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NY-ESO-1ᶜ²⁵⁹T for Advanced NSCLC

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ClinicalTrials.gov Identifier: NCT02588612
Recruitment Status : Active, not recruiting
First Posted : October 28, 2015
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This study is intended for men and women at least 18 years of age who have advanced lung cancer which has grown or returned after being treated. In particular, it is a study for subjects who have a blood test positive for human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 protein and a tumor test positive for NY-ESO-1 expression. The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with lung cancer. Subjects will be seen frequently by the Study Physician right after receiving their T cells back. Subjects will then be entered into a long-term follow up in order to monitor the subject. Subjects will be seen every 6 months by their Study Physician for the first 5 years after the T cell infusion. If the T cells are found in the blood at five years, then the subjects will continue to be seen once a year until the T cells are no longer found in the blood for a maximum of 15 years. If the T cells are no longer found in the blood at 5 years, then the subject will be contacted by the Study Physician for the next 10 years.

Condition or disease Intervention/treatment Phase
Neoplasms Genetic: NY-ESO-1ᶜ²⁵⁹T cell Drug: Cyclophosphamide Drug: Fludarabine Phase 1

Detailed Description:
This is a single-arm study of genetically engineered NY-ESO-1ᶜ²⁵⁹T cells in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive subjects with advanced (Stage IIIb or IV) NSCLC. Subjects with measurable disease will be screened for general health, performance status and disease stage. Following screening, subjects meeting all eligibility will undergo a large-volume leukapheresis to obtain cells for the manufacture of autologous NY-ESO-1ᶜ²⁵⁹ TCR bearing T cells. When the NY-ESO-1ᶜ²⁵⁹T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine . Subjects will visit the clinic for safety and efficacy assessments daily from T cell infusion (Day 1) through Day 5, Days 8, 10, 12, and then weekly until week 6 and then at 8, 10, 12, 16, 20 and 24 weeks, and every 3 months until 2 years and then every 6 months until progression of their disease (or withdrawal of consent for the interventional portion of the study). Subjects who have a confirmed response (or have stable disease for >4 months) but subsequent disease progression following the initial infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion. All subjects, completing or withdrawing from the interventional portion of the study, will enter a 15-year long-term follow-up phase for observation of delayed adverse events. All subjects will continue to be followed for overall survival during the long-term follow-up phase.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Open-Label Clinical Trial Evaluating the Safety and Efficacy of Autologous T Cells Expressing Enhanced TCRs Specific for NY-ESO-1 in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
Actual Study Start Date : February 1, 2016
Estimated Primary Completion Date : February 6, 2019
Estimated Study Completion Date : September 19, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Fludarabine

Arm Intervention/treatment
Experimental: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T
After Screening, eligible subjects will enter a leukapheresis phase, followed by lymphodepletion phase where they will be administered fludarabine and cyclophosphamide. On Day 1, subjects will be administered a single dose of NY-ESO-1ᶜ²⁵⁹T cell infusion. Subjects who have a confirmed response (or have stable disease for >4 months) but subsequent disease progression following the initial infusion and whose tumor continues to express the appropriate antigen target may be eligible for a second infusion.
Genetic: NY-ESO-1ᶜ²⁵⁹T cell
NY-ESO-1ᶜ²⁵⁹ T cell is an autologous genetically modified T-cell product.

Drug: Cyclophosphamide
Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Drug: Fludarabine
Fludarabine will be used as a lymphodepleting chemotherapy.




Primary Outcome Measures :
  1. Number of subjects with adverse events (AE), including serious adverse events (SAE) [ Time Frame: 24 months ]
    Determine if treatment with autologous genetically modified T cells, (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through assessment of AEs, including SAEs.

  2. Number of subjects with abnormal laboratory assessments [ Time Frame: 24 months ]
    Determine if treatment with autologous genetically modified T cells, (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through laboratory assessments including chemistry, hematology and coagulation.

  3. Number of subjects with abnormal cardiac and pulmonary assessments [ Time Frame: 24 months ]
    Determine if treatment with autologous genetically modified T cells, (NY-ESO-1ᶜ²⁵⁹T) is safe and tolerable through cardiac and pulmonary assessments, including electrocardiogram (ECG) and pulmonary function (pulse oximetry).


Secondary Outcome Measures :
  1. Proportion of subjects with a confirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment by assessment of the Overall Response Rate according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

  2. Interval between the date of first T cell infusion dose and first documented evidence of CR or PR [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment by assessment of time to first response.

  3. Interval between the date of first documented evidence of CR or PR until first documented disease progression or death due to any cause [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment by assessment of duration of response.

