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Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma

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ClinicalTrials.gov Identifier: NCT02992743
Recruitment Status : Active, not recruiting
First Posted : December 14, 2016
Last Update Posted : October 18, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: letetresgene autoleucel (GSK3377794) Drug: Cyclophosphamide Drug: Fludarabine Phase 2

Detailed Description:
New York esophageal antigen-1 (NY-ESO-1) and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types. Clinical trials using adoptively transferred T-cells directed against NY-ESO-1/LAGE-1a have shown objective responses. Letetresgene autoleucel (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study of NY-ESO-1c259T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma
Actual Study Start Date : December 6, 2016
Estimated Primary Completion Date : November 1, 2021
Estimated Study Completion Date : August 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: letetresgene autoleucel (GSK3377794)
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Drug: letetresgene autoleucel (GSK3377794)
Letetresgene autoleucel (GSK3377794) as an IV infusion.

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

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




Primary Outcome Measures :
  1. Overall Response Rate (ORR) per response evaluation criteria in solid tumors (RECIST) version 1.1 criteria by investigator assessment [ Time Frame: Up to 1 year ]
    ORR is defined as the proportion of participants with a confirmed complete response (CR) or partial response (PR) per RECIST version 1.1 criteria by investigator assessment relative to the total number of participants in the analysis population.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) per RECIST version 1.1 criteria by independent review [ Time Frame: Up to 1 year ]
    ORR is defined as the proportion of participants with a confirmed CR or PR per RECIST version 1.1 criteria by independent review relative to the total number of participants in the analysis population.

  2. Time to response (TTR) [ Time Frame: Up to 1 year ]
    Time to Response is defined as the interval between T-cell infusion to the initial date of the confirmed response.

  3. Duration of response (DOR) [ Time Frame: Up to 1 year ]
    Duration of response is defined as the interval between the initial date of the confirmed response to the date of progressive disease or death.

  4. Progression Free Survival (PFS) [ Time Frame: Up to 1 year ]
    Progression free survival is defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause.

  5. Number of participants with adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). [ Time Frame: Up to 1 year ]
    AEs, SAEs, and AESIs will be collected.

  6. Number of participants with clinically significant changes in hematology and clinical chemistry [ Time Frame: Up to 1 year ]
    Blood samples will be collected for assessment of hematology and clinical chemistry.

  7. Number of participants with replication competent lentivirus (RCL) [ Time Frame: Upto 1 year ]
    RCL exposure will be assessed by polymerase chain reaction (PCR) based assay

  8. Number of participants with insertional oncogenesis [ Time Frame: Upto 1 year ]
    Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood

  9. Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel [ Time Frame: Up to 1 year ]
    Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.

  10. Maximum transgene expansion (Cmax) of letetresgene autoleucel [ Time Frame: Up to 1 year ]
    Blood samples will be collected to measure Cmax

  11. Time to Cmax (Tmax) [ Time Frame: Up to 1 year ]
    Blood samples will be collected to measure Tmax

  12. Area under the time curve from zero to time t AUC(0-t) of letetresgene autoleucel [ Time Frame: Up to 1 year ]
    Blood samples will be collected to measure AUC (0-t)

  13. Number of participants with abnormal electrocardiogram (ECG) parameters [ Time Frame: Up to 1 year ]
    Participants with abnormal ECG parameters will be assessed.



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:

  • Participant is greater than equal to (>=)18 years of age at the time of signing the study informed consent.
  • Participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12).
  • Participant has measurable disease according to RECIST v1.1 criteria.
  • Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease.
  • Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
  • Participant must be HLA A*02:01, HLA A*02:05 and/or HLA-A*02:06 positive.
  • Participant's tumor (either the most recent archival specimen or a fresh biopsy) is positive for NY-ESO-1 expression by a designated central laboratory.
  • Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
  • Participant has a left ventricular ejection fraction >=45%.
  • Participant is fit for apheresis and has adequate venous access for the cell collection.
  • Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.

Exclusion Criteria:

  • Any previous gene therapy using an integrating vector.
  • Any previous allogeneic hematopoietic stem cell transplant.
  • Participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study.
  • Participant has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments.
  • Participant has known active brain or leptomeningeal metastases.
  • Participant has other prior malignancy that is not in complete remission.
  • Participant has uncontrolled intercurrent illness including, but not limited to:
  • (i) Ongoing or active infection.
  • (ii) Clinically significant cardiac disease
  • (iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
  • Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).

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): NCT02992743


Locations
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United States, Florida
GSK Investigational Site
Tampa, Florida, United States, 33612
United States, Michigan
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109
United States, Missouri
GSK Investigational Site
Saint Louis, Missouri, United States, 63110
United States, New York
GSK Investigational Site
New York, New York, United States, 10065
United States, Ohio
GSK Investigational Site
Columbus, Ohio, United States, 43210
United States, Texas
GSK Investigational Site
Houston, Texas, United States, 77030
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02992743    
Other Study ID Numbers: 208469
ADP-0011-007 ( Other Identifier: Adaptimmune Therapeutics )
First Posted: December 14, 2016    Key Record Dates
Last Update Posted: October 18, 2021
Last Verified: October 2021
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, key secondary endpoints and safety data 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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Myxoid/ round cell liposarcoma
Letetresgene autoleucel
Immuno-oncology
T Cell Receptor
Leukapheresis
NY-ESO-1
Adoptive TCR T-cell therapy
Additional relevant MeSH terms:
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Liposarcoma
Liposarcoma, Myxoid
Neoplasms, Adipose Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Sarcoma
Cyclophosphamide
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