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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 : April 11, 2018
Sponsor:
Information provided by (Responsible Party):
Adaptimmune

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 HLA-A*0201, HLA-A*205 and/or HLA-A*0206 protein and a tumor test positive for NY-ESO-1 expression (protein or gene). 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
Carcinoma, Non-Small-Cell Lung Genetic: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T Phase 1 Phase 2

Detailed Description:

This is a single-arm study of genetically engineered NY-ESO-1ᶜ²⁵⁹T cells in HLA-A*0201, HLA-A*0205 and/or HLA-A*0206 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 on Day -7, Day -6 and Day -5 followed by the cell infusion on Day 1.

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)
Study Start Date : November 2015
Estimated Primary Completion Date : January 2019
Estimated Study Completion Date : January 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T Genetic: Autologous Genetically modified T cells, NY-ESO-1ᶜ²⁵⁹T



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; laboratory assessments, including chemistry, hematology, coagulation and anti-NY-ESO-1ᶜ²⁵⁹T antibodies; cardiac and pulmonary assessments, including ECG and pulmonary function (pulse oximetry) , persistence of NY-ESO-1ᶜ²⁵⁹T, and circulating cytokines.


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 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 documented evidence of SD 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 stable disease

  5. 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

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


Other Outcome Measures:
  1. Correlation of NY-ESO-1ᶜ²⁵⁹T persistence, phenotype and functionality with response to treatment [ Time Frame: 24 months ]
    Flow cytometry will be used to assess the phenotype of transduced T cells in the manufactured product and in post-infusion samples.

  2. Investigation of antigen loss (NY-ESO-1) as an escape mechanism [ Time Frame: 24 months ]
    Assessment of expression of NY-ESO-1 in tumor samples after T cell infusion

  3. Correlation of clonal outgrowth of T cell populations with response following T cell infusion [ Time Frame: 24 months ]
    Assessment of the polyclonality status of the T cell population in peripheral blood (and tumor samples, if available) by TCR sequencing



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject has voluntarily agreed to participate by giving written informed consent
  2. Subject is ≥18 years of age
  3. Histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease. Subjects with known EGFR mutations or ALK or ROS1 gene rearrangements must have also failed prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively (PD or unacceptable toxicity). Subjects may have received PD-1 or PDL-1 inhibitors. There is no limit on lines of prior anti-cancer therapy.
  4. Measurable disease according to RECIST 1.1 criteria.
  5. Subject must be HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive.
  6. Subject's tumor (either an archival specimen or a fresh biopsy if archival tissue is unavailable) has been pathologically reviewed by a designated central laboratory confirming NY-ESO-1 and/or LAGE-1a expression.
  7. ECOG Performance Status 0-1 and anticipated life expectancy > 3 months.
  8. All subjects must have left ventricular ejection fraction ≥50%.
  9. Subject is fit for leukapheresis and has adequate venous access for the cell collection.
  10. Female subjects of childbearing potential (FPCP) must have a negative urine or serum pregnancy test. NOTE: FPCP is defined as premenopausal and not surgically sterilized. FPCP must agree to use maximally effective birth control or to abstain from heterosexual activity throughout the study, starting at the first dose of chemotherapy through 12 months after the infusion of cells and/or for 4 months after there is no evidence of persistence/gene modified cells in the blood, whichever is longer. Effective contraceptive methods include intra-uterine device, oral and/or injectable hormonal contraception, or 2 adequate barrier methods (e.g. diaphragm with spermicide, cervical cap with spermicide, or female condom with spermicide). Spermicides alone are not an adequate method of contraception.

    Or Male subjects must be surgically sterile or agrees to use a double barrier contraception method or abstain from heterosexual activity with a female of childbearing potential upon enrolment starting at the first dose of chemotherapy through and for 4 months thereafter or longer (if indicated in the country specific monograph/label for cyclophosphamide.

