NCT03159585

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
6

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Apr 2017

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 14, 2017

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

May 15, 2017

Completed
3 days until next milestone

First Posted

Study publicly available on registry

May 18, 2017

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 4, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 4, 2019

Completed
Last Updated

January 22, 2020

Status Verified

January 1, 2020

Enrollment Period

2.1 years

First QC Date

May 15, 2017

Last Update Submit

January 20, 2020

Conditions

Liver Cancer Stage IVGastric Cancer Stage IVEsophageal Cancer, Stage IVBone and Soft Tissue TumorsBreast Cancer Stage IVBladder Carcinoma Stage IVProstate Carcinoma Stage IVThyroid Cancer Stage IVOvarian Cancer Stage IVSolid Tumor

Keywords

TAEST16001

Outcome Measures

Primary Outcomes (1)

  • treatment-related adverse events as assessed by CTCAE v4.03

    The treatment-related adverse events of the patients received TAEST16001 treatment will be assessed by CTCAE v4.03

    28 Days

Secondary Outcomes (6)

  • assess overall response rate

    270 Days

  • assess duration of response

    270 Days

  • assess time to progress

    270 Days

  • assess progression free survival

    270 Days

  • assess overall survival

    270 Days

  • +1 more secondary outcomes

Study Arms (1)

TAEST16001

EXPERIMENTAL

Patients who meet the inclusion criteria receive TAEST16001treatment after lymphodepleting by fludarabine and cyclophosphamide.

Drug: TAEST16001

Interventions

TAEST16001DRUG

After completion of Lymphodepleting regimen pretreatment, the subject will receive an infusion of TAEST16001

TAEST16001

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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;
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Zhujiang Hospital of Southern Mediacl University

Guangzhou, Guangdong, 510282, China

Location

Related Publications (6)

  • Rapoport AP, Stadtmauer EA, Binder-Scholl GK, Goloubeva O, Vogl DT, Lacey SF, Badros AZ, Garfall A, Weiss B, Finklestein J, Kulikovskaya I, Sinha SK, Kronsberg S, Gupta M, Bond S, Melchiori L, Brewer JE, Bennett AD, Gerry AB, Pumphrey NJ, Williams D, Tayton-Martin HK, Ribeiro L, Holdich T, Yanovich S, Hardy N, Yared J, Kerr N, Philip S, Westphal S, Siegel DL, Levine BL, Jakobsen BK, Kalos M, June CH. NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma. Nat Med. 2015 Aug;21(8):914-921. doi: 10.1038/nm.3910. Epub 2015 Jul 20.

    PMID: 26193344BACKGROUND

  • Li Y, Moysey R, Molloy PE, Vuidepot AL, Mahon T, Baston E, Dunn S, Liddy N, Jacob J, Jakobsen BK, Boulter JM. Directed evolution of human T-cell receptors with picomolar affinities by phage display. Nat Biotechnol. 2005 Mar;23(3):349-54. doi: 10.1038/nbt1070. Epub 2005 Feb 20.

    PMID: 15723046BACKGROUND

  • Robbins PF, Kassim SH, Tran TL, Crystal JS, Morgan RA, Feldman SA, Yang JC, Dudley ME, Wunderlich JR, Sherry RM, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Li YF, El-Gamil M, Rosenberg SA. A pilot trial using lymphocytes genetically engineered with an NY-ESO-1-reactive T-cell receptor: long-term follow-up and correlates with response. Clin Cancer Res. 2015 Mar 1;21(5):1019-27. doi: 10.1158/1078-0432.CCR-14-2708. Epub 2014 Dec 23.

    PMID: 25538264BACKGROUND

  • Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.

    PMID: 21282551BACKGROUND

  • Johnson LA, Morgan RA, Dudley ME, Cassard L, Yang JC, Hughes MS, Kammula US, Royal RE, Sherry RM, Wunderlich JR, Lee CC, Restifo NP, Schwarz SL, Cogdill AP, Bishop RJ, Kim H, Brewer CC, Rudy SF, VanWaes C, Davis JL, Mathur A, Ripley RT, Nathan DA, Laurencot CM, Rosenberg SA. Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood. 2009 Jul 16;114(3):535-46. doi: 10.1182/blood-2009-03-211714. Epub 2009 May 18.

    PMID: 19451549BACKGROUND

  • Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006 Oct 6;314(5796):126-9. doi: 10.1126/science.1129003. Epub 2006 Aug 31.

    PMID: 16946036BACKGROUND

MeSH Terms

Conditions

Liver NeoplasmsStomach NeoplasmsEsophageal NeoplasmsSoft Tissue NeoplasmsBreast NeoplasmsUrinary Bladder NeoplasmsProstatic NeoplasmsThyroid NeoplasmsOvarian Neoplasms

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesLiver DiseasesGastrointestinal NeoplasmsGastrointestinal DiseasesStomach DiseasesHead and Neck NeoplasmsEsophageal DiseasesBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesUrologic NeoplasmsUrogenital NeoplasmsFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesUrinary Bladder DiseasesUrologic DiseasesMale Urogenital DiseasesGenital Neoplasms, MaleGenital Diseases, MaleGenital DiseasesProstatic DiseasesEndocrine Gland NeoplasmsEndocrine System DiseasesThyroid DiseasesOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleGenital Neoplasms, FemaleGonadal Disorders

Study Officials

  • Jian Zhang

    Southern Medical University, China

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: a single-center, open, single (or fractional) dose of safety and tolerability
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 15, 2017

First Posted

May 18, 2017

Study Start

April 14, 2017

Primary Completion

June 4, 2019

Study Completion

June 4, 2019

Last Updated

January 22, 2020

Record last verified: 2020-01

Locations

CN(1)