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

• ClinicalTrials.gov Identifier: NCT03168438
• Recruitment Status: Terminated
• First Posted: May 30, 2017
• Results First Posted: January 11, 2022
• Last Update Posted: January 11, 2022
• Sponsor: GlaxoSmithKline
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Neoplasms
• Interventions: Drug: Letetresgene autoleucel; Drug: Letetresgene autoleucel with pembrolizumab; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Pembrolizumab
• Enrollment: 6

Participant Flow

Recruitment Details	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.
Pre-assignment Details	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.

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description	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.	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.
Period Title: Overall Study
Started	3	3
Completed	3	2
Not Completed	0	1
Reason Not Completed
Long term follow-up declined, study terminated by sponsor	0	1

Baseline Characteristics

Arm/Group Title		GSK3377794	GSK3377794+Pembrolizumab	Total
Arm/Group Description		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.	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 of all reporting groups
Overall Number of Baseline Participants		3	3	6
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	3 participants	3 participants	6 participants
		66.0 (11.27)	64.3 (2.52)	65.2 (7.36)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	3 participants	6 participants
	Female	0 0.0%	0 0.0%	0 0.0%
	Male	3 100.0%	3 100.0%	6 100.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	3 participants	3 participants	6 participants
	White	3 100.0%	3 100.0%	6 100.0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description	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.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Any AE	3 100.0%	3 100.0%
Any SAE	2 66.7%	2 66.7%

2. Primary Outcome

Title	Number of Participants With Treatment Limiting Toxicities-GSK3377794+Pembrolizumab Arm Only
Description	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.
Time Frame	Up to 3 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK3377794+Pembrolizumab
Arm/Group Description:	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 Number of Participants Analyzed	3
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%

3. Primary Outcome

Title	Number of Participants With Worst-case Chemistry Results by Any Grade Increase Post-Baseline Relative to Baseline
Description	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.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Glucose (Hyperglycemia)	2 66.7%	2 66.7%
Glucose (Hypoglycemia)	0 0.0%	0 0.0%
Albumin (Hypoalbuminemia)	3 100.0%	2 66.7%
ALP increased	1 33.3%	1 33.3%
ALT increased	0 0.0%	1 33.3%
AST increased	0 0.0%	1 33.3%
Bilirubin increased	0 0.0%	1 33.3%
Creatinine increased	1 33.3%	3 100.0%
Potassium (Hyperkalemia)	0 0.0%	0 0.0%
Potassium (Hypokalemia)	1 33.3%	2 66.7%
Magnesium (Hypermagnesemia)	0 0.0%	0 0.0%
Magnesium (Hypomagnesemia)	2 66.7%	1 33.3%
Phosphate (Hypophosphatemia)	2 66.7%	2 66.7%
Sodium (Hypernatremia)	0 0.0%	0 0.0%
Sodium (Hyponatremia)	2 66.7%	1 33.3%
Calcium (Hypercalcemia)	1 33.3%	0 0.0%
Calcium (Hypocalcemia)	2 66.7%	3 100.0%

4. Primary Outcome

Title	Number of Participants With Worst-case Hematology Results by Any Grade Increase Post-Baseline Relative to Baseline
Description	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.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
Hemoglobin (Anemia)	2 66.7%	3 100.0%
Hemoglobin increased	0 0.0%	0 0.0%
Lymphocyte count decreased	3 100.0%	3 100.0%
Lymphocyte count increased	0 0.0%	0 0.0%
Neutrophil count decreased	3 100.0%	3 100.0%
Platelet count decreased	3 100.0%	3 100.0%
Leukocyte count decreased	3 100.0%	3 100.0%

5. Primary Outcome

Title	Number of Participants With Worst-case Results for Coagulation Parameters Relative to Normal Range Post-Baseline Relative to Baseline
Description	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.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	1	0
Measure Type: Count of Participants; Unit of Measure: Participants
Prothrombin Time; decrease to low	0 0.0%
Prothrombin Time; To normal or no change	0 0.0%
Prothrombin Time; increase to high	1 100.0%
PTT; decrease to low	0 0.0%
PTT; To normal or no change	1 100.0%
PTT; increase to high	0 0.0%

