A Study of Atezolizumab Plus Cobimetinib and Vemurafenib... | NCT02908672

NCT02908672

ID	Type	Description	Link
2016-002482-54	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo	Experimental	Run-In Period (Cycle 1=28 days): Participants will receive vemurafenib 960 mg (four, 240 mg tablets) PO BID along with cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21 followed by vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 22 to 28 and vemurafenib placebo (1 tablet) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive atezolizumab 840 mg IV infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.	Drug: Atezolizumab Drug: Cobimetinib Drug: Vemurafenib Drug: Vemurafenib Placebo
Atezolizumab Placebo + Cobimetinib + Vemurafenib	Experimental	Run-In Period (Cycle1=28 days): Participants will receive vemurafenib 960 milligrams (mg) (four, 240 mg tablets) orally (PO) twice a day (BID) along with cobimetinib 60 mg (three, 20 mg tablets) PO once a day (QD) on Days 1 to 21 followed by vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive ATZ placebo by intravenous (IV) infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, and vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.	Drug: Atezolizumab Placebo Drug: Cobimetinib Drug: Vemurafenib

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Atezolizumab	Drug	Will be administered as per the schedule described in individual arm.	Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	PFS was defined as the time from randomization to the first occurrence of 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 smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm).	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

Secondary Outcomes

Measure	Description	Time Frame
PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the IRC according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Females of child bearing potential and males with female partners must and use of contraceptive methods with a failure rate of less than or equal to (</=)1% per year is required during treatment and for 6 months post treatment. Males should not expose pregnant partners to sperm and refrain from donating sperm for 6 months post treatment. Women must refrain from donating eggs during this same period
Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally advanced) melanoma
Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) except adjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies or herbal therapies
Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archival or newly obtained) through use of a clinical mutation test approved by the local health authority
Eastern Cooperative Oncology Group Performance (ECOG) Status of 0 or 1
Measurable disease according to RECIST v1.1 (must be outside central nervous system (CNS))
Life expectancy >/=18 weeks
For participants not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) less than or equal to (</=) 1.5*upper limit of normal (ULN) within 28 days prior to initiation of study treatment
For participants receiving therapeutic anticoagulation: stable anticoagulant regimen and stable INR during the 28 days immediately preceding initiation of study treatment

Exclusion Criteria:

Cancer-Related Exclusion Criteria:

Major surgical procedure within 4 weeks prior study treatment initiation
Traumatic injury or palliative radiotherapy within 2 weeks prior study treatment initiation
Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancy within 3 years prior to screening are excluded, with the exception of resected melanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ of the breast, in situ prostate cancer, limited-stage bladder cancer, or any other curatively treated malignancies from which the participant has been disease-free for at least 3 years

Ocular Exclusion Criteria:

History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration

Cardiac Exclusion Criteria:

History of clinically significant cardiac dysfunction
Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or below 50%

Central Nervous System (CNS) Exclusion Criteria:

Untreated or actively progressing CNS lesions (carcinomatous meningitis)
History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal metastatic disease; or intracranial hemorrhage

Additional Exclusion Criteria:

Uncontrolled diabetes or symptomatic hyperglycemia
Current severe, uncontrolled systemic disease (including, but not limited to, clinically significant cardiovascular, pulmonary, or renal disease) other than cancer
History of malabsorption or other clinically significant metabolic dysfunction
Pregnant or breastfeeding, or intending to become pregnant during the study
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis, organizing pneumonia (example: bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
Active or history of autoimmune disease or immune deficiency
Known clinically significant liver disease, inherited liver disease and active viral disease
Active tuberculosis
Treatment with therapeutic oral or intravenous (IV) antibiotics; or with a live, attenuated vaccine; or systemic immunosuppressive medication
Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab, cobimetinib, or vemurafenib formulations
Any grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of study treatment
History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of study treatment

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
University of Alabama at Birmingham		Birmingham	Alabama	35294-3300	United States
Arizona Oncology Associates, PC - HAL

PubMed Identifier	Type	Citation	Retractions
36653848	Derived	Li SN, Wan X, Peng LB, Li YM, Li JH. Cost-effectiveness of immune checkpoint inhibition and targeted treatment in combination as adjuvant treatment of patient with BRAF-mutant advanced melanoma. BMC Health Serv Res. 2023 Jan 18;23(1):49. doi: 10.1186/s12913-023-09058-7.
36460017	Derived	Ascierto PA, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Zhukova N, Schachter J, Yan Y, Caro I, Hertig C, Xue C, Kusters L, McArthur GA, Gutzmer R. Overall survival with first-line atezolizumab in combination with vemurafenib and cobimetinib in BRAFV600 mutation-positive advanced melanoma (IMspire150): second interim analysis of a multicentre, randomised, phase 3 study. Lancet Oncol. 2023 Jan;24(1):33-44. doi: 10.1016/S1470-2045(22)00687-8. Epub 2022 Nov 29.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Run-in - Pbo + Cobi + Vem	Participants received vemurafenib, 960 milligrams (mg) (four, 240 mg tablets), orally (PO), twice a day (BID) along with cobimetinib, 60 mg (three, 20 mg tablets) PO, once a day (QD) on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Mar 16, 2023	Jun 26, 2025

Arm/Group Information

ID	Title	Description
BG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
BG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
BG002	Total	Total of all reporting groups

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), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

PFS was defined as the time from randomization to the first occurrence of 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 smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm).

ITT population included all randomized participants, whether or not study treatment was received.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Units	Counts
Participants	OG000258 OG001256

Title

Denominators

Categories

Title	Measurements
	OG00010.6(9.3 to 12.7) OG00115.1(11.4 to 18.4)

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		0.0224		Hazard Ratio (HR)	0.79			2-Sided	95	0.64	0.97			Stratified Hazard Ratio		Superiority

Secondary

PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1

PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the IRC according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm.

ITT population included all randomized participants, whether or not study treatment was received.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem

Secondary

Percentage of Participants With Objective Response (OR), as Determined by Investigator Using RECIST V1.1

OR rate was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD.

ITT population included all randomized participants, whether or not study treatment was received. Only participants with measurable disease at baseline were analyzed for this outcome measure.

Posted

Number

percentage of participants

Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Duration of Response (DOR), as Determined by Investigator Using RECIST v1.1

DOR was defined as the time from the first occurrence of a documented OR to 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 SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD.

ITT population included all randomized participants, whether or not study treatment was received. Only participants with measurable disease at baseline were analyzed for this outcome measure.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Overall Survival (OS)

OS was defined as the time from randomization to death from any cause.

ITT population included all randomized participants, whether or not study treatment was received.

Posted

Median

95% Confidence Interval

months

Baseline up to death due to any cause (up to approximately 85 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Percentage of Participants Who Have Survived at 2 Years

Percentage of participants with OS which was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate 2-year landmark survival rate. The 95% CI of landmark survival rate was calculated using the standard error derived from Greenwood's formula.

ITT population included all randomized participants, whether or not study treatment was received.

Posted

Number

95% Confidence Interval

percentage of participants

2 years

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Time to Deterioration in Global Health Status (GHS) Determined Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score

Time to deterioration in GHS/health related quality of life (HRQoL) was defined as the time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment. EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL.

ITT population included all randomized participants, whether or not study treatment was received.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Time to Deterioration in Physical Functioning (PF) Determined Using EORTC QLQ-C30 Scale Score

Time to deterioration in PF = time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed PF scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). PF are scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level, functioning/support.

ITT population included all randomized participants, whether or not study treatment was received.

Posted

Median

95% Confidence Interval

months

Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a participant when administered a pharmaceutical product regardless of the causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. All AEs were reported until 30 days and SAEs until 90 days after the final dose of study treatment or until initiation of subsequent anti-cancer therapy, whichever occurred first.

Safety population included all participants who received any amount of any atezolizumab, cobimetinib, or vemurafenib. 26 were included in the placebo+cobi+vem arm for safety evaluation (22 participants in atezo+cobi+vem arm stopped run-in treatment & didn't received atezo & 4 in atezo+cobi+vem arm completed the run-in treatment but did not receive atezo). During the study, 2 participants in placebo+cobi+vem arm received atezo & were considered in the atezo+cobi+vem arm for safety analysis.

Posted

Number

percentage of participants

Up to approximately 85 months

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Serum Concentration of Atezolizumab

Pharmacokinetic (PK)-evaluable population included all participants who have received any dose of atezolizumab and for whom at least one evaluable PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

micrograms per milliliters (ug/mL)

Pre-infusion Day 1 of Cycles 1-4; 30 minutes post-infusion Day 1 of Cycles 1 and 4; at Atezolizumab discontinuation (up to approximately 33 months) (1 Cycle = 28 days)

ID	Title	Description
OG000	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Units	Counts
Participants

Secondary

Plasma Concentration of Cobimetinib Dose: 20/40 mg

The Cobi PK-evaluable population included all participants who received any dose of cobimetinib 20/40 mg and for whom at least one evaluable PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Plasma Concentration of Cobimetinib Dose: 60 mg

The Cobi PK-evaluable population included all participants who received any dose of Cobimetinib 60 mg and for whom at least one evaluable PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Mean

Standard Deviation

Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Plasma Concentration of Vemurafenib

The Vem PK-evaluable population included all participants who received any dose of vemurafenib and for whom at least one evaluable PK sample was collected. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Geometric Mean

Geometric Coefficient of Variation

μg/mL

Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)

ID	Title	Description
OG000	Arm A: Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.
OG001	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Secondary

Percentage of Participants Positive for Anti-drug Antibodies (ADA) to Atezolizumab

Presence of ADAs against atezolizumab during the study relative to the presence of ADAs at baseline. The percentage of ADA-positive participants after drug administration were determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result.

The ADA-evaluable population included participants who received at least one dose of atezolizumab and had ≥ 1 post-baseline ADA result. Number analyzed is the number of participants with data available for analysis at the specified timepoint.

Posted

Number

percentage of participants

Pre-infusion Day 1 of Cycles 1-4 (1 Cycle=28 days); at Atezolizumab discontinuation (approximately up to 33 months)

ID	Title	Description
OG000	Arm B: Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period. During triple combination period (Cycle 1 onwards), participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Run-in - Atezo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets) PO, BID along with cobimetinib 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 720 mg (three, 240 mg tablets) PO, BID and vemurafenib matching placebo, PO, BID on Days 22 to 28 during the 28 day run-in period.	0	232	21	232	208	232
EG001	Run-in - Pbo + Cobi + Vem	Participants received vemurafenib, 960 mg (four, 240 mg tablets), PO, BID along with cobimetinib, 60 mg (three, 20 mg tablets) PO, QD on Days 1 to 21 only followed by vemurafenib 960 mg (four, 240 mg tablets), PO, BID on Days 22 to 28 during the 28 day run-in period.	25	279	50	279	262	279
EG002	Triple Combination: Pbo + Cobi + Vem	After the 28-day run-in, participants received atezolizumab matching placebo as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21 and vemurafenib 960 mg (four, 240 mg tablets) PO, BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.	149	279	81	279	222	279
EG003	Triple Combination: Atezo + Cobi + Vem	After the 28-day run-in period, participants received atezolizumab 840 mg as IV infusion on Days 1 and 15, cobimetinib, 60 mg (three, 20 mg tablets) PO, QD, on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28. Study treatment was continued until investigator determined PD, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurred first.	128	232	109	232	226	232

