Neoplasms
Conditions
Keywords
Myxoid/ round cell liposarcoma, Letetresgene autoleucel, Immuno-oncology, T Cell Receptor, Leukapheresis, NY-ESO-1, Adoptive TCR T-cell therapy
Brief summary
This trial will evaluate safety and efficacy of Letetresgene autoleucel (GSK3377794) in participants with advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
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 (GSK3377794) is the first generation of NY-ESO-1 specific T-cell receptor (TCR) engineered T-cells. This protocol investigates Letetresgene autoleucel treatment in Human Leukocyte Antigen (HLA)-A\*02+ participants with NY-ESO1+ advanced myxoid/round cell liposarcoma or high-grade myxoid liposarcoma.
Interventions
Letetresgene autoleucel (GSK3377794) as an IV infusion.
DRUGCyclophosphamide
Cyclophosphamide will be used as a lymphodepleting chemotherapy.
DRUGFludarabine
Fludarabine will be used as a lymphodepleting chemotherapy.
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is greater than equal to (\>=)18 years of age at the time of signing the study informed consent. * Participant has a diagnosis of advanced (metastatic or inoperable) high grade myxoid liposarcoma / myxoid round cell liposarcoma confirmed histologically and by the presence of the reciprocal chromosomal translocation t(12;16) (q13;p11) or t(12; 22) (q13;q12). * Participant has measurable disease according to RECIST v1.1 criteria. * Participant must have previously received or be intolerant to anthracycline based therapy for advanced (metastatic or inoperable) disease. * Participants who received neoadjuvant/adjuvant anthracycline based therapy and progressed within 6 months of completion of therapy will be eligible. * Participant must be HLA A\*02:01, HLA A\*02:05 and/or HLA-A\*02:06 positive. * Participant's tumor (either the most recent archival specimen or a fresh biopsy) is positive for NY-ESO-1 expression by a designated central laboratory. * Participant has an Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1. * Participant has a left ventricular ejection fraction \>=45%. * Participant is fit for apheresis and has adequate venous access for the cell collection. * Participants must satisfy pregnancy and contraceptive requirements per protocol and have adequate organ function per protocol specified values.
Exclusion criteria
* Any previous gene therapy using an integrating vector. * Any previous allogeneic hematopoietic stem cell transplant. * Participant has history of allergic reactions attributed to compounds of similar chemical or biologic composition to fludarabine, cyclophosphamide or other agents used in the study. * Participant has history of chronic or recurrent (within the last year prior to screening) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments. * Participant has known active brain or leptomeningeal metastases. * Participant has other prior malignancy that is not in complete remission. * Participant has uncontrolled intercurrent illness including, but not limited to: * (i) Ongoing or active infection. * (ii) Clinically significant cardiac disease * (iii) Interstitial lung disease (participants with existing pneumonitis as a result of radiation are not excluded, however, participants must not be oxygen dependent). * Participant has active infection with Human Immunodeficiency Virus (HIV), Hepatitis B virus (HBV), ), Hepatitis C virus (HCV) or human T-lymphotropic virus (HTLV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Up to 24 months | 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. |
| Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Up to 24 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) Assessed by Investigator | Up to 24 months | 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. |
| Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Up to 24 months | 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) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer | Up to 24 months | 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 (TTR) Assessed by Independent Reviewer | Up to 24 months | 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 (DOR) Assessed by Independent Reviewer | Up to 24 months | 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 (PFS) Assessed by Independent Reviewer | Up to 24 months | 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. |
| Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Up to 24 months | 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. |
| Number of Participants With Adverse Event of Special Interest (AESI) | Up to 24 months | 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. |
| Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Up to 24 months | 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. |
| Time to Response (TTR) Assessed by Investigator | Up to 24 months | 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. |
| Number of Participants With Replication Competent Lentivirus (RCL) | Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion | 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). |
| Number of Participants With Insertional Oncogenesis | Up to 2 years | 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. |
| Number of Participants With Positive Anti-drug Antibodies (ADAs) | Up to 24 Months | Serum samples were collected to analyze for the presence of ADAs using validated immunoassays. |
| Maximum Transgene Expansion (Cmax) of GSK3377794 | Day 2 to Day 15 | Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax. |
| Time to Cmax (Tmax) | Day 2 to Day 15 | Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax. |
| Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794 | Up to 28 days | 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). |
| Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | Baseline, Day 1, Day 4 and Day 8 | 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. |
| Change From Baseline in ECG Mean Heart Rate | Baseline, Day 1 (Pre-dose), Day 4 and Day 8 | 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. |
| Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Up to 24 months | 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. |
| Duration of Response (DOR) Assessed by Investigator | Up to 24 months | 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. |
Countries
United States
Participant flow
Recruitment details
This was an open-label study evaluating the safety and tolerability of autologous T-Cells expressing enhanced T-cell receptors (TCRs) specific for New York esophageal squamous cell carcinoma (NY-ESO)-1 (letetresgene autoleucel, lete-cel, GSK3377794) in Human Leukocyte Antigen (HLA)-A\*02:01, HLA-A\*02:05 and/or HLA-A\*02:06 participants with Advanced Myxoid/ Round Cell Liposarcoma.
Pre-assignment details
A total of 23 participants were enrolled in this study. Out of 23 participants, 20 participants received NY-ESO-1c259 T cell infusion.
Participants by arm
| Arm | Count |
|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 Eligible participants were leukapheresed to manufacture autologous NY-ESO-1c259 T cell receptors (TCR) bearing T-cells. Participants underwent lymphodepleting chemotherapy; cyclophosphamide 600 mg/m\^2/day plus fludarabine 30 mg/m\^2/day on day -7 through day -5 followed by a single infusion of GSK3377794 on Day 1. | 13 |
| Standard Lymphodepletion Dose Plus GSK3377794 Eligible participants were leukapheresed to manufacture autologous NY-ESO-1\^c259 TCR bearing T-cells. Participants underwent lymphodepleting chemotherapy consisting of cyclophosphamide 900 mg/m\^2/day starting on day -7 through day -5 plus fludarabine 30 mg/m\^2/day on day -8 through day -5 followed by a single infusion of GSK3377794 on Day 1. | 10 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death-Prior to T-Cell Infusion | 1 | 0 |
| Overall Study | Did Not Meet Inclusion/Exclusion | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | No measurable disease | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Reduced Lymphodepletion Dose Plus GSK3377794 | Standard Lymphodepletion Dose Plus GSK3377794 | Total |
|---|---|---|---|
| Age, Continuous | 50.0 YEARS STANDARD_DEVIATION 6.79 | 46.0 YEARS STANDARD_DEVIATION 11.61 | 48.3 YEARS STANDARD_DEVIATION 9.19 |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Other: More than one race | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 11 Participants | 10 Participants | 21 Participants |
| Sex: Female, Male Female | 6 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 7 Participants | 7 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 13 | 0 / 10 |
| other Total, other adverse events | 13 / 13 | 10 / 10 |
| serious Total, serious adverse events | 5 / 13 | 7 / 10 |
Outcome results
Primary
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
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 frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population, which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Partial Response (PR) | 2 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Progressive Disease (PD) | 0 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Stable Disease (SD) | 8 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Not Evaluable (NE) | 0 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Complete Response (CR) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Not Evaluable (NE) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Complete Response (CR) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Partial Response (PR) | 4 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Stable Disease (SD) | 5 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | Progressive Disease (PD) | 1 Participants |
Primary
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population, which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 20 Percentage of participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Investigator Assessment | 40 Percentage of participants |
Secondary
Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794
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).
Time frame: Up to 28 days
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794 | 727135.6 Days*copies per microgram genomic DNA | Geometric Coefficient of Variation 223.9 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) of GSK3377794 | 1142798.27 Days*copies per microgram genomic DNA | Geometric Coefficient of Variation 70.7 |
Secondary
Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population, which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Partial Response (PR) | 2 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Progressive Disease (PD) | 0 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Stable Disease (SD) | 8 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Not Evaluable (NE) | 0 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Complete Response (CR) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Not Evaluable (NE) | 3 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Complete Response (CR) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Partial Response (PR) | 4 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Stable Disease (SD) | 3 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Best Overall Response (BOR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer Assessment | Progressive Disease (PD) | 0 Participants |
Secondary
Change From Baseline in ECG Mean Heart Rate
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.