  4. Interval between the date of first T cell infusion and the earliest date of disease progression or death due to any cause [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment by assessment of progression-free survival.

  5. Disease control rate (DCR) [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment according to DCR, defined as the percentage of subjects with a confirmed stable disease (SD) or better as the best overall response (BOR) (i.e., PR, CR, or SD >=12 weeks).



Information from the National Library of Medicine

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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:

  • Subject has voluntarily agreed to participate by giving written informed consent in accordance with International Conference on Harmonization Good Clinical Practice (ICH GCP) Guidelines and applicable local regulations.
  • Subject has agreed to abide by all protocol required procedures including study related assessments, and management by the treating institution for the duration of the study and long-term follow up.
  • Subject is >=18 years of age on the day of signing informed consent.
  • Subject has a diagnosis of histologically or cytologically confirmed advanced non-small cell lung cancer (Stage IIIB or IV) or recurrent disease.
  • Subjects with known epidermal growth factor receptor (EGFR) mutations or ALK or ROS1 gene rearrangements must have failed (disease progression [PD] or unacceptable toxicity) prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively (PD or unacceptable toxicity). There is no limit to lines of prior anti-cancer therapy.
  • Subject has measurable disease according RECIST v1.1 criteria.
  • Subject is HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.
  • Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by an Adaptimmune- / GSK-designated central laboratory confirming NY-ESO-1 and/or LAGE-1a expression.
  • Subject has Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 10. Subject has an anticipated life expectancy >3 months.
  • Subject has left ventricular ejection fraction >=50%.
  • Subject is fit for leukapheresis and has adequate venous access for the cell collection.
  • Male or Female. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male subjects: Male subjects are eligible to participate if they agree to the following during the intervention period starting at the first dose of chemotherapy for at least 12 months after receiving the T-cell infusion, or 4 months after there is no evidence of persistence/ gene modified cells in the subject's blood, whichever is longer. A) Refrain from donating sperm Plus either: B) Be abstinent from heterosexual or homosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR C) Must agree to use contraception/barrier. Female subjects: A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP who will agree to use a barrier method (male condom) and use a contraceptive method that is highly effective during the intervention period and for at least 12 months after receiving the T-cell infusion, or 4 months after there is no evidence of persistence/ gene modified cells in the subject's blood, whichever is longer. WOCBP should also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. The Investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention.
  • Subject must have adequate organ function as indicated by the following laboratory values: a) Absolute Neutrophil count (ANC) >=1.0 x10^9 per liter (/L) (without G-CSF support); b) Platelets >= 75 x10^9/L; c) Hemoglobin >80 grams per deciliter (g/dL) (without transfusion support within 7 days from start of leukapheresis); d) Prothrombin Time or International Normalized Ratio (INR) <=1.5 times upper limit of normal (ULN) unless receiving therapeutic anticoagulation. e) Partial Thromboplastin Time (PTT) <=1.5 times upper limit of normal (ULN) unless receiving therapeutic anticoagulation. f) Calculated or measured creatinine clearance >=40 milliliters per minute (mL/min); g) Serum total bilirubin <=1.5 times ULN (unless subject had documented Gilbert's Syndrome); h) Alanine aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) <=2.5 times ULN.

Exclusion Criteria:

  • Current active liver or biliary disease (with the exception of Gilbert's syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per Investigator assessment). Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice or cirrhosis.
  • Subject who has had cytotoxic chemotherapy within 2 weeks prior to leukapheresis; Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors) or biological therapy with no wash-out times required; corticosteroids or any other immunosuppressive therapy within 2 weeks prior to leukapheresis; tyrosine kinase inhibitor (TKI) (e.g. erlotinib, gefitinib) and any other anti-cancer treatment within 1 week prior to leukapheresis; Investigational treatment within 4 weeks prior to leukapheresis; Experimental anti-cancer vaccine within 2 months prior to leukapheresis in the absence of response or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months prior to leukapheresis; Any prior gene therapy using an integrating vector.
  • Toxicity from previous anti-cancer therapy that has not recovered to <=Grade 1 prior to enrollment (except for non-clinically significant toxicities, e.g., alopecia, vitiligo). Subjects with existing pneumonitis as a result of radiation are not excluded; however, subjects cannot be oxygen dependent.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, or other agents used in the study.
  • Subject has central nervous system (CNS) metastases except if, on a case by case basis after risk-benefit evaluation in consultation with the Sponsor Medical Monitor or designee (all below points apply): Low CNS disease burden; Asymptomatic; Clinically stable; No history of bleeding within CNS metastases; No lesions in the brain stem; Not requiring escalating anti-epileptic treatment; Not requiring treatment with steroids; Not treated with whole brain radiotherapy within the prior 4 weeks; Not with leptomeningeal disease or carcinomatous meningitis. Note: Treatment with focal radiotherapy may be allowed (for example, gamma knife radiosurgery) with at least 2-week wash-out period
  • Subject has active brain metastases or leptomeningeal metastases. Subjects with prior history of brain metastasis who have undergone local therapy (i.e., metastatectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to Screening are eligible.
  • Investigational treatment within 4 weeks prior to leukapheresis; experimental anti-cancer vaccine within 2 months prior to leukapheresis in the absence of response or in the opinion of the Investigator is responding to an experimental vaccine given within 6 months prior to leukapheresis; any prior gene therapy using an integrating vector.
  • History of chronic or recurrent (within the last year prior to enrollment) severe autoimmune or active immune-mediated disease requiring steroids or other immunosuppressive treatments.
  • Subject has active brain metastases or leptomeningeal metastases. Subjects with prior history of brain metastasis who have undergone local therapy (i.e., metastasectomy and/or radiation) and show no evidence of local recurrence or progression over the past 3 months prior to Screening are eligible.
  • Other active malignancies besides NSCLC within 3 years prior to Screening. Exceptions: adequately treated malignancies not likely to require therapy (e.g., completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma). Subjects must be in complete remission from prior malignancy in order to be eligible to enter the study.
  • Unintended weight loss >10% in 6 months preceding study entry.
  • Corrected QT interval (QTc) >450 milliseconds (msec) or QTc >480 msec for subjects with Bundle Branch Block (BBB).
  • Uncontrolled intercurrent illness including, but not limited to: a) Ongoing or active infection; b) Clinically significant cardiac disease defined by chronic heart failure (CHF) New York Heart Association (NYHA) Class >1; uncontrolled clinically significant arrhythmia in last 6 months; Acute Coronary Syndrome (ACS) (angina or myocardial infarction [MI]) in last 6 months. c) Inadequate pulmonary function with mechanical parameters <40% predicted (forced expiratory volume in one second [FEV1], forced vital capacity [FVC], total lung capacity [TLC], diffusing capacity of the lungs for carbon monoxide [DLCO]). d) Interstitial lung disease (subjects with existing pneumonitis as a result of radiation are not excluded, however, subjects cannot be oxygen dependent).
  • Subjects who in the opinion of the Investigator will be unlikely to fully comply with protocol requirements.
  • Active infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) or human T-cell lymphotropic virus (HTLV) as minimally defined below: a) Positive serology for HIV. b) Active hepatitis B infection as determined by hepatitis B surface antigen. c) Active hepatitis C infection as determined by hepatitis C RNA; A subject who is HCV antibody positive will be screened for HCV ribonucleic acid (RNA) by any reverse transcriptase (RT) polymerase chain reaction (PCR) or bDNA assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value. d) Positive serology for HTLV 1 or 2.
  • Subject is pregnant or breastfeeding. Furthermore and prior to lymphodepleting chemotherapy, a subject meeting the following criteria is not eligible for participation in the study: 1) Subject has received: Cytotoxic chemotherapy within 3 weeks prior to lymphodepleting chemotherapy; Immune therapy (including monoclonal antibody therapy, checkpoint inhibitors) or biological therapy within 4 weeks prior lymphodepleting chemotherapy; Corticosteroids or any other immunosuppressive therapy within 2 weeks prior to lymphodepleting chemotherapy; Tyrosine kinase inhibitor (e.g. erlotinib, gefitinib) and any other anti-cancer treatment within 1 week prior to lymphodepleting chemotherapy; Major surgery within 4 weeks prior to lymphodepleting chemotherapy; subjects must have recovered from any surgical-related toxicities in the opinion of the Investigator; Radiotherapy that involves the lung or mediastinum within 3 months prior to lymphodepleting chemotherapy; however, electron beam radiotherapy to superficial structures in the chest is permitted.

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): NCT02588612


Locations
United States, Florida
GSK Investigational Site
Tampa, Florida, United States, 33612
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02588612     History of Changes
Other Study ID Numbers: 208749
ADP-0011-004 ( Other Identifier: Adaptimmune Therapeutics )
First Posted: October 28, 2015    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
Immuno-oncology
Cell Therapy
NY-ESO-1
T Cell Therapy
Previously Treated
T Cell Receptor

Additional relevant MeSH terms:
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites