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.
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
Interventions
Drug | Synonyms | Arms |
---|
letetresgene autoleucel (GSK3377794) | | letetresgene autoleucel (GSK3377794) |
Cyclophosphamide | | letetresgene autoleucel (GSK3377794) |
Fludarabine | | letetresgene 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
Name | Type | Description | Interventions |
---|
letetresgene autoleucel (GSK3377794) | Experimental | 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. | - 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