Time frame: Baseline, Day 1 (Pre-dose), Day 4 and Day 8
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | BASELINE | 73.0 Beats per minute (beats/minute) | Standard Deviation 12.34 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | DAY 1 | 1.6 Beats per minute (beats/minute) | Standard Deviation 10.08 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | DAY 4 | 20.1 Beats per minute (beats/minute) | Standard Deviation 16.34 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | DAY 8 | 5.4 Beats per minute (beats/minute) | Standard Deviation 12.72 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | DAY 8 | 9.1 Beats per minute (beats/minute) | Standard Deviation 16.37 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | BASELINE | 78.0 Beats per minute (beats/minute) | Standard Deviation 20.06 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | DAY 4 | 38.9 Beats per minute (beats/minute) | Standard Deviation 21.95 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in ECG Mean Heart Rate | DAY 1 | 4.8 Beats per minute (beats/minute) | Standard Deviation 14.2 |
Secondary
Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval
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.
Time frame: Baseline, Day 1, Day 4 and Day 8
Population: Modified Intent-to-Treat (mITT) population. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, DAY 4 | 2.3 Milliseconds (msec) | Standard Deviation 20.43 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, DAY 1 | -2.3 Milliseconds (msec) | Standard Deviation 8.66 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, DAY 4 | -10.7 Milliseconds (msec) | Standard Deviation 17.18 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, DAY 8 | -8.1 Milliseconds (msec) | Standard Deviation 14.9 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, BASELINE | 91.2 Milliseconds (msec) | Standard Deviation 16.53 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, DAY 1 | 2.8 Milliseconds (msec) | Standard Deviation 18.87 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, BASELINE | 152.9 Milliseconds (msec) | Standard Deviation 14.59 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, DAY 8 | -2.7 Milliseconds (msec) | Standard Deviation 25.75 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, BASELINE | 401.1 Milliseconds (msec) | Standard Deviation 11.71 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, DAY 1 | -6.4 Milliseconds (msec) | Standard Deviation 23.51 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, DAY 4 | -49.4 Milliseconds (msec) | Standard Deviation 38.59 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, DAY 8 | -16.7 Milliseconds (msec) | Standard Deviation 21.63 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, BASELINE | 427 Milliseconds (msec) | Standard Deviation 4.24 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, DAY 1 | 28 Milliseconds (msec) | — |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, DAY 4 | 10 Milliseconds (msec) | Standard Deviation 24.04 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, DAY 8 | 1 Milliseconds (msec) | — |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, BASELINE | 429.9 Milliseconds (msec) | Standard Deviation 23.75 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, DAY 1 | -10.1 Milliseconds (msec) | Standard Deviation 21.06 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, DAY 4 | -25.3 Milliseconds (msec) | Standard Deviation 36.62 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, DAY 8 | -7.5 Milliseconds (msec) | Standard Deviation 22.63 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, BASELINE | 842.6 Milliseconds (msec) | Standard Deviation 144.62 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, DAY 1 | -15.8 Milliseconds (msec) | Standard Deviation 98.77 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, DAY 4 | -162.5 Milliseconds (msec) | Standard Deviation 179.21 |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, DAY 8 | -71.6 Milliseconds (msec) | Standard Deviation 109.66 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, DAY 4 | -188 Milliseconds (msec) | Standard Deviation 11.31 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, BASELINE | 142 Milliseconds (msec) | Standard Deviation 12.72 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, BASELINE | 423.3 Milliseconds (msec) | Standard Deviation 19.35 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, DAY 1 | -2.2 Milliseconds (msec) | Standard Deviation 9.82 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, DAY 4 | 3.3 Milliseconds (msec) | Standard Deviation 31.1 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, DAY 4 | -4 Milliseconds (msec) | Standard Deviation 12.96 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, DAY 1 | 36.3 Milliseconds (msec) | Standard Deviation 34.03 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | PR Interval, DAY 8 | 1 Milliseconds (msec) | Standard Deviation 9.32 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, DAY 1 | 5.3 Milliseconds (msec) | Standard Deviation 43.1 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, BASELINE | 86.1 Milliseconds (msec) | Standard Deviation 15.01 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, DAY 4 | 8 Milliseconds (msec) | Standard Deviation 25.46 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, DAY 1 | 0.9 Milliseconds (msec) | Standard Deviation 6.49 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, DAY 8 | 16.2 Milliseconds (msec) | Standard Deviation 39.96 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, DAY 4 | 0.8 Milliseconds (msec) | Standard Deviation 5.75 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcB Interval, DAY 8 | 47 Milliseconds (msec) | Standard Deviation 50.27 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QRS Duration, DAY 8 | -1 Milliseconds (msec) | Standard Deviation 5.86 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, DAY 8 | -138.5 Milliseconds (msec) | Standard Deviation 77.72 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, BASELINE | 389.3 Milliseconds (msec) | Standard Deviation 33.57 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, BASELINE | 425.3 Milliseconds (msec) | Standard Deviation 16.18 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, DAY 1 | -8.1 Milliseconds (msec) | Standard Deviation 33.74 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | RR Interval, BASELINE | 807.6 Milliseconds (msec) | Standard Deviation 166.39 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, DAY 4 | -72.5 Milliseconds (msec) | Standard Deviation 47.65 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QTcF Interval, DAY 1 | 1.3 Milliseconds (msec) | Standard Deviation 17.36 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Change From Baseline in Electrocardiogram (ECG) Parameters- PR Interval, QRS Duration, QT Interval, QTcB Interval, QTcF Interval and RR Interval | QT Interval, DAY 8 | -4.4 Milliseconds (msec) | Standard Deviation 43.41 |
