence of clinically significant abnormal monocyte count changes from baseline

  105. Maximum Tolerated Dose Expansion: Serum Absolute Lymphocyte Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum absolute lymphocyte count as assessed by the incidence of clinically significant abnormal absolute lymphocyte count cha

  106. Maximum Tolerated Dose Expansion: Serum Alanine Aminotransferase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate clinically significant abnormal alanine aminotransferase (ALT) changes from baseline

  107. Maximum Tolerated Dose Expansion: Serum Aspartate Aminotransferase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum aspartate aminotransferase as assessed by the incidence of clinically significant abnormal Aspartate aminotransferase (AST) changes from baseline

  108. Maximum Tolerated Dose Expansion: Serum Creatinine Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum creatinine as assessed by the incidence of clinically significant abnormal creatinine changes from baseline

  109. Maximum Tolerated Dose Expansion: Red blood cell count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate red blood cell count as assessed by the incidence of clinically significant abnormal red blood cell count changes from baseline

  110. Maximum Tolerated Dose Expansion: Hemoglobin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate hemoglobin as assessed by the incidence of clinically significant abnormal hemoglobin changes from baseline

  111. :Maximum Tolerated Dose Expansion: Blood Activated Partial Thromboplastin Time Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Significant blood activated partial thromboplastin time as assessed by the incidence of clinically significant abnormal blood activated partial thromboplastin time changes from baseline

  112. Maximum Tolerated Dose Expansion: Blood Activated Partial Thromboplastin Time (aPTT) Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Significant changes from baseline activated partial thromboplastin time (aPTT) test results

  113. Maximum Tolerated Dose Expansion: Blood Platelet Count Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate blood platelet count as assessed by the incidence of clinically significant abnormal Platelet count changes from baseline

  114. Maximum Tolerated Dose Expansion: Serum Fibrinogen Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum fibrinogen as assessed by the incidence of clinically significant abnormal fibrinogen changes from baseline

  115. :Maximum Tolerated Dose Expansion: Blood Thrombin Time Analysis [ Time Frame: Up to Day 15 ]
    Evaluate blood thrombin time as assessed by the incidence of clinically significant abnormal thrombin time changes from baseline

  116. Maximum Tolerated Dose Expansion: Blood Prothrombin Time Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate blood prothrombin time as assessed by the incidence of clinically significant abnormal blood prothrombin time changes from baseline

  117. Maximum Tolerated Dose Expansion: Serum Direct Bilirubin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum direct bilirubin as assessed by the incidence of clinically significant abnormal direct bilirubin changes from baseline

  118. Maximum Tolerated Dose Expansion: Serum Total Bilirubin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum total bilirubin as assessed by the incidence of clinically significant abnormal total bilirubin changes from baseline

  119. Maximum Tolerated Dose Expansion: Total Blood Urea Nitrogen Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate total blood urea nitrogen as assessed by the incidence of clinically significant abnormal Total blood urea nitrogen (BUN) changes from baseline

  120. Maximum Tolerated Dose Expansion: Serum Phosphate Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum phosphate as assessed by the incidence of clinically significant abnormal phosphate changes from baseline

  121. Maximum Tolerated Dose Expansion: Serum Glucose Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum glucose as assessed by the incidence of clinically significant abnormal glucose changes from baseline

  122. Maximum Tolerated Dose Expansion: Serum Albumin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum albumin analysis as assessed by the incidence of clinically significant abnormal albumin changes from baseline

  123. Maximum Tolerated Dose Expansion: Serum Magnesium Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum magnesium as assessed by the incidence of clinically significant abnormal magnesium changes from baseline

  124. Maximum Tolerated Dose Expansion: Serum Triglycerides Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum triglycerides as assessed by the incidence of clinically significant abnormal triglyceride changes from baseline

  125. Maximum Tolerated Dose Expansion: Serum Potassium Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum potassium as assessed by the incidence of clinically significant abnormal potassium changes from baseline

  126. Maximum Tolerated Dose Expansion: Serum Chloride Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum chloride as assessed by the incidence of clinically significant abnormal chloride changes from baseline

  127. Maximum Tolerated Dose Expansion: Serum Troponin Analysis [ Time Frame: Up to Day 15 ]
    Evaluate serum troponin as assessed by the incidence of clinically significant abnormal troponin changes from baseline

  128. Maximum Tolerated Dose Expansion: Serum Calcium Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum calcium as assessed by the incidence of clinically significant abnormal calcium changes from baseline

  129. Maximum Tolerated Dose Expansion: Serum Cholesterol Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum cholesterol as assessed by the incidence of clinically significant abnormal cholesterol changes from baseline

  130. Maximum Tolerated Dose Expansion: Serum Alkaline Phosphatase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum alkaline phosphatase as assessed by the incidence of clinically significant abnormal alkaline phosphatase changes from baseline

  131. Maximum Tolerated Dose Expansion: International Normalized Ratio Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate international normalized ratio as assessed by the incidence of clinically significant abnormal international normalized ratio changes from baseline

  132. Maximum Tolerated Dose Expansion: Serum Total Protein Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum total protein as assessed by the incidence of clinically significant abnormal total protein changes from baseline

  133. Maximum Tolerated Dose Expansion: Serum Uric Acid Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum uric as assessed by the incidence of clinically significant abnormal uric acid changes from baseline

  134. Maximum Tolerated Dose Expansion: Serum Bilirubin Lactate Dehydrogenase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate serum bilirubin lactate dehydrogenase as assessed by the incidence of clinically significant abnormal bilirubin lactate dehydrogenase changes from baseline

  135. Maximum Tolerated Dose Expansion: Overall Survival Assessment [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate overall survival as assessed by RECIST 1.1

  136. Maximum Tolerated Dose Expansion: Objective Response Rate Assessment [ Time Frame: 3 months ]
    Evaluate objective response rate as assessed by RECIST 1.1

  137. Maximum Tolerated Dose Expansion: Progression-free Survival Assessment [ Time Frame: 3 months ]
    Evaluate progression-free survival 3-months as assessed by RECIST 1.1 every 3 months

  138. Maximum Tolerated Dose Expansion: Disease Control Rate Assessment [ Time Frame: 3 months ]
    Evaluate disease control rate at 3-months as assessed by RECIST 1.1

  139. Maximum Tolerated Dose Expansion: Urine Nitrite Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine nitrite as assessed by the incidence of clinically significant abnormal urine nitrite changes from baseline

  140. Maximum Tolerated Dose Expansion: Urine Protein [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine protein as assessed by the incidence of clinically significant abnormal urine protein changes from baseline

  141. Maximum Tolerated Dose Expansion: Urine Occult Blood Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine occult blood as assessed by the incidence of clinically significant abnormal urine occult blood changes from baseline

  142. Maximum Tolerated Dose Expansion: Urine Glucose Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine glucose as assessed by the incidence of clinically significant abnormal urine glucose changes from baseline

  143. Maximum Tolerated Dose Expansion: Urine pH Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine pH as assessed by the incidence of clinically significant abnormal urine pH blood changes from baseline

  144. Maximum Tolerated Dose Expansion: Urine Ketones Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine ketones as assessed by the incidence of clinically significant abnormal urine ketones changes from baseline

  145. Maximum Tolerated Dose Expansion: Urine Leukocyte Esterase Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine leukocyte esterase as assessed by the incidence of clinically significant abnormal urine leukocyte esterase changes from baseline

  146. Maximum Tolerated Dose Expansion: Evaluate Urine Bilirubin Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine bilirubin as assessed by the incidence of clinically significant abnormal urine bilirubin changes from baseline

  147. Maximum Tolerated Dose Expansion: Urine Specific Gravity Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine specific gravity as assessed by the incidence of clinically significant abnormal urine specific gravity changes from baseline

  148. Maximum Tolerated Dose Expansion: Urine Urobilinogen Analysis [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate urine urobilinogen as assessed by the incidence of clinically significant abnormal urine urobilinogen changes from baseline

  149. Maximum Tolerated Dose Expansion: Incidence of Abnormal Cardiac Rhythm Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate cardiac rhythm as assessed by the incidence of clinically significant abnormal abnormal cardiac rhythm changes from electrocardiogram baseline

  150. Maximum Tolerated Dose Expansion: Incidence of Abnormal Electrocardiogram Heart Rate [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate heart rate as assessed by the incidence of clinically significant abnormal changes from electrocardiogram baseline

  151. Maximum Tolerated Dose Expansion: Incidence of Abnormal Electrocardiogram RR Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate RR as assessed by the incidence of clinically significant abnormal RR Interval changes from electrocardiogram baseline

  152. Maximum Tolerated Dose Expansion: Incidence of Abnormal PR Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate PR interval as assessed by the incidence of clinically significant abnormal PR Interval changes from electrocardiogram baseline

  153. Maximum Tolerated Dose Expansion: Incidence of Abnormal QRS Interval Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QRS as assessed by the incidence of clinically significant changes abnormal QRS interval changes from electrocardiogram baseline

  154. Maximum Tolerated Dose Expansion: Incidence of Abnormal QT Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QT as assessed by the incidence of clinically significant abnormal QT interval changes from electrocardiogram baseline

  155. Maximum Tolerated Dose Expansion: Incidence of Abnormal QTcB Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QTc as assessed by the incidence of clinically significant abnormal QTc interval changes from electrocardiogram baseline

  156. Maximum Tolerated Dose Expansion: Incidence of Abnormal QTcF Electrocardiogram [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate QTcB as assessed by the incidence of clinically significant abnormal QTcB interval changes from electrocardiogram baseline

  157. Maximum Tolerated Dose Expansion: Use Standardized and Validated Eastern Cooperative Oncology Group Performance Assessment Scale with increasing severity from 0 (Fully Active) to 4 (Dead) to Assess Subject Condition [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate performance changes as assessed by the incidence of clinically significant performance changes from Eastern Cooperative Oncology Group baseline

  158. Maximum Tolerated Dose Expansion: Incidence of Abnormal General Appearance Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate general appearance as assessed by the incidence of clinically significant abnormal general appearance changes from PE baseline

  159. Maximum Tolerated Dose Expansion: Incidence of Abnormal Head Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate head as assessed by the incidence of clinically significant abnormal head changes from PE baseline

  160. Maximum Tolerated Dose Expansion: Incidence of Abnormal Ear Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate ear as assessed by the incidence of clinically significant abnormal ear changes from PE baseline

  161. Maximum Tolerated Dose Expansion: Incidence of Abnormal Eye Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate eye as assessed by the incidence of clinically significant abnormal eye changes from PE baseline

  162. Maximum Tolerated Dose Expansion: Incidence of Abnormal Nose Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate nose as assessed by the incidence of clinically significant abnormal nose changes from PE baseline

  163. Maximum Tolerated Dose Expansion: Incidence of Abnormal Throat Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate throat as assessed by the incidence of clinically significant abnormal throat changes from PE baseline

  164. Maximum Tolerated Dose Expansion: Incidence of Abnormal Thorax (Cardiovascular) Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate thorax (cardiovascular) as assessed by the incidence of clinically significant abnormal thorax changes from physical examination baseline

  165. Maximum Tolerated Dose Expansion: Incidence of Abnormal Thorax (Lungs) Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate thorax (lung) as assessed by the incidence of clinically significant abnormal thorax changes from physical examination baseline

  166. Maximum Tolerated Dose Expansion: Incidence of Abnormal Abdomen Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate abdomen as assessed by the incidence of clinically significant abnormal abdomen changes from physical examination baseline

  167. Maximum Tolerated Dose Expansion: Incidence of Clinically Significant Abnormal Musculoskeletal Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate musculoskeletal as assessed by the incidence of clinically significant abnormal musculoskeletal changes from physical examination baseline

  168. Maximum Tolerated Dose Expansion: Incidence of Abnormal Skin Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate skin as assessed by the incidence of clinically significant abnormal skin changes from physical examination baseline

  169. Maximum Tolerated Dose Expansion: Incidence of Abnormal Extremities Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate extremities as assessed by the incidence of clinically significant abnormal extremity changes from physical examination baseline

