A Study to Evaluate the Efficacy and Safety of Autogene C... | NCT03815058

ID	Type	Description	Link
2018-001773-24	EudraCT Number
2023-507389-15-00	Registry Identifier	EU CT Number

Name	Class
BioNTech SE	INDUSTRY

Label	Type	Description	Intervention Names
Safety Run-in Period: Autogene Cevumeran + Pembrolizumab	Experimental	Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by intravenous (IV) infusion followed by 200 mg pembrolizumab IV infusion every 3 weeks (Q3W) plus a recommended dose of autogene cevumeran.	Biological: Autogene cevumeran Drug: Pembrolizumab
Randomized Period: Arm A: Pembrolizumab	Active Comparator	Participants will receive 200 mg pembrolizumab administered by IV infusion Q3W. Participants in Arm A have the option to cross over to combination treatment with autogene cevumeran plus pembrolizumab (Arm B) after confirmed disease progression.	Drug: Pembrolizumab
Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab	Experimental	Participants will receive at least one cycle of 200 mg pembrolizumab monotherapy by IV infusion followed by 200 mg pembrolizumab IV infusion Q3W plus a recommended dose of autogene cevumeran.	Biological: Autogene cevumeran Drug: Pembrolizumab

Name	Type	Description	Arm Group Labels	Other Names
Autogene cevumeran	Biological	Participants will receive a recommended dose of autogene cevumeran administered by IV infusion at protocol-defined intervals.	Randomized Period: Arm B: Autogene Cevumeran + Pembrolizumab

Measure	Description	Time Frame
Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization	PFS was defined as the time from randomization to the first documented PD as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (KM) method was used to estimate median PFS.	From randomization to PD or death (up to approximately 60 months)

Measure	Description	Time Frame
Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization	ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off to the nearest whole number.

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
City of Hope Comprehensive Cancer Center		Duarte	California	91010	United States
University of California San Diego Moores Cancer Center

ID	Title	Description
FG000	Safety Run-in	Participants received pembrolizumab monotherapy, 200 milligrams (mg) as an intravenous (IV) infusion for at least 1 cycle, followed by pembrolizumab, 200 mg, IV infusion, every 3 weeks (Q3W) thereafter, along with RO7198457. Participants received RO7198457, 25 micrograms (µg), as an IV infusion, 4 doses every week (QW) and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).

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	Nov 14, 2023

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

Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v.1.1) After Randomization

PFS was defined as the time from randomization to the first documented PD as determined by the investigator according to RECIST v1.1 or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeters (mm). Kaplan-Meier (KM) method was used to estimate median PFS.

ITT population included all randomized participants.

Posted

Median

95% Confidence Interval

months

From randomization to PD or death (up to approximately 60 months)

ID	Title	Description
OG000	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.
OG001	Arm B: Pembrolizumab + RO7198457	Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).

Units	Counts
Participants	OG00041 OG00184

Title

Denominators

Categories

Title	Measurements
	OG0007.9(2.8 to 22.7) OG0018.3(6.9 to 26.9)

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		Log Rank		0.3284		Hazard Ratio (HR)	0.79			2-Sided	95	0.49	1.27					Superiority

Secondary

Objective Response Rate (ORR) According to RECIST V.1.1 After Randomization

ORR was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. Percentages have been rounded off to the nearest whole number.

ITT population included all randomized participants.

Posted

Number

95% Confidence Interval

percentage of participants

Up to approximately 60 months

ID	Title	Description
OG000	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.
OG001	Arm B: Pembrolizumab + RO7198457	Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).

Secondary

Overall Survival (OS) After Randomization

OS was defined as the time from randomization to death from any cause. KM method was used to estimate the median OS.

ITT population included all randomized participants.

Posted

Median

95% Confidence Interval

months

From randomization to death (up to approximately 63 months)

ID	Title	Description
OG000	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.
OG001	Arm B: Pembrolizumab + RO7198457	Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).

Units	Counts
Participants

Secondary

Duration of Response (DOR) According to RECIST V.1.1 After Randomization

DOR was defined as the time from the first occurrence of a documented objective response (OR) to PD or death from any cause, whichever occurred first, as determined by the investigator according to RECIST v1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on study (nadir), including baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. DOR was estimated using the KM methodology.

ITT population included all randomized participants. Overall number analyzed is the number of participants with an OR (CR or PR).

Posted

Median

95% Confidence Interval

months

Up to approximately 60 months

ID	Title	Description
OG000	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.
OG001	Arm B: Pembrolizumab + RO7198457	Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).

Secondary

Change From Baseline in Global Health Status (GHS)/Health-related Quality of Life (HRQoL) Score Assessed by European Organisation for Research and Treatment of Cancer 30-Item Quality of Life Questionnaire (EORTC QLQ-C30)

EORTC QLQ-C30 consists of 30 questions that assess participant functioning (physical, emotional, role, cognitive, and social), symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). Change in HRQoL was assessed using participant responses to questions regarding GHS (Question 29: GHS; "How would you rate your overall health during the past week?") and QoL (Question 30: QoL; "How would you rate your overall quality of life during the past week?") and were scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores were standardized. Scores range from 0-100. A higher score indicates a better QoL.

ITT population included all randomized participants. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

score on a scale

Baseline, Day 1 of Cycles 1 to 34, time of first PD, time to last dose, treatment discontinuation and study drug completion (up to approximately 29 months) (1 cycle = 21 days)

ID	Title	Description
OG000	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.

Secondary

ORR According to RECIST V.1.1 After Crossover

ORR was defined as the percentage of participants with a CR or PR on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to RECIST v1.1. CR was defined as disappearance of all target lesions or any pathological lymph nodes must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of all target lesions, taking as reference the baseline SOD, in the absence of CR.

Crossover ITT population included all randomized participants who entered crossover period.

Posted

Number

95% Confidence Interval

percentage of participants

Up to 54.7 months

ID	Title	Description
OG000	Crossover: Pembrolizumab + RO7198457	Participants in Arm A with confirmed PD were given the option to crossover & receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).

Units	Counts
Participants	OG000

Secondary

Number of Participants With Adverse Events (AEs)

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

SE population included all participants who received at least 1 dose of study treatment. 1 participant in Arm A didn't receive any study treatment & was excluded from safety. 4 participants in Arm B discontinued study treatment after receiving pembrolizumab but prior to receiving RO7198457 & were therefore considered in Arm A for safety analysis.

Posted

Count of Participants

Participants

Baseline up to 90 days after the final dose of study drug (Safety run-in and randomized stage: up to 32 months; Cross-over stage: up to 24 months)

ID	Title	Description
OG000	Safety Run-in	Participants received pembrolizumab monotherapy, 200 mg, as an IV infusion for at least 1 cycle, followed by pembrolizumab, 200 mg as an IV infusion, Q3W thereafter, along with RO7198457. Participants received RO7198457, 25 µg, IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
OG001	Arm A: Pembrolizumab

