Efficacy and Safety Study of Stereotactic Body Radiothera... | NCT03924869

ID	Type	Description
MK-3475-867	Other Identifier	MSD
KEYNOTE-867	Other Identifier	MSD
194909	Registry Identifier	JAPAC-CTI
2022-500413-11-00	Registry Identifier	EU CT
U1111-1275-8515	Registry Identifier	UTN
2018-004320-11	EudraCT Number

Label	Type	Description	Intervention Names
SBRT + Pembrolizumab	Experimental	Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via intravenous (IV) infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.	Radiation: Stereotactic Body Radiotherapy (SBRT) Biological: Pembrolizumab
SBRT + Placebo	Placebo Comparator	Participants receive SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle is 21 days.	Radiation: Stereotactic Body Radiotherapy (SBRT) Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Stereotactic Body Radiotherapy (SBRT)	Radiation	SBRT will be administered once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks.

Measure	Description	Time Frame
Event-free Survival (EFS)	EFS was defined as the time from randomization to the first occurrence of any of the following events: 1) local, regional, or distant recurrence of disease as assessed by radiographic recurrence by blinded independent central review (BICR), positive pathology by local assessment, physical examination by local assessment confirmed by positive pathology and/or radiographic recurrence by BICR, OR 2) death due to any cause. EFS was reported for each arm.	Up to approximately 56.8 months

Measure	Description	Time Frame
Overall Survival (OS)	OS was defined as the time from date of randomization to date of death from any cause. OS was reported for each arm.	Up to approximately 56.8 months
Time to Death or Distant Metastases (TDDM)

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has previously untreated non-small cell lung cancer (NSCLC) diagnosed by histology or cytology and confirmed as Stage I or II (T1 to limited T3, N0, M0) NSCLC (American Joint Committee on Cancer, AJCC) by chest computed tomography (CT) and positron emission tomography (PET) scan. Participants with pericardium invasion, >2 nodules or 2 nodules that cannot be treated in one field (>2 cm apart and/or total planned target volume [PTV] >163 cc) and diaphragm elevation suggestive of phrenic nerve invasion are excluded
Cannot undergo thoracic surgery due to existing medical illness(es) as determined by the site's multi-disciplinary tumor board. Medically operable participants who decide to treat with stereotactic body radiotherapy (SBRT) as definitive therapy rather than surgery are also eligible, if patient's unwillingness to undergo surgical resection is clearly documented
Has a Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
Is able to receive SBRT and does not have an ultra-centrally located tumor
Has adequate organ function within 7 days prior to the start of study treatment
A female is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a) not a women of childbearing potential (WOCBP) OR b) A WOCBP and uses contraceptive method that is highly effective (with a failure rate of <1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), during the intervention period and for at least 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 90 days after the last dose of radiotherapy: refrain from donating sperm plus either be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent or must agree to use contraception per study protocol, unless confirmed to be azoospermic
Has a radiation therapy plan approved by the central radiation therapy quality assurance vendor

Exclusion Criteria:

Has received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], tumor necrosis factor receptor superfamily member 4 [OX-40], tumor necrosis factor receptor superfamily member 9 [CD137])
Has received prior radiotherapy to the thorax, including radiotherapy to the esophagus, mediastinum, or breast
Has received a live vaccine within 30 days prior to the first dose of study intervention
Has received an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention administration
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. A prior NSCLC that occurred and was treated curatively at least 2 years prior to the date of the current diagnosis would be considered a separate primary lung cancer, and therefore an additional malignancy. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast c carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
Has a known hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
Has a known history of Hepatitis B or known active Hepatitis C virus infection
Has an active autoimmune disease that has required systemic treatment in past 2 years, except replacement therapy
Has an active infection requiring systemic therapy
Has a known history of human immunodeficiency virus (HIV) infection
Has a known history of active tuberculosis (TB; Bacillus tuberculosis)
Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of pembrolizumab/placebo and 180 days after the last radiotherapy dose
Have not adequately recovered from major surgery or have ongoing surgical complications
Has had an allogenic tissue/solid organ transplant

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama ( Site 0099)		Birmingham	Alabama	35233	United States
Infirmary Cancer Care ( Site 3044)

PubMed Identifier	Type	Citation	Retractions
39298144	Derived	Swaminath A, Parpia S, Wierzbicki M, Kundapur V, Faria S, Okawara GS, Tsakiridis TK, Ahmed N, Bujold A, Hirmiz K, Owen T, Leong N, Ramchandar K, Filion E, Lau H, Gabos Z, Thompson R, Yaremko B, Mehiri S, Louie AV, Quan K, Levine MN, Wright JR, Whelan TJ. Stereotactic vs Hypofractionated Radiotherapy for Inoperable Stage I Non-Small Cell Lung Cancer: The LUSTRE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2024 Nov;10(11):1571-1575. doi: 10.1001/jamaoncol.2024.3089. Epub 2024 Sep 19.

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Oct 11, 2024

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Event-free Survival (EFS)

EFS was defined as the time from randomization to the first occurrence of any of the following events: 1) local, regional, or distant recurrence of disease as assessed by radiographic recurrence by blinded independent central review (BICR), positive pathology by local assessment, physical examination by local assessment confirmed by positive pathology and/or radiographic recurrence by BICR, OR 2) death due to any cause. EFS was reported for each arm.

All randomized participants were analyzed according to the treatment arm they were randomized to.

Posted

Median

95% Confidence Interval

months

Up to approximately 56.8 months

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Units	Counts
Participants	OG000227 OG001221

Title

Denominators

Categories

Title	Measurements
	OG00031.2(22.5 to 39.1) OG00128.3(19.8 to 33.1)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Hazard ratio and 95% confidence intervals (CIs) were based on Cox regression model with Efron's method of tie handling with treatment as a covariate, stratified by Disease Stage (Stage I versus Stage II), ECOG Performance Status (0 or 1 versus 2), Geographic Region of Enrollment Site (East Asia versus non-East Asia), and Reason For Not Receiving Surgery ("medically inoperable" versus "refused surgery").	Log Rank		0.29320	1-sided p-value based on log-rank test stratified by Disease Stage, ECOG Performance Status, Geographic Region of Enrollment Site, and Reason For Not Receiving Surgery.	Hazard Ratio (HR)	0.92			2-Sided	95	0.69	1.24

Secondary

Overall Survival (OS)

OS was defined as the time from date of randomization to date of death from any cause. OS was reported for each arm.

All randomized participants were analyzed according to the treatment arm they were randomized to.

Posted

Median

95% Confidence Interval

months

Up to approximately 56.8 months

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Units	Counts
Participants

Secondary

Time to Death or Distant Metastases (TDDM)

TTDM was defined as the time from randomization to the first documented distant metastases or death from any cause, whichever occurred first. The TDDM was reported for each arm.

All randomized participants were analyzed according to the treatment arm they were randomized to.

Posted

Median

95% Confidence Interval

months

Up to approximately 56.8 months

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Units	Counts
Participants

Secondary

Number of Participants Who Experienced an Adverse Event (AE)

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an AE were reported.

The analysis population consisted of all participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 64 months

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Units	Counts

Secondary

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

The analysis population consisted of all participants who received at least 1 dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 16 months

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" were scored on a 7-point scale (1=Very Poor to 7=Excellent). The combined score of Global Health Status (EORTC QLQ-C30 Item 29) and Quality of Life (EORTC QLQ-C30 Item 30) was computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores ranged from 0-100. A higher score indicates a better outcome. The change from baseline in GHS/QoL combined score was reported for each arm.

All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-C30 assessment available were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

Score on a Scale

Baseline and up to 24 weeks

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Cough (Item 31) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the EORTC QLQ-LC13 question "How much did you cough?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in cough (EORTC QLQ LC13 Item 31) score was reported for each arm.

All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-LC13 assessment available were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and up to 24 weeks

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer Module 13 (EORTC QLQ-LC13) Chest Pain (Item 40) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score was reported for each arm.

All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-LC13 assessment available were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

Score on a Scale

Baseline and up to 24 weeks

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A lower score indicates a better outcome. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score was reported for each arm.

All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-C30 assessment available were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

Score on a Scale

Baseline and up to 24 weeks

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Secondary

Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning were scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores were standardized, so that scores ranged from 0 to 100. A higher score indicates a better quality of life. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score was reported for each arm.

All randomized participants who received at least 1 dose of study intervention and had at least 1 EORTC QLQ-C30 assessment available were analyzed.

Posted

Least Squares Mean

95% Confidence Interval

Score on a Scale

Baseline and up to 24 weeks

ID	Title	Description
OG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
OG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0004 events4 affected226 at risk EG0011 events1 affected218 at risk
Aplasia pure red cell	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Iron deficiency anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Angina pectoris	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Angina unstable	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0004 events4 affected226 at risk EG0011 events1 affected218 at risk
Cardiac arrest	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0012 events2 affected218 at risk
Cardiac failure	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected226 at risk EG0013 events2 affected218 at risk
Cardiac failure chronic	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Dilated cardiomyopathy	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Myocarditis	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Pericardial effusion	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Immune-mediated hyperthyroidism	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0012 events2 affected218 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Gastric ischaemia	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Haemorrhoidal haemorrhage	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Immune-mediated enterocolitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Oesophagitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Pancreatitis acute	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Asthenia	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Chest pain	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Death	General disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Drowning	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
General physical health deterioration	General disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Non-cardiac chest pain	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Bile duct stenosis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Cytokine release syndrome	Immune system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Abscess oral	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Bronchiolitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0015 events5 affected218 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected226 at risk EG0016 events6 affected218 at risk
Catheter site infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Cellulitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Conjunctivitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Erysipelas	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Periodontitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00023 events19 affected226 at risk EG0017 events7 affected218 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0006 events6 affected226 at risk EG0012 events2 affected218 at risk
Prostate infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Pyelonephritis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Sepsis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0007 events6 affected226 at risk EG0010 events0 affected218 at risk
Anastomotic stenosis	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Hand fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0011 events1 affected218 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Intraocular pressure increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
SARS-CoV-2 test positive	Investigations	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Diabetic metabolic decompensation	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Arthropathy	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Osteonecrosis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Polyarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0012 events2 affected218 at risk
Bladder cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Bowen's disease	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Cervix carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Colon cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Non-small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Non-small cell lung cancer recurrent	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0012 events2 affected218 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Small cell lung cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Cerebral infarction	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0004 events3 affected226 at risk EG0013 events2 affected218 at risk
Encephalitis autoimmune	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Epilepsy	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Headache	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Hydrocephalus	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Migraine	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Parkinson's disease	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Parkinsonism	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Presyncope	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Seizure	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Delirium	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Depression	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Disorientation	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Mania	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0010 events0 affected218 at risk
Renal failure	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0012 events2 affected218 at risk
Renal impairment	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Aspiration	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Bronchopneumopathy	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00024 events16 affected226 at risk EG00112 events10 affected218 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0003 events3 affected226 at risk EG0013 events3 affected218 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Hypoxia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0007 events7 affected226 at risk EG0011 events1 affected218 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0011 events1 affected218 at risk
Decubitus ulcer	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Aortic aneurysm rupture	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Embolism	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0001 events1 affected226 at risk EG0010 events0 affected218 at risk
Hypertension	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Hypotension	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0000 events0 affected226 at risk EG0011 events1 affected218 at risk
Peripheral arterial occlusive disease	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0002 events2 affected226 at risk EG0011 events1 affected218 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG00032 events28 affected226 at risk EG00118 events15 affected218 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG00013 events13 affected226 at risk EG0015 events5 affected218 at risk
Hypothyroidism	Endocrine disorders	MedDRA 27.1	Systematic Assessment	EG00041 events37 affected226 at risk EG00110 events10 affected218 at risk
Constipation	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00023 events20 affected226 at risk EG00123 events21 affected218 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00052 events38 affected226 at risk EG00143 events31 affected218 at risk
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00022 events17 affected226 at risk EG00130 events25 affected218 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00020 events18 affected226 at risk EG00111 events8 affected218 at risk
Asthenia	General disorders	MedDRA 27.1	Systematic Assessment	EG00022 events20 affected226 at risk EG00122 events18 affected218 at risk
Chest pain	General disorders	MedDRA 27.1	Systematic Assessment	EG00018 events15 affected226 at risk EG00122 events16 affected218 at risk
Fatigue	General disorders	MedDRA 27.1	Systematic Assessment	EG00061 events51 affected226 at risk EG00148 events43 affected218 at risk
Oedema peripheral	General disorders	MedDRA 27.1	Systematic Assessment	EG00012 events12 affected226 at risk EG00117 events15 affected218 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG00017 events14 affected226 at risk EG0015 events5 affected218 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00012 events12 affected226 at risk EG00118 events16 affected218 at risk
Pneumonia	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00014 events12 affected226 at risk EG00112 events10 affected218 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00016 events11 affected226 at risk EG00120 events16 affected218 at risk
Radiation pneumonitis	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG00022 events20 affected226 at risk EG00120 events19 affected218 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00023 events17 affected226 at risk EG00112 events10 affected218 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00018 events15 affected226 at risk EG00111 events10 affected218 at risk
Blood creatinine increased	Investigations	MedDRA 27.1	Systematic Assessment	EG00028 events20 affected226 at risk EG00125 events20 affected218 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00027 events26 affected226 at risk EG00116 events16 affected218 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00024 events18 affected226 at risk EG0019 events8 affected218 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG00013 events12 affected226 at risk EG00111 events8 affected218 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG00049 events40 affected226 at risk EG00117 events16 affected218 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG00017 events17 affected226 at risk EG00119 events18 affected218 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG00017 events13 affected226 at risk EG00114 events13 affected218 at risk
Dizziness	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG00014 events14 affected226 at risk EG00114 events13 affected218 at risk
Headache	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG00015 events13 affected226 at risk EG00122 events19 affected218 at risk
Insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG00016 events16 affected226 at risk EG00113 events13 affected218 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00020 events16 affected226 at risk EG00112 events10 affected218 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00039 events34 affected226 at risk EG00146 events39 affected218 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00047 events41 affected226 at risk EG00142 events39 affected218 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00018 events18 affected226 at risk EG0014 events4 affected218 at risk
Productive cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG00019 events15 affected226 at risk EG0019 events7 affected218 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG00010 events10 affected226 at risk EG00114 events13 affected218 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG00044 events39 affected226 at risk EG00135 events21 affected218 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG00053 events36 affected226 at risk EG00120 events16 affected218 at risk
Hypertension	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG00015 events13 affected226 at risk EG00112 events12 affected218 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
D011878	Radiotherapy
D013812	Therapeutics
D013238	Stereotaxic Techniques
D019635	Neurosurgical Procedures
D013514	Surgical Procedures, Operative
D008919	Investigative Techniques

ID	Title	Description
BG000	SBRT + Pembrolizumab	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
BG001	SBRT + Placebo	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab + SBRT	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gray [Gy] total) over approximately 2 weeks PLUS pembrolizumab 200 mg via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.	76	227	90	226	198	226
EG001	Placebo + SBRT	Participants received SBRT once every 3 days for 3, 4, 5, or 8 fractions (dependent on tumor type/location; 45-70 Gy total) over approximately 2 weeks PLUS placebo (normal saline solution) via IV infusion once every 3 weeks for up to 17 cycles (up to approximately 1 year). Each cycle was 21 days.	63	221	74	218	176	218