  170. Maximum Tolerated Dose Expansion: Incidence of Abnormal Neurological Physical Examination [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate neurological status as assessed by the incidence of clinically significant abnormal neurological changes from physical examination baseline

  171. Maximum Tolerated Dose Expansion: Incidence of Abnormal Cognitive Orientation as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate cognitive orientation as assessed by the incidence of clinically significant abnormal cognitive orientation changes from Mini Mental State Examination cognitive orientation baseline

  172. Maximum Tolerated Dose Expansion: Incidence of Abnormal Cognitive Attention as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate cognitive attention as assessed by the incidence of clinically significant abnormal cognitive attention changes from Mini Mental State Examination cognitive attention baseline

  173. Maximum Tolerated Dose Expansion: Incidence of Abnormal Cognitive Immediate Recall as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate cognitive immediate recall neurological as assessed by the incidence of cognitive immediate recall changes from Mini Mental State Examination cognitive immediate recall baseline

  174. Maximum Tolerated Dose Expansion: Incidence of Abnormal Cognitive Short-Term Recall as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate cognitive short-term recall as assessed by the incidence of clinically significant abnormal cognitive short-term recall changes from Mental State Examination cognitive short-term recall baseline

  175. Maximum Tolerated Dose Expansion: Incidence of Abnormal Cognitive Language as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate cognitive language as assessed by the incidence of clinically significant abnormal cognitive language from Mini Mental State Examination cognitive language baseline

  176. Maximum Tolerated Dose Expansion: Incidence of Abnormal Ability to Follow Simple Verbal Commands as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate ability to follow simple verbal commands as assessed by the incidence of Mental State Examination cognitive ability to follow verbal commands for clinically significant changes from MMSE baseline

  177. Maximum Tolerated Dose Expansion: Incidence of Abnormal Ability to Follow Simple Written Commands as Assessed by the Mini Mental State Examination, a Standardized Assessment Tool with Scoring of 24 to 30 Being Normal and 1 to 17: Being Severe Dementia [ Time Frame: Up to Day 60 ]
    Evaluate ability to follow simple written commands as assessed by the incidence of Mini Mental State Examination ability to follow simple written commands .baseline

  178. Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Maximum Concentration Pharmacokinetic Characteristics [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 as assessed by CD3-Positive/Tetramer-Positive T Cells maximum concentration

  179. Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Maximum Concentration pharmacokinetic characteristics [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 as assessed by CD3-Positive/Tetramer-Positive T Cells Time to maximum concentration

  180. Maximum Tolerated Dose Expansion TCRT-ESO-A2 Area Under the Plasma Concentration-Time Curve [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT - ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells Area Under the Plasma Concentration-Time Curve

  181. Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Area Under the Concentration Curve Zero to Infinity pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells Area Under the Concentration Curve Zero to Infinity

  182. Maximum Tolerated Dose Expansion: TCRT-ESO-A2 Half-Life pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells Half-Life

  183. Maximum Tolerated Dose Expansion: TCRT-ESO-A2 time last pharmacokinetic characteristic [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year ]
    Evaluate TCRT-ESO-A2 as assessed by CD3-positive/tetramer-positive T Cells

  184. Maximum Tolerated Dose Expansion: Evaluate Tumor for Complete Response as Assessed by RECIST 1.1. [ Time Frame: Baseline to disease progression averaging one year ]
    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

  185. Maximum Tolerated Dose Expansion: Evaluate Tumor for Partial Response as Assessed by RECIST 1.1. [ Time Frame: Baseline to disease progression averaging one year ]
    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

  186. Maximum Tolerated Dose Expansion: Evaluate Tumor for Stable Disease as Assessed by RECIST 1.1. [ Time Frame: Baseline to disease progression averaging one year ]
    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

  187. Maximum Tolerated Dose Expansion: Evaluate Tumor for Disease Progression as Assessed by RECIST 1.1. [ Time Frame: Baseline to disease progression averaging one year ]
    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

