Description:
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in
participants with advanced tumors.
Title
- Brief Title: 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
- 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)
Clinical Trial IDs
- ORG STUDY ID:
208467
- NCT ID:
NCT03967223
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| letetresgene autoleucel (lete-cel, GSK3377794) | | Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS |
| Fludarabine | | Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS |
| Cyclophosphamide | | Substudy 1: lete-cel in previously untreated advanced (metastatic or unresectable) SS or MRCLS |
Purpose
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in
participants with advanced tumors.
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
Letestresgene 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 Letestresgene 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).
Trial Arms
| Name | Type | Description | Interventions |
|---|
| 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. | - letetresgene autoleucel (lete-cel, GSK3377794)
- Fludarabine
- 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. | - letetresgene autoleucel (lete-cel, GSK3377794)
- Fludarabine
- Cyclophosphamide
|
Eligibility Criteria
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-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) confirmed by local histopathology Specifics requirements per substudy.
- 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.
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 10 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Substudy 1: Overall response rate (ORR) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
Secondary Outcome Measures
| Measure: | Substudy 1 and 2: Time to response |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Substudy 1 and 2: Duration of response (DOR) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Substudy 1 and 2: Disease control rate (DCR) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Substudy 1 and 2: Progression free survival (PFS) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | AEs, SAEs and AESIs will be collected. Severity of AEs and SAEs will be summarized using NCI-CTCAE, version 5.0. |
| Measure: | Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | RCL exposure will be assessed by polymerase chain reaction (PCR) based assay. |
| Measure: | Substudy 1 and 2: Number of participants with insertional oncogenesis (IO) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood. |
| Measure: | Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | Blood and urine samples will be collected for assessment of hematology, clinical chemistry and urinalysis parameters. |
| Measure: | Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | Whole blood samples will be collected at indicated time points for evaluation of Cmax. |
| Measure: | Substudy 1 and 2: Time to Cmax (Tmax) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | Whole blood samples will be collected at indicated time points for evaluation of Tmax. |
| Measure: | Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) |
| Time Frame: | Until disease progression (up to 5 years) |
| Safety Issue: | |
| Description: | Whole blood samples will be collected at indicated time points for evaluation of AUC(0-t). |
| Measure: | Substudy 2: Overall response rate (ORR) |
| Time Frame: | Up to 5 years |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Substudy 2: Overall Survival (OS) |
| Time Frame: | Up to 5 years |
| Safety Issue: | |
| Description: | Overall Survival is defined as the interval of time between the date of T-cell infusion and the date of death. |
| Measure: | Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel |
| Time Frame: | Up to 36 months |
| Safety Issue: | |
| Description: | Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays. |
Details
| Phase: | Phase 2 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | GlaxoSmithKline |
Trial 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
Last Updated
June 7, 2021
