Clincosm LogoSign in Get a demo

IGNYTE-ESO: 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

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03967223
Collaborator
(none)
97
Enrollment
38
Locations
2
Arms
79
Anticipated Duration (Months)
2.6
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
Phase 2

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)-A02+ 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-A02+ participants with NY-ESO-1+ advanced (metastatic or unresectable) SS or MRCLS who have progressed following treatment with anthracycline based chemotherapy (Substudy 2).

Study Design

Study Type:
Interventional
Anticipated Enrollment :
97 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
This will be an open-label study. Hence, there will be no masking.
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Dec 31, 2019
Anticipated Primary Completion Date :
Nov 30, 2022
Anticipated Study Completion Date :
Jul 31, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS

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

Drug: Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered.

Drug: Fludarabine
Fludarabine will be used as the lymphodepleting chemotherapy

Drug: Cyclophosphamide
Cyclophosphamide will be used as the lymphodepleting chemotherapy.
Experimental: Substudy 2: lete-cel in advanced (metastatic or unresectable) SS or MRCLS post anthracycline chemo

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

Drug: Letetresgene autoleucel (lete-cel, GSK3377794)
letetresgene autoleucel will be administered.

Drug: Fludarabine
Fludarabine will be used as the lymphodepleting chemotherapy

Drug: Cyclophosphamide
Cyclophosphamide will be used as the lymphodepleting chemotherapy.

Outcome Measures

Primary Outcome Measures

  1. Substudy 1: Overall response rate (ORR) [Until disease progression (up to 5 years)]

    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.

  2. Substudy 2: Overall response rate (ORR) as assessed by central independent review [Up to 5 years]

    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.

Secondary Outcome Measures

  1. Substudy 1 and 2: Time to response (TTR) [Until disease progression (up to 5 years)]

    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.

  2. Substudy 1 and 2: Duration of response (DOR) [Until disease progression (up to 5 years)]

    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.

  3. Substudy 1 and 2: Disease control rate (DCR) [Until disease progression (up to 5 years)]

    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.

  4. Substudy 1 and 2: Progression free survival (PFS) [Until disease progression (up to 5 years)]

    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.

  5. 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)]

    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.

  6. Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL) [Until disease progression (up to 5 years)]

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

  7. Substudy 1 and 2: Number of participants with insertional oncogenesis (IO) [Until disease progression (up to 5 years)]

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

  8. Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters [Until disease progression (up to 5 years)]

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

  9. Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel [Until disease progression (up to 5 years)]

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

  10. Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel [Until disease progression (up to 5 years)]

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

  11. Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel [Until disease progression (up to 5 years)]

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

  12. Substudy 2: Overall response rate (ORR) as determined by the local investigators [Up to 5 years]

    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.

  13. Substudy 2: Overall Survival (OS) [Up to 5 years]

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

  14. Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel [Up to 36 months]

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

Eligibility Criteria

Criteria

Ages Eligible for Study:
10 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Participant must be greater than or equal to 10 years of age on the day of signing informed consent.

  • Participant must be positive for HLA-A02:01, HLA-A02:05, 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.

  • Consultation for prior history per protocol specifications.

Exclusion Criteria:

  • Central nervous system metastases.

  • Any other prior malignancy that is not in complete remission.

  • Clinically significant systemic illness.

  • 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Duarte California United States 91010
2 GSK Investigational Site Stanford California United States 94305
3 GSK Investigational Site Denver Colorado United States 80218
4 GSK Investigational Site Jacksonville Florida United States 32224
5 GSK Investigational Site Chicago Illinois United States 60637
6 GSK Investigational Site Iowa City Iowa United States 52242-1009
7 GSK Investigational Site Boston Massachusetts United States 02114
8 GSK Investigational Site Boston Massachusetts United States 02114
9 GSK Investigational Site Ann Arbor Michigan United States 48109
10 GSK Investigational Site Minneapolis Minnesota United States 55455
11 GSK Investigational Site Rochester Minnesota United States 55905
12 GSK Investigational Site Saint Louis Missouri United States 63110
13 GSK Investigational Site New York New York United States 10065
14 GSK Investigational Site Durham North Carolina United States 27710
15 GSK Investigational Site Columbus Ohio United States 43210
16 GSK Investigational Site Portland Oregon United States 97239
17 GSK Investigational Site Pittsburgh Pennsylvania United States 15232
18 GSK Investigational Site Nashville Tennessee United States 37203
19 GSK Investigational Site Dallas Texas United States 75390-8565
20 GSK Investigational Site Dallas Texas United States 75390-9063
21 GSK Investigational Site Salt Lake City Utah United States 84112
22 GSK Investigational Site Richmond Virginia United States 23298
23 GSK Investigational Site Seattle Washington United States 98109-1024
24 GSK Investigational Site Milwaukee Wisconsin United States 53226
25 GSK Investigational Site Toronto Ontario Canada M5G 2M9
26 GSK Investigational Site Montreal Quebec Canada H1T 2M4
27 GSK Investigational Site Lyon cedex 08 France 69373
28 GSK Investigational Site Pessac cedex France 33604
29 GSK Investigational Site Milano Lombardia Italy 20133
30 GSK Investigational Site Rozzano (MI) Lombardia Italy 20089
31 GSK Investigational Site Amsterdam Netherlands 1066 CX
32 GSK Investigational Site Barcelona Spain 08025
33 GSK Investigational Site Hospitalet de Llobregat, Barcelona Spain 08907
34 GSK Investigational Site Madrid Spain 28040
35 GSK Investigational Site Sevilla Spain 41013
36 GSK Investigational Site London United Kingdom SW3 6JJ
37 GSK Investigational Site London United Kingdom WC1E 6AG
38 GSK Investigational Site Manchester United Kingdom M20 4BX

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03967223
Other Study ID Numbers:
  • 208467
First Posted:
May 30, 2019
Last Update Posted:
Feb 16, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
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
Additional relevant MeSH terms:
Cyclophosphamide
Fludarabine

Study Results

No Results Posted as of Feb 16, 2022