  188. Maximum Tolerated Dose Expansion: Evaluate Tumor for Progression-Free Survival as Assessed by RECIST 1.1. [ Time Frame: Baseline to disease progression averaging one year ]
    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

  189. Maximum Tolerated Dose Expansion: Evaluate Tumor for Overall Survival as Assessed by RECIST 1.1. [ Time Frame: Baseline to disease progression averaging one year ]
    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

  190. Maximum Tolerated Dose Expansion: Persistence of Genetically Modified T Cells in Vivo as Assessed by Functional Characteristics and Persistence in the Circulation [ Time Frame: Baseline to disease progression averaging one year ]
    Evidence of abundance of T cell subpopulations, antigen specific CD8+ cytotoxic T lymphocytes , functional characteristics and persistence in the circulation

  191. Maximum Tolerated Dose Expansion: Monitor Presence of Potentially Replication-Competent Lentivirus (RCL) before TCRT ESO A2 Infusion [ Time Frame: Day -7 ]
    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

  192. Maximum Tolerated Dose Expansion: Monitor Presence of Potentially Replication-Competent Lentivirus (RCL) after TCRT ESO A2 Infusion [ Time Frame: Days 90, 270 ]
    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

  193. Long Term Follow Up Period: Monitor VSV-G DNA qualitative PCR [ Time Frame: Progression of disease up to 15 years ]
    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

  194. Long Term Follow Up Period: Monitor New Incidence of Potentially Product-Related Infection [ Time Frame: Progression of disease up to 15 years ]
    Monitor new incidence of potentially product-related infection as assessed by annual or biannual long term follow-up interview

  195. Long Term Follow Up Period: Monitor New Incidence of malignancy [ Time Frame: Progression of disease up to 15 years ]
    Monitor incidence of new malignancy(ies) as reported in annual or biannual long term follow-up interview

  196. Long Term Follow Up Period: Monitor New Incidence or Exacerbation of a Pre-Existing Neurologic Disorder [ Time Frame: Progression of disease up to 15 years ]
    Monitor new incidence or exacerbation of a pre-existing neurologic disorder as reported in annual or biannual long term follow-up interview

  197. Long Term Follow Up Period: Monitor New Incidence or Exacerbation of a Prior Rheumatologic or Other Autoimmune Disorder [ Time Frame: Progression of disease up to 15 years ]
    Monitor new incidence or exacerbation of a prior rheumatologic or other autoimmune disorder

  198. Long Term Follow Up Period: Monitor New Incidence of a Hematologic Disorder [ Time Frame: Progression of disease up to 15 years ]
    Monitor new incidence of a hematologic disorder


Other Outcome Measures:
  1. Explore Persistence of Genetically Modified T cells in vivo. [ Time Frame: Baseline to disease progression averaging one year ]
    Characteristics of Persistence of Genetically Modified T cells in vivo will be assessed by multiple linear regression.

  2. Explore Phenotype of Genetically Modified T cells in vivo. [ Time Frame: Baseline to disease progression averaging one year ]
    Characteristics of phenotype of genetically modified T cells in vivo will be assessed by multiple linear regression.

  3. Explore Presence of CA-125 Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of CA-125 tumor biomarker before TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  4. Explore Presence of CA-125 Tumor Immune Biomarker after TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of CA-125 Tumor Biomarker After TCRT-ESO-A2 Infusion will be assessed by multiple linear regression.

  5. Explore Presence of CEA Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of CEA tumor immune biomarker before TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  6. Explore Presence of CEA Tumor Immune Biomarker After TCRT-ESO-A2 infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of CEA tumor immune biomarker after TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  7. Explore Presence of PSA Tumor Immune Biomarker Before TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of PSA tumor biomarker before TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  8. Explore Presence of PSA Tumor Immune Biomarker After TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of PSA tumor biomarker after TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  9. Explore Distribution of PSA Tumor immune Biomarker After TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The distribution of PSA tumor biomarker after TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  10. Explore Cytokine IFN-γ Presence Before TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of systemic cytokine IFN-γ before TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  11. Explore Cytokine IFN-γ Presence After TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of systemic cytokine IFN-γ after TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  12. Explore Presence of Targeted Antigen NY-ESO-1, Before TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    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.

  13. Explore Presence of Targeted Antigen NY-ESO-1 After TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate the presence and distribution of and targeted antigen NY-ESO-1 after TCRT-ESO-A2 infusion

  14. Explore Distribution of Targeted Antigen NY-ESO-1 After TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate the distribution of targeted antigen NY-ESO-1 after before TCRT-ESO-A2 infusion will be assessed by multiple linear regression.

  15. Explore Presence of PSA Tumor Immune Biomarker [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of PSA tumor biomarker will be assessed by multiple linear regression.

  16. Explore Presence of CEA Tumor Immune Biomarker [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of CEA tumor biomarker will be assessed by multiple linear regression.

  17. :Explore Persistence of Genetically Modified T cells in vivo. [ Time Frame: Baseline to disease progression averaging one year ]
    Characteristics of persistence of genetically modified T cells in vivo will be assessed by multiple linear regression.

  18. Explore Evaluate Presence of Cytokine IFN-γ MTD Expansion: Evaluate cytokine IFN-γ before and after TCRT-ESO-A2 infusion [ Time Frame: Baseline to disease progression averaging one year ]
    The presence of systemic cytokine IFN-y will be assessed by multiple linear regression

  19. Explore Evaluate Cytokine IFN-γ Before TCRT-ESO-A2 Infusion MTD Expansion: Evaluate cytokine IFN-γ before and after TCRT-ESO-A2 infusion [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate the presence of systemic cytokine IFN-y before TCRT-ESO-A2 infusion will be assessed by multiple linear regression

  20. Explore Presence of Targeted Antigen NY-ESO-1 Before TCRT-ESO-A2 Infusion [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate the presence of targeted antigen NY-ESO-1, before TCRT-ESO-A2 infusion will be assessed by multiple linear regression

  21. 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 [ Time Frame: Baseline to disease progression averaging one year ]
    Evaluate the subject tumor to determine cut-off high and low NY ESO - 1 expression.

  22. Explore Association Between Maximum TCRT ESO A2 Concentration time and Systemic Cytokine IFN-γ Level [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. ]
    The association between maximum TCRT ESO A2 concentration time and systemic cytokine IFN-γ level will be assessed by multiple linear regression.

  23. Explore Association Between Maximum TCRT ESO A2 Concentration time and Systemic Cytokine IL-6 Level [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. ]
    The association between maximum TCRT ESO A2 concentration time and systemic cytokine IL-6 level will be assessed by multiple linear regression.

  24. Explore Association Between Maximum TCRT ESO A2 Concentration time and Systemic Cytokine TNFα Level [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. ]
    The association between maximum TCRT ESO A2 concentration time and systemic cytokine IFN-γ level will be assessed by multiple linear regression.

  25. Explore Association Between Maximum Dose Concentration Time and Disease Appropriate Circulating Tumor Marker CA-125 [ Time Frame: Day 28 ]
    The association between pharmacokinetic maximum dose concentration time and pharmacodynamic disease appropriate circulating tumor marker CA-125 will be assessed by multiple linear regression.

  26. Explore Association Between Pharmacokinetic Maximum Dose Concentration Time and Disease Appropriate Circulating Tumor Marker CEA [ Time Frame: Day 28 ]
    The association between pharmacokinetic maximum dose concentration time and pharmacodynamic disease appropriate circulating tumor marker CEA will be assessed by multiple linear regression.

  27. Explore Association Between Pharmacokinetic Maximum Dose Concentration and disease Appropriate Circulating Tumor Marker PSA [ Time Frame: Day 28 ]
    The association between pharmacokinetic maximum dose concentration time and pharmacodynamic circulating tumor marker PSA will be assessed by multiple linear regression.

  28. Explore Association Between Pharmacokinetic Maximum TCRT ESO A2 Dose Concentration Time and Pharmacodynamic Adverse Events as Identified by CTCAE Version 5. [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. ]
    The association between pharmacokinetic parameters and pharmacodynamic adverse event incidence will be assessed by rank correlation.

  29. Explore Association Between Pharmacokinetic Maximum Dose Concentration time and Pharmacodynamic Adverse Event Incidence. [ Time Frame: 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.

  30. Explore Association Between Pharmacokinetic Maximum Dose Concentration and Area Under the Curve zero to infinity [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. ]
    The association between maximum tolerated dose and area under the curve zero to infinity will be assessed by multiple linear regression.

  31. Explore Pharmacokinetic Relationship with Tlast of CD3-positive/tetramer-positive T cells [ Time Frame: Day -7, 1,2,3, 4, 5, 8,15, 28, 60, 90, 180, 270 and every 3 months until disease progression averaging one year. ]
    The association between pharmacokinetic parameters and [variable] will be assessed by multiple linear regression.

  32. Explore Pharmacokinetic Relationship with Phenotype of Genetically Modified T cells in vivo [ Time Frame: Baseline to disease progression averaging one year ]
    The association between pharmacokinetic parameters and phenotype of genetically modified T cells in vivo will be assessed by multiple linear regression.

  33. Explore Pharmacokinetic Relationship with Tumor Objective Response Rate by RECIST 1.1 [ Time Frame: 3 months ]
    The association between pharmacokinetic parameters and objective response rate will be assessed by multiple linear regression.

  34. Explore Pharmacokinetic Relationship with Progression-Free Survival by RECIST 1.1 [ Time Frame: 3 months ]
    The association between pharmacokinetic parameters and progression-free survival will be assessed by multiple linear regression.

  35. Explore Pharmacokinetic Relationship With Disease Control Rate RECIST 1.1 [ Time Frame: 3-months ]
    The association between pharmacokinetic parameters and disease control rate will be assessed by multiple linear regression

  36. Explore Pharmacokinetic Relationship With Overall Survival RECIST 1.1 [ Time Frame: Baseline to disease progression averaging one year ]
    The association between pharmacokinetic parameters and overall survival will be assessed by multiple linear regression.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Able to understand and voluntarily sign an informed consent form (ICF).
  2. Age ≥18 years of age at the time of informed consent.
  3. HLA-A*0201 positive by high resolution testing.
  4. Any of the following solid tumors with positive NY-ESO-1 expression characterized by IHC:

    1. Head and neck cancer with ≥85% of tumor cells scored ≥1+.
    2. Hepatocellular carcinoma with ≥20% of tumor cells scored ≥1+.
    3. Lung squamous cell carcinoma with ≥20% of tumor cells scored ≥1+.
    4. Synovial sarcoma with ≥65% of cells scored ≥1+.
    5. Triple-negative breast cancer with ≥20% of cells scored ≥1+.
  5. 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.
  6. Measurable disease as defined per RECIST 1.1 (Eisenhauer 2009).
  7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤1.
  8. Life expectancy of >4 months.
  9. Adequate hematologic status as demonstrated by not requiring transfusion support or granulocyte-colony stimulating factor (G-CSF) to maintain:

    1. White blood cell count ≥3,000/mcL.
    2. Absolute neutrophil count ≥1,000/mcL.
    3. Platelet count ≥100,000/mcL.
    4. Hemoglobin ≥9.0 g/dL.
  10. Adequate liver function as demonstrated by:

    1. Serum alanine transaminase (ALT) and aspartate transaminase (AST) ≤3 × upper limit of normal, except in subjects with liver metastasis, who must have AST and ALT ≤5 × upper limit of normal.
    2. Total bilirubin ≤1.5 × upper limit of normal, except in subjects with Gilbert's Syndrome, who must have total bilirubin ≤3.0 × upper limit of normal.
  11. 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.
  12. Prior therapies:

    1. Targeted or immunotherapy must be completed at least 4 weeks prior to leukapheresis.
    2. Chemotherapy must be completed at least 3 weeks prior to leukapheresis.
    3. Systemic corticosteroid or other immunosuppressive therapy must be completed at least 2 weeks prior to leukapheresis.
  13. Recovered from previous surgery or treatment-related adverse reactions to <grade 2 CTCAE (except for toxicities such as alopecia or vitiligo or toxicities that may be permanent such as neuropathy) prior to lymphodepletion chemotherapy.
  14. Men who are sterile (including vasectomy confirmed by post vasectomy semen analysis) or agree to use a condom with spermicide and to not donate sperm during the study and until the persistence of TCRT-ESO-A2 is no longer detected by qPCR or up to 15 years.
  15. Women of non-child bearing potential due to surgical sterilization (at least 6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) confirmed by medical history or menopause (i.e., no menstrual bleeding for more than 12 months in a woman aged ≥45 years), OR women of childbearing potential who test negative for pregnancy at Screening based on serum pregnancy test must be using a highly effective method of contraception from the time of Screening until the persistence of TCRT-ESO-A2 is no longer detected by qPCR or up to 15 years. Note: Highly effective methods of contraception that result in a low failure rate (i.e., <1% per year) when used consistently and correctly include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. True abstinence, when in line with the preferred and usual lifestyle of the subject, is considered a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of study participation and until the persistence of TCRT-ESO-A2 is no longer detected by qPCR. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, and post-ovulation method) and withdrawal are not acceptable methods of contraception.

5.3 Exclusion Criteria

Eligible subjects must not have/be:

  1. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or AIDS).
  2. Known allergic reactions to any component of the treatments in this study.
  3. Echocardiography (ECHO) or multigated acquisition scan (MUGA) indicative of left ventricular ejection fraction (LVEF) ≤45%.

Exclusion Criteria:

  • Eligible subjects must not have/be:

    1. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease or AIDS).
    2. Known allergic reactions to any component of the treatments in this study.
    3. Echocardiography (ECHO) or multigated acquisition scan (MUGA) indicative of left ventricular ejection fraction (LVEF) ≤45%.
    4. Pulmonary function test of forced expiratory volume in the first second (FEV1) ≤60% in subjects with a prolonged history of cigarette smoking (e.g. ≥20 pack-year smoking history).
    5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements.
    6. Subjects with infection requiring treatment, including but not limited to active tuberculosis, COVID-19, known HIV positive subjects or subjects with clinically active hepatitis A, B and C.
    7. Planning to take the following medications within 4 weeks of TCRT-ESO-A2 infusion or during the study: long-term systemic use of steroid hormones, hydroxyurea, immunomodulatory drugs (such as interleukin 2, interferon α or γ, GM-CSF, mTOR inhibitor, cystatin, thymosin, etc.). Recent use of inhaled or topical steroids, topical 5-fluorouracil is not exclusionary, however, use of inhaled steroids before leukapheresis and blood draws should be discouraged.
    8. Untreated or symptomatic brain metastasis.
    9. History of organ transplantation or allogeneic stem cell transplantation.
    10. Known uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease or liver failure.
    11. Previous use of any gene therapy product.
    12. Not suitable for enrollment at the discretion of the Principal Investigator.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04878484


Contacts
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Contact: David Cutler, MD 19082905047 dcutler@athenex.com
Contact: Michelle Redman 17168925220 mredman@athenex.com

Locations
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United States, Texas
Baylor University Medical Cancer Hospital Recruiting
Dallas, Texas, United States, 75246
Contact: Oghenevovwero Sido, RN    214-818-8472    Oghenevovwero.Sido@bswhealth.org   
Contact: Joyce Ghormley    Ph: (214) 818-8961    Joyce.Ghormley@BSWHealth.org   
Sponsors and Collaborators
Athenex, Inc.
Investigators
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Principal Investigator: Carlos Becerra, MD Baylor University Medical Cancer Hospital
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Responsible Party: Athenex, Inc.
ClinicalTrials.gov Identifier: NCT04878484    
Other Study ID Numbers: AX TCRT 001
First Posted: May 7, 2021    Key Record Dates
Last Update Posted: February 3, 2022
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Final data will be shared with researchers via public presentations, Posters and may be listed in Investigator articles.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Athenex, Inc.:
NY-ESO-1
Additional relevant MeSH terms:
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Neoplasms