6. Primary Outcome

Title	Number of Participants With Worst-case Post Baseline Abnormal Electrocardiogram (ECG) Findings
Description	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.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	1 33.3%

7. Secondary Outcome

Title	Overall Response Rate
Description	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.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	33.3; (0.8 to 90.6)	66.7; (9.4 to 99.2)

8. Secondary Outcome

Title	Time to Response
Description	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).
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	1	2
Median (Full Range); Unit of Measure: Months
	0.7 [1]; (NA to NA)	0.7; (0.7 to 0.7)

[1]

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.

9. Secondary Outcome

Title	Duration of Response
Description	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).
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	1	2
Median (Full Range); Unit of Measure: Months
	2.1 [1]; (NA to NA)	2.1; (2.1 to 2.1)

[1]

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.

10. Secondary Outcome

Title	Progression-free Survival
Description	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).
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Median (Inter-Quartile Range); Unit of Measure: Months
	2.79; (1.31 to 5.16)	2.78; (2.76 to 2.79)

11. Secondary Outcome

Title	Maximum Persistence (Cmax) of GSK3377794
Description	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).
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Copies per microgram genomic DNA
	38509.67; (160.5%)	89640.56; (84.8%)

12. Secondary Outcome

Title	Time to Maximum Persistence
Description	Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.
Time Frame	Up to 108 weeks

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Median (Full Range); Unit of Measure: Days
	8.0; (5 to 15)	8.0; (7 to 15)

13. Secondary Outcome

Title	Area Under the Plasma Concentration-time Curve From Zero to Day 28 (AUC[0-28])
Description	Blood samples were collected to measure persistence of infused GSK3377794 using polymerase chain reaction of a vector specific sequence in DNA extracted from PBMC.
Time Frame	Up to Day 28

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	GSK3377794	GSK3377794+Pembrolizumab
Arm/Group Description:	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.	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 Number of Participants Analyzed	3	3
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: Days*Copies per microgram genomic DNA
	463989.35; (237.0%)	1498869.21; (90.4%)

Adverse Events

Time Frame	Non-serious AEs and SAEs were collected up to 108 weeks.
Adverse Event Reporting Description	Non-serious AEs and SAEs were collected in the ITT Population. All-cause mortality was collected in the modified ITT Population.
Arm/Group Title	GSK3377794		GSK3377794+Pembrolizumab
Arm/Group Description	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.		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.
All-Cause Mortality
	GSK3377794		GSK3377794+Pembrolizumab
	Affected / at Risk (%)		Affected / at Risk (%)
Total	2/3 (66.67%)		0/3 (0.00%)
Serious Adverse Events
	GSK3377794		GSK3377794+Pembrolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/3 (66.67%)		2/3 (66.67%)
Blood and lymphatic system disorders
Pancytopenia † 1	1/3 (33.33%)	1	1/3 (33.33%)	1
Cardiac disorders
Atrial flutter † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Infections and infestations
Bronchitis † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Pneumonia † 1	1/3 (33.33%)	2	0/3 (0.00%)	0
Musculoskeletal and connective tissue disorders
Back pain † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
1 Term from vocabulary, MedDRA 24.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	GSK3377794		GSK3377794+Pembrolizumab
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/3 (100.00%)		3/3 (100.00%)
Blood and lymphatic system disorders
Anaemia † 1	3/3 (100.00%)	6	3/3 (100.00%)	4
Thrombocytopenia † 1	1/3 (33.33%)	1	3/3 (100.00%)	4
Leukopenia † 1	1/3 (33.33%)	2	2/3 (66.67%)	2
Lymphopenia † 1	1/3 (33.33%)	1	2/3 (66.67%)	3
Neutropenia † 1	1/3 (33.33%)	4	2/3 (66.67%)	2
Cardiac disorders
Atrial fibrillation † 1	1/3 (33.33%)	1	2/3 (66.67%)	2
Endocrine disorders
Hypothyroidism † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Gastrointestinal disorders
Diarrhoea † 1	2/3 (66.67%)	2	2/3 (66.67%)	4
Nausea † 1	0/3 (0.00%)	0	2/3 (66.67%)	2
Constipation † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Stomatitis † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
General disorders
Fatigue † 1	1/3 (33.33%)	1	2/3 (66.67%)	2
Oedema peripheral † 1	1/3 (33.33%)	1	2/3 (66.67%)	3
Pyrexia † 1	1/3 (33.33%)	1	2/3 (66.67%)	2
Chills † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Influenza like illness † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Mucosal inflammation † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Non-cardiac chest pain † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Immune system disorders
Cytokine release syndrome † 1	1/3 (33.33%)	1	2/3 (66.67%)	2
Graft versus host disease in skin † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Seasonal allergy † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Infections and infestations
Rash pustular † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Upper respiratory tract infection † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Injury, poisoning and procedural complications
Femur fracture † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Rib fracture † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Wound † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Investigations
White blood cell count decreased † 1	2/3 (66.67%)	10	1/3 (33.33%)	2
Blood lactate dehydrogenase increased † 1	1/3 (33.33%)	1	1/3 (33.33%)	1
Lymphocyte count decreased † 1	2/3 (66.67%)	4	0/3 (0.00%)	0
Neutrophil count decreased † 1	2/3 (66.67%)	8	0/3 (0.00%)	0
Platelet count decreased † 1	2/3 (66.67%)	2	0/3 (0.00%)	0
Blood albumin decreased † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Blood alkaline phosphatase increased † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Blood calcium increased † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Blood phosphorus decreased † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Blood potassium decreased † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Blood uric acid increased † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Metabolism and nutrition disorders
Hypocalcaemia † 1	2/3 (66.67%)	2	1/3 (33.33%)	1
Hypoalbuminaemia † 1	2/3 (66.67%)	3	0/3 (0.00%)	0
Hyponatraemia † 1	2/3 (66.67%)	2	0/3 (0.00%)	0
Hypophosphataemia † 1	2/3 (66.67%)	7	0/3 (0.00%)	0
Decreased appetite † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Hypercalcaemia † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Hyperphosphataemia † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthralgia † 1	0/3 (0.00%)	0	2/3 (66.67%)	2
Bone lesion † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Bone pain † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Flank pain † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Muscular weakness † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Plasmacytoma † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Seborrhoeic keratosis † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Nervous system disorders
Amnesia † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Dizziness † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Headache † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Hypoaesthesia † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Immune effector cell-associated neurotoxicity syndrome † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Neuropathy peripheral † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Syncope † 1	0/3 (0.00%)	0	1/3 (33.33%)	2
Tremor † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Psychiatric disorders
Insomnia † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Mental status changes † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Renal and urinary disorders
Acute kidney injury † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Dysuria † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Respiratory, thoracic and mediastinal disorders
Cough † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Dyspnoea † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Epistaxis † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Hypoxia † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Pleural effusion † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Skin and subcutaneous tissue disorders
Alopecia † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Dermatitis acneiform † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Pruritus † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Rash maculo-papular † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Rash pruritic † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Skin lesion † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Stasis dermatitis † 1	0/3 (0.00%)	0	1/3 (33.33%)	1
Vascular disorders
Hypertension † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
Hypotension † 1	1/3 (33.33%)	1	0/3 (0.00%)	0
1 Term from vocabulary, MedDRA 24.0; † 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: NCT03168438
• Other Study ID Numbers: 208470; ADP-0011-008 ( Other Identifier: Adaptimmune Therapeutics ); KEYNOTE-487 ( Other Identifier: Merck Sharp and Dohme Corp. )
• First Submitted: May 24, 2017
• First Posted: May 30, 2017
• Results First Submitted: November 9, 2021
• Results First Posted: January 11, 2022
• Last Update Posted: January 11, 2022