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Brief Title: To Evaluate the Efficacy of NY-ESO-1-specific T Cell Receptor Affinity Enhancing Specific T Cell in Solid Tumors

Application of NY-ESO-1-specific TCR Affinity Enhancing Specific T Cell Therapy (TAEST16001) in Solid Tumors Except Non Small Cell Lung Cancer,Including Liver Cancer,Gastric Cancer,Esophageal Cancer and so on.

INTRODUCTION

  • Org Study ID: 2017-ZLZX-001
  • Secondary ID: N/A
  • NTC ID: NCT03159585
  • Sponsor: Zhujiang Hospital

BRIEF SUMMARY


The main purpose of this trial is to investigate the safety and tolerability of
TAEST16001(TCR Affinity Enhancing Specific T cell Therapy)in the multi-line treatment failed
advanced solid tumors except non small cell lung cancer,including liver cancer,gastric
cancer,esophageal cancer,bone and soft tissue tumors,breast cancer, bladder
carcinoma,prostate carcinoma,thyroid cancer, ovarian cancer and so on. The patients must meet
the two criteria: human leukocyte antigens (HLA)-A*0201+ and NY-ESO-1 positive cells≥25% by
immunohistochemistry.

DETAILED DESCRIPTION


TCR-T cell therapy has made a breakthrough for tumors in recent years. Phase I/II trial of
NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma, conducted by the
Rosenberg team at the National Cancer Institute, showed that 61% Synovial cell sarcoma and
55% melanoma had benefits, without severe side effects found in T cell receptor (TCR)
transduced T-Cell Immunotherapy. The US FDA has granted breakthrough TCR-T cell therapy for
patients with inoperable or metastatic synovial sarcoma. The European Medicines Agency has
also approved the same therapy to Priority Medicines(PRIME).

This clinical trial is mainly focused on cancer-testis antigen, because it is not expressed
in normal cells. NY-ESO-1 antigen as one member of cancer-testis antigen, is commonly
expressed in 10-50% of melanoma, lung, liver, esophageal, breast, prostate, bladder, thyroid
and ovarian cancer cases, 60% of multiple myeloma cases, and 70-80% of synovial sarcoma. The
NY-ESO-1 TCR cell therapy for synovial sarcoma and melanoma has benefited many patients, but
its effect on other solid tumors is still unknown. So we plan to explore its efficacy in many
types of solid tumors.

The trial is to investigate the safety and tolerability of TAEST16001 cell therapy in
multi-line treatment failed advanced solid tumors except non small cell lung cancer,including
liver cancer,gastric cancer,esophageal cancer,bone and soft tissue tumors,breast cancer,
bladder carcinoma,prostate carcinoma,thyroid cancer, ovarian cancer and so on. The patients
must meet the two criteria: HLA-A*0201+ and NY-ESO-1 positive cells≥25% by
immunohistochemistry.


  • Overall Status
    Recruiting
  • Start Date
    April 14, 2017
  • Phase
    Phase 1
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: treatment-related adverse events as assessed by CTCAE v4.03

Primary Outcome 1 - Timeframe: 28 Days

CONDITION

  • Liver Cancer Stage IV
  • Gastric Cancer Stage IV
  • Esophageal Cancer
  • Stage IV
  • Bone and Soft Tissue Tumors
  • Breast Cancer Stage IV
  • Bladder Carcinoma Stage IV
  • Prostate Carcinoma Stage IV
  • Thyroid Cancer Stage IV
  • Ovarian Cancer Stage IV
  • Solid Tumor

ELIGIBILITY


Inclusion Criteria:

- sign an informed consent before undertaking any trial-related activities;

- ≥18 and ≤75 years old;

- Multi-line treatment failed Solid Tumors except non small cell lung cancer,including
Liver Cancer,Gastric Cancer,Esophageal Cancer,Bone and Soft Tissue Tumors,Breast
Cancer, Bladder Carcinoma,Prostate Carcinoma,Thyroid Cancer, Ovarian Cancer and so on
diagnosed by licensed pathologist;

- multi-line treatment failed patients;

- with measurable lesions according to Response Evaluation Criteria In Solid Tumors1.1
or immune related response criteria standard;

- meet the two screening indicators: HLA-A*0201+, NYESO-1+(≥25% by
immunohistochemistry);

- Eastern Cooperative Oncology Group score 0-1;life expectancy is longer than 3 months;

- The patient did not receive anti-tumor therapy within 4 weeks before enrollment;

- A brain metastasis patient in a stable condition for one month after anti-tumor
therapy can be included;

- left ventricular ejection fraction≥50%

- Lab test results meet the following requirements:

white blood cell count≥3.0×10^9/L; absolute neutrophil count≥1.5 ×10^9/L (No human
granulocyte colony stimulating factor support); blood platelet≥75 ×10^9/L;
Hemoglobin≥10g/dL (No transfusion in the last 7 days); Prothrombin time or International
normalized rate ≤1.5×normal upper limit, except taking anticoagulant therapy; thrombin
time≤1.5×normal upper limit, except taking anticoagulant therapy; a 24-hour creatinine
clearance rate≥60mL/ min; Aspartate transaminase / serum glutamic oxaloacetic
transaminase≤2.5 ×upper limit of normal; Alanine aminotransferase/ serum glutamate pyruvate
transaminase≤2.5 ×upper limit of normal; total bilirubin≤1.5×upper limit of normal (expect
that the subject has Gilbert's syndrome).

- no pregnant women;female patients must use contraceptive measures during the study and
prohibit any homosexual or heterosexual;

- The patients can regularly visit the research institutions for related tests,
evaluations, and management during the study period.

Exclusion Criteria:

- lung cancer ;

- received major surgery, conventional chemotherapy, large-area radiotherapy, immune
therapy or any biological anti-tumor therapy 4 weeks before enrollment;

- allergic to ingredients in this trial;

- common terminology criteria for adverse events ≥2 because of the previous surgery or
treatment-related adverse reactions;

- with two types of primary solid tumors;

- poorly managed hypertension (systolic blood pressure >160 mmHg and / or diastolic
blood pressure > 90 mmHg) or clinically serious (for example, active) cerebrovascular
diseases such as cerebrovascular incident (within 6 months prior to signing the
informed consent), myocardial infarction (within 6 months prior to signing the
informed consent), unstable angina, grade II or above heart failure according to New
York Heart Association Grading Congestive, or severe arrhythmia can not be controlled
by medication or has a potential impact on the study; with consecutive three times of
obvious abnormality on electrocardiogram or average QT corrected interval ≥450
millisecond;

- combined with other serious organic and mental disorders;

- serious or active bacteria, viral or fungal infections that require systemic
treatment;

- with autoimmune diseases: such as a history of inflammatory bowel disease or other
autoimmune diseases determined by the investigator as unsuitable for the study (e.g.
systemic lupus erythematosus,vasculitis, invasive pulmonary disease);

- within 4 weeks prior the infusion, received chronic systemic steroid cortisone,
hydroxyurea, immunomodulatory treatment (for example: Interleukin 2, alpha or gamma
interferon, granulocyte colony stimulating factor, mammalian target of rapamycin
inhibitors, cyclosporine, Thymosin etc);

- with organ transplantation, autologous/allogeneic stem cell transplantation and renal
replacement therapy;

- with central nervous system metastasis but not receive treatment;

- with uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung
disease, or liver failure;

- alcohol and / or drug abuse;

- pregnant or lactating women;

- received concomitant medication prohibited by this trial;

- with any medical condition or disease determined by the investigators that may be
detrimental to this trial;

- without legal capacity / limited behavior.

Gender: All

Minimum Age: 75 Years

Maximum Age: 18 Years

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Jian Zhang

Role: Study Chair

Affiliation: Southern Medical University, China

Overall Contact

Name: Jian Zhang

Phone: +86 02062782356

Email: blacktiger@139.com

LOCATION

Facility Status Contact
Facility: Zhujiang Hospital of Southern Mediacl University
Guangzhou, Guang Dong 510282
China
Status: Recruiting Contact:
Jian Zhang, Ph.D.
+8602062782356
blacktiger@139.com