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Atrial fibrillation	Cardiac disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG0030 events0 affected10 at risk
Myocardial infarction	Cardiac disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Hypophysitis	Endocrine disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Eyelid ptosis	Eye disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Duodenitis	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Chest pain	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Chills	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Death	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Fatigue	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
General physical health deterioration	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Cholangitis acute	Hepatobiliary disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0022 events2 affected80 at risk EG003
COVID-19	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Cellulitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Device related infection	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Enteritis infectious	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Erysipelas	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Pneumonia	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0022 events2 affected80 at risk EG003
Post procedural sepsis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Septic shock	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Urosepsis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Craniofacial fracture	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Human bite	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0023 events3 affected80 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Liver function test abnormal	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Type 1 diabetes mellitus	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Cervical spinal stenosis	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0015 events5 affected44 at risk EG0023 events3 affected80 at risk EG003
Small intestine carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Basal ganglia haemorrhage	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Brain oedema	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Cauda equina syndrome	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Cerebral haematoma	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Epilepsy	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Headache	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Immune-mediated encephalitis	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Seizure	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0021 events1 affected80 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG00218 events12 affected80 at risk EG0032 events1 affected10 at risk
Eosinophilia	Blood and lymphatic system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0026 events3 affected80 at risk EG003
Lymphopenia	Blood and lymphatic system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0029 events8 affected80 at risk EG003
Microcytic anaemia	Blood and lymphatic system disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Bradycardia	Cardiac disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0020 events0 affected80 at risk EG003
Palpitations	Cardiac disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0027 events5 affected80 at risk EG003
Sinus tachycardia	Cardiac disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0025 events3 affected80 at risk EG003
Cerumen impaction	Ear and labyrinth disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Ear discomfort	Ear and labyrinth disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0024 events4 affected80 at risk EG003
Adrenal insufficiency	Endocrine disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG00210 events8 affected80 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0012 events2 affected44 at risk EG0029 events9 affected80 at risk EG003
Conjunctival haemorrhage	Eye disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Eye pruritus	Eye disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Periorbital oedema	Eye disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Vision blurred	Eye disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0015 events5 affected44 at risk EG0025 events4 affected80 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0016 events6 affected44 at risk EG0028 events8 affected80 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0022 events2 affected80 at risk EG003
Anal rash	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0018 events7 affected44 at risk EG00211 events10 affected80 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG00114 events10 affected44 at risk EG00236 events23 affected80 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0018 events8 affected44 at risk EG0027 events7 affected80 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0025 events5 affected80 at risk EG003
Dysphagia	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected44 at risk EG0022 events2 affected80 at risk EG003
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events2 affected44 at risk EG0022 events2 affected80 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0004 events3 affected6 at risk EG00114 events11 affected44 at risk EG00233 events22 affected80 at risk EG003
Oral pain	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events2 affected44 at risk EG0021 events1 affected80 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0016 events2 affected44 at risk EG0026 events4 affected80 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0015 events4 affected44 at risk EG00213 events11 affected80 at risk EG003
Asthenia	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0023 events3 affected80 at risk EG003
Axillary pain	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Chest pain	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0014 events2 affected44 at risk EG0024 events4 affected80 at risk EG003
Chills	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected44 at risk EG0024 events3 affected80 at risk EG003
Fatigue	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0005 events5 affected6 at risk EG00116 events13 affected44 at risk EG00248 events36 affected80 at risk EG003
Influenza like illness	General disorders	MedDRA Version 27.1	Systematic Assessment	EG00015 events3 affected6 at risk EG0015 events4 affected44 at risk EG00254 events14 affected80 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0021 events1 affected80 at risk EG003
Oedema peripheral	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected44 at risk EG0028 events7 affected80 at risk EG003
Peripheral swelling	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Pyrexia	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events1 affected44 at risk EG0028 events7 affected80 at risk EG003
Swelling	General disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0022 events2 affected80 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Portal vein thrombosis	Hepatobiliary disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Cytokine release syndrome	Immune system disorders	MedDRA Version 27.1	Systematic Assessment	EG00016 events3 affected6 at risk EG0010 events0 affected44 at risk EG0022 events2 affected80 at risk EG003
Drug hypersensitivity	Immune system disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Acute sinusitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
COVID-19	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG00216 events13 affected80 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0029 events8 affected80 at risk EG003
Rhinitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Sinusitis	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected44 at risk EG0022 events2 affected80 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected44 at risk EG0023 events2 affected80 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG00217 events13 affected80 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0020 events0 affected80 at risk EG003
Eye injury	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Fall	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0014 events3 affected44 at risk EG00213 events7 affected80 at risk EG003
Incision site pain	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected44 at risk EG002251 events62 affected80 at risk EG003
Procedural pain	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Skin laceration	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Vascular access site erythema	Injury, poisoning and procedural complications	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0014 events3 affected44 at risk EG0029 events8 affected80 at risk EG003
Amylase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG00214 events10 affected80 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0015 events4 affected44 at risk EG0027 events7 affected80 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0023 events3 affected80 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0024 events4 affected80 at risk EG003
Blood creatinine increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected44 at risk EG00213 events5 affected80 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0022 events2 affected80 at risk EG003
C-reactive protein increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events3 affected44 at risk EG0023 events3 affected80 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Lipase increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG00220 events11 affected80 at risk EG003
Weight decreased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events3 affected44 at risk EG0026 events6 affected80 at risk EG003
Weight increased	Investigations	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events2 affected44 at risk EG0022 events2 affected80 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0015 events5 affected44 at risk EG00214 events10 affected80 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0019 events5 affected44 at risk EG0020 events0 affected80 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0020 events0 affected80 at risk EG003
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0024 events3 affected80 at risk EG003
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0023 events3 affected80 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0015 events3 affected44 at risk EG0023 events3 affected80 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0013 events3 affected44 at risk EG0022 events1 affected80 at risk EG003
Iron deficiency	Metabolism and nutrition disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0022 events2 affected80 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0003 events3 affected6 at risk EG0019 events7 affected44 at risk EG00225 events20 affected80 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0018 events5 affected44 at risk EG00210 events7 affected80 at risk EG003
Bursitis	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0011 events1 affected44 at risk EG0022 events2 affected80 at risk EG003
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Joint swelling	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0015 events4 affected44 at risk EG0022 events2 affected80 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0019 events5 affected44 at risk EG00212 events12 affected80 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0027 events7 affected80 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0012 events2 affected44 at risk EG0027 events7 affected80 at risk EG003
Sacral pain	Musculoskeletal and connective tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Benign neoplasm of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG0023 events3 affected80 at risk EG003
Disturbance in attention	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Dizziness	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events1 affected6 at risk EG0013 events3 affected44 at risk EG00212 events7 affected80 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected44 at risk EG0023 events3 affected80 at risk EG003
Headache	Nervous system disorders	MedDRA Version 27.1	Systematic Assessment	EG0003 events2 affected6 at risk EG0013 events3 affected44 at risk EG00222 events15 affected80 at risk EG003
Anxiety	Psychiatric disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0023 events2 affected80 at risk EG003
Insomnia	Psychiatric disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0015 events5 affected44 at risk EG0025 events5 affected80 at risk EG003
Stress	Psychiatric disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Dysuria	Renal and urinary disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0023 events3 affected80 at risk EG003
Haematuria	Renal and urinary disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Nephrolithiasis	Renal and urinary disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0021 events1 affected80 at risk EG003
Renal cyst haemorrhage	Renal and urinary disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Urinary retention	Renal and urinary disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Genital rash	Reproductive system and breast disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0019 events6 affected44 at risk EG00213 events13 affected80 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0013 events3 affected44 at risk EG00211 events10 affected80 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0022 events2 affected80 at risk EG003
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Pharyngeal inflammation	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0022 events1 affected80 at risk EG003
Upper-airway cough syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0023 events3 affected80 at risk EG003
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0010 events0 affected44 at risk EG0024 events3 affected80 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0022 events2 affected80 at risk EG003
Eczema	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0011 events1 affected44 at risk EG0025 events5 affected80 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Nail discolouration	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Pain of skin	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG00113 events10 affected44 at risk EG00212 events11 affected80 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0018 events7 affected44 at risk EG00218 events16 affected80 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0005 events2 affected6 at risk EG0017 events5 affected44 at risk EG00210 events8 affected80 at risk EG003
Rash pruritic	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0000 events0 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Skin hypopigmentation	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0022 events2 affected80 at risk EG003
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0023 events3 affected80 at risk EG003
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0012 events2 affected44 at risk EG0029 events9 affected80 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0011 events1 affected44 at risk EG0020 events0 affected80 at risk EG003
Haematoma	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0021 events1 affected80 at risk EG003
Hot flush	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0023 events3 affected80 at risk EG003
Hypertension	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0016 events5 affected44 at risk EG00213 events9 affected80 at risk EG003
Hypotension	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0002 events2 affected6 at risk EG0012 events2 affected44 at risk EG0022 events1 affected80 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003
Subclavian vein thrombosis	Vascular disorders	MedDRA Version 27.1	Systematic Assessment	EG0001 events1 affected6 at risk EG0010 events0 affected44 at risk EG0020 events0 affected80 at risk EG003

