Study of Cemiplimab in Adults With Cervical Cancer | NCT03257267

NCT03257267

ID	Type	Description	Link
2017-000350-19	EudraCT Number

Status Module

Name	Class
Sanofi	INDUSTRY

Description Module

Label	Type	Description	Intervention Names
Experimental Therapy	Experimental	Cemiplimab	Drug: Cemiplimab
Control Therapy	Active Comparator	Investigator choice (IC) chemotherapy	Drug: Investigator Choice (IC) Chemotherapy

Name	Type	Description	Arm Group Labels	Other Names
Cemiplimab	Drug	Intravenous (IV) administration every 3 weeks (Q3W)	Experimental Therapy

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Survival (OS)	Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.	From first dose up to 90 following last dose (~42 months)
Overall Survival (OS) in the SCC Population	Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.	From first dose up to 90 following last dose (~42 months)

Secondary Outcomes

Measure	Description	Time Frame
Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)	PFS was defined as the time from randomization to the date of the first documented tumor progression (radiographic) or death due to any cause. Participants who did not have a documented tumor progression or death were censored on the date of their last evaluable tumor assessment.

Eligibility Module

Eligibility Criteria

The criteria listed below are not intended to contain all considerations relevant to a patient's potential participation in this clinical trial.

Key Inclusion Criteria:

Recurrent, persistent, and/or metastatic cervical cancer with squamous cell histology, for which there is not a curative-intent option (surgery or radiation therapy with or without chemotherapy).
- Acceptable histologies (squamous carcinoma, adenocarcinoma, and adenosquamous carcinoma) as defined in the protocol
Tumor progression or recurrence after treatment with platinum therapy (must have been used to treat metastatic, persistent, or recurrent cervical cancer)
Patient must have measurable disease as defined by RECIST 1.1.
Eastern Cooperative Oncology Group (ECOG) performance status ≤1
≥18 years old
Adequate organ or bone marrow function
Received prior bevacizumab therapy or had clinically documented reason why not administered
Received prior paclitaxel therapy or had clinically documented reason why not administered

Key Exclusion Criteria:

Ongoing or recent (within 5 years) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments
Prior treatment with an agent that blocks the PD-1/PD-L1 pathway
Prior treatment with other systemic immune-modulating agents that was
1. within fewer than 4 weeks (28 days) of the enrollment date, or
2. associated with irAEs of any grade within 90 days prior to enrollment, or
3. associated with toxicity that resulted in discontinuation of the immune modulating agent
Active or untreated brain metastases
Immunosuppressive corticosteroid doses (>10 mg prednisone daily or equivalent) within 4 weeks prior to the first dose of study drug cemiplimab or IC chemo)
Active infection requiring therapy
History of pneumonitis within the last 5 years
History of documented allergic reactions or acute hypersensitivity reaction attributed to antibody treatments
Concurrent malignancy other than cervical cancer and/or history of malignancy other than cervical cancer within 3 years of date of first planned dose of study drug cemiplimab or IC chemo), except for tumors with negligible risk of metastasis or death, such as adequately treated cutaneous squamous cell carcinoma or basal cell carcinoma of the skin or ductal carcinoma in situ of the breast. Patients with hematologic malignancies (eg, chronic lymphocytic leukemia) are excluded.

Note: Other protocol defined Inclusion/Exclusion apply

Name	Affiliation	Role
Clinical Trial Management	Regeneron Pharmaceuticals	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Arizona Oncology Associates		Phoenix	Arizona	85016	United States
Arizona Oncology Associates

PubMed Identifier	Type	Citation	Retractions
35922251	Derived	Oaknin A, Monk BJ, Vergote I, Cristina de Melo A, Kim YM, Lisyanskaya AS, Samouelian V, Kim HS, Gotovkin EA, Damian F, Chang CL, Takahashi S, Li J, Mathias M, Fury MG, Ivanescu C, Reaney M, LaFontaine PR, Lowy I, Harnett J, Chen CI, Tewari KS. EMPOWER CERVICAL-1: Effects of cemiplimab versus chemotherapy on patient-reported quality of life, functioning and symptoms among women with recurrent cervical cancer. Eur J Cancer. 2022 Oct;174:299-309. doi: 10.1016/j.ejca.2022.03.016. Epub 2022 Jul 31.
35139273

Label	URL
A Plain Language Summary is available on TrialSummaries.com	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
FG001

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	Apr 14, 2021	Mar 11, 2022

Arm/Group Information

ID	Title	Description
BG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
BG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
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

Overall Survival (OS)

Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.

The full analysis set (FAS) included all randomized participants.

Posted

Median

95% Confidence Interval

Months

From first dose up to 90 following last dose (~42 months)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
OG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Units	Counts
Participants	OG000304 OG001304

Title

Denominators

Categories

Title	Measurements
	OG00011.7(9.6 to 13.4) OG0018.5(7.5 to 9.6)

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		Stratified Log-rank Test		<0.00001	One-sided p-value	Hazard Ratio (HR)	0.665			2-Sided	95	0.555	0.796					Superiority

Secondary

Progression-free Survival (PFS) Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

PFS was defined as the time from randomization to the date of the first documented tumor progression (radiographic) or death due to any cause. Participants who did not have a documented tumor progression or death were censored on the date of their last evaluable tumor assessment.

The FAS included all randomized participants.

Posted

Median

95% Confidence Interval

Months

Time from randomization to the date of the first documented tumor progression or death due to any cause (assessed up to 40 months)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
OG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Secondary

Objective Response Rate (ORR) Assessed by Investigator Using RECIST 1.1

ORR was defined as the number of participants who achieved complete response (CR) or partial response (PR) as per RECIST 1.1. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeters (mm) (<1 centimeter [cm]). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

The FAS included all randomized participants.

Posted

Count of Participants

Participants

From date of randomization up to 40 months

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
OG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Secondary

Duration of Response (DOR) Assessed Per RECIST 1.1

DOR was defined as the time from the date of first response (CR or PR) to the date of the first documented progressive disease (per RECIST 1.1) or death due to any cause. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm (<1 cm). PR: At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Participants who never progressed while being followed was censored at the last valid tumor measurement. DOR was determined by Kaplan-Meier estimate.

The FAS included all randomized participants with confirmed CR or PR. Here 'n' = number of evaluable participants at a specified timeframe.

Posted

Median

95% Confidence Interval

Months

Time from the date of first response to the date of the first documented progressive disease or death due to any cause (up to 40 months)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
OG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Secondary

Quality of Life (QoL): Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) of Global Health Status /Quality of Life (GHS/QoL) and Physical Functioning Scales

EORTC QLQ-C30 is a 30-question tool used to assess the overall QoL in cancer participants. It consisted of 15 domains: 1 GHS/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Most items are scored 1 ("not at all") to 4 ("very much") except for the items contributing to the GHS/QoL, which are scored 1 ("very poor") to 7 ("excellent"). A linear transformation was applied to the raw scores so that all transformed scores lie between 0 to 100. For the GHS/QoL and 5 functional scales a high score indicates better global health status/functioning and a negative change from baseline indicated less improvement. For the symptom scales, a high score indicates a higher level of symptoms, and a negative change from baseline indicated an improvement in symptoms.

The FAS included all randomized participants.

Posted

Least Squares Mean

95% Confidence Interval

Score on a Scale

From Cycle 1 Day 1 up to 40 months (Each cycle = 42 days)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Secondary

Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, and TEAEs Leading to Death

An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A Treatment-emergent adverse event (TEAE) was defined as those that are not present at baseline or represent the exacerbation of a pre-existing condition during the on-treatment period. A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in any of the following outcomes: death, life- threatening, required initial or prolonged in-patient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or considered as medically important event. Any TEAE included participants with both serious and non-serious TEAEs. Number of participants with TEAEs, serious TEAEs, and TEAEs leading to death were reported.

The safety analysis set (SAF) included all randomized participants who received any study drug. Here 'n' = number of evaluable participants at a specified timeframe.

Posted

Count of Participants

Participants

From first dose up to 90 following last dose (~36 months)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Secondary

Number of Participants With New or Worsened Laboratory Results by National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) Grade

Laboratory parameters included hematology, electrolytes, chemistry (other), and liver function. Clinically significant abnormalities were determined by the investigator based on NCI-CTCAE Grade where Grade 1 = Mild, Grade 2 = moderate, Grade 3 = severe; Grade 4 = life threatening or disabling; Grade 5 = death. Participants with at least 1 lab abnormality Graded 3/4 in hematology, electrolytes, chemistry (other), or liver function reported.

The SAF included all randomized participants who received any study drug. Here 'n' = number of evaluable participants at a specified timeframe.

Posted

Count of Participants

Participants

From first dose up to 90 following last dose (~36 months)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
OG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

Primary

Overall Survival (OS) in the SCC Population

Overall survival was defined as the time from randomization to the date of death due to any cause. A participant who had not died was censored at the last known date of contact.

All randomized participants who presented SCC (Squamous cell carcinoma) histology. Here 'n' = the number of evaluable participants

Posted

Median

95% Confidence Interval

Months

From first dose up to 90 following last dose (~42 months)

ID	Title	Description
OG000	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.
OG001	Investigator Choice (IC) Chemotherapy	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.

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	Cemiplimab	Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.	234	300	100	300	239	300
EG001	Chemotherapy*	Participants received IC of chemotherapy (options listed by class): (1) Antifolate: pemetrexed 500 mg per meter square (mg/m^2) on Day 1; (2) Topoisomerase 1 inhibitor: topotecan 1 mg/m^2 daily for 5 days, starting on Day 1 or irinotecan 100 mg/m^2 weekly (Days 1, 8, 15 and 22), followed by 10 to 14 days rest, for a 42-day (6-week) cycle; (3) Nucleoside analogue: gemcitabine 1000 mg/m^2 on Days 1 and 8; (4) Vinca alkaloid: vinorelbine 30 mg/m^2 IV infusion based on body surface area for Q3W up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.	249	290	84	290	253	290
EG002	Chemotherapy to Cemiplimab*	Treatment until disease progression, unacceptable toxicity, or voluntary withdrawal from the study, or until 96 weeks (16 cycles, each 6 weeks). Participants received a fixed dose of 350 milligrams (mg) of cemiplimab intravenous (IV) infusion on Day 1 of every 3 weeks (Q3W) for up to 96 weeks (up to 16 cycles of 6 weeks each) or until progression of disease or unacceptable toxicity, voluntary withdrawal from the study.	2	8	1	8	4	8

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Urinary tract infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG00019 events15 affected300 at risk EG00113 events11 affected290 at risk EG0020 events0 affected8 at risk
Pneumonia	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0005 events5 affected300 at risk EG0014 events3 affected290 at risk EG0020 events0 affected8 at risk
Pyelonephritis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0004 events4 affected300 at risk EG0013 events3 affected290 at risk EG0020 events0 affected8 at risk
Cellulitis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0004 events1 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Pyelonephritis acute	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Catheter site infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Gastroenteritis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Gastroenteritis viral	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Infected lymphocele	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Neutropenic sepsis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Pelvic abscess	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Peritonitis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Respiratory tract infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Skin infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Staphylococcal bacteraemia	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Staphylococcal infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Streptococcal sepsis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Toxic shock syndrome streptococcal	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Urosepsis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0005 events3 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Clostridium difficile infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Device related infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Empyema	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Kidney infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0003 events2 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Ophthalmic herpes zoster	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Pyomyositis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Sepsis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Staphylococcal sepsis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Stoma site infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Urinary tract infection bacterial	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Viral rash	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Viral upper respiratory tract infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG00119 events14 affected290 at risk EG0020 events0 affected8 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG0016 events6 affected290 at risk EG0020 events0 affected8 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0014 events3 affected290 at risk EG0020 events0 affected8 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0013 events3 affected290 at risk EG0020 events0 affected8 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events2 affected300 at risk EG0013 events3 affected290 at risk EG0020 events0 affected8 at risk
Vomiting	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0013 events3 affected290 at risk EG0021 events1 affected8 at risk
Ileus	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Diverticular perforation	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Haematochezia	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Colitis	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Colonic fistula	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Duodenal ulcer	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Gastritis	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Nausea	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0010 events0 affected290 at risk EG0021 events1 affected8 at risk
Oral papule	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Rectal perforation	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0005 events5 affected300 at risk EG0013 events3 affected290 at risk EG0020 events0 affected8 at risk
Renal failure	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Chronic kidney disease	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Cystitis haemorrhagic	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Haematuria	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0004 events3 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Renal colic	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Renal impairment	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Ureteric obstruction	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Urinary tract obstruction	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Pyrexia	General disorders	MedDRA (25.1)	Systematic Assessment	EG0004 events4 affected300 at risk EG0017 events6 affected290 at risk EG0020 events0 affected8 at risk
Catheter site thrombosis	General disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Pain	General disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Performance status decreased	General disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Asthenia	General disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Death	General disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Hyperpyrexia	General disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Influenza like illness	General disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Soft tissue inflammation	General disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Sudden death	General disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Vascular stent thrombosis	General disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Transfusion reaction	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Overdose	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Cystitis radiation	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Device use error	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Spinal compression fracture	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Blood creatinine increased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Lymphocyte count decreased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Neutrophil count decreased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Blood creatine phosphokinase MB increased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Platelet count decreased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hypomagnesaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Flank pain	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Arthritis	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Groin pain	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Spondylolisthesis	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Seizure	Nervous system disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Ischaemic stroke	Nervous system disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Arterial haemorrhage	Vascular disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Deep vein thrombosis	Vascular disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hypotension	Vascular disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hypovolaemic shock	Vascular disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Embolism arterial	Vascular disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Subclavian vein thrombosis	Vascular disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Female genital tract fistula	Reproductive system and breast disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0012 events2 affected290 at risk EG0020 events0 affected8 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Uterine haemorrhage	Reproductive system and breast disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Cardiac failure	Cardiac disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Autoimmune pericarditis	Cardiac disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Pericardial effusion	Cardiac disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Hypersensitivity	Immune system disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Contrast media allergy	Immune system disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Device occlusion	Product Issues	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Hypothyroidism	Endocrine disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Cataract	Eye disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA (25.1)	Systematic Assessment	EG0004 events4 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Cholecystitis acute	Hepatobiliary disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA (25.1)	Systematic Assessment	EG0003 events3 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Anxiety	Psychiatric disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Personality change	Psychiatric disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Diarrhoea infectious	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Urethritis	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Proctalgia	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Proctitis	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Postrenal failure	Renal and urinary disorders	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0011 events1 affected290 at risk EG0020 events0 affected8 at risk
