Study of GSK3901961 In Previously Treated Advanced (Metastatic OR Unresectable) Synovial Sarcoma/ Myxoid/Round Cell Liposarcoma, and Previously Treated Metastatic Non-Small Cell Lung Cancer

• ClinicalTrials.gov Identifier: NCT06048705
• Recruitment Status: Terminated
• First Posted: September 21, 2023
• Results First Posted: May 10, 2024
• Last Update Posted: May 10, 2024
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neoplasms
• Interventions: Drug: GSK3901961; Drug: Cyclophosphamide; Drug: Fludarabine
• Enrollment: 7

Participant Flow

Recruitment Details
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.

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells	No Treatment
Arm/Group Description	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).	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).	No Treatment arm consisted of participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy and T cell infusion.
Period Title: Overall Study
Started	1	4	2
Transferred to Long-term Follow-up Study	0	2	0
Death Post Lymphodepletion	0	2	0
Completed [1]	0	4 [2]	0
Not Completed	1	0	2
Reason Not Completed
Physician Decision	1	0	0
Did not meet Inclusion/Exclusion Criteria	0	0	1
Death prior to lymphodepletion	0	0	1
[1] Participants who were transferred to the long-term follow-up protocol or have died are considered to have completed.; [2] 2 participants transferred to long-term follow-up study 208750 (NCT03391778) and 2 participants died post lymphodepletion.

Baseline Characteristics

Arm/Group Title		GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells	No Treatment	Total
Arm/Group Description		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).	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).	No Treatment arm consisted of participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy and T cell infusion.	Total of all reporting groups
Overall Number of Baseline Participants		1	4	2	7
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1 participants	4 participants	2 participants	7 participants
		27	51.5 (17.79)	43.0 (0.00)	45.6 (15.53)
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age, customized	Number Analyzed	1 participants	4 participants	2 participants	7 participants
	19-64	1 100.0%	3 75.0%	2 100.0%	6 85.7%
	>=65	0 0.0%	1 25.0%	0 0.0%	1 14.3%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	4 participants	2 participants	7 participants
	Female	1 100.0%	1 25.0%	1 50.0%	3 42.9%
	Male	0 0.0%	3 75.0%	1 50.0%	4 57.1%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	4 participants	2 participants	7 participants
	Hispanic or Latino	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Not Hispanic or Latino	1 100.0%	4 100.0%	2 100.0%	7 100.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
White	Number Analyzed	1 participants	4 participants	2 participants	7 participants
		1 100.0%	4 100.0%	2 100.0%	7 100.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants	Number Analyzed	1 participants	4 participants	2 participants	7 participants
Australia		0	1	0	1
Germany		0	2	1	3
Sweden		0	1	0	1
United States		1	0	1	2

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Dose Limiting Toxicities (DLTs)
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Measure Type: Count of Participants; Unit of Measure: Participants
	1 100.0%	1 25.0%

2. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious AEs Based on Maximum Severity
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Measure Type: Count of Participants; Unit of Measure: Participants
AEs, Grade 1	0 0.0%	0 0.0%
AEs, Grade 2	0 0.0%	0 0.0%
AEs, Grade 3	0 0.0%	0 0.0%
AEs, Grade 4	1 100.0%	3 75.0%
AEs, Grade 5	0 0.0%	1 25.0%
SAEs, Grade 1	0 0.0%	1 25.0%
SAEs, Grade 2	0 0.0%	0 0.0%
SAEs, Grade 3	1 100.0%	0 0.0%
SAEs, Grade 4	0 0.0%	0 0.0%
SAEs, Grade 5	0 0.0%	1 25.0%

3. Primary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events of Special Interest (AESI)
Description	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

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Measure Type: Count of Participants; Unit of Measure: Participants
Participants with any AESI	1 100.0%	4 100.0%
Cytokine Release Syndrome (CRS)	1 100.0%	3 75.0%
Graft versus host disease	1 100.0%	0 0.0%
Haematopoietic cytopenias (including pancytopenia and aplastic anaemia)	1 100.0%	4 100.0%
Immune Effector-Cell Associated Neurotoxicity Syndrome	0 0.0%	1 25.0%

4. Secondary Outcome

Title	Overall Response Rate (ORR) Assessed by Investigator According to RECIST v1.1
Description	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

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	100; (2.5 to 100)	50; (6.8 to 93.2)

5. Secondary Outcome

Title	Duration of Response (DoR)
Description	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

Outcome Measure Data

Analysis Population Description

Modified intent-to-treat (mITT) population. Only responders (CR or PR) by investigator assessment were included in this analysis.

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	2
Median (Full Range); Unit of Measure: Months
	1.22 [1]; (NA to NA)	2.96; (2.8 to 3.1)

[1]

Full range is not applicable as only a single participant was analyzed. Median value presented here is the duration of response for this single participant who was censored at their last tumor assessment prior to study withdrawal.

6. Secondary Outcome

Title	Maximum Transgene Expansion (Cmax) of GSK3901961
Description	Cmax was defined as peak cell expansion during the interventional phase. Blood samples were collected to measure Cmax.
Time Frame	Up to 21 days

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants from the mITT population for whom at least one persistence sample was obtained, analysed, and was measurable.

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Copies per microgram genomic DNA
	121973 [1]; (NA%)	29058.02; (401.296%)

[1]

Geometric coefficient of variation is not applicable as only a single participant was analyzed. Geometric mean value presented here is the actual Cmax.

7. Secondary Outcome

Title	Time to Cmax (Tmax) of GSK3901961
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population included participants from the mITT population for whom at least one persistence sample was obtained, analyzed, and was measurable.

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Median (Full Range); Unit of Measure: days
	21 [1]; (NA to NA)	7.5; (1 to 20)

[1]

Full range is not applicable as only a single participant was analyzed. Median value presented here is the actual Tmax for this single participant.

8. Secondary Outcome

Title	Area Under the Time Curve From Zero to Time 28 Days AUC(0-28)
Description	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

Outcome Measure Data

Analysis Population Description

Pharmacokinetic population

Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells	GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells
Arm/Group Description:	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).	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).
Overall Number of Participants Analyzed	1	4
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Days*copies per microgram genomic DNA
	2267635.372 [1]; (NA%)	374639.00; (371.441%)

[1]

Geometric coefficient of variation is not applicable as only a single participant was analyzed. Geometric mean value presented here is the actual AUC(0-28).

Adverse Events

Time Frame	All-cause mortality, non-serious adverse events (Non-SAEs) and serious adverse events (SAEs) were collected up to approximately 21 months.
Adverse Event Reporting Description	All-cause mortality, SAEs and non-SAEs were reported for intent-to-treat (ITT) population that included all participants who started leukapheresis procedure.
Arm/Group Title	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells		GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells		No Treatment
Arm/Group Description	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).		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).		No Treatment arm consisted of participants who underwent leukapheresis but did not go on to receive lymphodepletion chemotherapy and T cell infusion.
All-Cause Mortality
	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells		GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells		No Treatment
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/1 (0.00%)		2/4 (50.00%)		1/2 (50.00%)
Serious Adverse Events
	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells		GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells		No Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		2/4 (50.00%)		2/2 (100.00%)
Blood and lymphatic system disorders
Neutropenia † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Cardiac disorders
Atrial fibrillation † 1	0/1 (0.00%)	0	0/4 (0.00%)	0	1/2 (50.00%)	1
Pericardial effusion † 1	0/1 (0.00%)	0	0/4 (0.00%)	0	1/2 (50.00%)	1
General disorders
Non-cardiac chest pain † 1	1/1 (100.00%)	2	0/4 (0.00%)	0	0/2 (0.00%)	0
Pyrexia † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Immune system disorders
Graft versus host disease in skin † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Musculoskeletal and connective tissue disorders
Pain in extremity † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Haemoptysis † 1	0/1 (0.00%)	0	0/4 (0.00%)	0	1/2 (50.00%)	1
Pulmonary haemorrhage † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Skin and subcutaneous tissue disorders
Rash maculo-papular † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
1 Term from vocabulary, MedDRA (26.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	GSK3901961 1 × 10^9 - 8 × 10^9 Transduced Cells		GSK3901961 0.1 × 10^9 - 0.8 × 10^9 Transduced Cells		No Treatment
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1 (100.00%)		4/4 (100.00%)		1/2 (50.00%)
Blood and lymphatic system disorders
Anaemia † 1	1/1 (100.00%)	1	2/4 (50.00%)	3	1/2 (50.00%)	1
Thrombocytopenia † 1	1/1 (100.00%)	1	2/4 (50.00%)	2	0/2 (0.00%)	0
Leukopenia † 1	0/1 (0.00%)	0	2/4 (50.00%)	3	0/2 (0.00%)	0
Leukocytosis † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Neutropenia † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Eye disorders
Diplopia † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Eyelid ptosis † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Gastrointestinal disorders
Nausea † 1	1/1 (100.00%)	2	3/4 (75.00%)	4	0/2 (0.00%)	0
Constipation † 1	0/1 (0.00%)	0	2/4 (50.00%)	2	1/2 (50.00%)	1
Abdominal pain † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Anal incontinence † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Diarrhoea † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Gastrooesophageal reflux disease † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Lower gastrointestinal haemorrhage † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Vomiting † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
General disorders
Fatigue † 1	1/1 (100.00%)	1	1/4 (25.00%)	1	1/2 (50.00%)	1
Non-cardiac chest pain † 1	1/1 (100.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0
Pyrexia † 1	0/1 (0.00%)	0	2/4 (50.00%)	2	0/2 (0.00%)	0
Face oedema † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Injection site pain † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Mucosal dryness † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Pain † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Immune system disorders
Cytokine release syndrome † 1	1/1 (100.00%)	1	3/4 (75.00%)	3	0/2 (0.00%)	0
Infections and infestations
COVID-19 † 1	1/1 (100.00%)	1	2/4 (50.00%)	2	1/2 (50.00%)	1
Rhinovirus infection † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Staphylococcal infection † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Staphylococcal skin infection † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Urinary tract infection † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Investigations
Alanine aminotransferase increased † 1	1/1 (100.00%)	1	2/4 (50.00%)	2	0/2 (0.00%)	0
Aspartate aminotransferase increased † 1	1/1 (100.00%)	1	2/4 (50.00%)	2	0/2 (0.00%)	0
Neutrophil count decreased † 1	1/1 (100.00%)	1	2/4 (50.00%)	3	0/2 (0.00%)	0
Blood lactate dehydrogenase increased † 1	1/1 (100.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0
C-reactive protein increased † 1	0/1 (0.00%)	0	2/4 (50.00%)	4	0/2 (0.00%)	0
Procalcitonin increased † 1	0/1 (0.00%)	0	2/4 (50.00%)	3	0/2 (0.00%)	0
White blood cell count decreased † 1	1/1 (100.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0
Blood alkaline phosphatase increased † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Blood phosphorus decreased † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Blood potassium increased † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Interleukin level increased † 1	0/1 (0.00%)	0	1/4 (25.00%)	2	0/2 (0.00%)	0
Lymphocyte count decreased † 1	1/1 (100.00%)	2	0/4 (0.00%)	0	0/2 (0.00%)	0
Platelet count decreased † 1	0/1 (0.00%)	0	2/4 (50.00%)	2	0/2 (0.00%)	0
Serum ferritin increased † 1	0/1 (0.00%)	0	1/4 (25.00%)	2	0/2 (0.00%)	0
Troponin increased † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	1/2 (50.00%)	1
Hypoalbuminaemia † 1	1/1 (100.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0
Hypokalaemia † 1	1/1 (100.00%)	1	1/4 (25.00%)	1	0/2 (0.00%)	0
Hypercalcaemia † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Musculoskeletal and connective tissue disorders
Muscle spasms † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Myalgia † 1	0/1 (0.00%)	0	0/4 (0.00%)	0	1/2 (50.00%)	1
Sacral pain † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Metastases to central nervous system † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Tumour pain † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Nervous system disorders
Dizziness † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Dizziness postural † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Headache † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Hypoaesthesia † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
IIIrd nerve paresis † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Immune effector cell-associated neurotoxicity syndrome † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Neuralgia † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Paraesthesia † 1	0/1 (0.00%)	0	1/4 (25.00%)	2	0/2 (0.00%)	0
Paresis † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Somnolence † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Psychiatric disorders
Insomnia † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Renal and urinary disorders
Dysuria † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Reproductive system and breast disorders
Vaginal discharge † 1	1/1 (100.00%)	1	0/4 (0.00%)	0	0/2 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnoea † 1	1/1 (100.00%)	1	1/4 (25.00%)	2	1/2 (50.00%)	1
Cough † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Pleuritic pain † 1	0/1 (0.00%)	0	0/4 (0.00%)	0	1/2 (50.00%)	1
Skin and subcutaneous tissue disorders
Rash † 1	0/1 (0.00%)	0	2/4 (50.00%)	2	0/2 (0.00%)	0
Alopecia † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Pruritus † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
Skin fissures † 1	0/1 (0.00%)	0	1/4 (25.00%)	1	0/2 (0.00%)	0
1 Term from vocabulary, MedDRA (26.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343
• EMail: GSKClinicalSupportHD@gsk.com

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT06048705
• Other Study ID Numbers: 209012 Substudy 1
• First Submitted: September 15, 2023
• First Posted: September 21, 2023
• Results First Submitted: November 20, 2023
• Results First Posted: May 10, 2024
• Last Update Posted: May 10, 2024