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MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02592577
Recruitment Status : Active, not recruiting
First Posted : October 30, 2015
Last Update Posted : May 7, 2020
Sponsor:
Information provided by (Responsible Party):
Adaptimmune

Tracking Information
First Submitted Date  ICMJE October 20, 2015
First Posted Date  ICMJE October 30, 2015
Last Update Posted Date May 7, 2020
Actual Study Start Date  ICMJE November 2015
Actual Primary Completion Date March 11, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 5, 2020)
Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) [ Time Frame: 24 months ]
Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; cardiac and pulmonary assessments, including ECG and troponin.
Original Primary Outcome Measures  ICMJE
 (submitted: October 29, 2015)
Number of subjects with dose-limiting toxicity (DLT) and adverse events (AE), including serious adverse events (SAE) [ Time Frame: 24 months ]
Determine if treatment with autologous genetically modified T cells, (MAGE A10ᶜ⁷⁹⁶T ) is safe and tolerable through assessment of DLTs, AEs, including SAEs; laboratory assessments, including chemistry, hematology, and coagulation; and cardiac assessments, including ECG and ECHO/MUGA
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 5, 2020)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Best Overall Response (BOR) [ Time Frame: 24 months ]
    Best Overall Response (BOR), defined as the best response recorded from the date of T cell infusion until disease progression
  • To evaluate potential gene therapy-related delayed adverse events for 15 years post infusion. [ Time Frame: 15 years ]
    Presence of any of the following LTFU AEs:
    • New malignancies
    • New incidence or exacerbation of a pre-existing neurologic disorder
    • New incidence or exacerbation of a prior rheumatologic or other autoimmune disorder
    • New incidence of a hematologic disorder
    • Opportunistic and/or serious infections
    • Unanticipated illness and/or hospitalization deemed related to gene modified cell therapy Persistence of MAGE-A10c796T and replication-competent lentivirus (RCL) over time.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2015)
  • 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 irRC and RECIST v1.1
  • Percentage of subjects who have a CR, PR, and stable disease (SD) at 16 weeks [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment by assessment of the Clinical Benefit Rate according to irRC and RECIST v1.1
  • 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
  • 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
  • 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
  • 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
  • Interval between the date of first T cell infusion and date of death due to any cause [ Time Frame: 24 months ]
    Evaluation of the efficacy of the treatment by assessment of overall survival
  • Evaluation of the persistence of genetically modified T cells [ Time Frame: 24 months ]
    Evaluation of the persistence of the infused T cells in the periphery
  • Mean fluorescence intensity (expression) of specific surface markers on gene-modified T cells [ Time Frame: 24 months ]
    Killing profile and cytokine profile of genetically modified T cells will be evaluated using flow cytometry.
  • Percentage of total gene modified T cells with memory subtype [ Time Frame: 24 months ]
    Memory phenotype of genetically modified T cells will be evaluated using flow cytometry.
  • Percentage of total gene modified T cells with exhaustion marker expression [ Time Frame: 24 months ]
    Exhaustion profile of genetically modified T cells will be evaluated using flow cytometry
  • Evaluation of MAGE A10 expression pre and post infusion using IHC [ Time Frame: 24 months ]
    MAGE A10 will be assessed in tumor biopsies taken at baseline, Week 8 and at the time of disease progression by measuring frequency (percentage of positive cells) and intensity of expression (e.g. 1+, 2+, 3+). The results will be correlated to clinical outcome.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: October 29, 2015)
  • Correlation of candidate biomarkers with clinical response to treatment [ Time Frame: 24 months ]
    Biomarkers will be assessed in tumor biopsies taken at baseline, Week 8 and at the time of disease progression, and in peripheral blood by protein or gene expression analysis. Leukocyte infiltration (percentage); tumor microenvironment markers (expression level); epitope spreading (length and number of unique T cell CDR3 sequences); function and phenotype of TILs and gene-modified T cells will be assessed. The results will be correlated to clinical outcome.
  • Evaluation of cytokine levels. [ Time Frame: 24 months ]
    Analysis of serum cytokine levels taken before and after T cell infusion
  • Evaluation of germline polymorphisms in IL-6, TNF-α, IL-10, INF-γ and TGF-β and their association with cytokine release syndrome [ Time Frame: 24 months ]
    Assessment of germline polymorphisms in the listed cytokines though analysis of peripheral blood sample
 
