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

NCT ID: NCT02992743

Last Updated: 2023-04-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-12-06

Study Completion Date

2022-03-22

Brief Summary

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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

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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.

Conditions

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Neoplasms

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

letetresgene autoleucel (GSK3377794)

Intervention Type DRUG

Letetresgene autoleucel (GSK3377794) as an IV infusion.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Fludarabine

Intervention Type DRUG

Fludarabine will be used as a lymphodepleting chemotherapy.

Interventions

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letetresgene autoleucel (GSK3377794)

Letetresgene autoleucel (GSK3377794) as an IV infusion.

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Intervention Type DRUG

Fludarabine

Fludarabine will be used as a lymphodepleting chemotherapy.

Intervention Type DRUG

Eligibility Criteria

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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).
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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GlaxoSmithKline

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

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GSK Investigational Site

Tampa, Florida, United States

Site Status

GSK Investigational Site

Ann Arbor, Michigan, United States

Site Status

GSK Investigational Site

St Louis, Missouri, United States

Site Status

GSK Investigational Site

New York, New York, United States

Site Status

GSK Investigational Site

Columbus, Ohio, United States

Site Status

GSK Investigational Site

Houston, Texas, United States

Site Status

Countries

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United States

References

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D'Angelo SP, Druta M, Van Tine BA, Liebner D, Schuetze SM, Tap WD, Preston J, Goodison S, D'Souza JW, Kapoor GS, Suchindran S, Zajic S, Bhaskar A, Kaczynski H, Kim J, Klohe E, Corigliano E, Eleftheriadou I, Nathenson MJ, Somaiah N. Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma. J Clin Oncol. 2025 May 20;43(15):1777-1788. doi: 10.1200/JCO-24-01466. Epub 2025 Jan 21.

Reference Type DERIVED
PMID: 39836945 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ADP-0011-007

Identifier Type: OTHER

Identifier Source: secondary_id

208469

Identifier Type: -

Identifier Source: org_study_id

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