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

NCT06703346 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 208467 Substudy 2
• Study Type: interventional
• Target: 87
• 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

Outcome Measures

Primary Outcomes (1)

• ORR (Overall Response Rate)

  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 (14)

• DCR (Disease Control Rate)

  Up to approximately 36 months

• PFS (Progression Free Survival)

  Up to approximately 54 months

• OS (Overall survival)

  up to 15 years post-T-cell infusion

• DOR (Duration of response)

  Up to approximately 54 months

• TTR (Time to response)

  Up to approximately 54 months

Study Arms (1)

Letetresgene autoleucel

EXPERIMENTAL

Drug: Letetresgene autoleucel (Lete-Cel (GSK3377794)); Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

Letetresgene autoleucel (Lete-Cel (GSK3377794)) DRUG

Letetresgene autoleucel will be administered

Letetresgene autoleucel

Cyclophosphamide DRUG

Cyclophosphamide will be used as a lymphodepleting chemotherapy

Letetresgene autoleucel

Fludarabine DRUG

Fludarabine will be used as a lymphodepleting chemotherapy

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 ≥10 years of age at the time of signing the informed consent.
• Participant scheduled to receive clinical drug product supply must also weigh ≥40 kg.
• Participant has a diagnosis of synovial sarcoma or myxoid/round cell liposarcoma, confirmed by local histopathology with evidence of disease-specific translocation.
• Participant has advanced (metastatic or unresectable) synovial sarcoma or myxoid/round cell liposarcoma. Unresectable refers to a tumor lesion in which clear surgical excision margins cannot be obtained without leading to significant functional compromise.
• Male or female. Contraception requirements will apply at the time of leukapharesis and treatment.
• Life expectancy ≥24 weeks
• Participant has confirmed evidence of a relevant disease-specific translocation per below:
• For synovial sarcoma, presence of a translocation involving chromosome 18 (SYT gene) and/or chromosome X (SSX1, SSX2 or SSX4 genes).
• For myxoid/round cell liposarcoma, presence of a translocation involving chromosome 12 (DDIT3 gene) and/or chromosome 16 (FUS gene) and/or chromosome 22 (EWSR1 gene).
• Participant is either currently being treated with or has completed at least one standard-of-care treatment including anthracycline-containing regimens (e.g., doxorubicin alone, doxorubicin with ifosfamide) for advanced (metastatic or inoperable) disease. Participants who are intolerant to anthracycline may receive ifosfamide alone unless intolerant to or ineligible to receive ifosfamide. Participants who received anthracycline-based therapy in the neoadjuvant/adjuvant setting and progressed will be eligible.
• Participant must be positive for HLA-A\*02:01, HLA-A\*02:05, and/or HLA-A\*02:06 alleles by a validated test in a designated central lab prior to leukapheresis
• Participant's tumor has been pathologically reviewed by a designated central laboratory with confirmed positive NY-ESO-1 expression defined as ≥30% of cells that are 2+ or 3+ by immunohistochemistry.
• Left ventricular ejection fraction ≥45% with no evidence of clinically significant pericardial effusion.
• Performance status: for participants \<16 years of age, Lansky \>60, or for participants ≥16 and \<18 years of age, Karnofsky \>60, or for participants ≥18 years of age, Eastern Cooperative Oncology Group (ECOG) of 0-1.
• Participant must have adequate organ function and blood cell counts, within 7 days prior to the day of the leukapheresis procedure

You may not qualify if:

• Central nervous system (CNS) metastases.
• Any other prior malignancy that is not in complete remission.
• 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
• 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) or prior or active demyelinating disease
• Participant has received cytotoxic therapy within 3 weeks prior to lymphodepleting chemotherapy
• Systemic corticosteroids or any other immunosuppressive therapy within 2 weeks prior to lymphodepleting chemotherapy.
• Participant has received ≥50 Gy to a significant volume of the pelvis, long bones or spine, or a cumulative dose of radiation that, in the Investigator's opinion would predispose patients to prolonged cytopenia after lymphodepletion.
• All of the participant's measurable lesions have been irradiated within 3 months prior to lymphodepletion. An irradiated measurable lesion with unequivocal progression following irradiation may be considered a target lesion regardless of time from last radiotherapy dose.
• Participant has received an anti-cancer vaccine within 2 months in the absence of tumor response. The participant should be excluded if their disease is responding to an experimental vaccine given within 6 months.
• Participant has received live vaccine within 4 weeks prior to lymphodepletion or intends to receive live vaccine during the 3-month period following administration of lete-cel.
• Participant has received immune therapy (monoclonal antibody therapy, checkpoint inhibitors) within 4 weeks of lymphodepletion.
• Participant had major surgery ≥28 days of first dose of study intervention

Sponsors & Collaborators

• USWM CT, LLC: 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

Sarah Cannon Research Institute

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

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

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

Montreal, Quebec, H1T 2M4, 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, Lombardy, 20133, Italy

Location

Ircss Istituto Clinico Humanitas

Rozzano (MI), Lombardy, 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

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

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: November 21, 2024
• First Posted: November 25, 2024
• Study Start: December 31, 2019
• Primary Completion: March 1, 2024
• Study Completion (Estimated): July 31, 2026
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

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