Descriptive Information
Brief Title  ICMJE MAGE A10ᶜ⁷⁹⁶T for Advanced NSCLC
Official Title  ICMJE A Phase I Dose Escalation Open Label Clinical Trial Evaluating the Safety and Efficacy of MAGE A10ᶜ⁷⁹⁶T in Subjects With Stage IIIb or Stage IV Non-Small Cell Lung Cancer (NSCLC)
Brief Summary

This first time in human 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*02:01 and/or HLA-A*02:06 and a tumor test positive for MAGE A10 protein expression (protein or gene). This trial is a dose escalation trial that will evaluate 3 doses of transduced cells administered after a lymphodepleting chemotherapy regimen using a 3+3 dose escalation design .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.

When the MAGE A10ᶜ⁷⁹⁶T cells are available, subjects will receive lymphodepleting chemotherapy with cyclophosphamide and fludarabine, followed by the T cell 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. The study will evaluate three different cell dose levels in order to find out the target cell dose. Once the target cell dose is determined, additional subjects will be enrolled to further test the safety and effects at this cell dose.

Subjects will be seen frequently by the Study Physician right after receiving their T cells back and up to first 6 months. After that, subjects will be seen every three months. 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. Subjects who have a confirmed response or clinical benefit ≥4 weeks after the first T-cell 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 Phase 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-Small Cell Lung Cancer
  • Carcinoma
Intervention  ICMJE Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T
Study Arms  ICMJE Experimental: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T
Intervention: Biological: Autologous Genetically modified T cells, MAGEA10ᶜ⁷⁹⁶T
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 6, 2017)
28
Original Estimated Enrollment  ICMJE
 (submitted: October 29, 2015)
32
Estimated Study Completion Date  ICMJE December 2034
Actual Primary Completion Date March 11, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  1. Subject has histologically or cytologically confirmed diagnosis of advanced non-small cell lung cancer (stage IIIB or IV) or recurrent disease
  2. Subject has received at least one line of prior therapy
  3. Subjects with known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase receptor (ALK) or ROS1 gene rearrangements must have failed (progressive disease or unacceptable toxicity) at least one prior EGFR or ALK or ROS1 tyrosine kinase inhibitor, respectively. Subject may have received PD-1 or PDL-1 inhibitors and or chemotherapy. There is no limit on lines of prior anti-cancer therapy (a washout period applies for recent anti-cancer treatments).
  4. Subject has measurable disease according to RECIST v1.1 criteria prior to lymphodepletion.
  5. Subject is HLA-A*02:01 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 MAGE-A10 expression.
  7. Subject has an ECOG Performance Status 0-1 and anticipated life expectancy >6 months prior to apheresis and >3 months prior to lymphodepletion.
  8. Subject is ≥18 to ≤75 years of age
  9. Adequate organ function

Key Exclusion Criteria:

  1. Subject is HLA-A*02:05, HLA-B*15:01 and/or HLA-B*46:01 positive.
  2. 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.
  3. Subject has symptomatic CNS metastases. Subjects with prior history of symptomatic CNS metastasis must have received treatment and be neurologically stable for at least 1 month prior to leukapheresis and lymphodepletion.
  4. Active malignancy besides NSCLC within 3 years prior to screening.
  5. Uncontrolled intercurrent illness including, but not limited to:

    • Ongoing or active infection;
    • Clinically significant cardiac disease
    • Inadequate pulmonary function
    • Interstitial lung disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02592577
Other Study ID Numbers  ICMJE ADP 0022-003
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Adaptimmune
Study Sponsor  ICMJE Adaptimmune
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Ben Creelan, MD, MS H. Lee Moffitt Cancer Center
PRS Account Adaptimmune
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP