Brief Summary
This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.
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
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).
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Neoplasms
Eligibility Criteria
Inclusion Criteria:
* 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.
Exclusion Criteria:
* 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.
* 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.
Exclusion Criteria:
* 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.
Inclusion Criteria
Inclusion Criteria:
* 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.
* 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.
Gender
All
Gender Based
false
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
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
10 Years
NCT Id
NCT03967223
Org Class
Industry
Org Full Name
Adaptimmune
Org Study Id
208467
Overall Status
Active, not recruiting
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Substudy 1: Overall response rate (ORR)
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome 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 assessed by central independent review.
Outcome Measure
Substudy 2: Overall response rate (ORR) as assessed by central independent review
Outcome Time Frame
Up to 5 years
Secondary Outcomes
Outcome 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.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Time to response (TTR)
Outcome 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.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Duration of response (DOR)
Outcome 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.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Disease control rate (DCR)
Outcome 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.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Progression free survival (PFS)
Outcome Description
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.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Frequency of adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) according to severity
Outcome Description
RCL exposure will be assessed by polymerase chain reaction (PCR) based assay.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Number of participants with replication competent lentivirus (RCL)
Outcome Description
Peripheral blood mononuclear cells (PBMC) samples will be collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Number of participants with insertional oncogenesis (IO)
Outcome Description
Blood and urine samples will be collected for assessment of hematology, clinical chemistry and urinalysis parameters.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 2: Number of participants with clinically significant changes in hematology, clinical chemistry and urinalysis parameters
Outcome Description
Whole blood samples will be collected at indicated time points for evaluation of Cmax.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Maximum transgene expansion (Cmax) of letetresgene autoleucel
Outcome Description
Whole blood samples will be collected at indicated time points for evaluation of Tmax.
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Time to Cmax (Tmax) of letetresgene autoleucel
Outcome Description
Whole blood samples will be collected at indicated time points for evaluation of AUC(0-t).
Outcome Time Frame
Until disease progression (up to 5 years)
Outcome Measure
Substudy 1 and 2: Area under the concentration/persistence time curve from zero to time t (AUC[0-t]) of letetresgene autoleucel
Outcome 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.
Outcome Time Frame
Up to 5 years
Outcome Measure
Substudy 2: Overall response rate (ORR) as determined by the local investigators
Outcome Description
Overall Survival is defined as the interval of time between the date of T-cell infusion and the date of death.
Outcome Time Frame
Up to 5 years
Outcome Measure
Substudy 2: Overall Survival (OS)
Outcome Description
Serum samples will be collected to analyze for the presence of ADAs using validated immunoassays.
Outcome Time Frame
Up to 36 months
Outcome Measure
Substudy 2: Number of participants with positive anti-drug antibodies (ADA) and titers of ADA against letetresgene autoleucel
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
10
Investigators
Investigator Type
Principal Investigator
Investigator Name
David Loeb
Investigator Email
david.loeb@einsteinmed.org
Investigator Phone
718-741-2342
Categories Mesh Debug
Cancer --- NEOPLASMS
Endocrine System Cancers --- NEOPLASMS
Gastrointestinal (GI) Cancers --- NEOPLASMS
Gynecologic Cancers --- NEOPLASMS
Lung & Chest Cancers --- NEOPLASMS
Prostate Cancer --- NEOPLASMS
Sarcomas --- SARCOMA, SYNOVIAL
Brain, Spine & Nerve Cancers --- NEOPLASMS, CONNECTIVE AND SOFT TISSUE
Blood & Bone Marrow Cancers --- NEOPLASMS BY HISTOLOGIC TYPE
Cancer --- SARCOMA
Sarcomas --- SARCOMA
Sarcomas --- LIPOSARCOMA
MeSH Terms
NEOPLASMS
SARCOMA, SYNOVIAL
LIPOSARCOMA, MYXOID
NEOPLASMS, CONNECTIVE TISSUE
NEOPLASMS, CONNECTIVE AND SOFT TISSUE
NEOPLASMS BY HISTOLOGIC TYPE
SARCOMA
LIPOSARCOMA
NEOPLASMS, ADIPOSE TISSUE
FLUDARABINE
CYCLOPHOSPHAMIDE
PHOSPHORAMIDE MUSTARDS
NITROGEN MUSTARD COMPOUNDS
MUSTARD COMPOUNDS
HYDROCARBONS, HALOGENATED
HYDROCARBONS
ORGANIC CHEMICALS
PHOSPHORAMIDES
ORGANOPHOSPHORUS COMPOUNDS