Neoplasms
Conditions
Keywords
Adoptive T cell therapy, Advanced synovial sarcoma, Advanced Myxoid/Round Cell Liposarcoma, Advanced tumors, GSK3901961, T cell receptor, Leukapheresis, Non-Small Cell Lung Cancer
Brief summary
The primary purpose of this sub study is to assess the safety, tolerability and determine recommended Phase 2 dose (RP2D) of GSK3901961 in HLA A\*02:01, HLA-A\*02:05 and/or HLA A\*02:06 positive participants with New York esophageal squamous cell carcinoma (NY ESO 1) and/or Cancer testis antigen 2 (LAGE 1a) positive previously treated metastatic Non-Small Cell Lung Cancer (NSCLC) and previously treated, advanced (metastatic or unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma SS/MRCLS.
Detailed description
This study is a substudy of the Master record - (209012) NCT04526509.
Interventions
DRUGFludarabine
Fludarabine was administered as lymphodepleting chemotherapy.
DRUGGSK3901961
GSK3901961 was administered.
DRUGCyclophosphamide
Cyclophosphamide was administered as lymphodepleting chemotherapy.
Sponsors
Adaptimmune
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 must be \>=18 years of age and weighs ≥40 kg on the day of signing informed consent * Participant must be positive for HLA-A\*02:01, HLA-A\*02:05, and/or HLA-A\*02:06 alleles * Participant's tumor must have tested positive for NY-ESO-1 and/or LAGE-1a expression by a GSK designated laboratory * Performance status: Eastern Cooperative Oncology Group of 0-1 * Participant must have adequate organ function and blood cell counts 7 days prior to leukapheresis * Participant must have measurable disease according to RECIST v1.1. * Participant has advanced (metastatic or unresectable) SS or MRCLS confirmed by local histopathology with evidence of disease-specific translocation * Participant has completed at least one standard of care (SOC) treatment including anthracycline containing regimen unless intolerant to or ineligible to receive the therapy. * Participants who are not candidates to receive anthracycline should have received ifosfamide unless also intolerant to or ineligible to receive ifosfamide. Participants who received neoadjuvant/adjuvant anthracycline or ifosfamide based therapy and progressed will be eligible * Participant has histologically or cytologically confirmed Stage IV NSCLC * Participant has been previously treated with SOC for Stage IV NSCLC
Exclusion criteria
* Central nervous system (CNS) metastases, with certain exceptions for CNS metastases in NSCLC as specified in the protocol * Any other prior malignancy that is not in complete remission * Clinically significant systemic illness * Prior or active demyelinating disease * History of chronic or recurrent (within the last year prior to leukapheresis) severe autoimmune or immune mediated disease requiring steroids or other immunosuppressive treatments * Previous treatment with genetically engineered NY-ESO-1-specific T cells, NY-ESO-1 vaccine or NY-ESO-1 targeting antibody * Prior gene therapy using an integrating vector * Previous allogeneic hematopoietic stem cell transplant within the last 5 years or solid organ transplant * Washout periods for prior radiotherapy and systemic chemotherapy must be followed * Major surgery within 4 weeks prior to lymphodepletion * Pregnant or breastfeeding females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Up to 28 days | DLT events were graded according to NCI-CTCAE v5.0. DLTs were defined as Grade (Gr) 4 (life-threatening and death) related to GSK3901961 2) Gr 3 (Severe or medically significant) at least possibly related to GSK3901961 and do not resolve to Gr \<=1 (or Baseline) within 7 days from the onset of the event 3) Gr \>=3 non-infectious pneumonitis not responding to oxygen supplementation and systemic steroid treatment 4) Any Gr 3 cytokine release syndrome (CRS) at least possibly related to GSK3901961 that does not improve to Gr \<2 (moderate) toxicity within 7 days with or without dexamethasone 5) Any Gr 4 CRS at least possibly related to study product that does not improve to Gr \<=2 (or Baseline) within 7 days 6) Any Gr 3 or greater neurotoxicity that does not resolve to Gr \<=2 within 72 hours 7) Any Gr \>=3 organ toxicity (exclusive of CRS toxicity) involving major organ systems that persists for \>72 hours and occurs within 28 days of infusion. |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | Up to approximately 21 months | An adverse event (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. AEs and SAEs were graded according to NCI-CTCAE v5.0. 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. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent. SAEs are subset of AEs. Results for maximum severity grades has been presented. |
| Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Up to approximately 21 months | An AESI may be of scientific and medical concern related to the treatment, monitored, and rapidly communicated by investigator to sponsor. AESIs 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), Guillain-Barre Syndrome (GBS), Pneumonitis and treatment-related inflammatory response at tumor site(s) and Neutropenia Grade 4 lasting more than or equal to 28 days. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Cmax (Tmax) of GSK3901961 | Up to 21 days | Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax. |
| Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1 | Up to approximately 21 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 Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. Partial response (PR) was 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 (CR) was 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. |
| Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) | 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). |
| Duration of Response (DoR) | Up to approximately 21 months | DoR is defined as the interval of time (in months) from first documented evidence of the confirmed response (PR or CR) as assessed by local investigators to the date of disease progression per RECIST v1.1 or death due to any cause, among participants with a confirmed response of PR or CR. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. |
| Maximum Transgene Expansion (Cmax) of GSK3901961 | Up to 21 days | Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax. |
Countries
Australia, Canada, Germany, Netherlands, Sweden, United States
Participant flow
Pre-assignment details
This study is a sub study of the master protocol (NCT04526509). The study was terminated due to a change in GSK's R&D priorities.
