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

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Neoplasms

Treatments: Drug: Cyclophosphamide; Drug: letetresgene autoleucel (GSK3377794); Drug: Fludarabine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02992743

ADP-0011-007 (Other Identifier)

208469

Details and patient eligibility

About

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

Full 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.

Enrollment: 23 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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23 participants in 1 patient group

letetresgene autoleucel (GSK3377794)

Experimental group

Description:

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.

Treatment:

Drug: Cyclophosphamide

Drug: letetresgene autoleucel (GSK3377794)

Drug: Fludarabine