Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma
Study Details
Study Description
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 |
|---|---|---|
|
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.
Study Design
Arms and Interventions
| 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.
|
Outcome Measures
Primary Outcome Measures
- Overall Response Rate (ORR) per response evaluation criteria in solid tumors (RECIST) version 1.1 criteria by investigator assessment [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
- Overall Response Rate (ORR) per RECIST version 1.1 criteria by independent review [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.
- Time to response (TTR) [Up to 1 year]
Time to Response is defined as the interval between T-cell infusion to the initial date of the confirmed response.
- Duration of response (DOR) [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.
- Progression Free Survival (PFS) [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.
- Number of participants with adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESIs). [Up to 1 year]
AEs, SAEs, and AESIs will be collected.
- Number of participants with clinically significant changes in hematology and clinical chemistry [Up to 1 year]
Blood samples will be collected for assessment of hematology and clinical chemistry.
- Number of participants with replication competent lentivirus (RCL) [Upto 1 year]
RCL exposure will be assessed by polymerase chain reaction (PCR) based assay
- Number of participants with insertional oncogenesis [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
- Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel [Up to 1 year]
Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
- Maximum transgene expansion (Cmax) of letetresgene autoleucel [Up to 1 year]
Blood samples will be collected to measure Cmax
- Time to Cmax (Tmax) [Up to 1 year]
Blood samples will be collected to measure Tmax
- Area under the time curve from zero to time t AUC(0-t) of letetresgene autoleucel [Up to 1 year]
Blood samples will be collected to measure AUC (0-t)
- Number of participants with abnormal electrocardiogram (ECG) parameters [Up to 1 year]
Participants with abnormal ECG parameters will be assessed.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant is greater than equal to (>=)18 years of age at the time of signing the study informed consent.
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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).
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Participant has measurable disease according to RECIST v1.1 criteria.
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Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease.
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Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible.
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Participant must be HLA A02:01, HLA A02:05 and/or HLA-A*02:06 positive.
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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.
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Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1.
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Participant has a left ventricular ejection fraction >=45%.
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Participant is fit for apheresis and has adequate venous access for the cell collection.
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Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.
Exclusion Criteria:
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Any previous gene therapy using an integrating vector.
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Any previous allogeneic hematopoietic stem cell transplant.
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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.
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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.
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Participant has known active brain or leptomeningeal metastases.
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Participant has other prior malignancy that is not in complete remission.
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Participant has uncontrolled intercurrent illness including, but not limited to:
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(i) Ongoing or active infection.
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(ii) Clinically significant cardiac disease
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(iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent).
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Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Tampa | Florida | United States | 33612 |
| 2 | GSK Investigational Site | Ann Arbor | Michigan | United States | 48109 |
| 3 | GSK Investigational Site | Saint Louis | Missouri | United States | 63110 |
| 4 | GSK Investigational Site | New York | New York | United States | 10065 |
| 5 | GSK Investigational Site | Columbus | Ohio | United States | 43210 |
| 6 | GSK Investigational Site | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 208469
- ADP-0011-007