Secondary
Duration of Response (DOR) Assessed by Independent Reviewer
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only responders by independent reviewer were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Duration of Response (DOR) Assessed by Independent Reviewer | NA Months |
| Standard Lymphodepletion Dose Plus GSK3377794 | Duration of Response (DOR) Assessed by Independent Reviewer | 7.16 Months |
Secondary
Duration of Response (DOR) Assessed by Investigator
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only responders by investigator assessment were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Duration of Response (DOR) Assessed by Investigator | 5.31 Months |
| Standard Lymphodepletion Dose Plus GSK3377794 | Duration of Response (DOR) Assessed by Investigator | 7.47 Months |
Secondary
Maximum Transgene Expansion (Cmax) of GSK3377794
Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.
Time frame: Day 2 to Day 15
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Maximum Transgene Expansion (Cmax) of GSK3377794 | 66991.71 Copies per microgram genomic DNA | Geometric Coefficient of Variation 127 |
| Standard Lymphodepletion Dose Plus GSK3377794 | Maximum Transgene Expansion (Cmax) of GSK3377794 | 108485.91 Copies per microgram genomic DNA | Geometric Coefficient of Variation 53.4 |
Secondary
Number of Participants With Adverse Event of Special Interest (AESI)
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Adverse Event of Special Interest (AESI) | Cytokine release syndrome | 6 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Adverse Event of Special Interest (AESI) | Participants with any AESI | 10 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Adverse Event of Special Interest (AESI) | Haematopoietic cytopenias (including pancytopenia and aplastic anaemia) | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Adverse Event of Special Interest (AESI) | Participants with any AESI | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Adverse Event of Special Interest (AESI) | Cytokine release syndrome | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Adverse Event of Special Interest (AESI) | Haematopoietic cytopenias (including pancytopenia and aplastic anaemia) | 10 Participants |
Secondary
Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Glucose Hypoglycemia | 1 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Potassium Hypokalemia | 5 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | AST | 8 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Magnesium Hypermagnesemia | 5 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Alkaline Phosphatase | 4 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Magnesium Hypomagnesemia | 2 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Bilirubin | 3 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Phosphate | 9 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Albumin | 9 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Sodium Hypernatremia | 2 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Creatinine | 4 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Sodium Hyponatremia | 8 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | ALT | 7 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Calcium Corrected for Albumin Hypercalcemia | 2 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Potassium Hyperkalemia | 1 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Calcium Corrected for Albumin Hypocalcemia | 1 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Glucose Hyperglycemia | 5 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Calcium Corrected for Albumin Hypocalcemia | 7 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Glucose Hyperglycemia | 8 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Glucose Hypoglycemia | 4 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Albumin | 9 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Alkaline Phosphatase | 6 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | ALT | 7 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | AST | 8 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Bilirubin | 2 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Creatinine | 2 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Potassium Hyperkalemia | 1 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Potassium Hypokalemia | 9 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Magnesium Hypermagnesemia | 2 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Magnesium Hypomagnesemia | 6 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Phosphate | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Sodium Hypernatremia | 1 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Sodium Hyponatremia | 9 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Clinical Chemistry Results at Worst-case Post-baseline | Calcium Corrected for Albumin Hypercalcemia | 1 Participants |
Secondary
Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Neutrophils | 10 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Platelets | 9 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Lymphocyte count decreased | 10 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Leukocytes | 10 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Hemoglobin Anemia | 9 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Leukocytes | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Hemoglobin Anemia | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Lymphocyte count decreased | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Platelets | 10 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Any Grade Increase in Hematology Results at Worst-case Post-baseline | Neutrophils | 10 Participants |
Secondary
Number of Participants With Insertional Oncogenesis
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.
