This trial will evaluate safety and efficacy of human engineered T-cell therapies, in
participants with advanced tumors. This trial is a sub study of the Master study
NCT03967223.

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

Neoplasms

Letetresgene autoleucel

Cyclophosphamide

Fludarabine

Evaluation of Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

ORR is defined as the percentage of participants with a confirmed complete response (CR)
or confirmed partial response (PR) via investigator assessment per Response Evaluation
Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of
participants in the analysis population. CR is defined as disappearance of all target
lesions. Any pathological lymph nodes (whether target or non-target) must have reduction
in short axis to less than (<)10 millimeters (mm). PR is defined as at least a 30%
decrease in the sum of the diameters of target lesions, taking as a reference, the
baseline sum of the diameters (e.g., percent change from baseline). 95% CI is based on
Clopper-Pearson exact confidence interval.

Time to response was defined as the interval of time between the date of T-cell infusion
and the first documented evidence of the confirmed response (PR or CR), in the subset of
participants with a confirmed PR or CR as their best confirmed overall response. CR is
defined as disappearance of all target lesions. Any pathological lymph nodes (whether
target or non-target) must have reduction in short axis to less than (<)10 millimeters
(mm). PR is defined as at least a 30% decrease in the sum of the diameters of target
lesions, taking as a reference, the baseline sum of the diameters (e.g., percent change
from baseline).

Duration of response was defined as the interval between the initial date of confirmed
response (PR/CR) and the date of progressive disease as assessed by local investigators,
or death among participants with a confirmed response per RECIST 1.1. CR is defined as
disappearance of all target lesions. Any pathological lymph nodes (whether target or
non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is
defined as at least a 30% decrease in the sum of the diameters of target lesions, taking
as a reference, the baseline sum of the diameters (e.g., percent change from baseline).

DCR is defined as the percentage of participants with a confirmed CR, PR, or stable
disease (SD) with a minimal 12 weeks (84 days ± 7 day window) duration relative to the
total number of participants within the analysis population at the time of primary
analysis as determined by local investigators per RECIST v1.1. CR is defined as
disappearance of all target lesions. Any pathological lymph nodes (whether target or
non-target) must have reduction in short axis to less than (<)10 millimeters (mm). PR is
defined as at least a 30% decrease in the sum of the diameters of target lesions, taking
as a reference, the baseline sum of the diameters (e.g., percent change from baseline).
SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase
to qualify for progressive disease. The disease progression (PD) is defined as the date
of radiological disease progression based on imaging data per RECIST v1.1. 95% CI is
based on Clopper-Pearson exact confidence interval.

PFS is defined as the interval of time between from the date of T-cell infusion to the
earliest date of radiological progression of disease (PD) as assessed by local
investigator per RECIST v1.1, or death due to any cause. The PD is defined as the date of
radiological disease progression based on imaging data per RECIST v1.1.

An AE is any untoward medical occurrence in a clinical investigation participant,
temporally associated with the use of a medicinal product, whether or not considered
related to the medicinal product. SAE is defined as any untoward medical occurrence that,
at any dose results in death, is life-threatening, requires hospitalization or
prolongation of existing hospitalization, results in disability/incapacity, is a
congenital anomaly/birth defect, other situations which involve medical or scientific
judgment or is associated with liver injury and impaired liver function.

An AESI may be of scientific and medical concern related to the treatment, monitored, and
rapidly communicated by investigator to sponsor. AESIs included cytokine release syndrome
(CRS), hematopoietic cytopenias (including pancytopenia and aplastic anemia), graft vs
host disease (GVHD), ICANS, Guillain-Barre syndrome, treatment-related inflammatory
response at tumor site(s), and neutropenia Grade 4 lasting ≥28 days.

An AE is any untoward medical occurrence in a clinical investigation participant,
temporally associated with the use of a medicinal product, whether or not considered
related to the medicinal product. SAE is defined as any untoward medical occurrence that,
at any dose results in death, is life-threatening, requires hospitalization or
prolongation of existing hospitalization, results in disability/incapacity, is a
congenital anomaly/birth defect, other situations which involve medical or scientific
judgment or is associated with liver injury and impaired liver function. AEs and SAEs
were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse
Events (NCI-CTCAE) version 5.0. Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or
medically significant but not immediately life-threatening; Grade 4- Life-threatening
consequences; Grade 5- Death related to AE.

RCL was monitored using a polymerase chain reaction (PCR)-based assay that detects and
measures copies of the gene coding for the vector's envelope protein, namely vesicular
stomatitis virus G protein (VSV-G).

Instances of Insertional Oncogenesis (IO) was summarized descriptively.

Cmax was defined as maximum observed persistence, determined directly from the
persistence-time data. Blood samples were collected for PK analysis.

Tmax was defined as time to reach Cmax, determined directly from the persistence-time
data. Blood samples were collected for PK analysis.

Area under the persistence-time curve from time zero to Day 28. Blood samples were
collected for PK analysis.

Study to Evaluate Safety and Antitumor Activity of Lete-Cel (GSK3377794) in HLA-A2+ Participants With NY-ESO-1 Positive Previously Untreated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

About this trial

Study ID

Status

Type

Phase

Placebo

Accepting

Not accepting

Trial Timing

What is this trial about?

What are the participation requirements?