Procedural nausea	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Secondary adrenocortical insufficiency	Endocrine disorders	MedDRA (25.1)	Systematic Assessment	EG0001 events1 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG00074 events63 affected300 at risk EG001175 events100 affected290 at risk EG0020 events0 affected8 at risk
Vomiting	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG00065 events49 affected300 at risk EG001101 events66 affected290 at risk EG0020 events0 affected8 at risk
Constipation	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG00050 events46 affected300 at risk EG00164 events58 affected290 at risk EG0021 events1 affected8 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG00061 events35 affected300 at risk EG00160 events41 affected290 at risk EG0021 events1 affected8 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG00031 events28 affected300 at risk EG00152 events34 affected290 at risk EG0020 events0 affected8 at risk
Stomatitis	Gastrointestinal disorders	MedDRA (25.1)	Systematic Assessment	EG00012 events12 affected300 at risk EG00124 events22 affected290 at risk EG0020 events0 affected8 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG00099 events79 affected300 at risk EG001161 events128 affected290 at risk EG0020 events0 affected8 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG00011 events9 affected300 at risk EG00175 events45 affected290 at risk EG0020 events0 affected8 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA (25.1)	Systematic Assessment	EG0002 events2 affected300 at risk EG00117 events15 affected290 at risk EG0020 events0 affected8 at risk
Pyrexia	General disorders	MedDRA (25.1)	Systematic Assessment	EG00054 events36 affected300 at risk EG001117 events62 affected290 at risk EG0022 events2 affected8 at risk
Asthenia	General disorders	MedDRA (25.1)	Systematic Assessment	EG00037 events35 affected300 at risk EG00163 events45 affected290 at risk EG0020 events0 affected8 at risk
Fatigue	General disorders	MedDRA (25.1)	Systematic Assessment	EG00054 events52 affected300 at risk EG00181 events45 affected290 at risk EG0020 events0 affected8 at risk
Oedema peripheral	General disorders	MedDRA (25.1)	Systematic Assessment	EG00022 events22 affected300 at risk EG00116 events16 affected290 at risk EG0020 events0 affected8 at risk
Neutrophil count decreased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0007 events3 affected300 at risk EG00164 events26 affected290 at risk EG0020 events0 affected8 at risk
Alanine aminotransferase increased	Investigations	MedDRA (25.1)	Systematic Assessment	EG00014 events14 affected300 at risk EG00126 events20 affected290 at risk EG0020 events0 affected8 at risk
Aspartate aminotransferase increased	Investigations	MedDRA (25.1)	Systematic Assessment	EG00019 events14 affected300 at risk EG00125 events19 affected290 at risk EG0020 events0 affected8 at risk
Blood creatinine increased	Investigations	MedDRA (25.1)	Systematic Assessment	EG00026 events19 affected300 at risk EG00116 events16 affected290 at risk EG0020 events0 affected8 at risk
White blood cell count decreased	Investigations	MedDRA (25.1)	Systematic Assessment	EG0003 events2 affected300 at risk EG00135 events17 affected290 at risk EG0020 events0 affected8 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG00049 events46 affected300 at risk EG00155 events46 affected290 at risk EG0020 events0 affected8 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG00026 events23 affected300 at risk EG00119 events19 affected290 at risk EG0020 events0 affected8 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG00023 events22 affected300 at risk EG00120 events17 affected290 at risk EG0020 events0 affected8 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA (25.1)	Systematic Assessment	EG0004 events4 affected300 at risk EG00121 events16 affected290 at risk EG0020 events0 affected8 at risk
Urinary tract infection	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG00036 events27 affected300 at risk EG00125 events18 affected290 at risk EG0020 events0 affected8 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG00037 events33 affected300 at risk EG00129 events28 affected290 at risk EG0020 events0 affected8 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG00038 events33 affected300 at risk EG00111 events8 affected290 at risk EG0020 events0 affected8 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA (25.1)	Systematic Assessment	EG00020 events18 affected300 at risk EG0019 events8 affected290 at risk EG0020 events0 affected8 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA (25.1)	Systematic Assessment	EG00029 events19 affected300 at risk EG00122 events19 affected290 at risk EG0020 events0 affected8 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA (25.1)	Systematic Assessment	EG00019 events18 affected300 at risk EG00115 events15 affected290 at risk EG0020 events0 affected8 at risk
Headache	Nervous system disorders	MedDRA (25.1)	Systematic Assessment	EG00043 events22 affected300 at risk EG00119 events18 affected290 at risk EG0020 events0 affected8 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG00025 events20 affected300 at risk EG00128 events21 affected290 at risk EG0020 events0 affected8 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA (25.1)	Systematic Assessment	EG00028 events27 affected300 at risk EG00122 events18 affected290 at risk EG0020 events0 affected8 at risk
Insomnia	Psychiatric disorders	MedDRA (25.1)	Systematic Assessment	EG00021 events20 affected300 at risk EG00118 events17 affected290 at risk EG0020 events0 affected8 at risk
Pelvic pain	Reproductive system and breast disorders	MedDRA (25.1)	Systematic Assessment	EG00014 events13 affected300 at risk EG00116 events16 affected290 at risk EG0020 events0 affected8 at risk
Vaginal haemorrhage	Reproductive system and breast disorders	MedDRA (25.1)	Systematic Assessment	EG00016 events15 affected300 at risk EG0019 events6 affected290 at risk EG0020 events0 affected8 at risk
Hypothyroidism	Endocrine disorders	MedDRA (25.1)	Systematic Assessment	EG00017 events17 affected300 at risk EG0010 events0 affected290 at risk EG0020 events0 affected8 at risk
Subcutaneous abscess	Infections and infestations	MedDRA (25.1)	Systematic Assessment	EG0000 events0 affected300 at risk EG0010 events0 affected290 at risk EG0021 events1 affected8 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA (25.1)	Systematic Assessment	EG0008 events8 affected300 at risk EG00138 events13 affected290 at risk EG0021 events1 affected8 at risk
Hyperthyroidism	Endocrine disorders	MedDRA (25.1)	Systematic Assessment	EG0009 events9 affected300 at risk EG0010 events0 affected290 at risk EG0021 events1 affected8 at risk

ID	Term
D002294	Carcinoma, Squamous Cell
D012008	Recurrence
D009362	Neoplasm Metastasis

ID	Term
D002277	Carcinoma
D009375	Neoplasms, Glandular and Epithelial
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D018307	Neoplasms, Squamous Cell
D020969	Disease Attributes
D010335	Pathologic Processes
D013568	Pathological Conditions, Signs and Symptoms
D009385	Neoplastic Processes