ID	Title	Description
BG000	Safety Run-in	Participants received pembrolizumab monotherapy, 200 mg as an IV infusion for at least 1 cycle, followed by pembrolizumab, 200 mg, IV infusion, Q3W thereafter, along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
BG001	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.
BG002	Arm B: Pembrolizumab + RO7198457	Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).
BG003	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	Safety Run-in	Participants received pembrolizumab monotherapy, 200 mg as an IV infusion for at least 1 cycle, followed by pembrolizumab, 200 mg, IV infusion, Q3W thereafter, along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	2	6	3	6	6	6
EG001	Arm A: Pembrolizumab	Participants received pembrolizumab, 200 mg, as an IV infusion, Q3W until the occurrence of unacceptable toxicity or PD or death, whichever occurred first.	14	44	16	44	40	44
EG002	Arm B: Pembrolizumab + RO7198457	Participants received pembrolizumab, 200 mg, as an IV infusion for at least 1 cycle (1 cycle = 21 days), followed by pembrolizumab, 200 mg, Q3W along with RO7198457. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	30	80	25	80	78	80
EG003	Crossover: Pembrolizumab + RO7198457	Participants in Arm A with confirmed PD were given the option to crossover & receive RO7198457 in combination with pembrolizumab, 200 mg, as an IV infusion, Q3W. Participants received RO7198457, 25 µg, as an IV infusion, 4 doses QW and 4 doses Q3W as induction dosing and then maintenance dosing, every 8 cycles until the occurrence of unacceptable toxicity or PD or death, whichever occurred first (1 cycle = 21 days).	3	10	4	10	9	10