Lung Cancer, Nonsmall Cell, RecurrentPhase 1NCT03029273
NY-ESO-1 TCR （TAEST16001）for Patients With Advanced NSCLC
A Phase 1 study testing Cyclophosphamide and Fludarabine and Anti-NY-ESO-1 TCR transduced T cells in people with Lung Cancer, Nonsmall Cell, Recurrent, run by Guangzhou Institute of Respiratory Disease at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Lung Cancer, Nonsmall Cell, Recurrent
- What is being tested?
- Cyclophosphamide and Fludarabine and Anti-NY-ESO-1 TCR transduced T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- 21 Mar 2017to Mar 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥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;
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- 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.
Who cannot join
- 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;
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- 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;
- Received concomitant medication prohibited by the protocol;
- With any medical condition or disease determined by the investigators that may be detrimental to this trial;
- No capacity or limited capacity to make juridical acts.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
Shiyue Li, MD, 8620-83062896, lishiyue@188.com
Shiyue Li, MD
About this study
Official title: Pilot Study of Affinity-enhanced Anti-NY-ESO-1 TCR Engineered Autologous T Cells in NSCLC Patients
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.
Read the detailed description
This Phase 1 study is designed as a cell dose escalation trial evaluating the safety of TAEST16001 T cell therapy in subjects with NSCLC who have received prior therapy for their disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory objectives will be assessed. Subjects enter from a Screening Protocol and are positive for HLA-A2*02:01 and have tumor that express NY-ESO-1. The subjects will be evaluated DLT and MTD using a modified 3+3 cell dose escalation design to determine the cell dose range. Subjects will receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) on day -7 to day -5 followed by infusion of dose of about 5×109 TAEST16001 and IL-2(s.c.).
Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks, 12 weeks, 16 weeks and every 3 months until progression of their disease.
- Conditions
- Lung Cancer, Nonsmall Cell, Recurrent
- Being tested
- Cyclophosphamide and Fludarabine, Anti-NY-ESO-1 TCR transduced T cells
- Medical subject headings
- Lung Neoplasms, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide and FludarabineDrug
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 cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Cyclophosphamide and Fludarabine; Biological: Anti-NY-ESO-1 TCR transduced T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 Days
Secondary outcomes (1)
Number of participants with clinical responses
To evaluate the efficacy of NYESO-1 positive NSCLS patients treated with NY-ESO-1 antigen specific affinity-enhanced TCR transduced autologous T cell therapy.
Measured: 270 Days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2017 (estimated)
- Study start21 Mar 2017
- Primary completionMar 2019 (estimated)
- Study completionMar 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Cancer, Nonsmall Cell, RecurrentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou Institute of Respiratory Disease
- Sponsor type
- University, hospital or other
- Collaborators
- Xiangxue Life Science Research Center, Guangdong Xiangxue Precision Medical Technology Co., Ltd., Xiangxue Pharmaceutical
- Responsible party
- Principal investigator, ShiYue Li, Guangzhou Institute of Respiratory Disease
- Investigators
- Shiyue Li, MD, Principal investigator, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical UniversityChengzhi Zhou, MD, Principal investigator, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03029273
- Sponsor's protocol ID
- 2016-63
- Status last verified
- Jan 2019
- First submitted
- 20 Jan 2017
- Last updated
- 17 Jan 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 17 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Affinity-enhanced Anti-NY-ESO-1 TCR Engineered Autologous T Cells in NSCLC Patients
- ClinicalTrials.gov ID
- NCT03029273
- Acronym / sponsor ID
- 2016-63
- Conditions
- Lung Cancer, Nonsmall Cell, Recurrent
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Guangzhou Institute of Respiratory DiseaseUniversity, hospital or other
- Collaborators
- Xiangxue Life Science Research Center, Guangdong Xiangxue Precision Medical Technology Co., Ltd., Xiangxue Pharmaceutical
- Study start
- 21 Mar 2017 (actual)
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Mar 2019 (estimated)
- First posted
- 24 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This Phase 1 study is designed as a cell dose escalation trial evaluating the safety of TAEST16001 T cell therapy in subjects with NSCLC who have received prior therapy for their disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory objectives will be assessed. Subjects enter from a Screening Protocol and are positive for HLA-A2*02:01 and have tumor that express NY-ESO-1. The subjects will be evaluated DLT and MTD using a modified 3+3 cell dose escalation design to determine the cell dose range. Subjects will receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) on day -7 to day -5 followed by infusion of dose of about 5×109 TAEST16001 and IL-2(s.c.).
Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks, 12 weeks, 16 weeks and every 3 months until progression of their disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Anti-NY-ESO-1 TCR-transduced T cells | Experimental | Drug: Cyclophosphamide and Fludarabine, Biological: Anti-NY-ESO-1 TCR transduced T cellsNYESO-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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- ≥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+;
Key exclusion criteria (18 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cyclophosphamide and FludarabineSeven 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. | Drug | Anti-NY-ESO-1 TCR-transduced T cells |
| Anti-NY-ESO-1 TCR transduced T cellsA 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. | Biological | Anti-NY-ESO-1 TCR-transduced T cells |
Primary outcome
Number of participants with adverse events
Time frame: 30 Days
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.
1 secondary outcome
Number of participants with clinical responses
Time frame: 270 Days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jan 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shiyue Li, MD principal investigator
Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
Chengzhi Zhou, MD principal investigator
Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cyclophosphamide and Fludarabine and Anti-NY-ESO-1 TCR transduced T cells in people with Lung Cancer, Nonsmall Cell, Recurrent, run by Guangzhou Institute of Respiratory Disease at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shiyue Li, MD (8620-83062896, lishiyue@188.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with adverse events (time frame: 30 Days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jan 2019.