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

NCT02992743 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 208469ADP-0011-007
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

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.

Conditions

Neoplasms

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

  Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.

  Up to 24 months

• Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment

  The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response \[CR\] \> Confirmed Partial Response \[PR\] \> Stable Disease \[SD\] \> Progressive Disease \[PD\] \> Not Evaluable \[NE\]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST v1.1 Criteria.

  Up to 24 months

Secondary Outcomes (20)

• Time to Response (TTR) Assessed by Investigator

  Up to 24 months

• Duration of Response (DOR) Assessed by Investigator

  Up to 24 months

• Progression Free Survival (PFS) Assessed by Investigator

  Up to 24 months

• Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment

  Up to 24 months

• Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer

  Up to 24 months

Study Arms (1)

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.

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

Interventions

letetresgene autoleucel (GSK3377794) DRUG

Letetresgene autoleucel (GSK3377794) as an IV infusion.

letetresgene autoleucel (GSK3377794)

Cyclophosphamide DRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

letetresgene autoleucel (GSK3377794)

Fludarabine DRUG

Fludarabine will be used as a lymphodepleting chemotherapy.

letetresgene autoleucel (GSK3377794)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Tampa, Florida, 33612, United States

Location

GSK Investigational Site

Ann Arbor, Michigan, 48109, United States

Location

GSK Investigational Site

St Louis, Missouri, 63110, United States

Location

GSK Investigational Site

New York, New York, 10065, United States

Location

GSK Investigational Site

Columbus, Ohio, 43210, United States

Location

GSK Investigational Site

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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.

  PMID: 39836945 DERIVED

MeSH Terms

Conditions

Neoplasms; Liposarcoma, Myxoid

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Liposarcoma; Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Sarcoma

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2016
• First Posted: December 14, 2016
• Study Start: December 6, 2016
• Primary Completion: November 1, 2021
• Study Completion: March 22, 2022
• Last Updated: April 11, 2023
• Results First Posted: November 28, 2022

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

US (6)