Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered T Cells in NY-ESO-1 and/or LAGE-1a Positive Solid Tumors

NCT03967223 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 208467
• Study Type: interventional
• Target: 103
• 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.

Conditions

Neoplasms

Keywords

Adoptive T-cell therapy; Advanced metastatic disease; Advanced unresectable disease; Synovial sarcoma; Myxoid/round cell liposarcoma; GSK3377794; Positive solid tumors; T-cell receptors; Leukapheresis; Letetresgene autoleucel; Lete-cel

Outcome Measures

Primary Outcomes (2)

• Substudy 1: Overall response rate (ORR)

  Overall response rate is defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants within the analysis population at any time per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1. as determined by the local investigators.

  Until disease progression (up to 5 years)

• Substudy 2: Overall response rate (ORR) as assessed by central independent review

  Overall response rate is defined as the percentage of participants with a confirmed CR or PR relative to the total number of participants within the analysis population at any time per RECIST v1.1. as assessed by central independent review.

  Up to 5 years

Secondary Outcomes (14)

• Substudy 1 and 2: Time to response (TTR)

  Until disease progression (up to 5 years)

• Substudy 1 and 2: Duration of response (DOR)

  Until disease progression (up to 5 years)

• Substudy 1 and 2: Disease control rate (DCR)

  Until disease progression (up to 5 years)

• Substudy 1 and 2: Progression free survival (PFS)

  Until disease progression (up to 5 years)

• Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity

  Until disease progression (up to 5 years)

Study Arms (2)

Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS

EXPERIMENTAL

Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.

Drug: Letetresgene autoleucel (lete-cel, GSK3377794); Drug: Fludarabine; Drug: Cyclophosphamide

Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo

EXPERIMENTAL

Eligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.

Drug: Letetresgene autoleucel (lete-cel, GSK3377794); Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

Cyclophosphamide DRUG

Cyclophosphamide will be used as the lymphodepleting chemotherapy.

Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS; Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo

Letetresgene autoleucel (lete-cel, GSK3377794) DRUG

letetresgene autoleucel will be administered.

Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS; Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo

Fludarabine DRUG

Fludarabine will be used as the lymphodepleting chemotherapy

Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS; Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo

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 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

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

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; Sarcoma, Synovial; Liposarcoma, Myxoid

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Study Officials

• Michael Nathenson, MD

  USWM CT, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: This will be an open-label study. Hence, there will be no masking.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2019
• First Posted: May 30, 2019
• Study Start: December 31, 2019
• Primary Completion: March 1, 2024
• Study Completion (Estimated): July 31, 2026
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

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