Trial Outcomes & Findings for Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma (NCT NCT03168438)

Last Updated: 2022-01-11

Results Overview

An AE is any untoward medical occurrence in a participant or clinical investigation participant who received a study treatment and the event need not necessarily have a causal relationship with study treatment. An SAE is any AE that results in death; is life-threatening; requires hospitalization or prolongation of existing hospitalization; results in a persistent or significant disability; is a congenital anomaly/birth defect; is clinically significant or requires intervention to prevent one of the outcomes listed before.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

6 participants

Primary outcome timeframe

Up to 108 weeks

Results posted on

2022-01-11

Participant Flow

This was a pilot study to assess safety and tolerability of genetically engineered New York esophageal squamous cell carcinoma 1 (NY-ESO-1) (c259) T Cells Alone or in combination with pembrolizumab in participants with relapsed/refractory multiple myeloma. The study was conducted in the United States.

A total of 127 participants were screened of which 6 participants were enrolled in the study. The study was terminated due to challenging screening and enrollment combined with a rapidly changing treatment landscape.

Participant milestones

Participant milestones
Measure	GSK3377794 Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Overall Study STARTED	3	3
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK3377794 Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Overall Study Long term follow-up declined, study terminated by sponsor	0	1

Baseline Characteristics

Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.	Total n=6 Participants Total of all reporting groups
Age, Continuous	66.0 Years STANDARD_DEVIATION 11.27 • n=5 Participants	64.3 Years STANDARD_DEVIATION 2.52 • n=7 Participants	65.2 Years STANDARD_DEVIATION 7.36 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 108 weeks

Population: Intent-To-Treat (ITT) Population comprised of all participants who underwent leukapheresis

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	2 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to 3 weeks

Population: ITT Population. Treatment limiting toxicities were assessed in GSK3377794+pembrolizumab arm only.

The following toxicities were considered to be treatment limiting toxicities: any \>=Grade 4 AE; Grade 3 non-infectious pneumonitis and any other Grade 3 AE (excluding pneumonitis), that did not improve to Grade 2 within 7 days after onset despite medical management and supportive care. Exceptions included the following: Grade 3 or 4 leukopenia, lymphopenia, neutropenia, or febrile neutropenia; Grade 3 or 4 thrombocytopenia not associated with significant bleeding; Grade 3 anemia; Grade 4 cytokine release syndrome (CRS) or toxicities related to CRS that resolved to Grade \<=2 within 7 days; other Grade 3 laboratory abnormality determined to be not clinically significant by the Investigator; Grade 3 or 4 fever and chills; Grade 3 or 4 hypoalbuminemia or abnormal electrolytes that responded to supplementation/correction; AE related to the cancer or its progression.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Number of Participants With Treatment Limiting Toxicities-GSK3377794+Pembrolizumab Arm Only	0 Participants	—

PRIMARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population comprised of all participants in the ITT Population who received the NY-ESO-1c259T infusion.

Blood samples were collected for the assessment of following clinical chemistry parameters: glucose, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, creatinine, potassium, magnesium, phosphate, sodium and calcium. Laboratory parameters were graded according to National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case post Baseline is presented.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Glucose (Hyperglycemia)	2 Participants	2 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Glucose (Hypoglycemia)	0 Participants	0 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline ALP increased	1 Participants	1 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Albumin (Hypoalbuminemia)	3 Participants	2 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline ALT increased	0 Participants	1 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline AST increased	0 Participants	1 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Bilirubin increased	0 Participants	1 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Creatinine increased	1 Participants	3 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Potassium (Hyperkalemia)	0 Participants	0 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Potassium (Hypokalemia)	1 Participants	2 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Magnesium (Hypermagnesemia)	0 Participants	0 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Magnesium (Hypomagnesemia)	2 Participants	1 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Phosphate (Hypophosphatemia)	2 Participants	2 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Sodium (Hypernatremia)	0 Participants	0 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Sodium (Hyponatremia)	2 Participants	1 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Calcium (Hypercalcemia)	1 Participants	0 Participants
Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline Calcium (Hypocalcemia)	2 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population

Blood samples were collected for the assessment of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. Laboratory parameters were graded according to NCI-CTCAE version 4.03 where, Grade1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case post Baseline is presented.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Hemoglobin increased	0 Participants	0 Participants
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Lymphocyte count decreased	3 Participants	3 Participants
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Hemoglobin (Anemia)	2 Participants	3 Participants
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Lymphocyte count increased	0 Participants	0 Participants
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Neutrophil count decreased	3 Participants	3 Participants
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Platelet count decreased	3 Participants	3 Participants
Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline Leukocyte count decreased	3 Participants	3 Participants

PRIMARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population. Only those participants with data available at the specified time point is reported

Blood samples were collected for the assessment of following coagulation parameters: prothrombin time and partial thromboplastin time (PTT). A laboratory value that is outside the normal range is considered either high abnormal (value above the upper limit of the normal range) or low abnormal (value below the lower limit of the normal range). Participants were counted twice if the participant had values in 'Decreased to low' and 'Increased to high' during the post-Baseline period. Data for worst case post Baseline is presented.

Outcome measures

Outcome measures
Measure	GSK3377794 n=1 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline PTT; decrease to low	0 Participants	—
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline Prothrombin Time; decrease to low	0 Participants	—
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline Prothrombin Time; To normal or no change	0 Participants	—
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline Prothrombin Time; increase to high	1 Participants	—
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline PTT; To normal or no change	1 Participants	—
Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline PTT; increase to high	0 Participants	—

PRIMARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population

ECG was recorded using an ECG machine that automatically calculated the heart rate and measured PR, RR, QRS and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Data for number of participants with abnormal clinically significant ECG findings for worst case post-Baseline has been presented. Clinically significant abnormal laboratory findings are those which are not associated with the underlying disease, unless judged by the investigator to be more severe than expected for the participant's condition.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population

Overall response rate is defined as the percentage of participants with a best overall response (BOR) of confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) per International Myeloma Working Group (IMWG) Response Criteria (2016); where, PR: \>=50% reduction of serum M-Protein and reduction in 24-hour urinary M-protein by \>=90% or to \<200 milligrams (mg) per 24 hours; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level \<100 mg per 24 hours; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and \<= 5% plasma cells in bone marrow; or sCR: CR as defined by normal free light chain (FLC) ratio and absence of clonal cells by immunohistochemistry. Confidence intervals were calculated using the exact (Clopper-Pearson) method.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Overall Response Rate	33.3 Percentage of participants Interval 0.8 to 90.6	66.7 Percentage of participants Interval 9.4 to 99.2

SECONDARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population. Only those participants with a confirmed response per IMWG 2016 were analyzed.

Time to response is defined as the time interval (in months) from T-cell infusion to initial date of documented confirmed response (PR or better) in the subset of participants who showed a confirmed BOR of PR or better by Investigator assessment per IMWG (2016).

Outcome measures

Outcome measures
Measure	GSK3377794 n=1 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=2 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Time to Response	0.7 Months Full range is not applicable as only a single participant was analyzed. Median value presented here is the actual time to response for this single participant.	0.7 Months Interval 0.7 to 0.7

SECONDARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population. Only those participants with a confirmed response per IMWG 2016 were analyzed.

Duration of response is defined as the interval between the initial date of the confirmed response (sCR, CR, VGPR, or PR) and the initial assesment date of confirmed progressive disease or death among participants with a confirmed response per IMWG (2016).

Outcome measures

Outcome measures
Measure	GSK3377794 n=1 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=2 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Duration of Response	2.1 Months Full range is not applicable as only a single participant was analyzed. Median value presented here is the actual duration of response for this single participant.	2.1 Months Interval 2.1 to 2.1

SECONDARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population

Progression Free Survival is defined as the interval between the date of T-cell infusion and the initial assessment date of confirmed progressive disease as assessed by the investigator per IMWG (2016) or date of death. Progressive disease is defined as an increase of 25% from lowest confirmed response value in 1 or more of the following criteria: Serum M-protein with absolute increase of \>=0.5 grams per deciliter (g/dL); Serum M-protein increase \>=1 g/dL if the lowest M-component was \>=5 g/dL; Urinary M-protein (absolute increase must be \>=200 mg per 24 hours).

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Progression-free Survival	2.79 Months Interval 1.31 to 5.16	2.78 Months Interval 2.76 to 2.79

SECONDARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population

Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in deoxyribonucleic acid (DNA) extracted from peripheral blood mononuclear cell (PBMC).

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Maximum Persistence (Cmax) of GSK3377794	38509.67 Copies per microgram genomic DNA Geometric Coefficient of Variation 160.5	89640.56 Copies per microgram genomic DNA Geometric Coefficient of Variation 84.8

SECONDARY outcome

Timeframe: Up to 108 weeks

Population: Modified ITT Population

Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Time to Maximum Persistence	8.0 Days Interval 5.0 to 15.0	8.0 Days Interval 7.0 to 15.0

SECONDARY outcome

Timeframe: Up to Day 28

Population: Modified ITT Population

Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.

Outcome measures

Outcome measures
Measure	GSK3377794 n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 Participants Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC[0-28])	463989.35 Days*Copies per microgram genomic DNA Geometric Coefficient of Variation 237.0	1498869.21 Days*Copies per microgram genomic DNA Geometric Coefficient of Variation 90.4

Adverse Events

GSK3377794

Serious events: 2 serious events

Other events: 3 other events

Deaths: 2 deaths

GSK3377794+Pembrolizumab

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	GSK3377794 n=3 participants at risk Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of GSK3377794.	GSK3377794+Pembrolizumab n=3 participants at risk Eligible participants underwent leukapheresis to manufacture engineered T-cells. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single IV infusion of GSK3377794 in combination with pembrolizumab 200 milligrams (mg) administered as an IV infusion every 3 weeks up to Week 108.
Blood and lymphatic system disorders Pancytopenia	33.3% 1/3 • Number of events 1 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.	33.3% 1/3 • Number of events 1 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.
Cardiac disorders Atrial flutter	0.00% 0/3 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.	33.3% 1/3 • Number of events 1 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.
Infections and infestations Bronchitis	33.3% 1/3 • Number of events 1 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.	0.00% 0/3 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.
Infections and infestations Pneumonia	33.3% 1/3 • Number of events 2 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.	0.00% 0/3 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.
Musculoskeletal and connective tissue disorders Back pain	33.3% 1/3 • Number of events 1 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.	0.00% 0/3 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain	33.3% 1/3 • Number of events 1 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.	0.00% 0/3 • Non-serious AEs and SAEs were collected up to 108 weeks. Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER