Trial Outcomes & Findings for Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC) (NCT NCT02588612)

Last Updated: 2021-09-05

Results Overview

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or is clinically significant or requires intervention to prevent one of the outcomes listed before. Number of participants with common (greater than or equal to \[\>=\]5 percent\[%\]) non-serious AEs and SAEs are presented.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

10 participants

Primary outcome timeframe

Up to 24 months

Results posted on

2021-09-05

Participant Flow

This was an open-label study evaluating the safety and tolerability of autologous T-Cells expressing enhanced T-cell receptors (TCRs) specific for New York esophageal squamous cell carcinoma (NY-ESO)-1 (letetresgene autoleucel, lete-cel, GSK3377794) in Human Leukocyte Antigen (HLA)-A\*02:01, HLA-A\*02:05 and/or HLA-A\*02:06 participants with stage IIIb or stage IV non-small cell lung cancer (NSCLC).

Participants were screened for the specified HLA alleles and target antigen expression (NY-ESO-1), and evaluated for study eligibility. A total of 10 participants who met all the eligibility criteria were enrolled in this study which consisted of Intent-to-Treat (ITT) population. This study was conducted across 3 sites in the United States.

Participant milestones

Participant milestones
Measure	Lete-cel Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Overall Study STARTED	10
Overall Study Received T-cell Infusion	5
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Lete-cel Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Overall Study Physician Decision	1
Overall Study Leukapheresis did not yield enough cells	1
Overall Study Failed eligibility prior to chemotherapy	2
Overall Study Death prior to T-cell infusion	1

Baseline Characteristics

Letetresgene Autoleucel Engineered T Cells in NY-ESO -1 Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lete-cel n=10 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Age, Continuous Overall study	57.7 Years STANDARD_DEVIATION 12.91 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants
Race/Ethnicity, Customized White	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: ITT population consisted of all participants who were enrolled in the trial and met all eligibility criteria.

Outcome measures

Outcome measures
Measure	Lete-cel n=10 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) Non SAEs	6 Participants
Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	4 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: Modified (m)ITT population consisted of all participants in the ITT population who received NYESO-1 T cell infusion.

Blood samples were collected for the analysis of following hematology parameters: hemoglobin, lymphocytes, neutrophils, platelets and leukocytes. 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. Baseline is the most recent, non-missing value from a central laboratory within 7 days prior to the lymphodepleting chemotherapy. An increase in grade is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst-case post-Baseline is presented

Outcome measures

Outcome measures
Measure	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Hemoglobin increased	0 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Hemoglobin (Anemia)	3 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Lymphocytes increased	1 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Lymphocytes decreased	5 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Neutrophils	5 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Platelets	5 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Leukocytes (Leukocytosis)	0 Participants
Number of Participants With Hematology Results by Maximum Grade Increase Post-Baseline Leukocytes (Leukopenia)	5 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: mITT Population

Blood samples were collected for analysis of clinical chemistry parameters: glucose (Gl), albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (Bil), creatinine (Creat), potassium (Pot), magnesium (Mg), phosphate (Ph), sodium (Sod) and calcium. 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	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Gl, Hyperglycemia	2 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Gl, Hypoglycemia	0 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Albumin	2 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters ALP	2 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters ALT	3 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters AST	4 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Bil	1 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Creat	1 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Pot, Hyperkalemia	2 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Pot, Hypokalemia	1 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Mg, Hypermagnesemia	0 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Mg, Hypomagnesemia	2 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Ph	4 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Sod, Hypernatremia	0 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Sod, Hyponatremia	1 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Calcium, Hypercalcemia	1 Participants
Number of Participants With Any Grade Increase in Clinical Chemistry Parameters Calcium, Hypocalcemia	3 Participants

PRIMARY outcome

Timeframe: Up to 24 months

Population: mITT Population

12-lead ECGs were recorded in semi-supine position after 5 minutes rest 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 not clinically significant (NCS) and clinically significant (CS) ECG findings for worst case post-Baseline have 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	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Abnormal, NCS	2 Participants
Number of Participants With Worst Case Post-Baseline Abnormal Electrocardiogram (ECG) Findings Abnormal, CS	1 Participants

PRIMARY outcome

Timeframe: Baseline, Day 1 (pre-dose, 5, 15, and 30 minutes, 1, 1.5, 2, and 4 hours post dose), Days 2, 3, 4, 5, 8 and Week 2

Population: mITT Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in category titles).

Oxygen saturation measures the capacity of blood to transport oxygen to other parts of the body. Oxygen saturation was measured using a pulse oximeter. Baseline is the most recent, non-missing value within 7 days prior to initiating the lymphodepleting chemotherapy. Change from Baseline is the post-Baseline visit value minus Baseline value.

Outcome measures

Outcome measures
Measure	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Change From Baseline in Oxygen Saturation Day 2, n=4	2.5 Percentage of oxygen Interval 1.0 to 4.0
Change From Baseline in Oxygen Saturation Day 1, pre dose, n=5	2.0 Percentage of oxygen Interval -2.0 to 6.0
Change From Baseline in Oxygen Saturation Day 1, 5 minutes post dose, n=4	2.5 Percentage of oxygen Interval 1.0 to 3.0
Change From Baseline in Oxygen Saturation Day 1, 15 minutes post dose, n=4	2.0 Percentage of oxygen Interval -3.0 to 5.0
Change From Baseline in Oxygen Saturation Day 1, 30 minutes post dose, n=4	3.0 Percentage of oxygen Interval -2.0 to 3.0
Change From Baseline in Oxygen Saturation Day 1, 1 hour post dose, n=5	2.0 Percentage of oxygen Interval -2.0 to 5.0
Change From Baseline in Oxygen Saturation Day 1, 1.5 hours post dose, n=2	1.5 Percentage of oxygen Interval 1.0 to 2.0
Change From Baseline in Oxygen Saturation Day 1, 2 hours post dose, n=3	3.0 Percentage of oxygen Interval 2.0 to 5.0
Change From Baseline in Oxygen Saturation Day 1, 4 hours post dose, n=4	-1.0 Percentage of oxygen Interval -3.0 to 3.0
Change From Baseline in Oxygen Saturation Day 3, n=5	1.0 Percentage of oxygen Interval -1.0 to 4.0
Change From Baseline in Oxygen Saturation Day 4 , n=5	1.0 Percentage of oxygen Interval -3.0 to 4.0
Change From Baseline in Oxygen Saturation Day 5, n=5	-2.0 Percentage of oxygen Interval -3.0 to 4.0
Change From Baseline in Oxygen Saturation Day 8, n=4	0.0 Percentage of oxygen Interval -1.0 to 1.0
Change From Baseline in Oxygen Saturation Week 2, n=4	1.5 Percentage of oxygen Interval 1.0 to 3.0

SECONDARY outcome

Timeframe: Up to 24 Months

Population: mITT Population

ORR is defined as the percentage of participants with a confirmed Partial response (PR) or Complete response (CR) as the Best overall response (BOR), as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Confidence Interval (CI) was calculated using the exact method. Partial response is defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the Baseline sum diameters. Complete response is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters.

Outcome measures

Outcome measures
Measure	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Overall Response Rate (ORR)	20 Percentage of participants Interval 0.5 to 71.6

SECONDARY outcome

Timeframe: Up to 24 months

Population: mITT Population. Only those participants with data available at the specified data points were analyzed.

Time to response is defined as the interval of time (in months) between the date of T-cell infusion and the first documented evidence of response (PR or CR) in the subset of participants with a confirmed PR or CR as the BOR as assessed by the investigator per RECIST v1.1.

Outcome measures

Outcome measures
Measure	Lete-cel n=1 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Time to Response	12.09 Months

SECONDARY outcome

Timeframe: Up to 24 months

Population: mITT Population. Only those participants with data available at the specified data points were analyzed.

Duration of response (DoR), defined as the interval of time in months from first documented evidence of PR or better to the time when disease progression is documented as assessed by RECIST v1.1 or death due to any cause among participants with a confirmed PR or CR as the BOR.

Outcome measures

Outcome measures
Measure	Lete-cel n=1 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Duration of Response	6.18 Months

SECONDARY outcome

Timeframe: Up to 24 months

Population: mITT Population

DCR is defined as the percentage of participants with a stable disease (SD) or better as the BOR (Confirmed PR, confirmed CR, or SD \>=12 weeks), as assessed by the investigator per RECIST v1.1. CI was calculated using the exact method.

Outcome measures

Outcome measures
Measure	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Disease Control Rate (DCR)	20 Percentage of participants Interval 0.5 to 71.6

SECONDARY outcome

Timeframe: Up to 24 months

Population: mITT Population

Progression-free survival (PFS) is defined as the interval of time (in months) between the date of T-cell infusion and the earlier of the date of disease progression as assessed by the investigator and the date of death due to any cause. Progressive Disease (PD) is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. PFS based on responses assessed by investigator per RECIST v1.1 is presented. Median and inter-quartile range (first quartile and third quartile) are presented.

Outcome measures

Outcome measures
Measure	Lete-cel n=5 Participants Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Progression-Free Survival (PFS) by Investigator Assessment	1.81 Months Interval 0.99 to 5.29

Adverse Events

Lete-cel

Serious events: 4 serious events

Other events: 6 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Lete-cel n=10 participants at risk Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Immune system disorders Cytokine release syndrome	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Infections and infestations Pneumonia	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Blood and lymphatic system disorders Anaemia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Constipation	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Nausea	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Encephalopathy	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Haemorrhage intracranial	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Respiratory, thoracic and mediastinal disorders Respiratory distress	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Skin and subcutaneous tissue disorders Rash maculo-papular	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Vascular disorders Hypotension	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.

Other adverse events

Other adverse events
Measure	Lete-cel n=10 participants at risk Eligible participants were leukapheresed to manufacture lete-cel. Participants then underwent lymphodepleting chemotherapy with cyclophosphamide and fludarabine followed by a single intravenous (IV) infusion of lete-cel.
Investigations Lymphocyte count decreased	50.0% 5/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Investigations White blood cell count decreased	50.0% 5/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Investigations Neutrophil count decreased	40.0% 4/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Investigations Platelet count decreased	40.0% 4/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Investigations Alanine aminotransferase increased	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Investigations Aspartate aminotransferase increased	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Blood and lymphatic system disorders Anaemia	40.0% 4/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Blood and lymphatic system disorders Neutropenia	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Blood and lymphatic system disorders Leukocytosis	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Blood and lymphatic system disorders Lymph node pain	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Blood and lymphatic system disorders Pancytopenia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Nausea	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Abdominal distension	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Constipation	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Diarrhoea	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Gastrointestinal disorders Vomiting	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
General disorders Fatigue	30.0% 3/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
General disorders Oedema peripheral	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
General disorders Asthenia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
General disorders Chills	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
General disorders Pyrexia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Musculoskeletal and connective tissue disorders Back pain	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Musculoskeletal and connective tissue disorders Muscular weakness	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Musculoskeletal and connective tissue disorders Bone pain	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Headache	30.0% 3/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Lethargy	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Memory impairment	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Paralysis	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Peripheral sensory neuropathy	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Nervous system disorders Spinal cord compression	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Cardiac disorders Sinus tachycardia	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Cardiac disorders Supraventricular tachycardia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Cardiac disorders Ventricular tachycardia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Infections and infestations Bronchitis	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Infections and infestations Pneumonia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Infections and infestations Strongyloidiasis	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Infections and infestations Vulvovaginal mycotic infection	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Metabolism and nutrition disorders Decreased appetite	30.0% 3/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Metabolism and nutrition disorders Dehydration	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Metabolism and nutrition disorders Hyperkalaemia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Metabolism and nutrition disorders Hypocalcaemia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Metabolism and nutrition disorders Hypophosphataemia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Psychiatric disorders Confusional state	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Psychiatric disorders Insomnia	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Psychiatric disorders Anxiety	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Respiratory, thoracic and mediastinal disorders Hypoxia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Respiratory, thoracic and mediastinal disorders Pleural effusion	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Skin and subcutaneous tissue disorders Alopecia	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Skin and subcutaneous tissue disorders Rash macular	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Skin and subcutaneous tissue disorders Rash pruritic	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Skin and subcutaneous tissue disorders Urticaria	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Vascular disorders Hypotension	20.0% 2/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Renal and urinary disorders Urinary retention	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.
Reproductive system and breast disorders Pelvic pain	10.0% 1/10 • All-cause mortality, SAEs and common (>=5%) non-serious AEs were collected from the enrollment to 24 months All-cause mortality, SAEs and common non-serious AEs were reported for the ITT Population which comprised of all participants enrolled in the study.

Additional Information

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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.
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