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG0031 events1 affected232 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Acute coronary syndrome	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Acute myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Arrhythmia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0022 events1 affected279 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Cardiac arrest	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Cardiac failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Coronary artery occlusion	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Left ventricular failure	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Myocardial infarction	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Myocardial ischaemia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Palpitations	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Pericarditis	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Stress cardiomyopathy	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0021 events1 affected279 at risk EG003
Tachycardia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Ventricular arrhythmia	Cardiac disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Vertigo	Ear and labyrinth disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Hypophysitis	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Central serous chorioretinopathy	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Detachment of retinal pigment epithelium	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Eye pain	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Maculopathy	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Retinal artery embolism	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Uveitis	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Autoimmune colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Autoimmune pancreatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events1 affected279 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0011 events1 affected279 at risk EG0023 events3 affected279 at risk EG003
Faecaloma	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Gastric ulcer	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Gastritis erosive	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Ileus	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Intussusception	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Obstructive pancreatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Oesophagitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Oesophagitis haemorrhagic	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Pancreatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Pancreatitis acute	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Pancreatitis necrotising	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Rectal haemorrhage	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Volvulus	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Chest pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
General physical health deterioration	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0023 events3 affected279 at risk EG003
Influenza like illness	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0017 events7 affected279 at risk EG0027 events6 affected279 at risk EG003
Systemic inflammatory response syndrome	General disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Autoimmune cholangitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0024 events3 affected279 at risk EG003
Cholangitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Cholecystitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hepatic failure	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hepatitis	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hepatitis fulminant	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hepatotoxicity	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Hypertransaminasaemia	Hepatobiliary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hypersensitivity	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Sarcoidosis	Immune system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Appendicitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Arthritis bacterial	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Atypical pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Bacterial infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Bacterial prostatitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Bartholin's abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
COVID-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Cellulitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Encephalitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Erysipelas	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0012 events2 affected279 at risk EG0023 events2 affected279 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Herpes zoster	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0012 events2 affected279 at risk EG0020 events0 affected279 at risk EG003
Influenza	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Large intestine infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Localised infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Lower respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Meningitis aseptic	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Oral herpes	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Peritonitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Pharyngotonsillitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Pneumonia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0012 events2 affected279 at risk EG0023 events3 affected279 at risk EG003
Postoperative wound infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Renal abscess	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Sepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Septic shock	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Serratia bacteraemia	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Soft tissue infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Urosepsis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Vascular device infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Viral infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Face injury	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hand fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Humerus fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Ligament rupture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Lower limb fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Sternal fracture	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0016 events5 affected279 at risk EG0022 events2 affected279 at risk EG003
Body temperature increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Electrocardiogram QT prolonged	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hepatic enzyme increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0011 events1 affected279 at risk EG0021 events1 affected279 at risk EG003
Neutrophil count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
White blood cell count decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0021 events1 affected279 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Metabolic acidosis	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Fracture pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hypercreatinaemia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Osteoarthritis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Breast cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Fibroma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Lentigo maligna	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Lip neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Liposarcoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Malignant melanoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Malignant melanoma in situ	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Melanocytic naevus	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Meningioma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Papillary thyroid cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Aphasia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Bell's palsy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Brain dislocation syndrome	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Cerebral ischaemia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Cerebrovascular accident	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Encephalitis autoimmune	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Guillain-Barre syndrome	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Haemorrhage intracranial	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Haemorrhagic stroke	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0024 events2 affected279 at risk EG003
