Clinical Trials /

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

NCT02992743

Description:

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

Related Conditions:
  • Myxoid Liposarcoma
  • Round Cell Liposarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
  • Official Title: A Pilot Study of NY-ESO-1c259T Cells in Subjects With Advanced Myxoid/ Round Cell Liposarcoma

Clinical Trial IDs

  • ORG STUDY ID: 208469
  • SECONDARY ID: ADP-0011-007
  • NCT ID: NCT02992743

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
letetresgene autoleucel (GSK3377794)letetresgene autoleucel (GSK3377794)
Cyclophosphamideletetresgene autoleucel (GSK3377794)
Fludarabineletetresgene autoleucel (GSK3377794)

Purpose

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

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.
    

Trial Arms

NameTypeDescriptionInterventions
letetresgene autoleucel (GSK3377794)ExperimentalEligible 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.
  • letetresgene autoleucel (GSK3377794)
  • Cyclophosphamide
  • Fludarabine

Eligibility 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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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

Measure:Overall Response Rate (ORR) per RECIST version 1.1 criteria by independent review
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Time to response (TTR)
Time Frame:Up to 1 year
Safety Issue:
Description:Time to Response is defined as the interval between T-cell infusion to the initial date of the confirmed response.
Measure:Duration of response (DOR)
Time Frame:Up to 1 year
Safety Issue:
Description:Duration of response is defined as the interval between the initial date of the confirmed response to the date of progressive disease or death.
Measure:Progression Free Survival (PFS)
Time Frame:Up to 1 year
Safety Issue:
Description: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.
Measure:Number of participants with adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs).
Time Frame:Up to 1 year
Safety Issue:
Description:AEs, SAEs, and AESIs will be collected.
Measure:Number of participants with clinically significant changes in hematology and clinical chemistry
Time Frame:Up to 1 year
Safety Issue:
Description:Blood samples will be collected for assessment of hematology and clinical chemistry.
Measure:Number of participants with replication competent lentivirus (RCL)
Time Frame:Upto 1 year
Safety Issue:
Description:RCL exposure will be assessed by polymerase chain reaction (PCR) based assay
Measure:Number of participants with insertional oncogenesis
Time Frame:Upto 1 year
Safety Issue:
Description:Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood
Measure:Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel
Time Frame:Up to 1 year
Safety Issue:
Description:Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
Measure:Maximum transgene expansion (Cmax) of letetresgene autoleucel
Time Frame:Up to 1 year
Safety Issue:
Description:Blood samples will be collected to measure Cmax
Measure:Time to Cmax (Tmax)
Time Frame:Up to 1 year
Safety Issue:
Description:Blood samples will be collected to measure Tmax
Measure:Area under the time curve from zero to time t AUC(0-t) of letetresgene autoleucel
Time Frame:Up to 1 year
Safety Issue:
Description:Blood samples will be collected to measure AUC (0-t)
Measure:Number of participants with abnormal electrocardiogram (ECG) parameters
Time Frame:Up to 1 year
Safety Issue:
Description:Participants with abnormal ECG parameters will be assessed.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Myxoid/ round cell liposarcoma
  • Letetresgene autoleucel
  • Immuno-oncology
  • T Cell Receptor
  • Leukapheresis
  • NY-ESO-1
  • Adoptive TCR T-cell therapy

Last Updated

July 30, 2021