NY-ESO-1 TCR （TAEST16001）for Patients With Advanced NSCLC

NCT03029273 | Unknown Phase 1

• 1 other identifier: 2016-63
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

TCR-T cell therapy experienced a breakthrough for treating 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 therapeutic responses. Another report of a phase I / II clinical trial for multiple myeloma showed that 20 patients received high affinity anti-NY-ESO-1 and LAGE-1 specific TCR-T treatment, 16 of them (80%) had the average progression-free survival of 19.1 months with minor side effect. These achievements indicate that TCR-T cell therapy can target a variety of tumors including solid tumors without any severe side effects found in CAR-T trials. This study is mainly focused on tumor testis antigen (Cancer-Testis Antigen), because it is not expressed in normal cells. NY-ESO-1 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 cell sarcoma. Approximately 700,000 new cases of lung cancer are identified each year in China, 70% of them die within one to two years after diagnosis due to the lack of effective treatment. To address that unmet needs, our TCR-T treatment targets non-small cell lung cancer with NY-ESO-1 antigen expression. This study will investigate the safety and tolerability of TAEST16001 (TAEST: TCR Affinity Enhancing Specific T cell Therapy, autologous T cells transduced with affinity enhanced NY-ESO-1 TCR) cell therapy in subjects with NSCLC who have received prior therapy for their disease but their disease has progressed or relapsed.

Conditions

Lung Cancer, Nonsmall Cell, Recurrent

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events

  To evaluate the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced T cells in patients with HLA-A2+ NY-ESO-1 expressing NSCLC.

  30 Days

Secondary Outcomes (1)

• Number of participants with clinical responses

  270 Days

Study Arms (1)

Anti-NY-ESO-1 TCR-transduced T cells

EXPERIMENTAL

NYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with Cyclophosphamide (250-500mg/m2/day) and Fludarabine (25mg/m2/day) for 3 days. A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.

Drug: Cyclophosphamide and Fludarabine; Biological: Anti-NY-ESO-1 TCR transduced T cells

Interventions

Cyclophosphamide and Fludarabine DRUG

Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days.

Anti-NY-ESO-1 TCR-transduced T cells

Anti-NY-ESO-1 TCR transduced T cells BIOLOGICAL

A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.

Anti-NY-ESO-1 TCR-transduced T cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥18 and ≤75 years old while signing the informed consent;
• Sign an informed consent before undertaking any trial-related activities;
• Stage IIIb-IV NSCLC patients diagnosed by licensed pathologist, NY-ESO-1 positive cells \>10% by IHC.
• Received at least one run of standard therapy(surgery, chemo, radiation and targeted therapy) or first line and second line treatment failure; If the patient has EGFR mutation or ALK gene rearrangement, they can be enrolled after the appropriate EGFR or ALK tyrosine kinase inhibitor treatment failed;
• Have one positive indication of the following immunological biomarkers during the screening stage: HLA-A\*0201+, NYESO-1+;
• ECOG score 0-1(see appendix);Life expectancy is longer than 3 months;
• No Chinese herbal medicine usage within 4 weeks before enrollment;
• left ventricular ejection fraction≥50%
• Lab test results meet the following requirements:
• White blood cell count≥3.0×109/L; ANC≥1.5 ×109/L (No GCSF support); PLT≥75 ×109/L; Hemoglobin≥10g/dL (No transfusion in the last 7 days); Prothrombin time or INR ≤1.5× normal upper limit, except taking anticoagulant therapy; PTT≤1.5× normal upper limit, except taking Anticoagulant therapy;a 24-hour creatinine clearance rate≥60mL/ min; AST/SGOT≤2.5 ×ULN; ALT/SGPT≤2.5 ×ULN; ALP≤2.5 ×ULN; TBIL≤1.5×ULN (expect that the subject has Gilber's syndrome).
• Levels of calcium, potassium, and magnesium in serum are within the normal range;
• Pregnancy test is negative for female subjects with reproductive capability before participating the study；Female subjects must consent using birth control during the study or prohibit any homo or heterosexual behavior;
• Can regularly visit the research institutions for tests, evaluations, and monitoring throughout the study period.

You may not qualify if:

• SCLC;
• Received major surgery, conventional chemotherapy, large-area radiotherapy, immune therapy or any biological anti-tumor therapy within 4 weeks prior to the study;
• Allergic to any components of the therapy;
• Never recovered to \<2 grade CTCAE from prior surgery or treatment-related adverse events;
• With two types of primary solid tumors;
• Poorly managed hypertension (systolic blood pressure \>160 mmHg and / or diastolic blood pressure \> 90 mmHg) or clinically significant(for example, active) cardiovascular and 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 (See Appendix) 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 QTc interval ≥450 ms;
• With other serious organic disease and/or mental illness;
• With systemic active infections that need treatments, including active tuberculosis, HIV-positive or clinically active hepatitis A, B and C;
• With autoimmune diseases: such as a history of inflammatory bowel disease (IBD) or other autoimmune diseases determined by the investigator to be unsuitable for the study (e.g. systemic lupus erythematosus (SLE), 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, GCSF, mTOR inhibitors, cyclosporine etc.);
• History of organ allografts, autologous / allogeneic stem cell transplantation, and renal replacement therapy;
• With central nervous system metastasis. Patients with neurological symptoms need a brain CT/MRI examination to rule out brain metastases;
• With uncontrolled diabetes, pulmonary fibrosis, interstitial lung disease, acute lung disease, or liver failure;
• History of alcohol and / or drug abuse;
• Pregnant or lactating female patients;

Sponsors & Collaborators

• Guangzhou Institute of Respiratory Disease: lead
• Xiangxue Life Science Research Center: collaborator
• Guangdong Xiangxue Precision Medical Technology Co., Ltd.: collaborator
• Xiangxue Pharmaceutical: collaborator

Study Sites (1)

Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, 510120, China

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms; Recurrence

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Shiyue Li, MD

  Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

• Chengzhi Zhou, MD

  Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shiyue Li, MD

CONTACT

8620-83062896; lishiyue@188.com

Chengzhi Zhou, MD

CONTACT

8620-83062832; doctorzcz@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD,Professor

Model Details: One arm, open label, dose escalation, single dose phase I study of safety and tolerability. NYESO-1 TCR-T cell are prepared via lentiviral infection. DLT was administered in a dose escalation test according to the 3 + 3 design. Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days. Patients, who receive an infusion of TAEST16001, will remain in the hospital to be monitored for adverse events until they have recovered from the treatment. Patients will have frequent follow-up visit to monitor the persistence of modified T cells and efficacy of the treatment.

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: March 21, 2017
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: January 17, 2019

Record last verified: 2019-01

Locations

CN (1)