Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

NCT05993299 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: 208467 Substudy 1
• Study Type: interventional
• Target: 7
• Locations: 7 countries
• Sites: 38

Brief Summary

This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors. This trial is a sub study of the Master study NCT03967223.

Conditions

Neoplasms

Keywords

Adoptive T-cell therapy; Letetresgene autoleucel; Lete-cel; GSK3377794

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR is defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. CR is defined as 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). PR is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change from baseline). 95% CI is based on Clopper-Pearson exact confidence interval.

  Up to approximately 36 months

Secondary Outcomes (13)

• Time to Response (TTR)

  Up to approximately 54 months

• Duration of Response (DOR)

  Up to approximately 54 months

• Disease Control Rate (DCR)

  Up to approximately 36 months

• Progression Free Survival (PFS)

  Up to approximately 54 months

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)

  Up to approximately 54 months

Study Arms (1)

Letetresgene autoleucel

EXPERIMENTAL

Drug: Letetresgene autoleucel; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Cyclophosphamide DRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy.

Letetresgene autoleucel

Fludarabine DRUG

Fludarabine will be used as a lymphodepleting chemotherapy.

Letetresgene autoleucel

Letetresgene autoleucel DRUG

Letetresgene autoleucel will be administered.

Letetresgene autoleucel

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be greater than or equal to 10 years of age on the day of signing informed consent.
• Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg
• Participant must be positive for HLA-A\*02:01, HLA-A\*02:05, and/or HLA-A\*02:06 alleles by a designated central laboratory
• Participant's tumor is positive for NY-ESO-1 expression by a designated central laboratory.
• Participant has a diagnosis of synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS)
• Performance status: dependent on age - Lansky \> 60, Karnofsky \> 60, Eastern
• Cooperative Oncology Group 0-1.
• Participant must have adequate organ function and blood cell counts, within 7 days prior to leukapheresis.
• At time of treatment, participant has measurable disease according to RECIST v1.1.
• Male or female. Contraception requirements will apply at the time of leukapheresis and treatment.
• Consultation for prior history per protocol specifications.

You may not qualify if:

• Central nervous system metastases.
• Any other prior malignancy that is not in complete remission.
• Clinically significant systemic illness (.(Serious active infections or significant cardiac, pulmonary, hepatic or other organ dysfunction, that in the judgment of the Investigator would compromise the participant's ability to tolerate protocol therapy or significantly increase the risk of complications)
• Prior or active demyelinating disease.
• History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease (e.g. Crohn's disease, systemic lupus) requiring steroids or other immunosuppressive treatments.
• Previous treatment with genetically engineered NY-ESO-1-specific T cells.
• Previous NY-ESO-1 vaccine or NY-ESO-1 targeting antibody.
• Prior gene therapy using an integrating vector.
• Previous allogeneic hematopoietic stem cell transplant.
• Washout periods for prior radiotherapy and systemic chemotherapy must be followed.
• Participant had major surgery in less than or equal to 28 days of first dose of study intervention.
• Prior radiation exceeds protocol specified limits.

Sponsors & Collaborators

• USWM, LLC (dba US WorldMeds): lead

Study Sites (38)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford Hospital and Clinics

Stanford, California, 94305, United States

Location

Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Mayo Clinic Jacksonville

Jacksonville, Florida, 32224, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Iowa College of Medicine

Iowa City, Iowa, 52242-1009, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02114, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

University of Michigan Medical Center

Ann Arbor, Michigan, 48109, United States

Location

Minnesota Oncology Hematology

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Memorial Sloan Kettering cancer center

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Ohio State University-Columbus

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh, Hillman Cancer centre

Pittsburgh, Pennsylvania, 15232, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

University Of Texas Southwestern Medical Center

Dallas, Texas, 75390-8565, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390-9063, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109-1024, United States

Location

Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

CIUSSS de L'Est-De-Lile-De-Montreal

Montreal, Quebec, H1T 2M4, Canada

Location

Princess Margaret Cancer Centre

Toronto, M5G 2M9, Canada

Location

Centre Léon Bérard

Lyon, 69373, France

Location

CHU de Bordeaux GH Sud Hôpital Haut Lévêque

Pessac, 33604, France

Location

Fondazione IRCCS Instituto Nazionale Dei Tumori

Milan, 20133, Italy

Location

Ircss Istituto Clinico Humanitas

Romano di Lombardia, 20089, Italy

Location

The Netherlands Cancer Institute

Amsterdam, 1066 CX, Netherlands

Location

Hospital Santa Creu Y Sant Pau

Barcelona, 08025, Spain

Location

Ico Duran y Reynals l'Hospitalet de Llobrega

Hospitalet de Llobregat, Barcelona, 08907, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Virgen Del Rocio

Seville, 41013, Spain

Location

Royal Marsden Hospital

London, SW3 6JJ, United Kingdom

Location

University College Hospital-London

London, WC1E 6AG, United Kingdom

Location

Christie Hospital NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Cyclophosphamide; fludarabine

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

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: August 7, 2023
• First Posted: August 15, 2023
• Study Start: December 31, 2019
• Primary Completion: October 12, 2022
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 8, 2026
• Results First Posted: October 16, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (24); CA (2); FR (2); ES (4); NL (1); IT (2); GB (3)