Participants by arm
| Arm | Count |
|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells Eligible participants were leukapheresed to manufacture engineered T cells. Participants then received 1 × 10\^9 - 8 × 10\^9 cells of GSK3901961 as an intravenous (IV) infusion in two aliquots (approximately 30% on Day 1 and approximately 70% on Day 8) for sentinel participant after completing lymphodepleting chemotherapy regimen that generally consisted of 30 milligram (mg)/meter (m)\^2/day fludarabine for 4 days (Day -7 to -4) and 900mg/ m\^2/day cyclophosphamide for 3 days (Day -6 to -4). | 1 |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells Eligible participants were leukapheresed to manufacture engineered T cells. Participants then received 0.1 × 10\^9 - 0.8 × 10\^9 cells of GSK3901961 as an intravenous (IV) infusion on Day 1 after completing lymphodepleting chemotherapy regimen that generally consisted of 30 milligram (mg)/meter (m)\^2/day fludarabine for 4 days (Day -7 to -4) and 900mg/ m\^2/day cyclophosphamide for 3 days (Day -6 to -4). | 4 |
| No Treatment No Treatment arm consisted of participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy and T cell infusion. | 2 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death prior to lymphodepletion | 0 | 0 | 1 |
| Overall Study | Did not meet Inclusion/Exclusion Criteria | 0 | 0 | 1 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | No Treatment | Total |
|---|---|---|---|---|
| Age, Continuous | 27 years | 51.5 years STANDARD_DEVIATION 17.79 | 43.0 years STANDARD_DEVIATION 0 | 45.6 years STANDARD_DEVIATION 15.53 |
| Age, Customized Age, customized 19-64 | 1 Participants | 3 Participants | 2 Participants | 6 Participants |
| Age, Customized Age, customized >=65 | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 4 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 1 Participants | 4 Participants | 2 Participants | 7 Participants |
| Region of Enrollment Australia | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Germany | 0 participants | 2 participants | 1 participants | 3 participants |
| Region of Enrollment Sweden | 0 participants | 1 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 0 participants | 1 participants | 2 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 1 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 2 / 4 | 1 / 2 |
| other Total, other adverse events | 1 / 1 | 4 / 4 | 1 / 2 |
| serious Total, serious adverse events | 1 / 1 | 2 / 4 | 2 / 2 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
DLT events were graded according to NCI-CTCAE v5.0. DLTs were defined as Grade (Gr) 4 (life-threatening and death) related to GSK3901961 2) Gr 3 (Severe or medically significant) at least possibly related to GSK3901961 and do not resolve to Gr \<=1 (or Baseline) within 7 days from the onset of the event 3) Gr \>=3 non-infectious pneumonitis not responding to oxygen supplementation and systemic steroid treatment 4) Any Gr 3 cytokine release syndrome (CRS) at least possibly related to GSK3901961 that does not improve to Gr \<2 (moderate) toxicity within 7 days with or without dexamethasone 5) Any Gr 4 CRS at least possibly related to study product that does not improve to Gr \<=2 (or Baseline) within 7 days 6) Any Gr 3 or greater neurotoxicity that does not resolve to Gr \<=2 within 72 hours 7) Any Gr \>=3 organ toxicity (exclusive of CRS toxicity) involving major organ systems that persists for \>72 hours and occurs within 28 days of infusion.
Time frame: Up to 28 days
Population: DLT Evaluable included participants in the mITT population (all ITT participants (All participants who started leukapheresis procedure) who received any dose of New York esophageal antigen-1 \[NY ESO 1\] specific T cells) who are part of the dose confirmation phase that either had a DLT or have completed the DLT assessment period of 28 days since last T cell infusion.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity
An adverse event (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. AEs and SAEs were graded according to NCI-CTCAE v5.0. 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. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent. SAEs are subset of AEs. Results for maximum severity grades has been presented.
Time frame: Up to approximately 21 months
Population: Modified intent-to-treat (mITT) population included all ITT participants (All participants who started leukapheresis procedure) who received any dose of NY ESO 1 specific T cells.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 1 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 2 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 3 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 4 | 1 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 5 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 1 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 2 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 3 | 1 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 4 | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 5 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 3 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 1 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 1 | 1 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 2 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 5 | 1 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 3 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 2 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 4 | 3 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | SAEs, Grade 4 | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity | AEs, Grade 5 | 1 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events 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. AESIs 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), Guillain-Barre Syndrome (GBS), Pneumonitis and treatment-related inflammatory response at tumor site(s) and Neutropenia Grade 4 lasting more than or equal to 28 days. AEs which start or worsen on or after T-cell infusion are classified as treatment emergent.
Time frame: Up to approximately 21 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Cytokine Release Syndrome (CRS) | 1 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Haematopoietic cytopenias (including pancytopenia and aplastic anaemia) | 1 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Graft versus host disease | 1 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Immune Effector-Cell Associated Neurotoxicity Syndrome | 0 Participants |
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Participants with any AESI | 1 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Immune Effector-Cell Associated Neurotoxicity Syndrome | 1 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Participants with any AESI | 4 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Cytokine Release Syndrome (CRS) | 3 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Graft versus host disease | 0 Participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI) | Haematopoietic cytopenias (including pancytopenia and aplastic anaemia) | 4 Participants |
Secondary
Area Under the Time Curve From Zero to Time 28 Days AUC(0-28)
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: Pharmacokinetic population
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) | 2267635.372 Days*copies per microgram genomic DNA | — |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Area Under the Time Curve From Zero to Time 28 Days AUC(0-28) | 374639.00 Days*copies per microgram genomic DNA | Geometric Coefficient of Variation 371.441 |
Secondary
Duration of Response (DoR)
DoR is defined as the interval of time (in months) from first documented evidence of the confirmed response (PR or CR) as assessed by local investigators to the date of disease progression per RECIST v1.1 or death due to any cause, among participants with a confirmed response of PR or CR. PR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm.
Time frame: Up to approximately 21 months
Population: Modified intent-to-treat (mITT) population. Only responders (CR or PR) by investigator assessment were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Duration of Response (DoR) | 1.22 Months |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Duration of Response (DoR) | 2.96 Months |
Secondary
Maximum Transgene Expansion (Cmax) of GSK3901961
Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.
Time frame: Up to 21 days
Population: Pharmacokinetic population included participants from the mITT population for whom at least one persistence sample was obtained, analysed, and was measurable.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Maximum Transgene Expansion (Cmax) of GSK3901961 | 121973 Copies per microgram genomic DNA | — |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Maximum Transgene Expansion (Cmax) of GSK3901961 | 29058.02 Copies per microgram genomic DNA | Geometric Coefficient of Variation 401.296 |
Secondary
Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1
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 Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1 relative to the total number of participants in the analysis population. Partial response (PR) was 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 (CR) was 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 approximately 21 months
Population: Modified intent-to-treat (mITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1 | 100 percentage of participants |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1 | 50 percentage of participants |
Secondary
Time to Cmax (Tmax) of GSK3901961
Tmax was defined as time to peak cell expansion during the interventional phase. Blood samples were collected to measure Tmax.
Time frame: Up to 21 days
Population: Pharmacokinetic population included participants from the mITT population for whom at least one persistence sample was obtained, analyzed, and was measurable.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells | Time to Cmax (Tmax) of GSK3901961 | 21 days |
| GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells | Time to Cmax (Tmax) of GSK3901961 | 7.5 days |