Time frame: Up to 2 years
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Number of participants analyzed comprises participants for whom integration site analysis was conducted.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Insertional Oncogenesis | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Insertional Oncogenesis | 0 Participants |
Secondary
Number of Participants With Positive Anti-drug Antibodies (ADAs)
Serum samples were collected to analyze for the presence of ADAs using validated immunoassays.
Time frame: Up to 24 Months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only those participants with post-baseline ADA results were analyzed.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Positive Anti-drug Antibodies (ADAs) | 0 Participants |
Secondary
Number of Participants With Replication Competent Lentivirus (RCL)
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).
Time frame: Day 1 (pre-infusion), and at Week 12, Week 24, and 1 year post-infusion
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794.. Only those participants with RCL assessed post T-cell infusion were included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Replication Competent Lentivirus (RCL) | 0 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Replication Competent Lentivirus (RCL) | 0 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs
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.
Time frame: Up to 24 months
Population: Intent-to-Treat (ITT) Population, which included all participants who underwent leukapheresis.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | SAEs | 5 Participants |
| Reduced Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Non-SAEs | 13 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | SAEs | 7 Participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Number of Participants With Serious Adverse Events (SAEs) and Non-SAEs | Non-SAEs | 10 Participants |
Secondary
Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer
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 frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population, which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer | 20 Percentage of participants |
| Standard Lymphodepletion Dose Plus GSK3377794 | Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 by Independent Reviewer | 40 Percentage of participants |
Secondary
Progression Free Survival (PFS) Assessed by Independent Reviewer
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Progression Free Survival (PFS) Assessed by Independent Reviewer | 4.67 Months |
| Standard Lymphodepletion Dose Plus GSK3377794 | Progression Free Survival (PFS) Assessed by Independent Reviewer | 9.03 Months |
Secondary
Progression Free Survival (PFS) Assessed by Investigator
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Progression Free Survival (PFS) Assessed by Investigator | 5.36 Months |
| Standard Lymphodepletion Dose Plus GSK3377794 | Progression Free Survival (PFS) Assessed by Investigator | 8.74 Months |
Secondary
Time to Cmax (Tmax)
Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.
Time frame: Day 2 to Day 15
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only those participants with data available at the specified data points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Time to Cmax (Tmax) | 2 Days |
| Standard Lymphodepletion Dose Plus GSK3377794 | Time to Cmax (Tmax) | 4 Days |
Secondary
Time to Response (TTR) Assessed by Independent Reviewer
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only responders by independent reviewer were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Time to Response (TTR) Assessed by Independent Reviewer | 2.366 Months |
| Standard Lymphodepletion Dose Plus GSK3377794 | Time to Response (TTR) Assessed by Independent Reviewer | 1.889 Months |
Secondary
Time to Response (TTR) Assessed by Investigator
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.
Time frame: Up to 24 months
Population: Modified Intent-to-Treat (mITT) population which included all participants who underwent leukapheresis and received GSK3377794. Only responders by investigator assessment were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Reduced Lymphodepletion Dose Plus GSK3377794 | Time to Response (TTR) Assessed by Investigator | 1.856 Months |
| Standard Lymphodepletion Dose Plus GSK3377794 | Time to Response (TTR) Assessed by Investigator | 1.938 Months |