Letetresgene Autoleucel Engineered T Cells in NY-ESO-1 Positive Participants With Advanced Myxoid/ Round Cell Liposarcoma

Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via investigator assessment per RECIST (Response Evaluation Criteria In Solid Tumors Criteria) v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the 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). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.

The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response [CR] > Confirmed Partial Response [PR] > Stable Disease [SD] > Progressive Disease [PD] > Not Evaluable [NE]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by the investigator per RECIST v1.1 Criteria.

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. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.

Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the 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. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.

Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.

The Best Overall Response (BOR) with confirmation for a participant is defined as the best confirmed response (Confirmed Complete Response [CR] > Confirmed Partial Response [PR] > Stable Disease [SD] > Progressive Disease [PD] > Not Evaluable [NE]) from first T cell infusion until disease progression or initiation of new anti-cancer therapy, whichever is earlier, as assessed by independent reviewer per RECIST v1.1 criteria.

Overall response rate (ORR) defined as the percentage of participants with a confirmed complete response (CR) or confirmed partial response (PR) via independent reviewer assessment per RECIST v1.1 relative to the total number of participants in the analysis population. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the 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). Confidence intervals (CI) were calculated using the exact (Clopper-Pearson) method.

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. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm.

Duration of response was defined as the interval between the initial date of confirmed response (PR/CR) and the date of progressive disease or death among participants with a confirmed response per RECIST 1.1. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 mm. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.

Progression free survival was defined as the interval between the date of T cell infusion and the earliest date of disease progression or death due to any cause. Progressive disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by independent reviewer per RECIST v1.1 is presented. Kaplan-Meier Median and 95% confidence intervals are presented. Confidence intervals were calculated using the Brookmeyer-Crowley method.

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose can result in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth or is medically significant or requires intervention to prevent one or the outcomes listed above.

An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. The AESI included events of Cytokine release syndrome (CRS), Haematopoietic cytopenias (including pancytopenia and aplastic anaemia), Graft versus host disease (GvHD), Immune Effector-Cell Associated Neurotoxicity Syndrome (ICANS), and Guillain-Barre syndrome.

Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets, leukocytes. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.0, where Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to baseline grade. Data of number of participants with any grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented.

Blood samples were collected for the analysis clinical chemistry parameters: glucose, albumin, alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, potassium, magnesium, sodium, phosphate, calcium. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.0, where Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to baseline grade. Data of number of participants with any grade increase at worst-case post-baseline (maximum grade increase post-baseline) is presented.

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).

Peripheral blood mononuclear cells (PBMC) samples were collected for monitoring insertional oncogenesis by PCR for gene modified cells in the blood. DNA from participant identified with >1% PBMC at >=1 year post T-cell infusion was sent for integration site analysis. Integration site analysis was used to assess the possibility of insertional oncogenesis. Participants with insertional oncogenesis were participants with any clones representing >20% of the total.

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

Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.

Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.

Area under the cell expansion-time curve from first T-cell infusion to Day 28. Blood samples were collected to measure AUC (0-28 days).

Triplicate 12-Lead ECGs were collected at baseline visit and single ECGs at other timepoints. At each time point during the study ECG was taken using an ECG machine that automatically calculates the heart rate and measured the PR interval, QRS duration, QTcB, QTcF intervals, RR interval and uncorrected QT interval. Baseline is the most recent, non-missing value within 7 days prior to the lymphodepleting chemotherapy. Change from baseline was to be calculated by subtracting post-dose value from baseline value.

Single 12-lead ECG was to be obtained at designated time points during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. Baseline is the most recent, non-missing value within 7 days prior to the lymphodepleting chemotherapy. Change from baseline was to be calculated by subtracting post-dose value from baseline value.