  11. Subject must have adequate organ function as indicated by the following laboratory values in the table below:

    • Absolute Neutrophil count (ANC) ≥1.0 x10⁹/L (without G-CSF support)
    • Platelets ≥ 75 x10⁹/L
    • Hemoglobin >80 g/dL (without transfusion support within 7 days from start of leukapheresis)
    • Prothrombin Time or INR ≤1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation.
    • Partial Thromboplastin Time (PTT) ≤1.5x upper limit of normal (ULN) unless receiving therapeutic anticoagulation.
    • Calculated or measured creatinine clearance ≥ 40 mL/min
    • Serum total bilirubin ≤1.5 x ULN (unless subject had documented Gilbert's Syndrome)
    • Alanine aminotransferase (ALT)/Serum Glutamic Pyruvic Transaminase (SGPT) ≤2.5x ULN

Exclusion Criteria:

  1. Subject who has had cytotoxic chemotherapy within 3 weeks prior to leukapheresis; immune therapy or biological therapy within 4 weeks prior to leukapheresis; 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.
  2. 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.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to cyclophosphamide, fludarabine, or other agents used in the study.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Unintended weight loss >10% in 6 months preceding study entry.
  9. Electrocardiogram (ECG) showing clinically significant abnormality at Screening or showing an average QTc interval ≥450 msec in males and ≥470 msec in females (≥480 msec for subjects with Bundle Branch Block (BBB) over 3 consecutive ECGs).
  10. Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection;
    • Clinically significant cardiac disease defined by CHF New York Heart Association (NYHA) Class > 1; uncontrolled clinically significant arrhythmia in last 6 months; Acute Coronary Syndrome (ACS) (angina or MI) in last 6 months.
    • Inadequate pulmonary function with mechanical parameters < 40% predicted (FEV1, FVC, TLC, DLCO).
    • 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.
    • Clinically significant psychiatric illness/social situations that would limit compliance with study requirements.
  11. Active infection with HIV, HBV, HCV or HTLV as minimally defined below:

    • Positive serology for HIV.
    • Active hepatitis B infection as determined by hepatitis B surface antigen.
    • Active hepatitis C infection as determined by hepatitis C RNA; A subject who is HCV antibody positive will be screened for HCV RNA by any RT polymerase chain reaction (PCR) or bDNA assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value.
    • Positive serology for HTLV 1 or 2.

Furthermore and prior to lymphodepleting chemotherapy, a subject meeting the following criteria is not eligible for participation in the study:

  1. Subject who has had cytotoxic chemotherapy within 3 weeks prior to lymphodepleting chemotherapy; immune therapy (including monoclonal antibody therapy, checkpoint inhibitors or biological therapy within 4 weeks prior to lymphodepleting chemotherapy; corticosteroids or any other immunosuppressive therapy within 2 weeks prior to lymphodepleting chemotherapy; tyrosine kinase inhibitor (TKI) (e.g. erlotinib, gefitinib) within 1 week prior to lymphodepleting chemotherapy.
  2. Radiotherapy that involves the lung or mediastinum within 3 months prior to chemotherapy. (Note: there is no washout period for palliative radiation to non-target organs other than the lung or mediastinum. If radiation was to an intended target lesion within 3 months of baseline imaging studies, and the lesion is progressing within this time frame it may be considered as a target lesion after review and discussion with the Sponsor.)

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, California
City of Hope
Duarte, California, United States, 91010
United States, Florida
University of Miami, Sylvester Comprehensive Cancer Center
Miami, Florida, United States, 33136
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Maryland
University of Maryland, Greenebaum Cancer Center
Baltimore, Maryland, United States, 21157
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, Missouri
Washington University, School of Medicine
Saint Louis, Missouri, United States, 63110
United States, Tennessee
Tennessee Oncology- Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Adaptimmune
Investigators
Principal Investigator: John Heymach, MD, PhD M.D. Anderson Cancer Center

Responsible Party: Adaptimmune
ClinicalTrials.gov Identifier: NCT02588612     History of Changes
Other Study ID Numbers: ADP-0011-004
First Posted: October 28, 2015    Key Record Dates
Last Update Posted: April 11, 2018
Last Verified: April 2018

Studies a U.S. FDA-regulated Drug Product: Yes

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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases