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NeoplasmsPhase 2IGNYTE-ESONCT03967223

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

A Phase 2 study testing Letetresgene autoleucel (lete-cel, GSK3377794), Fludarabine and Cyclophosphamide in people with Neoplasms, run by USWM CT, LLC at 38 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors. Read more about this study

Who is it for?
Ages 10 years and older
Conditions the study is for
Neoplasms
What is being tested?
Letetresgene autoleucel (lete-cel, GSK3377794), Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
103 participants
Where
38 sitesin 7 countries
Study dates
31 Dec 2019to 31 Jul 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 12Show fewer
  • 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.

Trial locations and contacts

38 sites in 7 countries.

38 sites in 7 countries

United States24 sites

  • University of Michigan Medical Center

    Ann Arbor, Michigan, 48109

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02114

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • University of Chicago

    Chicago, Illinois, 60637

  • Ohio State University-Columbus

    Columbus, Ohio, 43210

  • University Of Texas Southwestern Medical Center

    Dallas, Texas, 75390-8565

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390-9063

  • Sarah Cannon Research Institute

    Denver, Colorado, 80218

  • City of Hope National Medical Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • University of Iowa College of Medicine

    Iowa City, Iowa, 52242-1009

  • Mayo Clinic Jacksonville

    Jacksonville, Florida, 32224

  • Froedtert Hospital

    Milwaukee, Wisconsin, 53226

  • Minnesota Oncology Hematology

    Minneapolis, Minnesota, 55455

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Memorial Sloan Kettering cancer center

    New York, New York, 10065

  • University of Pittsburgh, Hillman Cancer Centre

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • Mayo Clinic Rochester

    Rochester, Minnesota, 55905

  • University of Utah

    Salt Lake City, Utah, 84112

  • Fred Hutchinson Cancer Research

    Seattle, Washington, 98109-1024

  • Washington University

    St Louis, Missouri, 63110

  • Stanford Hospital and Clinics

    Stanford, California, 94305

Other trials in United States

Spain4 sites

  • Hospital Santa Creu Y Sant Pau

    Barcelona, 08025

  • Ico Duran y Reynals l'Hospitalet de Llobrega

    Hospitalet de Llobregat, Barcelona, 08907

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Hospital Virgen Del Rocio

    Seville, 41013

Other trials in Spain

United Kingdom3 sites

  • Royal Marsden Hospital

    London, SW3 6JJ

  • University College Hospital-London

    London, WC1E 6AG

  • Christie Hospital NHS Foundation Trust

    Manchester, M20 4BX

Other trials in United Kingdom

Canada2 sites

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

    Montreal, Quebec, H1T 2M4

  • Princess Margaret Cancer Centre

    Toronto, Ontario, M5G 2M9

Other trials in Canada

France2 sites

  • Centre Léon Bérard

    Lyon, 69373

  • CHU de Bordeaux GH Sud Hôpital Haut Lévêque

    Pessac, 33604

Other trials in France

Italy2 sites

  • Fondazione IRCCS Instituto Nazionale Dei Tumori

    Milan, Lombardy, 20133

  • Ircss Istituto Clinico Humanitas

    Rozzano (MI), Lombardy, 20089

Other trials in Italy

Netherlands1 site

  • The Netherlands Cancer Institute

    Amsterdam, 1066 CX

Other trials in Netherlands

About this study

Official title: Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, Alone or in Combination With Other Agents, in HLA-A2+ Participants With NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO)

This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.

Read the detailed description

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 (lete-cel, GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor engineered T cells. This is a master protocol investigating T-cell therapies. It will initially consist of a core protocol with two independent substudies investigating Letetresgene autoleucel in previously untreated (1L) Human Leukocyte Antigen (HLA)-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCLS) (Substudy 1) and Letetresgene autoleucel as second line or higher (2L+) treatment in HLA-A*02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) SS or MRCLS who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).

Conditions
Neoplasms
Being tested
Letetresgene autoleucel (lete-cel, GSK3377794), Fludarabine, Cyclophosphamide
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
Medical subject headings
Neoplasms, Sarcoma, Synovial, Liposarcoma, Myxoid

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Letetresgene autoleucel (lete-cel, GSK3377794)Drug

    letetresgene autoleucel will be administered.

  • FludarabineDrug

    Fludarabine will be used as the lymphodepleting chemotherapy

  • CyclophosphamideDrug

    Cyclophosphamide will be used as the lymphodepleting chemotherapy.

Study groups in NCT03967223
Study groupRoleWhat they receive
Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLSExperimentalEligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
Receives: Drug: Letetresgene autoleucel (lete-cel, GSK3377794); Drug: Fludarabine; Drug: Cyclophosphamide
Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemoExperimentalEligible participants will be leukapheresed to manufacture engineered T cells. Participants will then receive letetresgene autoleucel.
Receives: Drug: Letetresgene autoleucel (lete-cel, GSK3377794); Drug: Fludarabine; Drug: Cyclophosphamide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Until disease progression (up to 5 years)

  2. 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.

    Measured: Up to 5 years

Secondary outcomes (14)

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

    Time to response is defined as time from date of T-cell administration to first documented evidence of confirmed (CR or PR) as assessed by local investigators per RECIST v1.1.

    Measured: Until disease progression (up to 5 years)

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

    Duration of response is defined as, in the subset of participants who show a confirmed CR or PR as assessed by local investigators, the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

    Measured: Until disease progression (up to 5 years)

  3. Substudy 1 and 2: Disease control rate (DCR)

    Disease control rate is defined as the percentage of participants with a confirmed CR, PR, or stable disease (SD) with minimal 12 weeks duration relative to the total number of participants within the analysis population at the time of primary analysis as determined by Investigators per RECIST v1.1.

    Measured: Until disease progression (up to 5 years)

  4. Substudy 1 and 2: Progression free survival (PFS)

    Progression free survival is defined as the time from the date of T-cell administration until first documented sign of disease progression per RECIST v1.1, or death.

    Measured: Until disease progression (up to 5 years)

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

    AEs, SAEs and AESIs will be collected. Severity of AEs and SAEs will be summarized using National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 5.0.

    Measured: Until disease progression (up to 5 years)

  6. Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL)

    RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.

    Measured: Until disease progression (up to 5 years)

  7. Substudy 1 and 2: Number of participants with insertional oncogenesis (IO)

    Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.

    Measured: Until disease progression (up to 5 years)

  8. Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters

    Blood and urine samples will be collected for assessment of hematology, clinical chemistry and urinalysis parameters.

    Measured: Until disease progression (up to 5 years)

  9. Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel

    Whole blood samples will be collected at indicated time points for evaluation of Cmax.

    Measured: Until disease progression (up to 5 years)

  10. Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel

    Whole blood samples will be collected at indicated time points for evaluation of Tmax.

    Measured: Until disease progression (up to 5 years)

  11. Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel

    Whole blood samples will be collected at indicated time points for evaluation of AUC(0-t).

    Measured: Until disease progression (up to 5 years)

  12. Substudy 2: Overall response rate (ORR) as determined by the local investigators

    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 determined by the local investigators.

    Measured: Up to 5 years

  13. Substudy 2: Overall Survival (OS)

    Overall Survival is defined as the interval of time between the date of T-cell infusion and the date of death.

    Measured: Up to 5 years

  14. Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel

    Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.

    Measured: Up to 36 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 May 2019
  2. Study start31 Dec 2019
  3. Primary completion1 Mar 2024
  4. Study completion31 Jul 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
103 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03967223
Sponsor's protocol ID
208467
Acronym
IGNYTE-ESO
Status last verified
Aug 2026
First submitted
10 May 2019
Last updated
11 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Letetresgene autoleucel (lete-cel, GSK3377794), Fludarabine and Cyclophosphamide in people with Neoplasms, run by USWM CT, LLC at 38 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 38 sites in United States, Spain, United Kingdom, Canada, France and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Substudy 1: Overall response rate (ORR) (time frame: Until disease progression (up to 5 years)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03967223.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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