Hydrocephalus	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Hypertonia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Immune-mediated encephalitis	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Lethargy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Loss of consciousness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Peripheral sensorimotor neuropathy	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Seizure	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Syncope	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Alcohol abuse	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Confusional state	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Delirium	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Acute kidney injury	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Nephritis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Prerenal failure	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Renal colic	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Renal failure	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0021 events1 affected279 at risk EG003
Ureterolithiasis	Renal and urinary disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Ovarian cyst	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Ovarian rupture	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Pelvic pain	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Prostatitis	Reproductive system and breast disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0023 events3 affected279 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Vocal cord leukoplakia	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Angioedema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Drug reaction with eosinophilia and systemic symptoms	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0012 events2 affected279 at risk EG0020 events0 affected279 at risk EG003
Erythema multiforme	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0012 events2 affected279 at risk EG0020 events0 affected279 at risk EG003
Neutrophilic dermatosis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0021 events1 affected279 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0022 events2 affected279 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0015 events5 affected279 at risk EG0020 events0 affected279 at risk EG003
Rash erythematous	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0014 events4 affected279 at risk EG0020 events0 affected279 at risk EG003
Rash papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Stevens-Johnson syndrome	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Toxic skin eruption	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0020 events0 affected279 at risk EG003
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003
Hypotension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0011 events1 affected279 at risk EG0022 events2 affected279 at risk EG003
Shock haemorrhagic	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0020 events0 affected279 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected232 at risk EG00111 events9 affected279 at risk EG00262 events37 affected279 at risk EG00378 events44 affected232 at risk
Lymphopenia	Blood and lymphatic system disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected232 at risk EG0013 events3 affected279 at risk EG00219 events13 affected279 at risk EG003
Hyperthyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0011 events1 affected279 at risk EG00231 events28 affected279 at risk EG003
Hypothyroidism	Endocrine disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0013 events3 affected279 at risk EG00224 events23 affected279 at risk EG003
Central serous chorioretinopathy	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0009 events9 affected232 at risk EG00119 events19 affected279 at risk EG00234 events27 affected279 at risk EG003
Dry eye	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0012 events2 affected279 at risk EG0022 events2 affected279 at risk EG003
Uveitis	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG00214 events12 affected279 at risk EG003
Vision blurred	Eye disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected232 at risk EG0019 events8 affected279 at risk EG00217 events12 affected279 at risk EG003
Abdominal pain	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected232 at risk EG00111 events9 affected279 at risk EG00239 events22 affected279 at risk EG003
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected232 at risk EG00111 events11 affected279 at risk EG00229 events21 affected279 at risk EG003
Constipation	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00010 events9 affected232 at risk EG00121 events21 affected279 at risk EG00224 events16 affected279 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00090 events78 affected232 at risk EG001131 events113 affected279 at risk EG002186 events85 affected279 at risk EG003
Dry mouth	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected232 at risk EG0012 events2 affected279 at risk EG00210 events10 affected279 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG0008 events8 affected232 at risk EG0015 events5 affected279 at risk EG00223 events16 affected279 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00038 events37 affected232 at risk EG00141 events41 affected279 at risk EG00296 events64 affected279 at risk EG003
Stomatitis	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00015 events12 affected232 at risk EG0016 events6 affected279 at risk EG00215 events11 affected279 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 27.0	Systematic Assessment	EG00018 events16 affected232 at risk EG00131 events31 affected279 at risk EG00272 events45 affected279 at risk EG003
Asthenia	General disorders	MedDRA 27.0	Systematic Assessment	EG00012 events11 affected232 at risk EG00122 events19 affected279 at risk EG00268 events36 affected279 at risk EG003
Chills	General disorders	MedDRA 27.0	Systematic Assessment	EG0009 events8 affected232 at risk EG00113 events13 affected279 at risk EG00219 events11 affected279 at risk EG003
Fatigue	General disorders	MedDRA 27.0	Systematic Assessment	EG00035 events34 affected232 at risk EG00141 events38 affected279 at risk EG00284 events56 affected279 at risk EG003
Influenza like illness	General disorders	MedDRA 27.0	Systematic Assessment	EG0003 events2 affected232 at risk EG0014 events4 affected279 at risk EG00214 events12 affected279 at risk EG003
Mucosal inflammation	General disorders	MedDRA 27.0	Systematic Assessment	EG0007 events7 affected232 at risk EG0015 events5 affected279 at risk EG00216 events12 affected279 at risk EG003
Oedema peripheral	General disorders	MedDRA 27.0	Systematic Assessment	EG00010 events9 affected232 at risk EG00114 events13 affected279 at risk EG00236 events27 affected279 at risk EG003
Pain	General disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0011 events1 affected279 at risk EG0028 events8 affected279 at risk EG003
Pyrexia	General disorders	MedDRA 27.0	Systematic Assessment	EG00055 events46 affected232 at risk EG00154 events48 affected279 at risk EG002120 events58 affected279 at risk EG003
COVID-19	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG0027 events5 affected279 at risk EG003
Conjunctivitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0013 events3 affected279 at risk EG00214 events13 affected279 at risk EG003
Folliculitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG00219 events12 affected279 at risk EG003
Influenza	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0011 events1 affected279 at risk EG00213 events10 affected279 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected232 at risk EG0013 events3 affected279 at risk EG00241 events27 affected279 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected232 at risk EG0014 events4 affected279 at risk EG00223 events22 affected279 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0013 events3 affected279 at risk EG00217 events10 affected279 at risk EG003
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG00224 events18 affected279 at risk EG003
Sunburn	Injury, poisoning and procedural complications	MedDRA 27.0	Systematic Assessment	EG00014 events12 affected232 at risk EG00110 events10 affected279 at risk EG00250 events26 affected279 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00014 events14 affected232 at risk EG00125 events24 affected279 at risk EG00269 events52 affected279 at risk EG003
Amylase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0009 events9 affected232 at risk EG00120 events17 affected279 at risk EG00272 events40 affected279 at risk EG003
Aspartate aminotransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00014 events14 affected232 at risk EG00122 events20 affected279 at risk EG00261 events42 affected279 at risk EG003
Blood alkaline phosphatase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00015 events13 affected232 at risk EG00120 events19 affected279 at risk EG00246 events33 affected279 at risk EG003
Blood bilirubin increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected232 at risk EG0018 events8 affected279 at risk EG00218 events11 affected279 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00052 events48 affected232 at risk EG00174 events67 affected279 at risk EG002308 events96 affected279 at risk EG003
Blood creatinine increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00017 events17 affected232 at risk EG00117 events17 affected279 at risk EG00262 events35 affected279 at risk EG003
Blood lactate dehydrogenase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected232 at risk EG0015 events5 affected279 at risk EG00215 events9 affected279 at risk EG003
Blood thyroid stimulating hormone increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0010 events0 affected279 at risk EG00212 events11 affected279 at risk EG003
Ejection fraction decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0012 events2 affected279 at risk EG0026 events6 affected279 at risk EG003
Gamma-glutamyltransferase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0015 events5 affected279 at risk EG00221 events16 affected279 at risk EG003
Lipase increased	Investigations	MedDRA 27.0	Systematic Assessment	EG00025 events21 affected232 at risk EG00127 events20 affected279 at risk EG002200 events75 affected279 at risk EG003
Weight decreased	Investigations	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0017 events7 affected279 at risk EG00212 events8 affected279 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG00012 events12 affected232 at risk EG00120 events19 affected279 at risk EG00238 events25 affected279 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected232 at risk EG0017 events7 affected279 at risk EG00223 events11 affected279 at risk EG003
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected232 at risk EG0015 events4 affected279 at risk EG00217 events12 affected279 at risk EG003
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 27.0	Systematic Assessment	EG0005 events5 affected232 at risk EG0013 events3 affected279 at risk EG00227 events15 affected279 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00034 events33 affected232 at risk EG00148 events42 affected279 at risk EG002134 events70 affected279 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0012 events2 affected279 at risk EG00220 events18 affected279 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0011 events1 affected279 at risk EG0029 events8 affected279 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG00018 events17 affected232 at risk EG00114 events12 affected279 at risk EG00262 events42 affected279 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.0	Systematic Assessment	EG0009 events8 affected232 at risk EG0018 events8 affected279 at risk EG00238 events25 affected279 at risk EG003
Skin papilloma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0011 events1 affected279 at risk EG00222 events15 affected279 at risk EG003
Dizziness	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected232 at risk EG0014 events4 affected279 at risk EG00213 events12 affected279 at risk EG003
Dysgeusia	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG0007 events7 affected232 at risk EG0015 events5 affected279 at risk EG0026 events6 affected279 at risk EG003
Headache	Nervous system disorders	MedDRA 27.0	Systematic Assessment	EG00011 events11 affected232 at risk EG00116 events16 affected279 at risk EG00271 events45 affected279 at risk EG003
Insomnia	Psychiatric disorders	MedDRA 27.0	Systematic Assessment	EG0004 events4 affected232 at risk EG0015 events5 affected279 at risk EG00219 events17 affected279 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0002 events2 affected232 at risk EG0018 events8 affected279 at risk EG00232 events26 affected279 at risk EG003
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0003 events3 affected232 at risk EG0014 events4 affected279 at risk EG00219 events18 affected279 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0006 events5 affected232 at risk EG0015 events4 affected279 at risk EG00212 events10 affected279 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0010 events0 affected279 at risk EG00218 events13 affected279 at risk EG003
Actinic keratosis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0000 events0 affected232 at risk EG0013 events2 affected279 at risk EG00222 events14 affected279 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0012 events2 affected279 at risk EG00227 events25 affected279 at risk EG003
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00013 events12 affected232 at risk EG00128 events28 affected279 at risk EG00234 events23 affected279 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0006 events6 affected232 at risk EG0017 events7 affected279 at risk EG00224 events21 affected279 at risk EG003
Erythema	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00010 events10 affected232 at risk EG00117 events15 affected279 at risk EG00251 events33 affected279 at risk EG003
Hyperkeratosis	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG0001 events1 affected232 at risk EG0012 events2 affected279 at risk EG00213 events8 affected279 at risk EG003
Photosensitivity reaction	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00016 events16 affected232 at risk EG00142 events40 affected279 at risk EG00266 events45 affected279 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00028 events24 affected232 at risk EG00119 events18 affected279 at risk EG00266 events34 affected279 at risk EG003
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00067 events62 affected232 at risk EG00196 events81 affected279 at risk EG002106 events63 affected279 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 27.0	Systematic Assessment	EG00034 events31 affected232 at risk EG00151 events44 affected279 at risk EG00211 events10 affected279 at risk EG003
Hypertension	Vascular disorders	MedDRA 27.0	Systematic Assessment	EG00011 events11 affected232 at risk EG00121 events21 affected279 at risk EG00252 events39 affected279 at risk EG003

ID	Term
D018358	Neuroendocrine Tumors
D017599	Neuroectodermal Tumors
D009373	Neoplasms, Germ Cell and Embryonal
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D009380	Neoplasms, Nerve Tissue
D018326	Nevi and Melanomas
D012878	Skin Neoplasms
D009371	Neoplasms by Site
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D013449	Sulfonamides
D000577	Amides
D009930	Organic Chemicals
D013450	Sulfones
D013457	Sulfur Compounds
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds

ID	Term
C000594389	atezolizumab
C574276	cobimetinib
D000077484	Vemurafenib